DOI: 10.1002/pbc.26772
Pediatric
Blood &
Cancer
The American Society of
Pediatric Hematology/Oncology
49th CONGRESS OF THE INTERNATIONAL SOCIETY
OF PAEDIATRIC ONCOLOGY (SIOP)
WASHINGTON, DC, USA, OCTOBER 12–15, 2017, SIOP ABSTRACTS
ABSTRACT CONTENTS:
Numbers
Numbers
O-001 - O-213
Nurses
O-177 - O-209
Award Session
AW-01-AW-08
PPO - Educational Day - Fertility
O-210 - O-213
Free Paper Session: Solid Tumours - Biology
O-001 - O-004
POSTER DISCUSSIONS
PD-001 - PD113
Free Paper Session: Epidemiology - I
O-005 - O-008
Haematology - Acute Lymphoblastic Leukaemia
PD-001 - PD-006
Free Paper Session: Supportive Care
O-009 - O-012
Haematology - Myeloid Leukemias,
Myelodysplastic and Myeloproliferative
Syndromes
PD-007 - PD-011
Haematology - Lymphomas
PD-012 - PD-016
PD-017
ORAL PRESENTATIONS
Free Paper Session: Brain Tumours - I
O-013 - O-017
Free Paper Session: All - Clinical
O-018 - O-023
Free Paper Session: Late Effects
O-024 - O-029
Free Paper Session: Myeloid Leukemia And
Transplant
O-030 - O-035
Haematology - Stem Cell Transplantation
(Haematological Diseases/Technique and
Supportive Care)
Free Paper Session: Solid Tumour Therapy
O-036 - O-041
Solid Non Brain Tumours - Neuroblastoma
PD-018 - PD-022
Free Paper Session: Brain Tumours - Ii
O-042 - O-047
Solid Non Brain Tumours - Renal Tumours
PD-023 - PD-024
Free Paper Session: Leukemia - Biology
O-048 - O-051
Solid Non Brain Tumours - Bone Tumours
PD-025 - PD-027
Free Paper Session: Neuroblastoma - Clinical
O-052 - O-055
Solid Non Brain Tumours - Soft Tissue Sarcomas
PD-028 - PD-032
Free Paper Session: Bone Tumours - Nollenburg
Prize
O-056 - O-059
Solid Non Brain Tumours - Retinoblastoma
PD-033 - PD-035
Solid Non Brain Tumours - Liver Tumours
PD-036 - PD-037
Free Paper Session: PODC
O-060 - O-065
Solid Non Brain Tumours - Germ Cell Tumours
PD-038
Free Paper Session: Neuroblastoma - Biology
O-066 - O-071
Solid Non Brain Tumours - Rare Tumours
PD-039 - PD-040
Free Paper Session: Renal Tumours
O-072 - O-077
Brain Tumours
PD-041 - PD-046
Free Paper Session: Supportive Care And
Palliative Care
O-078 - O-083
Treatment and Care - New Drugs/Experimental
Therapeutics
PD-047 - PD-052
Free Paper Session: Soft Tissue Sarcomas
O-084 - O-089
Free Paper Session: Immunotherapy
O-090 - O-095
Free Paper Session: PPO - I
O-096 - O-101
Free Paper Session: PPO - Ii
O-102 - O-107
Free Paper Session: PODC Supportive Care
O-108 - O-113
Free Paper Session: Epidemiology - Ii
O-114 - O-119
Free Paper Session: Leukemia And Lymphoma
O-120 - O-125
Free Paper Session: Liver Tumours And Rare
Tumours
O-126 - O-131
CCI - Childhood Cancer International
O-132 - O-147
Treatment and Care - Supportive Care
PD-053 - PD-057
Treatment and Care - Psychosocial (PPO)
PD-058 - PD-077
Treatment and Care - Nursing
PD-078 - PD-087
Treatment and Care - Biology and Pathology
PD-088 - PD-089
Epidemiology - Pathway of Care
PD-090 - PD-094
Late Effects
PD-095 - PD-099
IPSO Poster Discussion
PD-100 - PD-113
POSTER PRESENTATIONS
P-001 - P-592
Haematology - Acute Lymphoblastic Leukaemia
P-001 - P-064
P-065 - P-078
IPSO
O-148 - O-176
Session 1: Neuroblastoma & Fertility
O-148 - O-152
Haematology - Myeloid Leukemias,
Myelodysplastic and Myeloproliferative
Syndromes
Session 2: Renal Tumours & Lung Metastasis
O-153 - O-159
Haematology - Lymphomas
P-079 - P-109
(PBC-Session): The Robert Arceci Best Of IPSO
O-160 - O-163
O-164 - O-170
Haematology - Stem Cell Transplantation
(Haematological Diseases/Technique and
Supportive Care)
P-110 - P-121
Rare Tumors (+ 1 education)
Liver Tumors, GCT and RMS (+ 1 education)
O-171 - O-176
Solid Non Brain Tumours - Neuroblastoma
P-122 - P-166
Pediatr Blood Cancer. 2017;64:e26772.
https://doi.org/10.1002/pbc.26772
wileyonlinelibrary.com/journal/pbc
c 2017 Wiley Periodicals, Inc.
S1 of S518
SIOP ABSTRACTS
S2 of S518
Numbers
Numbers
Solid Non Brain Tumours - Renal Tumours
P-167 - P-191
POSTER VIEWING
PO-001 -PO-135
Haematology - Acute Lymphoblastic Leukaemia
PO-001 - PO-010
PO-011 - P-013
Solid Non Brain Tumours - Bone Tumours
P-192 - P-206
Solid Non Brain Tumours - Soft Tissue Sarcomas
P-207 - P-227
Solid Non Brain Tumours - Retinoblastoma
P-228 - P-249
Haematology - Myeloid Leukemias,
Myelodysplastic and Myeloproliferative
Syndromes
Solid Non Brain Tumours - Liver Tumours
P-250 - P-260
Haematology - Lymphomas
PO-013 - PO-017
Solid Non Brain Tumours - Germ Cell Tumours
P-261 - P-266
PO-018 - PO-020
Solid Non Brain Tumours - Rare Tumours
P-267 - P-288
Haematology - Stem Cell Transplantation
(Haematological Diseases/Technique and
Supportive Care)
Solid Non Brain Tumours - Histiocytosis
P-289 - P-294
Solid Non Brain Tumours - Neuroblastoma
PO-021 - PO-028
Brain Tumours
P-295 - P-355
Solid Non Brain Tumours - Renal Tumours
PO-029 - PO-031
Treatment and Care - Surgery (IPSO)
P-356 - P-360
Solid Non Brain Tumours - Bone Tumours
PO-032 - PO-037
Treatment and Care - Radiation Oncology (PROS)
P-361 - P-379
Solid Non Brain Tumours - Soft Tissue Sarcomas
PO-038 - PO-043
Treatment and Care - New Drugs/Experimental
Therapeutics
P-380 - P-394
Solid Non Brain Tumours - Retinoblastoma
PO-044 - PO-047
Solid Non Brain Tumours - Liver Tumours
PO-048 - PO-049
Solid Non Brain Tumours - Germ Cell Tumours
PO-050 - PO-052
Solid Non Brain Tumours - Rare Tumours
PO-053 - PO-054
Solid Non Brain Tumours - Histiocytosis
PO-055
Brain Tumours
PO-056 - PO-065
Treatment and Care - Surgery (IPSO)
PO-066 - PO-075
PO-076
Treatment and Care - Supportive Care
P-395 - P-475
Treatment and Care - Palliative Care
P-476 - P-485
Treatment and Care - Psychosocial (PPO)
P-486 - P-494
Treatment and Care - Nursing
P-495 - P-514
Treatment and Care - Biology and Pathology
P-515 - P-525
Imaging
P-526 - P-531
Epidemiology - Pathway of Care
P-532 - P-556
Treatment and Care - New Drugs/Experimental
Therapeutics
Late Effects
P-557 - P-579
Treatment and Care - Supportive Care
PO-077 - PO-095
Childhood Cancer International (CCI)
P-580 - P-586
Treatment and Care - Palliative Care
PO-096
Other
P-587 - P-592
Treatment and Care - Psychosocial (PPO)
PO-097 - PO-129
Epidemiology - Pathway of Care
PO-130 - PO-134
Late Effects
PO-135
Pediatric
Blood &
Cancer
A B ST R AC T S
The American Society of
Pediatric Hematology/Oncology
SIOP ABSTRACTS
SI OP AWARD S
AW-01 Procedural Sedation in Pediatric
Oncology by non Anaesthesiologists- A Randomized
Comparative Trial of Ketamine - Midazolam
Combination vs Propofol
M. Kalra1 , V. C2 , A. Bakshi2 , G. Mandhani1 , A. Mahajan1
1 Indraprastha
Apollo Hospital, Pediatric Hematology Oncology, Delhi,
India; 2 Indraprastha Apollo Hospital, Pediatrics, Delhi, India
Background/Objectives: Both ketamine-midazolam and
propofol are frequently used in pediatric-oncology units for
procedural sedation. However, there are no prospective, randomized comparative trials (RCT) comparing them. This
is especially important for developing countries where due
to limited resources; non-anesthesiologists (trained pediatricians) usually perform the procedural sedation.
Objective is to compare ketamine+midazolam (Group A)
and propofol (Group B) as sedative agents for intrathecal
chemotherapy.
Design/Methods: A partially-blinded, RCT was conducted
between July 2015-February 2017 after institutional ethics
approval. Children aged 1-12 years requiring intravenous
sedation for intrathecal chemotherapy were included. Patients
were randomized using computer generated randomization
tables after obtaining written consent. Initial doses used were,
ketamine at 2mg/kg, midazolam at 0.2 mg/kg and propofol
at 2.5mg/kg as per standard recommendations. Time to sedation, dose required, depth of sedation (using Modified Ramsey
scale), vital parameters, time and smoothness of recovery and
emergence phenomenon were documented.
Results: A total of 152 patients were enrolled (Group A: 76,
Group B: 76). Nine patients had failure of sedation (all in
Group B). Thirteen in group A and 51 in-group B required
top up sedation. Mean time to sedation in-group B was shorter
(p=0.000). Mean heart rate in-group A was higher (p=0.000).
Transient drop in saturation was noted in 10 patients in-group
A and in 20 in-group B (p=0.174). Mean depth of sedation ingroup A was greater than in-group B (p=0.000). Mean time to
recovery in-group B was shorter than in-group A (p=0.000).
Emergence symptoms were experienced by 38 patients ingroup A and 7 in-group B (p=0.000).
Conclusions: Ketamine-Midazolam combination appears
to be safer and more effective when used by nonanaesthesiologists. Propofol has a significantly faster onset,
quicker recovery, smoother emergence from sedation, but
at the recommended initial doses it provides inadequate
sedation.
AW-02 Treatment Results of a Strategy for the
Management of Mature B-Cell Malignancies in
Central America. A Report of the Cooperative
Group AHOPCA
A. Pena-Hernandez1 , R. Ortiz2 , C. Garrido3 , W. Gomez-Garcia4 , S.
Fuentes-Alabi5 , R. Martinez6 , M. Metzger7 , R.C. Ribeiro7 , G.
Chantada8
1 Hospital
Escuela, Oncology, Tegucigalpa, Honduras; 2 Hospital La
Mascota, Oncology, Managua, Nicaragua; 3 UNOP, Oncology, Guatemala,
Guatemala; 4 Hospital Infantil Reid Cabral, Oncology, Santo Domingo,
Dominican Republic; 5 Hospital Bloom, Oncology, El Salvador, El Salvador;
6 Hospital de San Pedro Sula, Oncology, San Pedro Sula, Honduras; 7 St
Jude Children's Research Hospital, Oncology, memphis, USA; 8 St Jude
Children's Research Hospital, International Outreach, Memphis, USA
Background/Objectives: Treatment of mature B-cell malignancies in lower-middle income countries is challenging because of increased risk of toxicity associated with
advanced disease at presentation and limited supportive care.
AHOPCA, a collaborative group in Central America, implemented a modified BFM-based treatment regimen.
Design/Methods: Newly diagnosed patients with histologically or immunocytological diagnosis of mature B-cell malignancies diagnosed between 03/2004 and 06/2016 at 6 institutions. reatment: Murphy's Stages I-II, prephase and blocks A,
B, A (methotrexate dose 1 g/m2 in 3 hour infusion); Stage
III, prephase and blocks A,B,A,B,A,B; Stage IV, prephase
and blocks A,B,A,B,A,B (methotrexate dose 3 g/m2 in 3 hour
infusion). Patients in poor clinical conditions during induction
were given a second prephase before proceeding with Blocks
A or AA. Poor responders to the first 2 cycles were given AA
and BB blocks for the remaining cycles. Ifosfamide dose was
400 mg/m2 in blocks A or AA. Difficult cases were discussed
at Cure4kids.org.
Results: With a median follow-up of 49 months, 405 patients
were registered (386 eligible). Four patients with HIV, eight
previously treated, three cases with wrong diagnosis and
SIOP ABSTRACTS
S4 of S518
three cases treated with another treatment protocol were
excluded.177 cases had immunohistochemical characterization. Distribution was Stages I-II, 30; III, 248; IV, 99; NA,
9. The 3-year overall survival was 70% for the whole group
(86% for stages I-II, 75% for stage III and 58% for stage IVB-ALL). Events included: Death on induction (n=32), abandonment (n=23), relapse/progression (n=23), death in complete remission (n=9), second malignancy (n=1) and death of
unknown cause (n=1).
Conclusions: This simplified adapted treatment is feasible
and associated with acceptable results in settings with limited
resources. Efforts to improve results should focus on educating the community providers about the early signs of the disease and prompt referral. Improving histologic techniques is
critical to decrease the number of wrong diagnosis and allow
proper classification.
AW-03 Mapping Relapse and Relapse Detection
of Wilms Tumour - A Report from The SIOP Renal
Tumour Study Group
J. Brok1 , M. Lopez2 , V.T. Harm2 , T.D. Treger3 , R. Furtwängler4 , N.
Graf4 , C. Bergeron5 , M.M. van den Heuvel-Eibrink6 , B. de
Camargo7 , A. Verschuur8 , K. Pritchard-Jones1 , O. Olsen9 , F.
Spreafico10
1 University
College Great Ormond Street Institute of Child Health, Cancer
section, London, United Kingdom; 2 Netherlands Cancer Institute, Dept
Biometrics, Amsterdam, The Netherlands; 3 University of Cambridge, Dept.
of Paediatrics, Cambridge, United Kingdom; 4 Saarland University
Hospital, Dept. Haematology and Oncology, Homburg, Germany; 5 Centre
Léon Bérard-, Institut d'haematology and d'oncology paediatric, Lyon,
France; 6 Princess Maxima Center, Pediatric Oncology, Utrecht, The
Netherlands; 7 Instituto Nacional do Cancer, Paediatric Haemato-Oncology
Program- Research Center, Rio de Janeiro, Brazil; 8 Hôpital de la Timone
Enfant, Department of Pediatric Hematology and Oncology, Marseille,
France; 9 University College Great Ormond Street Institute of Child Health,
Dept Radiology, London, United Kingdom; 10 Fondazione IRCCS Istituto
Nazionale dei Tumori, Dept. of Hematology and Pediatric
Onco-Hematology, Milano, Italy
Background/Objectives: Children with Wilms tumor (WT)
require regular relapse surveillance, usually with abdominal
ultrasound and chest X-ray starting after surgery. We mapped
the site, timing and mode of detection of first WT relapse
using the SIOP WT 2001 study database and assessed prognostic factors for post-relapse mortality. Data were used to
evaluate current surveillance recommendations.
Design/Methods: All patients with WTs registered (20012016) in the SIOP WT 2001 study and treated with preoperative chemotherapy as per protocol were included in the
analyses.
Results: Of 4348 registered patients, 538 (12%) relapsed.
Relapse site involved lung (65%) and/or abdomen (49%), liver
(11%), bone (1%) and central nervous system (1%). Most
relapses (80%) occurred within 2 years post-surgery, with
high-risk histology tumours relapsing faster (89% by 2y).
Post-relapse overall 5-year survival rate was 61% (95% CI:
57%-66%). Surveillance imaging captured 78% of the relapses
and the remaining relapses presented with clinical symptoms ‘outside’ of routine follow-up. Relapse was identified
by abdominal ultrasound (32%), chest X-ray (30%), CT scan
of chest/abdomen (23%/7%), abdominal MRI (4%) or other
(4%). The majority (69%) of relapses were not detectable by
medical examination and only 33% of relapses were accompanied by symptoms. In multivariable analyses, overall survival
after relapse was statistically significantly (P < 0.05) poorer
for; surgery to relapse interval < 6 months, symptomatic presentation ‘outside’ planned follow-up, higher tumour volume
at initial surgery, and advanced stage/histological risk group.
Conclusions: WT relapses predominantly involve the lung
and generally occur within 2 years of nephrectomy and without symptoms. Routine surveillance imaging captured the
majority of relapses and these patients seemed to have better
post-relapse survival. In the absence of prospective trials, our
evidence indicates that current recommendations for imaging
follow-up intervals are effective and duration should focus on
the first 2-3 years after nephrectomy.
AW-04 Perinatal and Familial Risk Factors for
Soft-Tissue Sarcomas in Children, Adolescents, and
Young Adults: A Population-Based Birth Cohort
Study, Sweden, 1973-2012
P. Lupo1 , R. Luna-Gierke1 , B. Tavelin2 , M. Scheurer1 , B. Melin2 ,
K. Papworth2
1 Baylor
College of Medicine, Pediatrics, Houston, USA; 2 Umeå University,
Radiation Sciences, Umeå, Sweden
Background/Objectives: Perinatal factors have been associated with soft-tissue sarcomas (STS) in case-control studies.
However, (1) the specific contributions of factors including
fetal growth remain unknown, (2) these factors have not been
examined in large cohort studies, and (3) few assessments
have evaluated risk in specific STS subtypes. Therefore, we
sought to identify the role of perinatal and familial factors on
the risk of STS in a large population-based birth cohort.
Design/Methods: We identified 5,063,499 individuals in the
Swedish Birth Registry born during 1973-2012. Subjects
were linked to the Swedish Cancer Registry, where incident
STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including: fetal
growth, gestational age, presence of a congenital anomaly,
and parental age. Poisson regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for
associations between selected factors and STS overall, as well
as by common subtypes.
SIOP ABSTRACTS
Results: There were 673 children, adolescents, and young
adults diagnosed with STS in 77.5 million person-years of
follow-up. Having a congenital anomaly was associated with
STS risk (IRR=1.70, 95% CI: 1.23-2.35). This association
was stronger (IRR=2.89, 95% CI: 1.25-6.70) in more recent
years (2000-2012). High fetal growth was also associated with
STS during the same time period (IRR=1.87, 95% CI: 1.063.30). Being born preterm (<37 weeks) was associated with
developing embryonal rhabdomyosarcoma (IRR=2.02, 95%
CI: 1.01-4.04). Notably, advanced paternal age (>35 years)
was inversely associated with the risk of developing synovial
sarcoma (IRR=0.50, 95% CI: 0.26-0.94).
Conclusions: In this cohort study, those with congenital
anomalies and other adverse birth outcomes were more likely
to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways influencing the risk of STS. Our findings could
implicate novel mechanisms underlying susceptibility to STS
and may inform future surveillance, prevention, and treatment
efforts.
S5 of S518
in Wilms tumors, CDKN2A/B deletion in neuroblastoma, and
CDK4 amplification in rhabdomyosarcoma. Genetic patterns
unique to anatomic sub-compartments in individual patients
had functional consequences for gene expression at the RNA
and protein levels. Four general patterns of tumour evolution
were identified of which at least one strongly correlated to
clinically aggressive.
Conclusions: Even in very young patients, high-risk cancer
is a genetically dynamic disease over space and time. Intratumour genetic diversity is common and is a significant source
of error in biomarker assessment. Certain evolutionary patterns may be useful as future clinical predictors.
AW-06 CRISPR/CAS9 Based Reverse Genetics
Identifies Therapeutic Targets to Improve Therapy
Response in Paediatric Acute Lymphoblastic
Leukemia
M. Butler1 , L. van der Meer1 , J. Yu2,3 , T. Beeby1 , R. Kuiper2,3 , F.
van Leeuwen2
1 Radboudumc
AW-05 A Geography of Clones: Mapping
Somatic Mutations Over Anatomic Space in
Children with Cancer
D. Gisselsson1 , J. Karlsson1 , A. Valind1 , C. Jansson1
1 Laboratory
medicine - Lund, Clinical Genetics, Lund, Sweden
Background/Objectives: To chart genetic intratumour diversity in childhood cancer over multiple anatomic locations
and/or time points during treatment in order to (1) delineate
common routes of cancer cell evolution, (2) reveal candidate
mechanisms behind treatment resistance, and (3) gain information on intrapatient variability of clinical biomarkers.
Design/Methods: Patients were included based on the availability of two or more informative samples from the primary
tumour, taken with a minimum intersample distance of 10
mm. A total of 54 patients with neuroblastoma (n=24), Wilms
tumour (n=20) or sarcoma (n=10) have so far been subjected
to multiregional analysis of tumour tissue with high resolution
whole genome genotyping arrays (all patients) complemented
in selected cases by whole exome sequencing, targeted deep
DNA sequencing, and RNA sequencing. Between two and 20
tumour samples were analyzed per patient with a total of 230
informative tumour samples genotyped so far.
Results: The majority of cases exhibited intratumour genetic
diversity with branching evolution, including variability of
several suggested clinical biomarkers. Subclones were the
major arena of genome evolution in most primary tumors.
There were clear features of convergent evolution, including
trisomies and monosomies of whole chromosomes as well
as specific somatic gene alterations such as TP53 mutation
Amalia Children's Hospital, Laboratory of Pediatric
Oncology/ Pediatrics, Nijmegen, The Netherlands; 2 Princess Máxima
Center for Pediatric Oncology, Pediatric Hema-Oncology, Utrecht, The
Netherlands; 3 Radboud university medical center and Radboud Insitute for
Molecular Life Sciences, Department of Human Genetics, Nijmegen, The
Netherlands
Background/Objectives: The genomic characterization of
‘acute lymphoblastic leukemia’ (ALL) has greatly improved
the recognition of patients with a high relapse risk. Despite
the success of intensified treatment for ‘high-risk’ patients,
relapse and associated therapy resistance remain a significant
problem. In this study we aimed to identify therapeutic targets
that synergize with standard-of-care drugs in treating ALL.
Design/Methods: We used a CRISPR/Cas9 based loss-offunction screen to identify novel genes that control tumor
cell sensitivity towards prednisolone and asparaginase, key
components of current ALL treatment protocols. To facilitate
rapid translation to clinical practice, we focused our screen
on kinases, as potential candidates for pharmacological inhibition. Results were validated using targeted knockout and
small-molecule inhibitors.
Results: The CRISPR/Cas9 based screen has identified
genes that modulate sensitivity towards the tested drugs,
both inducing resistance as well as enhancing the susceptibility towards drug induced apoptosis. The anti-tumor
effects of asparaginase treatment impinge on changes in cell
metabolism as a result of amino acid starvation. Consistent
with this notion, we found genes either directly involved in the
amino acid response route (TRIB3) or aminoacid metabolism
(GCN2). Indeed, targeted knockout of GCN2 sensitizes cells
to asparaginase treatment whereas depletion of TRIB3 was
sufficient to render these cells more resistant.
SIOP ABSTRACTS
S6 of S518
Surprisingly, sensitivity for prednisolone was controlled by
kinases involved in Toll-like receptor signaling and betaadrenergic receptor signaling. Consistent with these findings, the use of clinically approved compounds that modulate
these pathways dramatically potentiate the anti-tumor effect
of prednisolone. Inhibition of the beta-adrenergic receptorincreased sensitivity to prednisolone mediated apoptosis up
to 30 fold.
Conclusions: We conclude from these results that our
CRISPR/Cas9 based screens can be used to (i) delineate pathways that contribute therapy resistance and (ii) identify targets
that can be selectively inhibited to improve therapy response.
AW-07 Pseudoprogression in Pediatric
Low-Grade Glioma After Radiation Therapy
D.S. Tsang1 , E.S. Murphy2 , J.T. Lucas Jr.1 , P. Lagiou3, 4 , S.
Acharya1 , T.E. Merchant1
1 Department
of Radiation Oncology, St. Jude Children's Research Hospital,
Memphis TN, USA; 2 Department of Radiation Oncology, Cleveland Clinic,
Cleveland OH, USA; 3 Department of Epidemiology, Harvard T.H. Chan
School of Public Health, Boston MA, USA; 4 Department of Hygiene,
Epidemiology and Medical Statistics, School of Medicine, National and
Kapodistrian University of Athens (NKUA), Athens, Greece
Background/Objectives: This goal of this study was to report
the incidence, management and risk factors for pseudoprogression after radiation therapy (RT) in patients with pediatric
low-grade glioma (LGG).
Design/Methods: This retrospective study included patients
aged ≤21 years with intracranial LGG treated with curativeintent RT at a single institution. Pseudoprogression was
defined as an increase in tumour size by ≥10% in at least 2
dimensions between two or three consecutive MR imaging
studies. Overall survival (OS) and event-free survival (EFS)
were measured from the first day of RT. EFS was defined
as survival without true progression or secondary high-grade
glioma.
Results: Sixty-two of 221 patients developed pseudoprogression, with a 10-year cumulative incidence of 29.0% (95%
CI 23.0-35.2). Median time to pseudoprogression was 6.1
months after RT (interquartile range [IQR] 3.5-14.6). 68% of
tumours with pseudoprogression were observed, with eventual stabilization (48%) or reduction in size (20%) over time.
Symptomatic pseudoprogression was managed with subtotal
resection, shunt/Ommaya reservoir placement, or corticosteroids in 11 (18%), 7 (11%), and 2 patients (3%), respectively. Patients with pilocytic astrocytoma (PA) had 5.4fold greater odds of developing pseudoprogression relative
to other tumours (odds ratio 95% CI 2.5–11.4, P < 0.0001).
Among 127 patients with PA, the 10-year cumulative incidence of pseudoprogression was 42.9%. In this subgroup,
pseudoprogression was associated with improved 10-year
EFS (84.5% vs. 58.5%, P = 0.008) and OS (98.0% vs. 91.2%,
P = 0.03).
Conclusion: Pseudoprogression after radiation therapy was
common, particularly in patients with pilocytic astrocytoma,
and was associated with improved survival. Awareness of the
incidence and temporal dynamics of pseudoprogression may
help avoid unnecessary salvage treatments.
AW-08 Mutations in CIC, DMD and PHOX2B
Activate the RAS-MAPK Pathway in
Neuroblastoma and Activation of this Pathway
Causes Tumor Progression
T.F. Eleveld1,2 , L. Schild1 , J. Koster2 , D.A. Zwijnenburg2 , L. Alles1 ,
M.E. Ebus1 , R. Volckmann2 , G.A. Tijtgat3 , P. van Sluis2 , H.N.
Caron3 , R. Versteeg2 , J.J. Molenaar1 ,
1 Department
of Translational Research, Princess Maxima Centre for
Childhood Oncology, Utrecht, the Netherlands; 2 Department of
Oncogenomics, Academic Medical Center of the University of Amsterdam,
Amsterdam, the Netherlands; 3 Department of Pediatric Oncology, Emma
Children′ s Hospital, Academic Medical Center of the University of
Amsterdam, Amsterdam, the Netherlands
Background/Objectives: It was recently shown that mutations affecting the RAS-MAPK pathway occur frequently in
neuroblastoma relapse tumors. We hypothesized that activation of this pathway could be associated with poor prognosis
and tumor progression. Hence the objectives were to detect
the activation state of the RAS-MAPK pathway in tumors,
correlate this to prognosis, and find and characterize additional mutations that can serve as biomarkers for pathway
activation.
Design/Methods: We generated a gene signature that can
identify the activation state of the RAS-MAPK pathway in
cell lines and tumors. These data were correlated to Whole
Genome Sequencing data to identify novel mutations that
influence activation of this pathway. Candidate mutations
were induced in cell lines using gene editing and characterized both in vitro and in vivo.
Results: We show that in primary neuroblastoma tumors activation of the RAS-MAPK pathway correlates with poor survival, and is associated with known activating mutations in
ALK and other bona fide RAS-MAPK pathway genes. From
integrative analysis, we identify mutations in PHOX2B, CIC
and DMD that activate the RAS-MAPK pathway in vitro and
we show that activation of this pathway causes tumor progression in vivo.
Conclusion: These results identify novel biomarkers of RASMAPK activation and reinforce this pathway as a promising
target in high risk neuroblastoma. Further research should
determine whether the identified mutations also function as
biomarkers for sensitivity to MEK inhibition.
SIOP ABSTRACTS
FR EE PA PER SE SSI O N : SO L I D
TUMOURS - B IOLOGY
O-001 Highly-Accumulated HIF-1A is a Potential
Therapeutic Target in the Treatment of Wilms
Tumor
M. Nelson1 , Y. Liu1 , C. Bailey1 , Y. Liu1 , J. Dome1 , Y. Wang1
1 Children's
National Medical Center, Center for Cancer and Immunology
Research, Washington- DC, USA
Background/Objectives: Five-year survival of patients with
Wilms tumor (WT) is over 90%. However, 40% of patients
with anaplastic histology WT (AHWT) and 15% of patients
with favorable histology WT (FHWT) will suffer recurrence.
Patients who survive with additional therapy are at risk
for toxicities such as infertility. Hypoxia-inducible factor 1�
(HIF-1�) is upregulated in a number of malignancies and
implicated in chemoresistance and recurrence. We investigate the prevalence of HIF-1� accumulation, its role in WT
growth, and response to treatment with echinomycin, a known
HIF-1� inhibitor, in pre-clinical WT models.
Design/Methods: Immunofluorescent staining for HIF-1�
was performed on 64 WT samples, which were scored on a
scale according to percentage of cells positively stained. HIF1� was knocked-out in the WiT49 cell line (WiT49-HIF1�ko) employing the CRISPR/Cas9 system and tumor growth
in NSG mice was compared to WiT49-wild type (WiT49-wt).
The effect of echinomycin on viability was assessed in three
patient-derived WT cell lines, including two AHWT samples,
using the MTT assay. The effect of liposomal echinomycin
(Lipo-E) on tumor growth was assessed in a patient-derived
AHWT xenograft model.
Results: Fifty percent of WT samples (n=32) had the highest
HIF 1� staining intensity score of 3 (>50% of cells staining
positively). Mice injected WiT49-wt cells resulted in tumors
with incidence of 100%, while no tumors grew from injected
WiT49-HIF1�-ko cells (P<0.001). Echinomycin was toxic
against WiT49 and all three ex-vivo WT cases in cell culture (IC50 at 1350 pM). AHWT xenografts treated with LipoE showed significant growth inhibition compared to vehicle
(P=0.04).
Conclusions: HIF-1� is prevalent in WT samples and its presence is essential for tumor growth in mice. Echinomycin treatment of AHWT xenografts impairs tumor growth. Therefore,
echinomycin holds promise as a targeted agent against WT.
O-002 Insights from the Evolutionary
Trajectories of Wilms Tumor
G. Cresswell1 , T. Chagtai2 , R. Al-Saadi2 , T. Treger2 , R. Williams2 ,
N.M. Luscombe1 , K. Pritchard-Jones2 , W. Mifsud2
S7 of S518
1 The
Francis Crick Institute, Bioinformatics and Computational Biology
Laboratory, London, United Kingdom; 2 UCL Great Ormond Street Institute
of Child Health, Developmental Biology and Cancer, London, United
Kingdom
Background/Objectives: We previously demonstrated intratumor genetic heterogeneity in multi-sampled Wilms tumors
(WT), which occurs despite a low number of genetic changes
per tumor. Frequent multifocality or bilaterality are significant treatment challenges with poorly understood mechanisms. Furthermore, only circa 50% of relapses can be predicted with current stratification criteria. To address these
issues, we need to understand better the evolutionary processes of WT development. Current experimental approaches
to tumor evolution utilise whole-genome/exome (WGS/WES)
sequencing in multi-sampled tumors, but WGS/WES may not
be an efficient approach in tumors with relatively few mutations.
Design/Methods: We combined targeted sequencing and Illumina CoreExome SNP arrays to assess genome-wide, allelespecific copy-number profiles and mutational status in a panel
of 181 genes. We developed a mixture model-based method
to model B-allele frequencies and infer cellularities of copynumber aberration (CNA) segments. We inferred per-sample
subclones by clustering segments with similar cellularities;
subclones were compared across multiple samples, and an
evolutionary trajectory was calculated for each tumor. Combined SNP array and sequencing data were available for 32
multi-sampled WTs, and SNP array data only for an additional
30 WTs.
Results: We inferred 1-10 clones per WT, showing a wide
range of evolutionary trajectories. A subset of cases show
marked evolutionary divergence, and this may explain diagnostic difficulty in diffuse anaplasia. Another subset show
striking convergent evolution for CNAs and point mutations.
Conclusions: Accurate evolutionary trajectories can be
inferred in multi-sampled WT, regardless of tumor multifocality or bilaterality, and without resource-intensive WGS/WES,
despite the low number of passenger as well as driver mutations per tumor. Many tumors show a surprisingly high number of clones/tumor, comparable to adult cancers, and there
is a wide range of evolutionary trajectories, generally unlike
adult cancers. Cases with convergent evolution suggest a previously unsuspected strong selection pressure in a subset of
WT.
O-003 Preclinical Rationale for Entinostat in
Alveolar and Embryonal Rhabdomyosarcoma
N. Bharathy1
1 Children's Cancer Therapy Development Institute, Biotechnology,
Beaverton, Usa
SIOP ABSTRACTS
S8 of S518
Background/Objectives: Rhabdomyosarcoma (RMS) is the
most common soft tissue sarcoma of childhood yet often
also occurs in adolescents and young adults. Clinically, survival amongst metastatic RMS patients has remained dismal yet unimproved for years, if not several decades. We
previously identified the class I specific histone deacetylase
inhibitor, entinostat, as a pharmacological agent that transcriptionally suppresses the Pax3:Foxo1 tumor-driving fusion
gene found in many alveolar rhabdomyosarcomas. The purpose of this study is to examine whether entinostat may
provide real therapeutic benefit for patients with embryonal
rhabdomyosarcoma (eRMS) and alveolar rhabdomyosarcoma
(aRMS).
Design/Methods: We investigated the comparative efficacy
of entinostat to other HDAC inhibitors for the full spectrum of Pax3:Foxo1/Pax7:Foxo1 positive aRMS and fusion
negative eRMS using both in vitro and in vivo models that
includes orthotopic allografts and patient derived xenografts.
In-addition, to understand the mechanism of entinostat action
in aRMS and eRMS; RNAseq, ChIP-exo, and CRISPR studies were carried out.
Results: We find that entinostat most effectively silences
Pax3:Foxo1. Entinostat delays tumor engraftment in aRMS
after radiation treatment. In combination with the chemotherapy vincristine, entinostat has strong anti-tumor activity
in aRMS/eRMS orthotopic allografts and patient-derived
xenografts. Mechanistic interrogation by RNAseq, ChIP-exo,
and CRISPR studies suggest that HDAC3 inhibition is the
primary mechanism of Pax3:Foxo1 downregulation in aRMS
and cell-autonomous cytoreduction in eRMS, but that the
myogenic differentiation effect of chemotherapy-entinostat
therapy in eRMS is driven by crosstalk with the tumor
microenvironment.
Conclusions: These studies support the emerging clinical
trial concepts for the use of entinostat with chemotherapy for
aRMS and eRMS. It addresses the clinical need with preclinical evidence that suggests entinostat, may provide therapeutic
benefit in RMS. We present both in vitro and in vivo evidence
to not only document entinostat's therapeutic effect on RMS
tumors, but also to understand the mechanism underlying its
activity in both aRMS and eRMS.
O-004 Integrated Genetic and Epigenetic
Analysis Defines Novel Molecular Subgroups in
Hepatoblastoma
E. Hiyama1 , S. Kurihara1 , S. HIrano2 , F. Irisuna2 , Y. Ueda1 , M.
Kawashima1
1 Hiroshima
University Hospital, Peditric Surgery, Hiroshima, Japan;
University, Natural Science Center for Basic Research and
Development, Hiroshima, Japan
2 Hiroshima
Background/Objectives: Hepatoblastoma (HB) is the most
prevalent liver malignancies and its molecular pathogenesis
is incompletely understood. HB incidence is significantly high
in the children with extremely low-birth weight and some HB
patients diagnosed at old ages showed poor outcomes.
Design/Methods: Here we describe an integrated molecular
study in which we performed exome, transcriptome and, as
well as array-based copy number and methylation analyses
in a total 130 HBL cases. Among them, we also performed
whole-genome sequence (WGS) and whole-genome methylation (WGM) analysis in the 30 and 12 cases.
Results: Exome and WGS analysis revealed that HB tumors
have the few mutations. Younger patients showed the fewer
somatic mutations but there are no difference of mutation rates
between the patients with low-birth weight and those with normal birth weight. The mutation signatures revealed two characteristic patterns. Most dominant alterations were CTNNB1
exon 3 and other mutation of Wnt signal genes including
AXIN1 and FAP genes. However, RNA sequencing did not
showed the activation of Wnt signaling genes. Some cases
showed the mutations of ARID1A, KCNN3, and MLL2, but
the number of these mutations were less than 10. Based on
methylation patterns, HBL is clustered into four distinct subtypes named C1-4. C1 showed the similar pattern of noncancerous liver tissues and C2 was highly correlated with 11p
UPD. Interestingly, no cases with extreme low-birth weight
exhibited 11pUPD.C3 and C4 involved the cases diagnosed
at older age. All C3 cases were alive but more than half of C4
cases showed poor outcomes.
Conclusions: This integrated molecular analysis unmasked
new correlations between DNA methylation including UPD,
gene mutations, gene expression and copy number profiles,
enabling the stratification of clinical risks for patients with
HB. Molecular analysis provides new important clusters of
the HB patients to be stratified in future clinical trials.
FREE PA PER SESSION:
EPIDEMIOLOGY - I
O-005 Maternal use of Hormonal Contraceptives
and Risk of Childhood Leukaemia – A Nationwide
Population-Based Cohort Study
M. Hargreave1 , L.S. Mørch1 , J.F. Winther2 , K. Schmiegelow3 , S.K.
Kjaer1
1 Danish
Cancer Society, Virus- Lifestyle and Genes, Copenhagen,
Denmark; 2 Danish Cancer Society, Childhood Cancer Survivorship
Research Group- Survivorship Unit, Copenhagen, Denmark; 3 Copenhagen
University hospital Rigshospitalet, Paediatric and Adolescent Medicine,
Copenhagen- Denmark, Denmark
SIOP ABSTRACTS
S9 of S518
Background/Objectives: Following the discovery, that
diethylstilboestrol (i.e. a synthetic oestrogen) can cause cancer in children exposed in utero, few case-control studies have
investigated the effect of maternal contraceptive use on the
risk of cancer in children, and with inconsistent results. The
aim of this study was to assess the association between maternal use of hormonal contraceptives and childhood leukaemia,
using the unique Danish registries.
Design/Methods: The analysis was based on 5,192 children
with cancer (age 0-14) from 6 prefectural cancer registries
in Japan and 21,295 children diagnosed in England, during
1993-2010. Age-standardised incidence rates (ASRs) were
calculated using weights of the world standard population.
Poisson regression models were used to evaluate changes in
incidence rates over time. Overall 1-year, 5-year and 10-year
survival was estimated using the Kaplan-Meier method.
Design/Methods: We followed a nationwide cohort of
1,185,157 live born children between 1996 and 2014 through
individual linkage to Danish registries. Redeemed prescription data from the National Register of Medicinal Product
Statistics provided information on maternal hormonal contraceptive use, categorized as: never before birth (reference), > 3
months prior to conception and < 3 months before conception
to birth (that is, recent use). Cox proportional hazards models
were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) adjusted for potential confounders.
Results: Incidence of all childhood cancers combined has
decreased in Japan throughout 1993-2010 (ASR 1993-1998:
127 per million person-years vs 2005-2010:116), which was
mainly explained by a decrease in registration of infant neuroblastoma. Incidence for all cancers in England increased
between 1993-1998 and 1999-2004, then plateaued (ASR
1993-1998:129, 1999-2004: 133, 2005-2010:134). Incidence
for Hodgkin lymphoma, renal tumours, and Ewing sarcomas
in England were more than twice as high as those in Japan.
Incidence of germ cell tumours, hepatic tumours, neuroblastoma, acute myeloid leukaemia (AML) was higher in Japan
than in England.
Results: During 11,028,171 person-years of observation
(mean: 9.4 years), 598 children were diagnosed with
leukaemia. An increased risk of leukaemia was found in children born to women with a recent use of any type of hormonal contraception (HR: 1.48; 95% CI: 1.10-2.00) compared
to children of never users. Specifically for non-lymphatic
leukaemia, the risk was more than doubled (HR: 2.41; 95% CI:
1.32-4.38). The increase was mainly observed for recent use
of combined products (progestin/oestrogen combined), both
for any type of leukaemia (HR: 1.55; 95% CI: 1.14-2.12) and
for non-lymphatic leukaemia (HR: 2.68; 95% CI: 1.47-4.88)
compared to never users.
Conclusions: Maternal use of hormonal contraception up to
or in early pregnancy may increase the risk of leukaemia in
children.
O-006 Trends in Childhood Cancer Incidence
and Survival in Japan and England
K. Nakata1,2,3 , Y. Ito1 , W. Magadi2 , A. Bonaventure2 , C. Stiller4 , K.
Katanoda5 , T. Matsuda5 , I. Miyashiro1 , K. Pritchard-Jones3 , B.
Rachet2
1 Osaka
International Cancer Center, Cancer Control Center, Osaka,
Japan; 2 London School of Hygiene & Tropical Medicine, Cancer Survival
Group, London, United Kingdom; 3 UCL Great Ormond Street Institute of
Child Health, Developmental Biology and Cancer Programme, London,
United Kingdom; 4 Public Health England, National Cancer Registration
and Analysis Service, Oxford, United Kingdom; 5 Center for Cancer Control
& Information Services- National Cancer Center, Center for Cancer
Registries, Tokyo, Japan
Background/Objectives: This study aimed to compare the
time trends in cancer incidence and survival for children diagnosed in Japan and England, using population-based cancer
registry data.
For many cancers, 5-year survival improved in both countries
and the differences in survival between countries narrowed
over time. The improvement in survival in chronic myeloid
leukaemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in
both countries for AML, brain tumours, soft tissue sarcomas,
malignant bone tumours, and neuroblastoma in children aged
1-14 years.
Conclusions: There were significant differences in incidence
of several cancers between England and Japan, suggesting ethnic variation in susceptibility. The decrease in incidence in
infant neuroblastoma in Japan coincided with cessation of the
national screening programme. The great improvement in survival from CML in both countries coincided with the introduction of effective therapy (imatinib).
O-007 Parental Socioeconomic Factors
Influencing Childhood Cancer Mortality in
Finland: A Nationwide Register-Based Study
A. Tolkkinen1 , J. Pitkäniemi1,2 , M. Taskinen3 , L.
Madanat-Harjuoja1,4 , M. Rantanen1 , N. Malila1,5
1 Finnish
Cancer Registry, Finnish Cancer Registry, Helsinki, Finland;
of Helsinki, Department of Public Health, Helsinki, Finland;
3 Helsinki University Hospital, Division of Pediatric Hematology- Oncology
and Stem Cell Transplantation, Helsinki, Finland; 4 Helsinki University
Hospital, Department of Pediatric and Adolescent Medicine, Helsinki,
Finland; 5 University of Tampere, School of Health Science, Tampere,
Finland
2 University
Background/Objectives: Parental socioeconomic status has
been suggested to have an influence on childhood cancer mortality even in high-income countries. Our study investigated
SIOP ABSTRACTS
S10 of S518
if parental socioeconomic factors influence childhood cancer
mortality in Finland.
Design/Methods: Using nationwide population-based registries we identified 4,437 patients diagnosed with cancer
under the age of 20 from 1990 to 2009. The outcome was
death from primary cancer in 10 years follow-up. Identification of parents and information on socioeconomic factors
were retrieved from the central population registry and Statistics Finland. Poisson regression models were adjusted for
follow-up time, age at cancer diagnosis and diagnostic period.
Results: Mortality was lower in the highest quartile of combined parental disposable income (HR 0.72, CI 95% 0.550.93) compared to the lowest quartile. After adding parental
education to the model, the result was still statistically significant. Compared to individuals with Finnish decent, mortality was higher if the patient (n=58, HR 2.18, CI 95 % 1.383.44), the mother (n=113, HR 2.29, CI 95 % 1.66-3.16) or the
father (n=121, HR 2.04, CI 95 % 1.47-2.82) was an immigrant
and born aboard. Mortality was also higher if the maternal
(n=115, HR 2.35, CI 95 % 1.71-3.23) or paternal native language (n=119, HR 2.16, CI 95 % 1.57-2.98) was other than
Finnish or Swedish. The results for origin of birth and native
language remained significant in the 5-year follow-up even
after adjusting for parental income, employment status and
education.
Conclusions: In Finland, despite public health care and comprehensive social security, high parental income predicted
lower mortality after childhood cancer compared to those with
low parental income. Parental immigrant status and being
born abroad were predictors of increased mortality. Underlying factors related to patient pathways should be explored
to better understand and prevent these disparities in the
future.
O-008 Pathways of Care for Adolescent and
Young Adult Patients with Cancer Diagnosed in
2012 or 2013 in France
E. Desandes1 , L. Brugieres2 , J. Clavel3 , A. Monnereau4 , B. Lacour1
1 CHRU
Nancy, Registre National des Tumeurs Solides de l'Enfant, Nancy,
France; 2 Institut Gustave Roussy, Département d'oncologie de l'enfant et de
l'Adolescent, Villejuif, France; 3 Université Paris-Sorbonne, Registre
National des Cancers de l'Enfant- Inserm UMRS-1153- CRESS équipe 7,
Paris, France; 4 Faculté de Médecine de Purpan, Réseau français des
registres de cancer-FRANCIM, Toulouse, France
Background/Objectives: In France, as in other countries,
there is a need for a population-based view of access to care
and modalities of treatment for adolescents and young adults
(AYA) with cancer. The aim is to evaluate their pathway and
quality of care in general population settings.
Design/Methods: All AYA cases diagnosed with cancer in
2012-2013, aged from 15 to 24 years, and living in 19 French
administrative areas (covering rate:23%) were identified by
the French cancer registries. Data on diagnosis and treatment delays, management with multidisciplinary decisional
approach (MDT), and pathways of care were collected in medical records.
Results: Overall, 412 adolescents and 581 young adults were
included. Time to diagnosis was significantly longer for young
adults than for adolescents (10 weeks [4-23] vs 8 weeks
[3-21], P-value =0.03), especially for soft-tissue sarcomas
(P=0.02). Decisions for treatment initiation were made within
the context of MDT in 86% of adolescents and in 85% of
young adults, and 23% of the MDT meetings for adolescents
involved both pediatric and adult oncologists (vs. 10% for
young adults). Most of AYA cases (67%) consulted general
practitioner before referral to a specialist for investigation. The
main institutions involved in the management of AYA with
cancer were: University hospitals (56%), and private hospitals
(26%). The main services were adult oncology units (84%),
while 21% of adolescents and 10% of young adults with cancer were cared in dedicated AYA units. Overall, 39.5% of adolescents and 16.8% of young adults were included in clinical
studies.
Conclusions: Compared to the previous French study (period
2006-07) [Desandes E et al. 2012], the organization of care
for 15-19-year-old adolescents with cancer shifted toward an
increasing involvement of pediatricians (especially for 15-17
years), an increasing management within the context of MDT
and in specialized cancer health institutions, and an increasing
participation in clinical studies.
FREE PA PER SESSION:
S UP P O RT IVE CARE
O-009 Meta-Analytic Validation of the Picnicc
Prediction Model for the Risk of Microbiologically
Defined Infection in Febrile Neutropenic Episodes
R. Phillips1 , L. Stewart1 , C. PICNICC1
1 University
of York, Centre for Reviews and Dissemination, York, United
Kingdom
Background/Objectives: Risk stratified management of
febrile neutropenia (FN), also known as “fever with neutropenia”, allows intensive management of high-risk cases
and early discharge of low-risk cases. Validation of prediction rules are important, as geographical, temporal and chance
variability may affect any derived rule, and calibration is
advised. Validating across different data sources allows exploration of the possible reasons for differences and calibrations
to be applied.
SIOP ABSTRACTS
Design/Methods: Using data derived from the “Predicting
Infectious ComplicatioNs In Children with Cancer” (PICNICC) collaboration, we assessed the value of the PICNICC
microbiologically defined infection (MDI) prediction rule in
new datasets and combined study-level data using different
random-effects meta-analysis approaches, study-level recalibration and bootstrapping to estimate variances. The multivariable risk prediction model has six components: Tumour
type, temperature, clinically “severely unwell”, haemoglobin,
white cell count and absolute monocyte count.
Results: Seven data sets from six locations, reporting
27-648 episodes of fever and neutropenia were included.
The raw model over-estimated the likelihood of MDI
(Expected/Observed ratio 1.49, 95% CI 0.89 to 2.1) with only
a moderate C-statistic 0.59 (95% CI 0.41 to 0.79) compared
with 0.72 (95% CI 0.71 to 0.76) in the derivation cohort.
The analysis showed marked heterogeneity (I-squared 47%
to 56%). Different approaches to meta-analysis led to similar
estimates. After re-calibration in the large, and assessed at a
threshold of 10% to define ‘low risk’, the model had a pooled
sensitivity of 89% (95% CI 72% to 97%) but pooled specificity
of only 12% (95% CI 5% to 24%). No clear explanation for heterogeneity was found by assessing in-patient status, continent,
or case-mix.
Conclusions: This meta-analysis of the PICNICC risk prediction model for microbiologically defined infection shows
marked variation in validation across multiple data sets. This
argues for local validation of any prediction rules before use.
O-010 Experience of Chemotherapy-Induced
Nausea and Vomiting in Children, an
Undermanaged Symptom?
S. Mouffak1,2 , A. Petit1 , H. Boutroux1 , M. Simonin1 , K. Morand2 ,
G. Leverger1
1 Trousseau
Hospital - APHP, Department of Pediatric Hematology and
Oncology, PARIS, France; 2 Trousseau Hospital - APHP, Department of
Pharmacy, PARIS, France
Background/Objectives: Chemotherapy-induced nausea
and vomiting (CINV) are toxicities that impact children's
quality of life and complicate cancer treatments. Imprecise
international recommendations, difficulties in nausea detection in children and the low priority which is sometimes
given to this symptom are risks of non-optimal management
of CINV. The purpose of this study was to assess children
nausea and vomiting during their chemotherapy treatment.
Design/Methods: We conducted a monocentric retrospective
survey on children treated in a french paediatric cancers reference center. Patients were asked about their CINV experiences, in terms of frequency, severity and timing of the
S11 of S518
symptoms. When children could not answer, the questions
were asked to their parents.
Results: From July to October 2016, 48 children aged from
1 to 17 were surveyed. Twenty-four children had received
highly emetogenic chemotherapy, 21 had received moderately emetogenic chemotherapy, and 3 had received low
emetogenic chemotherapy. In the overall population analysed,
83% of the patients indicated they had already experienced
nausea and/or vomiting during chemotherapy treatments
and 40% had experienced it from the first chemotherapy
administration. Eight percent of children described anticipatory symptoms, 65% described acute CINV and 54%
experienced delayed CINV. Patients receiving highly emetogenic chemotherapy were more exposed to these symptoms
(p=0.02): in this population, 100% of children experienced
nausea or vomiting during their treatment and 46% of them
experienced vomiting systematically or frequently.
Conclusions: This study showed that most children experienced CINV during their treatment. These symptoms
occurred even if antiemetic prophylaxis were in accordance
with local guidelines, but these guidelines were not updated,
according to international guidelines. For 30 years, the emetogenic risk in adults with cancer has strongly decreased
from 100% to 15%, thanks to therapeutic innovations and
CINV management improvements. These improvements are
required in paediatrics, and prospects of optimisation exist,
starting by convincing and raising awareness among the medical community.
O-011 A Longitudinal Study of Pediatric Promis
Symptom Clusters in Children Undergoing
Chemotherapy
S. Jacobs1 , J. Wang2 , D. Dewalt3 , E. Stern1 , G. Heather4 , P. HInds5
1 Children's
National Medical Center, Oncology, Washington, USA;
National Medical Center, Division of Biostatistics and Study
Methodology, Washington, USA; 3 University of North Carolina- Chapel
HIll, Division of General Medicine and Clinical Epidemiology, Chapel
HIll- NC, USA; 4 University of North Carolina- Chapel HIll, Sheps Center
for Health Services Research, Chapel HIll- NC, USA; 5 Children's National
Medical Center, Department of Nursing Research and Quality Outcomes,
Washington, USA
2 Children's
Background/Objectives: Children in treatment for cancer
experience multiple, troubling and interrelated symptoms.
Analyzing the interrelatedness of symptoms and how that
might change during treatment is an important focus in cancer
symptom research. Applying advanced analytic approaches to
this interrelatedness could identify clinically relevant patient
profiles. The aims were to identify a) pediatric profiles with
respect to fatigue, depression, anxiety and pain, b) changes in
profile status throughout a chemotherapy cycle, c) if a baseline fatigue item score could significantly predict symptom
profile.
SIOP ABSTRACTS
S12 of S518
Design/Methods: In a longitudinal, single-site, three data
point design, children between 8 and 18 years completed the
PROMIS Pediatric short form measures for fatigue, depression, anxiety and pain and a fatigue item from the Symptom
Distress Scale. Latent class analysis (LCA) and latent transition analysis (LTA) were applied to the prospective symptom
data
Results: 96 children participated; 58.3% were between 13 and
18 years and 54.2% were male. The symptom mean scores
remained relatively unchanged between the first two data
points but significantly declined at the final data point (end
of the course of chemotherapy). The LPA results indicated a
2-profile model (‘Less severe symptoms, ‘Severe symptoms).
The fatigue score did significantly predict to which profile a
child was a member. The LTA findings indicated that only a
small proportion of the sample changed profile groups across
the three data points.
Conclusions: Children experiencing troubling symptoms
during cancer treatment are not a homogenous group. The four
measured symptoms in this study represent at least two relatively stable profiles that can be identified with high accuracy
early in a child's course of chemotherapy, and the transitions
in the profile status were significantly predicted by a baseline
single-item fatigue measure.
O-012 Seizure in Children with Brain Tumour: A
Retrospective Analysis and A Proposal for A Future
Study
C. Pilotto1,2 , J. Liu2 , D.A. Walker2 , W.P. Whitehouse3,4
1 University
of Udine, Department of Medical and Biological Science,
Udine, Italy; 2 University of Nottingham, Children's Brain Tumour Research
Centre, Nottingham, United Kingdom; 3 University of Nottingham, School of
Medicine, Nottingham, United Kingdom; 4 Nottingham Children's Hospital,
Department of Paediatric Neurology, Nottingham, United Kingdom
Background/Objectives: There is no consensus on the treatment and its withdrawal of brain tumour related epilepsies in
children and young people. We describe the experience of
epileptic seizures in children with brain tumours treated in
a neuro-oncology centre, the related risk factors, the seizure
treatments and the withdrawal of antiepileptic drugs (AEDs).
Design/Methods: Retrospective case note review of
120 newly diagnosed brain tumour patients referred
between 01/2010 and 12/2014 to the regional paediatric
neuro-oncology service was carried out to determine
patient, tumour, seizure characteristics, their treatment and
outcomes
Results: Data on 117/120 (98%) children and young people
were analysed: 67 were male (57%), median age at tumour
◦
◦
presentation was 8.1 years (IQR 25 -75 : 3.6-12.7) with median
◦
◦
follow up: 33 months (IQR 25 -75 : 24-56). Anatomical dis-
tribution was posterior fossa 36%, cerebral hemisphere 28%,
supratentorial midline 24%, spinal cord 5%, metastatic 7%.
35/117 (29%) experienced seizures. A significant risk factor
for seizure occurrence was a cortical tumour location (OR:
◦
◦
7.1 IC 95% 2.9-17.3). 24 months (IQR25 -75 : 15-48) was the
median seizure follow up: 15/35 (43%) were seizure free (SF)
on AEDs, 13/35 (37%) were SF and off AEDs, and 7/35 (20%)
experienced continuing epileptic seizures. 34/35 (97%) were
treated with AEDs. 12/34 (35%) patients withdraw AED. The
median duration of AED before withdrawal was 11 months
◦
◦
(IQR25 -75 5-14 months), and the median follow up after
◦
◦
withdrawal was 15 months (IQR25 -75 5-34 months). 4/34
(12%) had seizure relapse, all after further acute events.
Conclusions: We suggest that AEDs are withdrawn after a
period of three months seizure freedom, in particular in children with only one acute symptomatic seizure, and an uncomplicated course, without on-going epileptogenic complications. This time of withdrawal is proposed as a service evaluation target for future studies
Acknowledgements: Prof Richard Grundy, Dr Sophie Wilne,
EMCYPICS, and Children's Brain Tumour Research Centre
(Nottingham)
F REE PA P ER SES S IO N: BRAIN
TUMOURS - I
O-013 ACNS0334: Treatment of Young Children,
with Supratentorial PNET (SPNET) and High Risk
Medulloblastoma(HRMB) without or with High
Dose Methotrexate(HDMTX). A Report from
Children's Oncology Group
C. Mazewski1 , G. Kang2 , S. Kellie3 , L. Hayes4 , A. Reddy5 , D.
Shaw6 , P. Burger7 , A. Judkins8 , J.R. Geyer9 , A. Gajjar10 , I. Pollack11
1 Emory
University School of Medicine- Children's Healthcare of Atlanta,
Department of Pediatrics, Alpharetta, USA; 2 St Judes Research Hospital,
Biostatistics, Memphis- TN, USA; 3 University of Sydney-Children's
Hospital at Westmead, Paediatric and Child Health, Westmead, Australia;
4 Sarcred Heart Healthcare Systems, Radiology, Pennsacola- FLA, USA;
5 University of Alabama, Neurology, Birmingham- Ala, USA; 6 Seattle
Children's Hospital, Radiology, Seattle- WA, USA; 7 John's Hopkins
University, Pathology, Baltimore- MD, USA; 8 Children's Hospital of Los
Angeles, Pathology, Los Angeles- CA, USA; 9 Seattle Children's Hospital,
Hematology Oncology, Seattle- WA, USA; 10 St Judes Research Hospital,
Oncology, Memphis- TN, USA; 11 Children's Hospital of PittsburghUniversity of Pittsburgh School of Medicine, Neurological Surgery,
Pittsburgh- PA, USA
Background/Objectives: ACNS0334's primary objective
was to determine if children <36 months old with HRMB and
SPNET treated with intensive chemotherapy plus HDMTX
results in higher complete response (CR) rates than the same
regimen without methotrexate(w/oMtx).
SIOP ABSTRACTS
Design/Methods: Between 08/2007 and 05/2014,
ACNS0334 enrolled 91 patients. Patients received 3 Induction Cycles (Cyclophosphamide/Etoposide/Vincristine/Cisplatin+/- HDMTX) followed by 3 Consolidation Cycles (Carboplatin/Thiotepa then autologous stem cell rescue(ASCR)).
After completing consolidation, radiation(RT) was at treating
physician's discretion.
Results: Seventy-seven patients were eligible after central
pathology review, 59 were evaluable for response by central
radiology.
After Induction 3/20 patients with HRMB treated w/oMTX
achieved CR versus 7/19 treated with HDMTX. After Consolidation 6/20 without and 12/19 with HDMTX achieved
CR(p=0.038).
For HRMB, not desmoplastic, not large cell, after Induction
1/11 achieved CR w/oMTX and 5/12 with HDMTX. After
Consolidation 3/11 treated without and 7/12 with HDMTX
achieved CR (p= 0.21).
For SPNET after Induction 4/9 without and 3/11 with
HDMTX achieved CR and 7/9 without and 3/11 with
HDMTX after Consolidation (p=0.07).
Estimated 2 and 5-year Event Free Survival (EFS) for
46 eligible HRMB=68.2+/-9.6% and 68.2+/-14.5% for the
HDMTX arm and 45.8+/-9.7% and 45.8+/-13.8% for the
arm w/oMTX(p=0.17). Twenty-six patients are in follow-up
(Median 4.6 years, range 2.5-8.3 years).
Estimated 2 and 5-year EFS rates for 31 eligible SPNET
=29.2+/-11% and 29.2+/-17.4% with Methotrexate
(N=16) and 40+/-11.7% and 40+/-17.9% for the arm
w/oMTX(N=15) (p=0.44).Eleven patients are in follow-up
(Median 4.2 years, range1.2-7.4 years).
Of 34 survivors, 24(71%) were never irradiated, 10 were irradiated (6 before relapse and 4 after relapse).
Conclusions: Post-consolidation CR rate and 5-yr EFS were
better for HRMB treated with HDMTX versus those treated
with the same regimen w/oMTX. The 5-year EFS for HRMB
patients on ACNS0334 HDMTX arm is better than the EFS
reported in the literature for CCG9921, COG 99703 and
HeadStart.
O-014 ACNS1221: A Phase II Study for Non
Metastatic Desmoplastic Medulloblastoma in
Children < 4 Years of Age. A Report of the
Children Oncology Group
L. Lafay-Cousin1 , E. Bouffet2 , G. Robinson3 , A. Onar4 , C. Billups4 ,
C. Hawkins5 , C. Eberhart6 , C. Horbinski7 , D. Strother1 , L. Heier8 ,
M. Souweidane9 , M. Fouladi10 , A. Gajjar3
1 Alberta
Children's Hospital, Pediatric Hematology Oncology and Bone
Marrow Transplantation, Calgary, Canada; 2 Hospital for Sick Children,
Pediatric brain tumor program, Toronto, Canada; 3 Saint Jude Children's
S13 of S518
Research Hospital, Neuro oncology program, Memphis, USA; 4 Saint Jude
Children's Research Hospital, Biostatistics, Memphis, USA; 5 Hospital for
Sick Children, Pediatric Laboratory Medecine, Toronto, Canada; 6 Sidney
Kimmel Cancer Center, Neuro pathology, Baltimore, USA; 7 Ann and Robert
H Lurie Children's Hospital of Chicago, Pathology, Chicago, USA; 8 Weill
Medical College of Cornell University, Diagnostic Imaging, New York,
USA; 9 Memorial Sloan Kettering Cancer Center, Neurological Surgery,
New York, USA; 10 Cincinnati Children's Hospital Medical Center,
Neuro-Oncology Program, Cincinnati, USA
Background/Objectives: Nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity
(ND/MBEN) have been associated with a more favorable
outcome in younger children. However, treatment-related
neurotoxicity remains a significant concern in this vulnerable
group of patients.
Design/Methods: We prospectively conducted a single-arm
multicenter trial of conventional chemotherapy for nonmetastatic ND/MBEN patients < 4 y old, based on a modified HIT SKK 2000 regimen excluding intraventricular
methotrexate, aiming to achieve similar outcome with a
reduced treatment-related neurotoxicity. The design required
37 patients and targeted a 2y PFS ≥ 90%. Secondary objectives included feasibility of timely central pathology review,
evaluation of molecular profile and neurocognitive outcome.
Results: Between 12/2013 and 07/2016, 26 patients (16
males, 10 females) were enrolled. Nineteen patients had ND
and 7 had MBEN histology. The median age at diagnosis was
19.7 months (7.1-42.9). Four patients had residual disease at
baseline. All cases were reviewed within 10 days by at least 2
of the 3 central neuropathologists. The study closed early for
higher than expected relapse rate. At last follow-up, 7 patients
had relapsed (3 local, 2 distant and 2 combined) at a median
time of 9.7 months from diagnosis(range, 9.5-13.7). One
patient died of disease. At the median follow-up time of 1 year
(range, 0.2-1.9 years) the 1y PFS was 66.2 (SE 12.2%). ND
histology (p=0.009) and older age (p=0.07) may be associated with worse PFS. None of the MBEN patients relapsed. A
detailed molecular analysis utilizing DNA methylation arrays,
next-generation sequencing of tumor and matched germline
is underway to characterize biologic heterogeneity that could
predict for a differential response.
Conclusions: The proposed modified regimen of chemotherapy without intraventricular methotrexate failed to achieve the
desirable 2 y PFS of 90%, leading to premature closure of
the study. The results of the molecular characterization of this
ND/MBEN cohort may help uncover patients who may still
benefit from this regimen.
O-015 Time, Pattern and Outcome of
Medulloblastoma Relapse is Biology and
Therapy-Dependent
SIOP ABSTRACTS
S14 of S518
R. Hill1 , S. Richardson1 , J. Lindsey1 , S. Crosier1 , E. Schwalbe1 , D.
Hicks1 , G. Rafiee1 , A. Smith1 , A. Joshi2 , K. Robson3 , S. Wharton4 ,
T.S. Jacques5 , S. Bailey1 , S. Clifford1
behavior of recurrence, and its exploitation to improve
therapies.
1 Northern
Institute for Cancer Research, Wolfson Childhood Cancer
Research Centre, Newcastle upon Tyne, United Kingdom; 2 Great North
Children's Hospital, Pathology Department, Newcastle upon Tyne, United
Kingdom; 3 University of Nottingham, Children's Brain Tumour Research
Centre, Nottingham, United Kingdom; 4 University of Sheffield, Sheffield
Institute for Translational Neuroscience, Sheffield, United Kingdom; 5 UCL
Institute of Child Health, Neural Development Unit, London, United
Kingdom
Background/Objectives: Medulloblastoma relapse occurs in
30-40% of patients, is almost universally fatal, and accounts
for ∼10% of childhood cancer deaths.
Design/Methods: We undertook a comprehensive characterisation of the clinical features of medulloblastoma recurrence
(e.g. time-to-relapse/pattern-of-relapse) in a cohort of 249
relapsed patients. We related these to clinico-molecular features at diagnosis (e.g. high-risk prognostic factors), with the
aim of establishing whether disease characteristics at diagnosis are associated with the nature of recurrence and subsequent
disease course.
Results: Disease course following relapse was therapydependent. Survival was rare (9/187 (5%)) in patients receiving standard-upfront-treatment (neurosurgery, craniospinalirradiation (CSI), chemotherapy) across all disease demographics. Notable survival rates were only observed following non-CSI treatment at diagnosis (11/62 (18%) patients); all
were <4 years at diagnosis, and overall survival in this cohort
was associated with desmoplastic/nodular histology and CSI
at relapse (p=0.0077 and p=0.00157; log-rank).
In patients relapsing following upfront-CSI (n=187), timeto-relapse and pattern-of-relapse were subgroup-dependent.
MBGroup4 patients had a longer time-to-relapse (2.0 years
mean, 0.3-8.9 years range; p=0.003 log-rank), and MBGroup3
a shorter time (1.3 years, 0.2-5.5 years; p=0.00019). Acquisition of metastatic/distant recurrence occurred at similar
rates across all subgroups (50-60% patients). However, final
incidence of metastatic recurrences was subgroup-dependent.
MBGroup4 relapses were frequently metastatic (57/63, 90%;
p=0.0272, Fisher's exact), whereas MBSHH were less frequently so (12/21, 57%; p=0.0017), reflecting the lower rate
of metastasis at presentation in MBSHH. Distantly-relapsed
MBSHH patients were associated with leptomeningeal disease
(p= 0.00012, Fisher's exact) and MYCN amplification at diagnosis (p= 0.0092), while MBGroup3 and MBGroup4 demonstrated nodular and diffuse distant relapses.
Conclusions: Recurrence remains the most significant challenge in medulloblastoma, with cure only observed in a subset
of radio-naïve infants. In conventionally-treated patients, subgroup predicts time-to-relapse and pattern-of-relapse, with
clear potential to inform disease monitoring/management.
Further work is essential to understand the biology/clinical
O-016 An International Expert Consensus
Survey for A Treatment Versus Observation
Strategy of Newly Diagnosed Patients with NF1
Associated Optic Pathway Glioma
D.A. Walker1 , C. Pilotto1,2 , I. Beshlawi3 , E. Opocher4 , A.A. Aziz5 ,
A.M. Sehested6 , M.J. Fisher7 , T. Jaspan8 , I. Simmons9 , R.E.
Ferner10 , J. Grill11 , R. Deasy1 , D. Hargrave12 , P. Hernaiz Driever13 ,
G. Evans14 , J. Liu1
1 University
of Nottingham, Children's Brain Tumour Research Centre,
Nottingham, United Kingdom; 2 University of Udine, Department of Medical
and Biological Science, Udine, Italy; 3 Nottingham University Hospital,
NHS Trust, Nottingham, United Kingdom; 4 University of Padua,
Department of Pediatrics, Padua, Italy; 5 Medical University of Vienna,
Department of Pediatrics and Adolescent Medicine, Vienna, Austria;
6 Copenhagen University Hospital, Department of Pediatrics, Copenhagen,
Denmark; 7 Children's Hospital of Philadelphia, Department of Pediatrics,
Philadelphia- Pennsylvania, USA; 8 Nottingham University Hospitals NHS
Trust, Department of Radiology, Nottingham, United Kingdom; 9 Leeds
Teaching Hospitals NHS Trust, Departments of Ophthalmology and
Paediatric Oncology, Leeds, United Kingdom; 10 Guy's and St. Thomas’
NHS Foundation Trust, Neurofibromatosis Service- Department of
Neurology, London, United Kingdom; 11 Institut de Cancérologie, Gustave
Roussy, Villejuif, France; 12 Great Ormond Street Hospital for Children,
NHS Foundation Trust, London, United Kingdom;
13 Charité-Universitätsmedizin, Department of Pediatric Oncology and
Hematology, Berlin, Germany; 14 St Mary's Hospital, Department of
Genetic Medicine-, Manchester, United Kingdom
Background/Objectives: Optic pathway glioma (OPG)
develop in 15-20% of children with neurofibromatosis type
1 (NF-1), threatening vision loss but not survival. There is no
consensus about the most appropriate strategy for selecting
newly diagnosed patients with NF-1 for treatment or observation.
Design/Methods: 25 representative case scenarios, derived
from a risk-adapted matrix of newly diagnosed children with
NF-1 OPG, previously entered the SIOP LGG 2004 trial, were
used for a strategy selection consensus survey. The respondents were 98 multi-disciplinary specialists for the first survey (10 cases) and 46 for the second survey (15 cases) from
an international multi-professional expert group. Respondents
selected cases for initial observation (O) initial treatment
(T) or randomisation between the two (R), justifying their
selection with free text comments. A qualitative analysis of
the free text comments describing reasoning was carried out
by two reviewers and a mediator, following the grounded
theory approach, allocating reasons to 8 themes, developed
inductively.
Results: Greater than 70% agreement between survey respondents occurred for initial observation in 4/25 cases, initial
treatment in 10/25 cases, less than 70% consensus occurred
in 11/25 cases. The associated 808 free text comments
SIOP ABSTRACTS
justifying selection for O: 173; T: 426 and R: 209 were allocated by 2 reviewers to 8 themes (agreement; k: 0.762). Consensus selection for: observation was justified by risk of progression (39%) and visual function (33%); for treatment by
visual function (39%); for randomization by visual function
(31%), risk of progression (22%), site/dimension of tumour
(15%) and age and gender (12%).
Conclusions: This survey and its qualitative analysis identifies a new consensus of justified criteria for initial observation versus treatment, in 11/25 scenarios no consensus was
reached. These criteria are proposed as eligibility criteria for
future trials where a randomised trial of indications for initial
management could be included.
on behalf of the SIOPE NF-1 OPG Nottingham, UK, Workshop (Participating centers: Berlin, Copenhagen, GOS, Hamburg, Leeds, Nottingham, Padua, Paris, Vienna)
O-017 Comparison of Academic Achievement
Scores After Proton and Photon Therapy in
Children and Young Adults with
Craniopharyngioma
T. Merchant1 , D. Indelicato2 , C.H. Hua1 , S. Wu3 , H. Conklin4
1 St.
Jude Children's Research Hospital, Department of Radiation Oncology,
Memphis, USA; 2 University of Florida Proton Therapy Institute,
Department of Radiation Oncology, Jacksonville, USA; 3 St. Jude Children's
Research Hospital, Department of Biostatistics, Memphis, USA; 4 St. Jude
Children's Research Hospital, Department of Psychology, Memphis, USA
Background/Objectives: Patients with craniopharyngioma
treated with radiation therapy risk deficits in cognitive function. Proton therapy reduces the volume and dose of normal
tissue exposure compared to photon therapy. Cognitive testing results from two prospective trials were used to compare
proton (NCT01419067) and photon (NCT00187226) cohorts.
Design/Methods: Patients (age < 22 years) with craniopharyngioma were enrolled on prospective trials that included
proton (2011-2016) or photon (1998-2010) therapy and serial
cognitive testing. Proton therapy (54CGE) was administered
using passive scattering methods targeting the post-operative
residual tumor and tumor bed surrounded by an anatomicallyconstrained 5mm clinical target volume margin (CTV). Photon therapy (54Gy) was administered using conformal or
intensity-modulated methods targeting a 5-10mm CTV. Tests
of academic achievement (reading and math) were administered before and after treatment. Test scores were modeled with normal tissue dose variables to compare scores by
modality.
Results: Fifty-two patients treated with proton therapy were
compared to 70 treated with photon therapy. Whole brain dose
(median, range) was lower for the proton cohort (7.63CGE,
0.25-16.40CGE) compared to the photon cohort (17.35Gy,
S15 of S518
11.00-27.56Gy) (p < 0.0001). There was no difference comparing scores based on modality. When mean brain dose
was included in the model, patients treated with photon therapy had a greater decline in reading and math scores. Rate
of change (points/CGE or Gy/month) in reading scores was
0.001274 for proton and -0.1020 for photon (p = 0.0018). The
rate of change in math scores was 0.000614 for proton and 0.08266 for photon (p = 0.0263). Score estimates based on
median doses (baseline vs. 36 month) for reading and math
were 103.08 vs. 103.13 and 100.98 vs. 101 for proton compared to 100.55 vs. 96.87 and 99.33 vs. 96.36 for photon.
Conclusions: The results from a prospective trial of proton therapy for craniopharyngioma demonstrate preservation
of academic achievement when compared to treatment using
photons.
F REE PA P ER SES S IO N: ALL C L I N I CA L
O-018 Delayed Intensification (DI) Enhances
Continuous Complete Remission (CCR) Rates for
Patients with B-ALL when Combined with
Intravenous Methotrexate: Childrens Oncology
Group Study (COG) POG 9904/9905
N. Winick1 , P. Martin2 , M. Devidas3 , M. Borowitz4 , P. Bowman5 ,
E. Larsen6 , J. Pullen7 , S. Hunger8 , W. Carroll9 , B. Camitta10
1 University
of Texas Southwestern Medical Center, Pediatrics, Dallas, USA;
University, Pediatrics, Durham, USA; 3 University of Florida,
Biostatistics, Gainesville, USA; 4 Johns Hopkins University/Sidney Kimmel
Cancer Center, Pathology, Baltimore, USA; 5 University of North Texas
Health Science Center, Pediatrics, Ft Worth, USA; 6 Maine Children's
Cancer Program, Pediatrics, Scarborough, USA; 7 University of Mississippi
Medical Center, Pediatrics, Jackson, USA; 8 Childrens Hospital of
Philadelphia, Pediatrics, Philadelphia, USA; 9 Laura and Isaac Perlmutter
Cancer Center at New York University Langone, Pediatrics, New York,
USA; 10 Childrens Hospital of Wisconsin, Pediatrics, Milwaukee, USA
2 Duke
Background/Objectives: Legacy POG 9904 and 9905 trials (2000-05) assessed the impact of DI on outcome for low
(LR), standard (SR) and a subset of NCI high risk (HR) pts,
treated with therapy that included six courses of IV MTX
(1 gm/m2/24 hrs).
Design/Methods: NCISR patients received a dexamethasonebased 3-drug and NCIHR pts a prednisone-based 4-drug
induction. Post-induction, all NCISR pts except those with trisomy of chromosomes 4+10 and NCIHR pts who met refined
age and WBC criteria (excluding those with t(9;22), t(4;11),
or CNS3) were eligible to participate in the DI randomization.
Consolidation included 6 courses of IV MTX with leucovorin
rescue with randomization to +/- DI after the 3rd IV MTX
course (week 16). DI included: weekly vincristine and dauno-
SIOP ABSTRACTS
S16 of S518
mycin weeks 16-18 with daily dexamethasone 6 mg/m2, PEG
asparaginase week 16 and intrathecal MTX weeks 16, 20, 21,
Cyclophosphamide week 20, subcutaneous Ara-C daily x 4,
weeks 20 and 21, and 6-thioguanine weeks 21-22. End induction minimal residual disease (MRD) was measured but not
used to alter therapy.
Results: Administration of DI improved 10-year CCR from
75.5 +/- 2.5% (n=707) to 81.8 +/- 2.2% (n=689; p=0.0016),
but did not have a significant effect on overall survival (OS):
no DI 10-year OS 90.9 +/- 1.7% versus 91.4 +/- 1.6%
(p=0.2518) without DI. MRD was highly predictive of outcome with 10 yr CCRs of 87.7 + 2.2 and 82.1 + 2.5% among
the MRD<0.01% patients with/without DI and 54.3 + 8 and
44 + 8% for the MRD≥0.01% patients with/without DI (p <
0.001).
Conclusions: A delayed intensification phase enhances the
CCR rate for a broad population of patients with B-ALL
including those with and without end induction MRD at <
0.01%, but does not impact OS. Expected EFS rates obtained
in this study are lower than obtained with more contemporary
trials.
O-019 Substitution with Cyclophosphamide and
Etoposide does not Improve Outcome for Children
and Young Adults with Very High Risk
B-Lymphoblastic Leukemia: Children's Oncology
Group Study AALL1131
M. Burke1 , W. Salzer2 , S. Chen3 , M. Devidas3 , L. Gore4 , J.
Hilden4 , E. Larsen5 , E. Raetz6 , N. Winick7 , W. Carroll8 , S.
Hunger9 , M. Loh10
1 Children's
Hospital of Wisconsin, Pediatrics, Milwaukee, USA; 2 U.S. Army
Medical Research and Materiel Command, Pediatrics, Fort Detrick, USA;
3 University of Florida, Biostatistics, Gainesville, USA; 4 Children's Hospital
of Colorado, Pediatrics, Aurora, USA; 5 Maine Children's Cancer Program,
Pediatrics, Scarborough, USA; 6 Primary Children's Hospital, Pediatrics,
Salt lake City, USA; 7 UT Southwestern, Pediatrics, Dallas, USA; 8 New York
University, Pediatrics, New York, USA; 9 Children's Hospital of
Philadelphia, Pediatrics, Philadelphia, USA; 10 UCSF, Pediatrics, San
Francisco, USA
Background/Objectives: With modern chemotherapy regimens, >90% of patients with pediatric acute lymphoblastic
leukemia (ALL) are now cured. However, subsets of patients
can be identified who remain at very high risk (VHR) of
relapse with expected 4-year DFS <80% and are appropriate
candidates for more intensive therapeutic strategies designed
to improve survival. AALL1131 aimed to determine, in a randomized fashion, if the substitution with cyclophosphamide +
etoposide (CPM/ETOP) (Experimental Arm 1; Exp1) would
improve the 4-year DFS of children, adolescents, and young
adults with VHR B-ALL compared to a modified BerlinFrankfurt-Münster regimen; (Control Arm; CA).
Design/Methods: Patients 1-30 years of age with newly diagnosed VHR B-ALL were randomized post-Induction in a
1:2 fashion to CPM/cytarabine/mercaptopurine (CA) or CPM
(440mg/m2 days 1-5)/ETOP (100mg/m2 days 1-5) (Exp 1)
during Part 2 of Consolidation (CONS) and Delayed Intensification (DI). Both arms included the same dose and schedule of PEG-asparaginase on day 43 and vincristine days 43
and 50 of CONS and DI. Prospective interim monitoring rules
for efficacy and futility were included where futility would be
determined for a one-sided p-value ≥ 0.7664.
Results: There were no significant differences in Grade 3/4
adverse events or delays in starting Interim Maintenance
between the 2 arms (Table 1). Using a data cutoff date of
12/31/2016, 41 total events occurred between arms (CA:
10/228 vs. Exp1: 31/458) resulting in a log-rank test statistic of -1.3904 (one-sided p-value = 0.9178). The study was
stopped for futility as the interim monitoring boundary was
crossed [Hazard Ratio 0.606 (95% CI: 0.297 - 1.237)] (Figure 1) and the VHR arm of AALL1131 was closed February
2017.
Conclusions: Substitution of therapy for VHR B-ALL
patients on COG AALL1131 randomized to CPM/ETOP during Part 2 of CONS and DI did not improve EFS.
O-020 Dasatinib Maintains Outstanding 5-Year
Survival Outcomes in Children with PH+ ALL, but
does not Prevent CNS Relapses: Children's
Oncology Group (COG) AALL0622 Trial
W. Slayton1 , K. Schultz2 , J. Kairalla3 , D. Meenakshi4 , M.
Pulsipher5 , L. Silverman6 , M. Borowitz7 , A. Carroll8 , N. Heerema9 ,
J. Gastier-Foster10 , S. Mizrahy11 , B. Wood12 , T. Merchant13 , V.
Brown14 , E. Raetz15 , N. Winick16 , M. Loh17 , W. Carroll18 , S.
Hunger19
1 University
of Florida, Pediatrics, Gainesville- FL, USA; 2 BCs Children's
Hospital, Pediatrics, Victoria- BC, Canada; 3 Children's Oncology Group
Statistical Office, Department of Biostatistics, Gainesville- FL, USA;
4 Children's Oncology Group Statistical Office, Biostatistics, GainesvilleFL, USA; 5 University of California- Los Angeles, Pediatrics, Los AngelesCA, USA; 6 Dana Farber Cancer Institute/Harvard, Pediatrics, Boston- MA,
USA; 7 Johns Hpkins University School of Medicine, Hematopathology,
Baltimore- MD, USA; 8 University of Alabama, Deparment of Pathology and
Genetics, Birmingham-AB, USA; 9 Ohio State University Wexner Medical
Center, Pathology, Columbus- OH, USA; 10 Nationwide Children's Hospital,
Pathology, Columbus- OH, USA; 11 University of Florida, Medicine,
Gainesville- Fl, USA; 12 University of Washington, Pathology, Seattle- WA,
USA; 13 St. Jude Research Hospital, Radiation Therapy, Memphis- TN,
USA; 14 Children's Hospital Hershey, Pediatrics, Hershey- PA, USA;
15 University of Utah, Pediatrics, Salt Lake City- UT, USA; 16 University of
Texas Southwestern Medical Center, Pediatrics, Dallas - TX, USA;
17 University of California-San Francisco, Pediatrics, San Francisco- CA,
USA; 18 New York University, NYU Langone Cancer Center, New York- NY,
USA; 19 University of Pennsylvania, Pediatrics, Philadelphia- PA, USA
Background/Objectives: Ph+ ALL patients treated with
intensive chemotherapy plus continuous imatinib had a 68%
5-year event-free survival (EFS) rate (COG AALL0031).
SIOP ABSTRACTS
Compared to imatinib, dasatinib has increased potency, better CNS penetration, and activity against imatinib-resistant
clones.
Design/Methods: AALL0622 tested AALL0031 chemotherapy plus dasatinib 60 mg/m2 /day in Ph+ ALL subjects (1-30
years). Cohort 1 subjects received dasatinib 2 weeks during
each 3-4 week block; Cohort 2 subjects received dasatinib
continuously. Stem cell transplant (SCT) was recommended
for subjects with a sibling donor and high-risk (HR) subjects
defined by minimal residual disease at end induction and
consolidation. The remaining standard-risk (SR) subjects
were treated with chemotherapy plus dasatinib. While all
AALL0031 subjects received cranial radiotherapy (CRT),
only CNS3 cases on AALL0622 received CRT.
Results: For 60 evaluable subjects, 5-year EFS and overall
survival (OS) rates were 60±7% and 86±5%. 5-year EFS/OS
rates were 61±7%/87±5% for SR subjects (n=48, 19% underwent SCT) and 67±19%/89±13% for HR subjects (n=9, 89%
underwent SCT). AALL0622 subjects had a 5-year cumulative incidence rate of isolated or combined CNS relapse of
10.6±4.1% vs 3.7±2.6% (p = 0.20) for those treated with
continuous imatinib on AALL0031. No difference in outcome was seen between AALL0031 subjects receiving imatinib continuously and AALL0622 cohorts 1 and 2 (5-yr DFS
68±7% for AALL0031 vs 60±7% on AALL0622, p=0.31; 5year OS 81±6% vs 86 ± 5%, p = 0.63). IKZF1 deletion was
present in 57% of tested AALL0622 subjects (25/44) and was
associated with significantly inferior 5-year EFS (52±10% vs
82.1±10.1%, p=0.04) and OS (80±8% vs 100%, p=0.04).
Conclusions: There was a non-significant trend toward
increased rates of CNS relapse on AALL0622, but similar rates of 5-year EFS/OS were obtained with intensive
chemotherapy, imatinib and CRT (AALL0031) and intensive chemotherapy plus dasatinib without CRT (AALL0622).
IKZF1 deletions were associated with inferior EFS/OS.
O-021 Osteonecrosis (ON) is Associated with
Improved Event Free Survival (EFS) in High-Risk
Acute Lymphoblastic Leukemia (HR-ALL): Results
of Children's Oncology Group (COG) Study
AALL0232
S17 of S518
York City- New York, USA; 8 Maine Children's Cancer Program, Pediatric
Oncology, Scarborough- Maine, USA
Background/Objectives: ON is a well-characterized
ALL therapeutic toxicity attributed to glucocorticoids,
asparaginase (ASNase), and methotrexate (MTX) that
disproportionately affects adolescents. In CCG-1961,
alternate-week dexamethasone (AWD; DEX) during double
delayed intensification (DI) reduced ON vs continuous DEX
(CD) with single DI in rapid early responders (RER) ≥10y.
Design/Methods: HR-ALL patients 1-30y on AALL0232
(2004-11) received COG augmented therapy with a 2x2 randomization to: (1) induction (IND) DEX (10 mg/M2 d1-14)
vs prednisone (PDN) (60 mg/M2 d1-28), and (2) interim
maintenance (IM) high-dose MTX (HD-MTX) vs escalatingdose MTX/asparaginase (eMTX/ASNase). RER received single, and slow early responders (SER) double, IM/DI. Initially, all received monthly DEX maintenance (MTC) pulses,
patients ≥13y received DI AWD, and patients ≤12y received
DI CD. There were 2 ON-related amendments: after 10/2006
all patients ≥10y received DI AWD; after 6/2008 all patients
≥10y were assigned to IND PDN, and all patients received DI
AWD and MTC PDN pulses.
Results: ON was confirmed in 315/2817 patients. Cumulative 5y incidence (CI) increased with age: 1-9y 2.6%, 10-12y
15.3% (AWD 11.7% vs CD 28.0%; P=0.0085), ≥13y 19.7%,
≥21y 31.6%. Among randomized RER patients ≥13y, ON
CI differed by glucocorticoid (DEX 26.2% vs PDN 15.2%;
P=0.0016) but not MTX assignment (HD-MTX 19.9% vs
eMTX/ASNase 21.4%; P=0.66). Among randomized SER
patients ≥13y, CI was 22.0% with no difference by regimen. Five-year EFS was significantly higher among randomized patients ≥10y with vs without ON (88.5% vs 72.9%;
P<0.0001); this finding was present in different age ranges
(≥10y, ≥13y, ≥16y) and RER/SER subsets within each, especially in the ≥13y RER (92.9% vs 80.6%; P=0.0046) and SER
(74.8% vs 41.5%; P<0.0001) cohorts. Across groups ASNase
allergy was significantly associated with reduced ON risk
(≥10y: HR 0.43; P=0.0013).
Conclusions: Patients who develop ON have significantly
increased EFS, suggesting host differences that increase sensitivity to develop ON and render ALL cells more chemoresponsive.
L.A. Mattano1 , M. Devidas2 , S. Chen2 , E. Raetz3 , M. Loh4 , N.
Winick5 , S.P. Hunger6 , W.L. Carroll7 , E. Larsen8
1 HARP
Pharma Consulting, Pediatric Hematology/Oncology, MysticConnecticut, USA; 2 University of Florida, COG Data Center- Biostatistics,
Gainesville- Florida, USA; 3 University of Utah Primary Children's
Hospital, Pediatric Hematology/Oncology, Salt Lake City- Utah, USA;
4 UCSF Medical Center, Pediatric Hematology/Oncology, San FranciscoCalifornia, USA; 5 UT Southwestern/Simmons Cancer Center, Pediatric
Hematology/Oncology, Dallas- Texas, USA; 6 Children's Hospital of
Philadelphia, Pediatric Hematology/Oncology, Philadelphia- Pennsylvania,
USA; 7 NYU Langone Cancer Center, Hassenfeld Children's Center, New
O-022 Outcome of B-ALL Treated with A
Risk-Stratified and Response-Adapted Protocol:
Interim Analysis of A Single-Institution Pilot Study
for A Multicenter Collaborative Protocol from India
G. Narula1 , B. Arora1 , P. Subramanian2 , P. Tembhare2 , N. Patkar2 ,
D. Shetty3 , M. Prasad1 , S. Gujral2 , S. Banavali1
SIOP ABSTRACTS
S18 of S518
1 Tata
Memorial Center, Medical Oncology Pediatric Division, Mumbai,
India; 2 Tata Memorial Center, Hematopathology, Mumbai, India; 3 Tata
Memorial Center, Cytogenetics, Mumbai, India
Background/Objectives: Childhood ALL in developed
countries has OS exceeding 95%, but remains challenging in
developing countries. Since 2012, multiple centers in India
have collaborated to devise a protocol for uniform management of ALL using comprehensive risk-stratification and
response-based adaption. The standard arms of this protocol
were piloted in our institution since 2013, and an interim analysis was done at 3-year time-point.
Design/Methods: Prospectively maintained records of BALL patients treated on a uniform strategy from Feb-2013
to Dec-2015 were analyzed. Risk-stratification was done
based on NCI criteria, further adapted by day-8 prednisolone
response (D-8PR), and flowcytometric day-35 bone-marrow
MRD (D35BM-MRD). Data was analyzed by descriptive analytical tools and Kaplan-Meier method on SPSS-v24TM .
Results: Seven-hundred and twenty-six children with B-ALL
were registered in the study period. Thirteen were excluded
due to ambiguous classification or protocol deviation. Median
age was 5 yrs (0.5-15) and median WBC-10x103 /cmm
(0.1-543x103 /cmm). Bulky disease was seen in 253(35%),
tumor lysis in 297(42%), CSF involvement in 34(5%), and
Hypodiploidy in 100(14%). Cytogenetic abnormalities were
trisomies in 257(36%), ETV6-RUNX1 101(14%), t(1:19)
50(7%), BCR-ABL 39(6%), MLL-rearrangements 15(2%),
with 215(34%) no abnormalities. Poor D-8PR occurred in
98(14%). The initial risk-stratification was Standard Risk
(SR)-219(31%), Intermediate (IR)-267(37%), and High (HR)227(32%). Of 666 evaluable by D35BM-MRD, 147(22%)
were positive. Projected 3-year OS was 90.4±1.4% with
median follow-up of 23 months (range, 1-48), while EFS was
70.7±2.3%. 70% of mortality occurred in intensive phases
of treatment, and 86% of all events in non-SR arms. Threeyear OS for SR, IR and HR were 95.1±2%, 89.5±2.3% and
87.2±2.6% (p<0.01), while EFS was 86±3.2%, 63.6±4.7%,
and 62.2±4.1% (p<0.001) respectively. D35BM-MRD status predicted EFS-68.2±4.8% in positive versus 76.7±2.5%
in negative cases (p<0.001).
Conclusions: A risk-stratified response-adapted protocol
helped improve outcomes for childhood B-ALL over historical results. D35BM-MRD positivity predicted poorer EFS.
Early mortality and relapse in non-SR B-ALL remain the
biggest challenges.
O-023 Polymorphisms in the Thymidylate
Synthetase (TYMS) Gene in Relation to
Methotrexate-Induced Oral Mucositis in Children
with Acute Lymphoblastic Leukemia
N. Oosterom1 , M. Berrevoets2 , M. Den Hoed1 , S. Pluijm1 , R.
Pieters1 , R. De Jonge3 , W. Tissing4 , M. Van den Heuvel-Eibrink1 ,
S. Heil2
1 Princess
Máxima Center for Pediatric Oncology, Department of Pediatric
Oncology, Utrecht, The Netherlands; 2 Erasmus Medical Center,
Department of Clinical Chemistry, Rotterdam, The Netherlands; 3 VU
Medical Center, Department of Clinical Chemistry, Amsterdam, The
Netherlands; 4 Beatrix Children's Hospital- University of GroningenUniversity Medical Center Groningen, Department of Pediatric Oncology,
Groningen, The Netherlands
Background/Objectives: Methotrexate (MTX) is a potent
drug in the treatment of pediatric acute lymphoblastic
leukemia (ALL). MTX is cytotoxic as it impairs DNA
and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (DHFTR) and thymidylate synthase (TYMS).
Twenty percent of patients with ALL receiving high-dose
MTX regimens develop MTX-induced oral mucositis. The
association between MTX-induced toxicity and genetic variants within the Thymidylate Synthase (TYMS) gene has been
studied, but results are contradictory and inconsistent. We
studied the association between three previously described
variants within the TYMS gene in relation to MTX-induced
oral mucositis in a prospective cohort of Dutch children with
ALL.
Design/Methods: We analyzed a 28-base pair repeat
(2R3R; rs34743033), a single nucleotide polymorphism
present within the 28-base pair repeat on the 3R allele
(3RG>C; rs2853542) and a 6-base pair deletion (TTAAAG;
rs151264360) within the TYMS gene in germline DNA of
117 pediatric ALL patients treated with 5 gram m-2 MTX
(DCOG ALL-10 protocol). Clinically relevant oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria. Data were analyzed for the individual
rs3474303 (2R3R) and rs151264360 (6bp deletion) polymorphisms; rs2853542 (3RG>C) was combined with rs3474303
(2R3R) and analyzed according to predicted expression levels
of TYMS: low expression (2R2R, 2R3RC, 3RC3RC) versus
median expression (2R3RG, 3RC3RG) and high expression
(3RG3RG).
Results: rs3474303 (2R3R) and rs151264360 (6bp deletion)
polymorphisms were not associated with the development of MTX-induced oral mucositis (OR 2.49 [0.689.20] and OR 0.79 [0.20-3.10] respectively). Patients
carrying the low expression TYMS genotype had a
trend towards developing MTX-induced oral mucositis,
although not significantly (OR 2.42 [0.86 – 6.80], p-value
0.09).
Conclusions: We could not confirm the association
between TYMS polymorphisms and MTX-induced
mucositis. However, the strong effect size suggests a
possible role of the low expression genotype in MTXinduced mucositis. This needs to be addressed in a
meta-analysis.
SIOP ABSTRACTS
FREE PA PER SESSION: LAT E
EFFECTS
O-024 Dose Volume Parameters of the Radiation
Dose Distribution in Cerebral Arteries are Highly
Predictive of Long Term Risk of Stroke after
Childhood Cancer Radiotherapy
F. de Vathaire1 , C. El-Fayech2 , N. Haddy1 , R. Sètchéou Allodji1 , C.
Veres1 , D. Llanas1 , A. Jackson1 , S. Vincent1 , C. Rubino1 , H.
Pacquement3 , C. Teinturier4 , B. Fresneau2 , G. Vu-Bezin1 , I. Diallo1
1 Gustave
Roussy, INSERM Unit 1018 - Team Radiation and Cancer,
Villejuif, France; 2 Gustave Roussy, Pediatry, Villejuif, France; 3 Institut
Curie, Pediatry, Paris, France; 4 Hopital Kremlin Bicêtre, Paediatric
Endocrinology, Le Kremlin Bicêtre, France
Background/Objectives: Stroke is one of the major potential
long term iatrogenic risk of childhood cancer radiation therapy. Nevertheless, present knowledge is insufficient to predict
the long-term risk of stroke following radiation therapy as the
dose-response to fractionated high doses of radiation to the
brain is not known.
Design/Methods: We carried out an analysis in a cohort
7030 5-years survivors of a solid childhood cancer treated
in France before 2001, of whom 4150 treated by radiotherapy, and followed 20 years in average, by self-questionnaire
and cross-linkage with French National Hospital and Medical Insurance Database (SNIIR-AM). During the follow-up,
139 patients developed a permanent stroke which could be
validated. Each of them was matched to 8 controls of the
same cohort on gender, age at childhood cancer and follow-up
duration. Radiation dose distribution in cerebral arteries was
individually reconstructed for each case and controls treated
by radiotherapy using medical records and anthropometric
phantoms.
Results: As compared to children not treated by radiation
therapy, and when controlling for chemotherapy, children who
received less than 1 Gy, in average, to the cerebral arteries had
a 1.8 (95%CI: 0.80-3.9) times higher risk of stroke, whereas
those who received more than 20 Gy to cerebral arteries had
a risk 26.0 (10.0-67.8) times higher. These risk factors were
higher for ischemic strokes than for haemorrhagic ones.
To take into account dose-volume parameters allowed to
improve risk predictions. High radiation doses strongly
increased stroke risk. As an example, to received during childhood 30Gy or more to only 1 to 5% of the cerebral arteries volume increased the long term risk of stroke by 2.6 (1.3-5.5).
Conclusions: This study confirms that average radiation dose
to the cerebral arteries is not the best parameter for predicting long term risk of stroke, and that classical dose-volume
parameters may be used for such predictions.
S19 of S518
O-025 Long-Term Efficacy of
Thyroid-Stimulating-Hormone (TSH)-Suppression
during Radiotherapy (RT) for Medulloblastoma
(MBL) and Hodgkin Lymphoma (HL)
M. Massimino1 , L. Gandola2 , M. Podda1 , F. Spreafio1 , V. Biassoni1 ,
E. Pecori1 , E. Schiavello1 , A. Indini1 , B. Diletto1 , M. Casanova1 , A.
Ferrari1 , R. Luksch1 , C. Meazza1 , N. Puma1 , S. Chiaravalli1 , E.
Seregni1 , L. Bergamaschi1 , F. Pallotti1 , C. Morosi1 , M. Terenziani1
1 Fondazione
IRCCS Istituto Nazionale dei Tumori, Pediatrics, Milano,
Italy; 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy,
Milano, Italy
Background/Objectives: Hypothyroidism is very frequent
after neck/mediastinum RT, whose effects also depend on
circulating TSH, a sensitive marker of thyroid damage. In
1998 we evaluated the protective effect of pharmacological TSH-suppression during craniospinal-RT for MBL and
neck/mediastinum RT for HL, and relative preliminary results
at medium 7/8 years were promising. Our aim is updating a
definitive message to our community.
Design/Methods: Children scheduled for craniospinal-RT for
MBL or RT for HL underwent thyroid ultrasound and FT3,
FT4, TSH evaluation at beginning/end of RT. From 14 days
before and up to the end of RT, patients received L-thyroxine;
every 3 days, TSH-suppression was checked to ensure TSH
<0.3 mM/ml. Blood tests and ultrasound were repeated after
1 year; primary hypothyroidism was defined as TSH over normal range.
Results: 25 MBL and 14 HL patients had a median followup of 175/185 months of their thyroid status, respectively.
At RT end we divided patients according to TSH either ˂0.3
mM/ml or ≥ 0.3 throughout their radiation treatment (representing the cohorts of TSH-suppression or not, respectively).
Though numerically small, the cohorts were well matched
(gender/age/disease stage/chemotherapy courses/thyroid bed
RT/duration of follow-up). Hypothyroidism-free survival
rates were significantly different after doubling the followup of the previous publications. In MBL group it was
62.5% for the TSH-suppression cohort and 20% for the non
TSH-suppression cohort (P=0.02), respectively; for the HL
group, 75% and 0% (P=0.0009), respectively. The appearance of colloidal cysts/solid nodules did not differ in the two
groups.
Conclusions: Thyroid dysfunction may develop from a few
months to years after RT end. In children with lengthy antineoplastic treatments, endocrine disorders have a negative
effect on growth and development into adulthood. We showed
how hypothyroidism can be possibly easily and cheaply prevented in the long-term in two populations at great risk of lateeffects after RT.
SIOP ABSTRACTS
S20 of S518
O-026 Impact of Ovarian Transposition on
Ovarian Function among Long-Term Survivors of
Childhood Hodgkin Lymphoma: A Report from the
ST. Jude Lifetime Cohort Study
I. Fernandez-Pineda1 , A.M. Davidoff1 , L. Lu2 , B.N. Rao1 , C.L.
Wilson2 , D.K. Srivastava3 , J.L. Klosky4 , M.L. Metzger5 , M.J.
Krasin6 , K.K. Ness2 , C.H. Pui5 , L.L. Robison2 , M.M. Hudson2 ,
C.A. Sklar7 , D.M. Green2 , W. Chemaitilly8
1 St
Jude Children's Research Hospital, Department of Surgery, Memphis,
USA; 2 St Jude Children's Research Hospital, Department of Epidemiology
& Cancer Control, Memphis, USA; 3 St Jude Children's Research Hospital,
Department of Biostatistics, Memphis, USA; 4 St Jude Children's Research
Hospital, Department of Psychology, Memphis, USA; 5 St Jude Children's
Research Hospital, Department of Oncology, Memphis, USA; 6 St Jude
Children's Research Hospital, Department of Radiation Oncology,
Memphis, USA; 7 Memorial Sloan Kettering Cancer Center, Department of
Epidemiology & Endocrinology, New York, USA; 8 St Jude Children's
Research Hospital, Department of Endocrinology, Memphis, USA
Background/Objectives: Data regarding the efficacy of ovarian transposition (OT) to preserve ovarian function among
childhood cancer survivors are limited. We aimed to determine the effect of OT on ovarian function among long-term
survivors of childhood Hodgkin lymphoma (HL) treated with
pelvic radiotherapy.
Design/Methods: Female participants in the St. Jude Lifetime Cohort Study (SJLIFE) (10+ years from diagnosis, age
18+ years) treated with pelvic radiotherapy for HL were clinically evaluated for premature menopause (PM). Multivariable
logistic regression was used to study associations between
demographic and treatment-related risk factors as well as OT
and PM. Survivors with a history of surgical menopause or
bilateral oophorectomy before age 40 years were excluded.
Results: Of 184 eligible females with HL, 158 (86%) were
treated with pelvic radiotherapy. Of these, 84 (53%) participated in SJLIFE including 45 who underwent OT before
pelvic radiotherapy. Median age was 16 years (range 4-22)
at HL diagnosis and 38 years (range 25-60) at study. Pelvic
radiotherapy > 1,500 cGy (HR = 5.54, 95% CI = 1.69 to
18.19; P= 0.005) and cumulative cyclophosphamide equivalent dose > 12,000 mg/m2 (HR = 4.71, 95% CI =2.04 to
10.86; P<.001) were associated with PM. There was no significant association between OT and occurrence of PM (HR
= 1.21, 95% CI = 0.42 to 3.49; p = 0.720). Among women
with PM, median age at menopause was not significantly different in patients with (25 years; range, 13-38.5) or without
(21.5 years; range, 14-37) (P= 0.530) OT.
Conclusions: OT did not seem to modify the risk of PM
in this historic cohort of long-term survivors of HL treated
with gonadotoxic therapy. Further research in younger cohorts
is needed given continued improvements in radiotherapy
delivery techniques. Modern fertility preservation modalities
such as mature oocyte cryopreservation should be offered to
patients at risk whenever feasible.
O-027 Second and Subsequent Malignant
Neoplasms after Cancer in Childhood in Finland: A
Population-Based Registry Study
L. Madanat-Harjuoja1,2 , J. Pitkäniemi2 , M. Rantanen2 , N. Malila2 ,
P.M. Lähteenmäki3 , K. Vettenranta4
1 HUCH
Children's Hospital, Pediatric Oncology, Helsinki, Finland;
Cancer Registry, Childhood Cancer, Helsinki, Finland; 3 Turku
University Hospital, Department of Pediatrics, Helsinki, Finland;
4 Children's Hospital and Helsinki University Central Hospitals, Division of
pediatric hemato-oncology and stem cell transplantation, Helsinki, Finland
2 Finnish
Background/Objectives: Our aim was to evaluate the relative
risk of second malignant neoplasms (SMNs) among survivors
of childhood cancer (diagnosed under age 15) and investigate
whether modern treatment regimens have resulted in reductions in the occurrence of second malignant neoplasms.
Design/Methods: Childhood cancer patients and their second
malignant neoplasms diagnosed between 1953 and 2007 were
identified from the Finnish Cancer Registry. Risk of second
malignancy was evaluated using standardized incidence ratios
(SIRs). The effect of temporal characteristics including diagnostic era and length of follow-up and disease related characteristics were assessed.
Results: We observed 372 subsequent malignancies among
7696 survivors with 112,809 person-years of follow up. The
relative risk of developing a second malignancy was nearly
five times higher than expected (SIR 4.83, 95% CI, 4.35-5.34).
SIRs were equal in both genders (p=0.9). The risk of SMNs
stayed elevated in patients treated in the most modern eras
with SIRs of 8.99 (95% CI 5.86-13.8). SIRs were highest
within one year after the primary cancer (SIR 11.2, 95% CI,
6.15-18.4) and decreased linearly until reaching the population cancer risk after 50 years of follow-up.
Conclusions: Childhood cancer survivors are at elevated risk
of SMNs. This elevated risk applies also to those diagnosed
in the more recent eras and does not reach a plateau during
follow-up of up to 50 years. Patients should be encouraged to
take part in cancer screening programs and avoid exposure to
carcinogens such as tobacco and UV-radiation.
O-028 Mental Healthcare use and Severe
Psychiatric Diagnoses in Adult Survivors of
Childhood Cancer: A Population-Based Study
Using Health Services Data
S. Gupta1 , A. Nachman2 , P. Kurdyak3 , R. Sutradhar4 , J. Pole5 , P.
Nathan1
1 The
Hospital for Sick Children, Haematology/Oncology, Toronto, Canada;
of Toronto, Institute of Medical Science, Toronto, Canada;
3 Institute for Clinical Evaluative Sciences, Mental Health & Addictions
Research Program, Toronto, Canada; 4 Institute for Clinical Evaluative
Sciences, Cancer Research Program, Toronto, Canada; 5 Pediatric
Oncology Group of Ontario, POGO Research Unit, Toronto, Canada
2 University
SIOP ABSTRACTS
S21 of S518
Background/Objectives: Though physical late effects in
childhood cancer survivors are well-documented, risks for
adverse mental health outcomes are less clear; existing evidence is contradictory. Health services data offer an objective
method to measure population-based mental health outcomes.
Design/Methods: Using a provincial registry with detailed
disease, treatment, and outcome data, we assembled a cohort
of all five-year childhood cancer survivors diagnosed <18
years and treated in an Ontario pediatric cancer Centre
between 1987-2008. Patients were linked to population-based
healthcare data capturing inpatient, outpatient, and emergency department (ED) visits. The primary outcome was
the rate of mental healthcare visits (primary care, psychiatrist, ED or hospital). Secondary outcomes included time to a
severe mental health event (ED visit, hospitalization, suicide)
both overall and by psychiatric diagnostic categories. Outcomes were compared between survivors and matched controls using recurrent event and survival analyses, and predictors of adverse outcomes modeled.
Results: When compared to 20,269 controls, 4,117 survivors
had a significantly higher rate of mental health visits [47.1 vs.
36.1 visits/100 person-years; adjusted relative rate (RR) 1.3,
95th% confidence interval (CI) 1.2-1.5]. Higher rates were
associated with female gender (RR 1.4, CI 1.1-1.7; p=0.008)
and adolescent age at diagnosis (RR 2.0, CI 1.3-3.0; p=0.004).
Cancer type, treatment intensity or treatments targeting the
central nervous system were not significant predictors. The
hazard of a severe mental health event did not differ between
survivors and controls. Though rare in both groups, survivors
were at increased risk of a severe event due to a psychotic disorder (HR 1.8, CI 1.1-2.8; p<0.05).
Conclusions: Childhood cancer survivors experience higher
rates of mental health visits than the general population, but
are no more likely to experience a severe mental health event.
Their risk is not attributable to a specific diagnosis or aspect
of treatment. An increased risk of severe psychotic disorders
requires confirmation in other cohorts.
O-029 Role of Ace Inhibitors in
Anthracycline-Induced Cardiotoxicity: A
Randomized Double Blind Placebo Controlled Trial
(enalapril) in anthracycline induced cardiotoxicity in children
with hematological malignancies.
Design/Methods: Randomized double blind placebo controlled trial was conducted in University teaching hospital
over 26 months (Trial no. CTRI/2015/09/006174). 84 patients
with leukemia (41) and lymphoma (43) were randomized to
receive either enalapril [group A (44)] or placebo [group B
(40)] for 6 months. Patients received anthracyclines (doxorubicin and/or daunorubicin) (cumulative dose >200 mg/m2 ) as
per protocol. Cardiac biomarkers (cTnI, ProBNP, CKMB) and
left ventricular ejection fraction (LVEF) were assessed at base
line and after 6 months. Primary outcome was decrease in left
ventricular ejection fraction (decrease ≥20% significant). Secondary outcomes were changes in cardiac biomarkers, development of heart failure, arrhythmias and side effects such as
dizziness and hypotension.
Results: Cardiac biomarkers increased at 6 months in all
patients with more increase in group B. It was significant for
pro BNP (49.60 ± 35.97 vs 98.60 ± 54.24, p value <0.001)
and cTnI (0.01 ± 0.0007 vs 0.011 ± 0.0026, p value 0.035) and
not significant for CKMB (1.08 ± 0.18 vs 1.21 ± 0.44, p value
0.079). 9.1% patients in group A showed increase in ProBNP
level ≥100 pg/ml compared to 37.5% patients in Group B
(p=0.001). LVEF decreased in both groups, more in group
B (62.25 ± 5.49 vs 56.15 ± 4.79, p = 0.04). ≥20% decrease
in LVEF was seen in 3 patients in group B and none in group
A (p value 0.04). LVEF remained ≥50% in both groups at 6
months. No patient developed heart failure.
Conclusions: Enalapril has a role in reducing acute cardiac
toxicity after anthracycline administration. Further studies are
needed to assess long term protection.
FREE PA PER SESSION: MYELOID
LEUKEMIA AND TRANSPLANT
O-030 Characteristics and Outcome of Myeloid
Sarcoma in Children at A Tertiary Care Centre
from India: A Study of 126 Patients
V. Gupta , S.K. Singh , V. Agrawal , T.B. Singh
A. Kumar1 , A. Tyagi1 , R. Pramanik1 , A. Batra1 , A. Chopra2 , S.
Bakhshi1
1 Institute
of Medical Sciences- Banaras Hindu University, Pediatrics,
Varanasi, India; 2 Institute of Medical Sciences- Banaras Hindu University,
Cardiology, Varanasi, India; 3 Institute of Medical Sciences- Banaras Hindu
University, Biostatistics, Varanasi, India
1 All
Background/Objectives: Anthracyclines cause dose-related
cardiotoxicity in children. Several measures including drugs
have been tried to reduce cardiac toxicity. Lack of randomized trials prompted this study to assess role of ACE inhibitor
Background/Objectives: Myeloid sarcoma (MS) is a rare
entity and it can precede or appear concomitantly with acute
myeloid leukemia. Conventionally, it has been treated on lines
of acute myeloid leukemia (AML). However, paucity of data
1
1
2
3
India Institute of Medical Sciences, Department of Medical Oncology2nd Floor- BRA IRCH, New Delhi, India; 2 All India Institute of Medical
Sciences, Department of Lab Oncology- 4th Floor- BRA IRCH, New Delhi,
India
SIOP ABSTRACTS
S22 of S518
in larger number of patients has led to difficulty in understanding its nature and management.
DNR+Ara-C (Ara-C group) followed by maintenance therapy for 1.5 years.
Design/Methods: Present study was undertaken among children with MS presenting at a large tertiary care center in India
from June, 2008 to Feb, 2016. All patients were treated on a
uniform chemotherapy treatment protocol; radiotherapy was
not used during the management.
Results: Between May 2010 and December 2016, 66 consecutive pediatric (≤14years old) patients who were genetically confirmed with a new diagnosis of APL were admitted
in our hospital. Among 66 patients, 43 were male and 23 were
female. All patients achieved complete remission (CR) except
one who gave up treatment. During induction therapy, all toxicity events were reversed after appropriate management. No
patient died at consolidation, and only one patient relapsed.
In addition, there was no difference in outcomes between the
two groups.
Results: Among 570 patients of AML (non–promyelocytic)
attending our pediatric oncology clinic, 126 patients (22.1%)
had MS at presentation. Median age was 6 years (0.3–18
years) and incidence was more common among males (M:
F = 2.4:1). Cytogenetic parameters were available in 100
patients; good risk cytogenetics were found in 54% patients;
this was significantly higher than non MS associated cohort
(p=0.0001) wherein the good risk cytogenetics was observed
in 28.2%of subjects. All 54 patients in good risk group of the
MS cohort had t(8:21). At median follow-up of 21 months,
median event free survival was 19.4 months in MS group versus 11.1 months in non MS associated AML (p=0.003). Overall survival was 37.2 months versus 16.2 months in MS group
versus non MS group, respectively (p=0.0009).
Conclusions: MS are present in about one-fifth of AML
patients; this is distinctly more than the worldwide prevalence.
The cohort with MS had a higher proportion of good risk
cytogenetics with a striking association with t(8:21). Presently
adopted AML like treatment strategy in such patients has
resulted in favorable outcome in comparison to the non MS
associated cohort.
O-031 Arsenic Trioxide and All-Trans-Retinoic
Acid Based Trial May Eliminate the Need for
Cytarabine In Pediatric Acute Promyelocytic
Leukemia: Results from CCAPL2010
(NCT01191541)
L. Zhang1 , Z. xiaofan1 , Z. Yao Zou1 , C. Yumei1 , G. Ye1 , Y.
Wenyu1 , C. xiaojuan1 , W. shuchun1 , L. xiaoming1 , R. min1 , Z.
jiayuan1 , L. tianfeng1 , L. fang1 , Q. benquan1
1 State
Key Laboratory of Experimental Hematology- Institute of
Hematology and Blo, Department of Pediatrics, tianjin, China
Background/Objectives: The objective of this study was to
evaluate the efficacy and safety of using all-trans-retinoic acid
(ATRA) and arsenic trioxide (ATO) to treat paediatric patients
with newly diagnosed acute promyelocytic leaukemia (APL).
Additionly, we assessed whether cytosine arabinoside (AraC) could be omitted in ATO- and ATRA- based trials.
Design/Methods: Patients were assigned to receive ATRA
plus ATO for induction followed by idarubicin (IDA) and
ATO. Then, patients were randomly assigned to receive
2 courses of daunorubicin (DNR, no Ara-C group) or
After a median follow-up of 32 months, EFS was 97.0±3.0%,
and OS was 100%. No factor impacted relapse or survival in
our study. There was no difference in the median arsenic concentrations in plasma, urine, hair, and nail samples between
patients in whom arsenic treatment had been ceased for more
than 12 months and normal controls.
Conclusions: The results of our study indicate that ATO is
safe and effective in paediatric APL and that Ara-C can be
omitted, at least when using regimens similar to ours. Our
analysis of arsenic levels in the plasma, urine, hair and nails of
patients indicated that there was no significant accumulation
of arsenic after ATO was discontinued for 12 months.
O-032 Efficacy and Safety of Nilotinib in
Pediatric Patients with Philadelphia
Chromosome–Positive (PH+) Chronic Myeloid
Leukemia (CML): Results from A PHASE 2 Trial
N. Hijiya1 , A. Maschan2 , C. Rizzari3 , H. Shimada4 , C. Dufour5 , H.
Goto6 , H.J. Kang7 , T. Guinipero8 , Z. Karakas9 , F. Bautista10 , A.
Kheradpour11 , S. Ducassou12 , K.H. Yoo13 , W. Mendes14 , S.
Quenet15 , S. Hertle16 , D. Sosothikul17
1 Ann
& Robert H. Lurie Children's Hospital of Chicago, Department of
Hematology/Oncology, Chicago, USA; 2 Dmitrii Rogachev Federal
Research Center for Pediatric Hematology- Oncology and Immunology,
Pediatric Hematology- Oncology and Immunology, Moscow, Russia;
3 Pediatric Hematology Oncology Unit- University of Milano BicoccaMBBM Foundation, Department of Pediatrics, ASST Monza, Italy; 4 Keio
University School of Medicine, Department of Pediatrics, Shinjuku-ku,
Japan; 5 I.R.C.C.S. Istituto Giannina Gaslini, Department of General and
Specialized Pediatrics Functional Department Hematology-Oncology,
Genova, Italy; 6 Kanagawa Children's Medical Center, Division of
Hemato-Oncology/Regenerative Medicine, Yokohama, Japan; 7 Seoul
National University College of Medicine- Seoul National University
Children's Hospital, Department of Pediatrics, Seoul, Republic of Korea;
8 Nationwide Children's Hospital, Division of Hematology/ Oncology/ Bone
Marrow Transplantation, Columbus, USA; 9 Istanbul University- Istanbul
Medical Faculty, Department of Pediatric Hematology and Oncology,
Istanbul, Turkey; 10 Hospital Niño Jesus, Pediatric Oncology Service,
Madrid, Spain; 11 Loma Linda University Cancer Center, Pediatric
Hematology/Oncology, Loma Linda, USA; 12 Groupe Hospitalier Pellegrin Hôpital des Enfants, Pediatric Oncology and Hematology Unit, Bordeaux,
France; 13 Samsung Medical Center- Sungkyunkwan University School of
Medicine, Department of Pediatrics, Seoul, Republic of Korea; 14 Novartis
Pharmaceuticals Corporation, Clinical Department, East Hanover, USA;
SIOP ABSTRACTS
S23 of S518
15 Novartis
Pharma AG, Statistical Deartment, Basel, Switzerland;
Pharma AG, GDO Trial Management – Oncology, Basel,
Switzerland; 17 Chulalongkorn Hospital, Div. of Hematology/Oncology
Department of Pediatrics, Bangkok, Thailand
16 Novartis
Background/Objectives: This ongoing phase 2 study is evaluating nilotinib in pediatric patients with CML.
Design/Methods: Eligible patients (1-<18y) had CML in
chronic or accelerated phase (CP/AP) resistant/intolerant to
imatinib/dasatinib, or newly-diagnosed CML-CP; no patients
with CML-AP enrolled. Patients were to receive oral nilotinib 230mg/m2 BID (rounded to nearest 50mg) for 66 28day cycles; data from primary analysis (when all patients had
completed 12 cycles or discontinued) are reported. Primary
endpoint for resistant/intolerant cohort was major molecular response rate (MMR; BCR-ABL1 ≤0.1% on International
Scale) at 6 cycles; coprimary endpoints for newly-diagnosed
cohort were MMR rate by 12 cycles and complete cytogenetic
response (CCyR) rate at 12 cycles.
Results: Fifty-eight patients (resistant/intolerant, n=33;
newly-diagnosed, n=25) enrolled and received nilotinib
(median age, 13y for both cohorts; median time on-treatment,
16 and 15 months, respectively). Results in the resistant/intolerant cohort were: 13/33 patients had MMR at 6
cycles (39.4%; 95% CI, 22.9%-57.9%); 6/13 had MMR at
baseline. Median time to MMR was 2.8 (range, 0-11.3)
months among 19 patients in MMR by the data cutoff.
Twenty-seven patients (81.8%) had CCyR by 12 cycles;
14/27 had CCyR at baseline. One patient progressed to
AP/blast crisis after 10.1 months on-treatment. Results in
newly-diagnosed patients were: rates of MMR by 12 cycles
and CCyR at 12 cycles were both 64.0% (16/25; 95% CI,
42.5%-82.0%). Median time to response was 5.6 months
for both MMR and CCyR among 17 and 21 patients with
those responses, respectively, by the data cutoff. All patients
had ≥1 AE; all-grade AEs with incidences >30% overall
were headache (46.6%), pyrexia (32.8%), and blood bilirubin
increased (31.0%). Rates of serious AEs and AE-related discontinuations (all-grade) were 13.8% and 15.5%, respectively.
No deaths were reported.
230mg/m2
BID was efficacious in
Conclusions: Nilotinib
pediatric patients with newly-diagnosed or resistant/intolerant
CML-CP, with an AE profile comparable to that in
adults.
O-033 Prognostic Biomarkers for the
Development of Respiratory Failure Post Allogeneic
Hematopoietic Cell Transplantation
C.M. Rowan1 , M.W. Geraci2 , N. Swigonski1 , S. Paczesny1
1 Indiana
2 Indiana
University School of Medicine, Pediatrics, Indianapolis, USA;
University School of Medicine, Medicine, Indianapolis, USA
Background/Objectives: Currently, there is not a method for
predicting respiratory failure in the allogeneic hematopoietic
cell transplant (HCT) recipient. Biomarkers may be effective
for risk recognition, understanding etiology, and serving as
therapeutic targets. The study's aim was to identify prognostic
biomarkers for the development of respiratory failure.
Design/Methods: This is a single center analysis of an existing cohort from a clinico-biologic repository. Plasma samples at days 7, 14, 21, and 30 post-HCT were used to measure four proteins by ELISA: STimulation-2 (ST2), the IL33
receptor, interleukin 6 (IL6), tumor necrosis factor receptor 1
(TNFR1) and osteopontin (OPN). Data is presented in medians and were compared using Wilcoxon rank sum test. ROC
curves were also done for each protein.
Results: A total of 122 adult and pediatric allogeneic HCT
recipients were included with 24.6% (n=30) developing respiratory failure within 1 year post-transplant. The median day
to respiratory failure was 27.0. The medians of all four proteins were significantly higher in the group that developed respiratory failure at multiple time points: Day 7 ST2 [57.0 vs
24.9, p-0.003], IL6 [100.0 vs 39.2] p=0.002, TNFR1 [4184.0
vs 2425.6 p=0.02]; Day 14 ST2 [58.5 vs 22.0, p-0.003], IL6
[91.8 vs 32.5 p=0.001], TNFR15499.2 vs 3121.9 p=0.006],
OPN [340.0 vs 277.8, p=0.04]; Day 21 ST2 [50.0 vs 25.0,
p<0.0001], IL6 [62.8, 21.0, p=0.006], TNFR1 [5793.0 vs
3314.0 p=0.003], OPN [332.0 vs 220.0, p=0.003]; Day 30
ST2 [40.0 vs 20.0, p<0.0001], IL6 [53.0, 18.1, p=0.006],
TNFR1 [5518.0 vs 3024.6 p=0.001], OPN [275.0 vs 185.0,
p=0.02]. ROC curves indicate that these proteins allowed
for good discrimination for the development of respiratory failure within 45 days of transplant (AUCs: ST2=0.83,
TNFR1=0.78, OPN=0.78, and IL6=0.73).
Conclusions: ST2, IL6, TNFR1, and OPN were all significantly elevated at multiple time points in those that develop
respiratory failure post-allogeneic HCT.
O-034 Hepatic Sinusoidal Obstruction Syndrome
(SOS) in Children Undergoing Autologous Stem
Cell Transplant (ASCT) Following High Dose
Chemotherapy (HDCT) - A Single Centre
Experience from the UK
N. Roy Moulik1 , L. Van Bruggen1 , I. Johnson1 , T. Petterson1 , J.
Mycroft1 , S. Vaidya1
1 Royal
Marsden Hospital, Paediatric Oncology, Greater London, United
Kingdom
Background/Objectives: Hepatic sinusoidal obstruction
syndrome (SOS) or veno-occlusive disease (VOD) is a serious
complication of autologous stem cell transplant (ASCT) with
historically high mortality rate. Defibrotide has shown proven
SIOP ABSTRACTS
S24 of S518
benefit in its treatment and has a modest role in prevention.We
report our experience with SOS in paediatric ASCT.
Design/Methods: Case records of 82 consecutive patients
undergoing ASCT following HDCT between 2010 and 2017
were reviewed, relevant data were retrieved and analysed
using conventional statistics. Defibrotide was used for treatment of all cases of SOS. It was available for prophylaxis of
SOS in patients receiving busulfan based conditioning until
2014 due to funding issues.
Results: Fourteen of the 82 children (17%) were diagnosed with SOS. The incidence was significantly higher in
those receiving busulfan based conditioning (13/42 vs.1/40)
(p=0.008).The mean time to diagnosis of SOS was 19±5.6
days following stem cell rescue.Seven of 14 patients had
bilirubin <34 micromoles/l and 3 had normal ultrasound.
Coagulopathy was noted in 10 cases; 1 child developed multiorgan involvement. Nine children had mild SOS. Five cases
had moderate or severe SOS, of which 4 needed PICU support. Patients with SOS had significantly delayed platelet
recovery, higher transfusion requirement and longer hospital
stay. The unavailability of defibrotide prophylaxis for 17/42
patients receiving busulfan post-2014 did not significantly
increase the incidence of SOS (6 /17 vs. 7/25; p=0.74). No significant difference in clinical course or severity was observed
in 7 children who developed SOS despite defibrotide prophylaxis when compared to the 6 without it. No SOS related mortality was seen in either group.
Conclusions: Hepatic SOS was more commonly seen in
children receiving busulfan conditioning. Changing practice of not using defibrotide prophylaxis did not seem to
increase the incidence or severity of SOS. Overall outcome was excellent with supportive care and treatment with
defibrotide.
O-035 Implementation of A Pediatric Early
Warning System in Pediatric Patients Undergoing
Hematopoietic Stem Cell Transplantation in Latin
America
P. Vergara1 , S. Saez1 , J. Palma1 , D. Soberanis2 , A. Agulnik3
1 Hospital
Luis Calvo Mackenna, Unidad de Trasplante de Médula Osea,
Santiago, Chile; 2 Unidad Nacional de Oncologia Pediatrica, Oncologia,
Ciudad de Guatemala, Guatemala; 3 St. Jude Children's Research Hospital,
Department of Global Pediatric Medicine, Memphis, USA
Background/Objectives: Patients undergoing hematopoietic
stem cell transplantation (HSCT) are at high risk for clinical
deterioration due to their immunosuppression and expected
complications. Pediatric Early Warning Systems (PEWS) are
nursing-administered clinical acuity tools to aid with early
identification of clinical deterioration in hospitalized patients.
While these tools are commonly used in hospitals caring
for HSCT patients in high-resource settings, they have not
previously been applied to HSCT patients hospitalized in
Latin America. The objective of this study is to describe the
implementation of PEWS in the HSCT Unit of Luis Calvo
Mackenna Hospital (HLCM), a pediatric hospital in Santiago,
Chile.
Design/Methods: The PEWS used at Boston Children's Hospital, previously validated in HSCT patients, was modified at HLCM by a multidisciplinary team of physicians
and nurses from the Oncology, BMT and Pediatric Intensive Care Unit (PICU) to adjust for practice variations
between our hospitals. The modified PEWS was initially trialed as a one-month pilot, and, after adjustments, implemented as a part of clinical practice in the unit. During
this period, we analyzed compliance with PEWS documentation, error rates, abnormal (red) scores, and unplanned PICU
transfers.
Results: A total of 12 nurses, 12 nursing technicians, 3 staff
physicians and 6 residents were trained in PEWS. Compliance
with PEWS documentation was 89%, with an average of 37
PEWS calculated per day and 3.7% errors. The most common
errors were interpretation of heart rate (38%) and oxygen use
(36%). During 6 months of data collection, here were a total of
41 red PEWS among 8 patients, 3 of them required unplanned
PICU transfer (37.5%).
Conclusions: We describe the successful implementation
of PEWS in a pediatric HSCT unit in Latin America
with low error rates and appropriate identification of clinical deterioration. Sustainability of this program requires
continuous reinforcement and monitoring to achieve 100%
compliance.
F REE PA P ER SES S IO N: SO LID
TUM O UR TH ERAP Y
O-036 Results from the UK Children's Cancer
and Leukaemia Group Study of Extracranial Germ
Cell Tumours in Children and Adolescents (GC III)
S. Depani1 , J. Nicholson2 , S. Stoneham3 , M. Krailo4 , C. Xia5 , J.
Hale6
1 University
of Birmingham, Cancer Research UK Clinical Trials UnitInstitute of Cancer and Genomic Sciences, Birmingham, United Kingdom;
2 University Cambridge Hospitals NHS Trust, Paediatric Oncology and
Haematology, Cambridge, United Kingdom; 3 University College London
Hospitals NHS Trust, Children and Young Peoples Cancer Service, London,
United Kingdom; 4 University of Southern California, Keck School of
Medicine, Los Angeles- CA, USA; 5 Children's Oncology Group, Statistics
and Data Center, Monrovia CA, USA; 6 Newcastle upon Tyne Hospitals
NHS Foundation Trust, Paediatric and Adolescent Haematology and
Oncology, Newcastle upon Tyne, United Kingdom
SIOP ABSTRACTS
Background/Objectives: For extracranial malignant germ
cell tumours (MGCT) in the UK, the GCII study used carboplatin and demonstrated equivalent survival to cisplatincontaining protocols. GCIII, a single arm observational
study, used new risk stratification, replaced consolidation
chemotherapy with standard number of cycles and introduced
surveillance for all Stage 1 MGCTs with the aim of deescalating treatment where possible whilst maintaining excellent survival with the use of carboplatin.
Design/Methods: Patients with a diagnosis of MGCT were
stratified to three risk group - low (LR), intermediate (IR),
high (HR), using a combination of stage and prognostic factors. Patients with AFP >10,000U/L or Stage IV disease
(except testis <5 and all germinomas) and Stage II-IV thoracic were classified as HR. Stage I tumours (LR) were monitored and received chemotherapy only if disease progressed.
IR patients received 4 cycles of JEB (etoposide 120mg/m2 i.v
d 1,2,3; bleomycin 15mg/m2 iv d3 and carboplatin i.v on d2);
HR patients received 6 cycles. Carboplatin dose was calculated to give an AUC of 7.9ml/m2.min.
Results: Eighty-six patients with MGCT were treated on
the study between 2005 -2009: 59% female, median age 5.7
years (0 – 17.5 years). Twenty-five (29%) were LR, 23 (27%)
IR and 38 (44%) HR. Seven LR patients (28%) had disease progression at a median of 3 months; all were cured
with chemotherapy. Five year event-free-survival for IR/HR
patients was 90.2% (95% CI, 79.4%-95.5%) (IR 87%; HR
92%) and overall survival 94.9% (95%CI, 85.0%-98.3%) (IR
96%; HR 95%). JEB was well tolerated with manageable
toxicity. No patients developed significant oto- or nephrotoxicity. There was no discernible difference in carboplatin
dose whether calculated by body surface-area or creatinine
clearance.
Conclusions: JEB chemotherapy using this risk stratification
resulted in excellent survival with manageable toxicity. Carboplatin should be evaluated against cisplatin for paediatric
GCTs in a large randomised prospective study.
O-037 Treatment of Refractory Germ Cell
Tumors in Children with Paclitaxel, Ifosfamide and
Carboplatin: Results of the Children's Oncology
Group AGCT0521 Study
F. Pashankar1 , L. Frazier2 , M. Krailo3 , A. Pappo4 , T. Olson5 , C.
Rodriguez-Galindo6
1 Yale
University School of Medicine, Pediatrics, New Haven, USA; 2 Dana
Farber Cancer Cancer Institute and Boston Children's Hospital, Pediatrics,
Boston, USA; 3 University of Southern California, Preventive Medicine, Los
Angeles, USA; 4 Saint Jude Children's Research Hospital, Pediatrics,
Memphis, USA; 5 Children's Healthcare of Atlanta, Pediatrics, Atlanta,
USA; 6 Saint Jude Children-s Research Hospital, Global Pediatric Medicine,
Memphis, USA
S25 of S518
Background/Objectives: Currently there is no standard regimen for relapsed pediatric malignant germ cell tumors
(MGCT). In adults, a salvage regimen commonly used is TIP
(paclitaxel, ifosfamide, cisplatin) which is associated with
overall survival of 50-70%. Further doses of cisplatin in young
children, however, can be associated with significant short and
long term toxicities. Because carboplatin has been shown to
be effective in pediatric GCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin.
The primary aim was to evaluate response after 2 cycles of
paclitaxel, ifosfamide, and carboplatin (TIC) in children with
relapse or refractory MGCT.
Design/Methods: This Phase II study, conducted by the
Children's Oncology Group between November 2007 and
June 2011, included children < 21y with relapsed or
chemotherapy-resistant MGCT, who had previously received
a regimen containing cisplatin. “TIC” consists of paclitaxel
135 mg/m2/day Day 1, ifosfamide 1800 mg/m2/dose Days 15 and carboplatin AUC 6.5 Day 1. The endpoint of trial was
response after 2 cycles.
Results: 20 patients (12 male, median age 13.5 years) were
enrolled. By RECIST criteria, 8 patients achieved a partial
response (PR) during protocol therapy (response rate 40%),
10 patients had stable disease (SD) and 2 patients had progressive disease. Of the 8 patients with PR, all had elevated markers at enrollment (5 AFP, 2 B HCG, 1 both), and 6/8 patients
(75%) had at least a 1 log reduction in tumor markers. Of the
10 patients with SD, 9 had elevated markers at enrollment (8
AFP, 1 BHCG), and 6/9 (67%) had at least 1 log decrease
Conclusions: Evaluation after 2 cycles of TIC therapy indicates reasonable efficacy, particularly if one uses the metric of an appropriate AFP decline. Taxol-based regimens,
either with carboplatin, as in this regimen or cisplatin, as in
adult regimens, should be considered for salvage therapy in
children
O-038 Ovarian Yolk SAC Tumors: Does Age
Matter?
C. Faure Conter1 , C. Xia2 , D. Gershenson3 , J. Hurteau4 , A.
Covens5 , F. Pashankar6 , M. Krailo7 , D. Billmire8 , B. Fresneau9 , C.
Patte9 , F. Shaikh10 , S. Stoneham11 , J. Nicholson12 , M. Murray12 , L.
Frazier13
1 Centre
Léon Bérard, paediatry, Lyon, France; 2 Children's Oncology
Group, statistics, Monrovia, USA; 3 MD Anderson Cancer Center, oncology,
Houston, USA; 4 North Shore University Health System, oncology, Evanston,
USA; 5 Sunnybrook Health Sciences Center, oncology, Toronto, Canada;
6 Yale university, pediatry, New Haven, USA; 7 University of Southern
California, statistics, Los Angeles, USA; 8 Riley Hospital for Children,
surgery, Indianapolis, USA; 9 Gustave Roussy, pediatry, Villejuif, France;
10 Hospital for Sick Children, pediatry, Toronto, Canada; 11 Children's and
Young Persons Cancer Services, pediatry, London, United Kingdom;
12 Cambridge University Hospitals NHS Foundation Trust, pediatry,
Cambridge, United Kingdom; 13 Dana-Farber/Boston Childrens Cancer and
Blood Disorders Center, pediatry, Boston, USA
SIOP ABSTRACTS
S26 of S518
Background/Objectives: Whereas among pediatric oncologists, ovarian yolk sac tumor (O-YST) is considered a chemo
sensitive tumor, it is often cited as an adverse prognostic factor in adult women with ovarian germ cell tumors.
Design/Methods: The MaGIC dataset included 6 pediatric
clinical trials (United States, United Kingdom and France)
and 2 adult gynecology clinical trials (United States). Any
patient with an O-YST that was ≥ FIGO Stage IC and treated
with a platinum-based chemotherapy was eligible. Age was
modeled as a continuous and a categorical variable (children:
0-10y; adolescents; 11-17y and adults: ≥18y). In addition,
analyses to establish the optimal cut-point for age were conducted. Tumors were coded as pure YST (YST +/- teratoma),
mixed YST (YST + other malignant germ cell component) or
putative YST (‘mixed’ germ cell tumor + alpha-fetoprotein
(AFP) >1000 ng/ml). Histology, stage (II/III vs. IV), preoperative AFP levels (<1.000, 1.000-10.000 or >10.000 ng/ml),
and chemotherapeutic regimen (carboplatin vs. cisplatin) were
analyzed as covariates.
Results: Two hundred fifty one patients (median age: 13 y,
range 0-38) were identified (78 children, 139 adolescents and
34 adults). Histology was pure, mixed and putative in 129,
56 and 66 cases, respectively. Twenty six patients were Stage
IV, similarly distributed in the 3 age-groups. Median follow
up was 5.8 years. The overall 5-year EFS and OS was 91%
(95% CI, 87%-94%) and 96% (92%-98%), respectively. Age
did not affect risk of event or death, modeled either as a categorical or continuous variable. Analysis failed to identify an
age cut-point that affected risk. None of the other covariates
investigated had a prognostic impact on EFS or OS.
Conclusions: O-YST have an excellent outcome across all
age-groups. Age has no apparent impact on the probability of
event or death, allowing pediatric and gynecologic oncologist
to enroll patients onto joint pediatric and adult trials.
O-039 Pulmonary Nodule Size Measurements in
Children with Wilms Tumours: Do Radiologists
Agree?
S. Shelmerdine1 , J. Brok2 , S. Irtan3 , K. Pritchard-Jones2 , O. Olsen1
1 Great
Ormond Street Hospital for Children NHS Foundation Trust,
Clinical Radiology, London, United Kingdom; 2 University College Great
Ormond Street Institute of Child Health- UCL- London- UK., Clinical
Oncology, London, United Kingdom; 3 APHP Armand Trousseau Hospital,
Paediatric Surgery, Paris, France
Background/Objectives: Children with pulmonary metastases from Wilms tumours are allocated treatment regimens
based upon lung lesion(s) size and response to chemotherapy.
In the upcoming SIOP-protocol (UMBRELLA), chest CT will
be used to measure lung lesions with thresholds of <3, 3-5,
and >5 mm determining treatment intensity. This study aims
to measure inter- and intra-observer variability in the radiological assessment of pulmonary nodule size.
Design/Methods: CT thoraces from 15 patients at diagnosis enrolled in the multicentre ’Improving Population Outcomes of Renal Tumours of childhood’ (IMPORT) study were
assessed. Five radiologists (3 chest, 2 paediatric) from different centres (4 UK, 1 Netherlands) assessed nodule size
on two occasions, 6 months apart. Readers were blinded to
patient symptoms and original radiology reports. Modified
Bland Altman graphs were created to measure inter and intraobserver limits of agreement for the nodules detected by all
readers.
Results: 93 different nodules were seen by at least one reader
on both of their individual assessments of the same scan 6
months apart. Only 14 nodules were seen by all readers at both
assessments.
Of these, inter-observer limits of agreement (in millimetres)
for the 5 readers were ±2.0 and ±1.7 (antero-posterior diameter), ±1.8 and ±2.0 (transverse diameter) and ±2.0 and ±1.9
(cranio-caudal distance) at assessments 1 and 2, respectively.
Intra-observer mean differences in measurement and limits of
agreement across the three dimensions were 0.1 ±1.5mm, 0.2
±2.1mm, 0.3 ±1.7mm, 0.3± 2.4mm, and 0.1 ±2.5mm (readers 1-5, respectively).
Applying UMBRELLA criteria, only seven patients (∼ 45%)
would be allocated to the same treatment arm across all radiology assessments.
Conclusions: The demonstrated intra- and inter-observer
variability of detection and measurement of pulmonary nodules on CT thorax has important implications for the diagnosis
and risk stratified treatment of metastatic disease.
O-040 Clinicopathological Study on the
Sensitivity and Specificity of Indocyanine Green
Fluorescent Imaging Test in the Pulmonary
Metastases Resections of Hepatoblastoma
M. Yoshida1 , M. Tanaka1 , N. Kitagawa2 , M. Shinkai2 , H. Goto3 , Y.
Tanaka1
1 Kanagawa
Children's Medical Center, Pathology, Yokohama, Japan;
Children's Medical Center, Surgery, Yokohama, Japan;
3 Kanagawa Children's Medical Center, Hemato-oncology & Regenerative
medicine, Yokohama, Japan
2 Kanagawa
Background/Objectives: Pulmonary metastasis resection of
hepatoblastoma using indocyanine green fluorescent imaging
(ICG) is effective for lesions that cannot be detected by CT
or are nonpalpable during operations. However, the detailed
evaluation of the sensitivity and specificity of ICG tests was
insufficient.
Design/Methods: The subjects were 378 specimens submitted to the pathology department as pulmonary metastatic
SIOP ABSTRACTS
S27 of S518
lesions of hepatoblastoma that were resected using ICG imaging tests in Kanagawa Children's Medical Center from January 2013 to March 2017. In total, there were 61 operations
for 16 cases. By collating operation records and pathological
reports, we studied the sensitivity and specificity of the ICG
tests.
Results: Among 378 specimens, 4 specimens were falsenegative (ICG-negative and tumor-positive), and the sensitivity of the ICG tests was 0.98. There were also 112 falsepositive specimens (ICG-positive and tumor-negative) with
a specificity of 0.018 and a positive predictive value of
0.70. All the false-negative specimens were resected from
the same case. In false-positive specimens, as far as operation records could confirm, the ICG-positive regions were
generally smaller than 2 mm in diameter. Even if the ICGpositive regions were relatively wide, the ICG uptake patterns
were weak, heterogeneous, and poorly marginated. Microscopically, false-positive specimens often contained necrosis, fibrosis, granuloma, infiltrates of inflammatory cells,
hemorrhage, thrombus, and/or unspecified mesenchymal tissue, which sometimes suggests the presence of preceding
metastatic lesions.
Conclusions: Our study demonstrated that ICG tests had
high sensitivity but occasionally yielded false-negative specimens. The specificity was low, but false-positive specimens
showed relatively uniform ICG uptake patterns by which the
absence of viable tumors was predictable. These findings suggested high ICG test reliability as a technique to detect pulmonary metastases when considering high sensitivity to be
more important. Closer communication between surgeons and
pathologists about the ICG uptake patterns of the specimens
might improve the usefulness of these tests.
O-041 Intensive Multi-Modality Therapy for
Extra-Ocular Retinoblastoma (RB): A Children's
Oncology Group (COG) Trial (ARET0321)
1
2
3
4
I.J. Dunkel , M.D. Krailo , G.L. Chantada , A. Banerjee , S.
Abouelnaga5 , J. Buchsbaum6 , T.E. Merchant7 , M. Granger8 , R.F.
Jubran9 , M. Kellick10 , J. Weinstein11 , D.H. Abramson12 , C.
Rodriguez-Galindo13 , M.M. Chintagumpala14
1 Memorial
Sloan Kettering Cancer Center, Pediatrics, New York, USA;
Oncology Group, Biostatistics, Arcadia, USA; 3 Hospital JP
Garrahan, Hemato-oncologia, Buenos Aires, Argentina; 4 UCSF, Pediatrics,
San Francisco, USA; 5 Children's Cancer Hospital Foundation 57357,
Pediatric oncology, Cairo, Egypt; 6 National Cancer Institute, Radiation
oncology, Rockville, USA; 7 St. Jude Children's Research Hospital,
Radiation oncology, Memphis, USA; 8 Cook Children's Medical Center,
Pediatrics, Fort Worth, USA; 9 Children's Hospital Los Angeles, Pediatrics,
Los Angeles, USA; 10 Memorial Sloan Kettering Cancer Center, Pharmacy,
New York, USA; 11 Lurie Children's Hospital, Pediatrics, Chicago, USA;
12 Memorial Sloan Kettering Cancer Center, Ophthalmology, New York,
USA; 13 St. Jude Children's Research Hospital, Pediatrics, Memphis, USA;
14 Texas Children's Cancer Center, Pediatrics, Houston, USA
2 Children's
Background/Objectives: Metastatic RB is associated with
a poor prognosis. COG opened this prospective, multiinstitutional, international trial to study whether intensified
systemic chemotherapy with or without radiation therapy
(RT) would improve outcomes in this population.
Design/Methods: Patients with regional extra-ocular RB
(stage 2 or 3) received 4 cycles of chemotherapy (vincristine
0.05 mg/kg/day, cisplatin 3.5 mg/kg/day, cyclophosphamide
65 mg/kg x 2 days, etoposide 4 mg/kg x 2 days) followed
by involved-field RT (4,500 cGy). Two strata of patients
with metastatic RB [stage 4a: no central nervous system
(CNS) involvement; and stage 4b: CNS metastases/trilateral
RB)] also received 4 cycles of chemotherapy. Patients with
≥ partial response then received 1 cycle of high-dose carboplatin (Calvert formula with AUC=7/day, maximum 16.7
mg/kg/day) on days -8 to -6, thiotepa (10 mg/kg/day), &
etoposide (8.3 mg/kg/day) on days -5 to -3 with autologous hematopoietic stem cell rescue on day 0. Patients
with metastatic RB who achieved an inadequate response to
chemotherapy received RT.
Results: Sixty subjects (20 in each stratum) were enrolled; 57
eligible were included in the analyses (data current to 6-3016). Toxicity was significant as expected and included 2 therapy related deaths. Event-free survival (EFS) at 36 months
was 87.7% (90% CI 65.4 to 96.0%) for subjects with stage 2
or 3 disease, 79.3% (90% CI 54.2 to 91.6%) for subjects with
stage 4a disease and 8.0% (90% CI 1.0 to 25.1%) for subjects
with stage 4b/trilateral disease. The observed results significantly improved the EFS in each stratum compared with historical results used for planning the study.
Conclusions: Intensive multi-modality therapy is highly
effective for patients with regional extra-ocular RB and
metastatic RB not involving the CNS. More effective therapy
is required for patients with CNS RB.
F REE PA P ER SES S IO N: BRAIN
TUMOURS - II
O-042 Proteogenomic Approach Discriminates
Pediatric and Adult Pilocytic Astrocytoma as
Distinct Biological Entities
D. Picard1,2,3 , J. Felsberg3 , M. Langini4,5 , D. Pauck1,2,3 , V.
Marquardt1,2,3 , F. Meyer1,2,3 , A. Stefanski4,5 , K. Stühler4,5 , A.
Borkhardt2 , G. Reifenberger3 , C. Faria6,7 , M. Remke1,2,3
1 German
Cancer Consortium DKTK and German Cancer Research Center
DKFZ, Department of Pediatric Neuro-Oncogenomics, Düsseldorf,
Germany; 2 Hematology- and Clinical Immunology- Medical FacultyUniversity Hospital Düsseldorf, Department of Pediatric Oncology,
Dusseldorf, Germany; 3 Heinrich Heine University Düsseldorf- Medical
Faculty, Department of Neuropathology, Düsseldorf, Germany; 4 BMFZHeinrich-Heine-University Düsseldorf, Molecular Proteomics Laboratory,
SIOP ABSTRACTS
S28 of S518
Dusseldorf, Germany; 5 University Hospital DüsseldorfHeinrich-Heine-University Düsseldorf, Institute for Molecular Medicine,
Düsseldorf, Germany; 6 Instituto de Medicina Molecular- da Universidade
de Lisboa, Faculdade de Medicina, Lisbon, Portugal; 7 Hospital de Santa
Maria- Centro Hospitalar Lisboa Norte, Department of Neurosurgery,
Lisbon, Portugal
Background/Objectives: Pilocytic astrocytoma (PA) comprise the most common primary brain tumor in childhood.
Genome-wide profiling and next-generation sequencing studies point towards a single-pathway disease with oncogenic
activation of MAPK signaling, typically driven by BRAF
alterations. Incompletely resected tumors recur frequently
despite radiation and/or chemotherapy. Less favorable therapeutic responses are observed in adults compared their
pediatric counterparts. Thus, we utilized a proteogenomic
approach to reveal the biological heterogeneity of PA across
all age-groups to identify novel therapeutic targets.
Design/Methods: Our proteogenomic approach encompasses
RNA sequencing (RNAseq) and LC/MS-based proteomic
profiling in pediatric (n=55) and adult patients (n=24) with
PA. Unsupervised hierarchical clustering (HCL) analyses
were applied to determine the biological heterogeneity of
the disease. Integrative genomics combined with downstream
pathway analysis were used to identify specific pathway
activation in biological subgroups. Lastly, we performed
high-throughput drug screening encompassing conventional
chemotherapeutics and targeted therapeutics (n=211) currently evaluated in phase III and IV clinical trials to validate
novel molecular targets in PA primary culture models (n=8).
Results: Pediatric and adult PA segregate into two main subgroups identified by unsupervised HCL using RNAseq and
proteomic profiling (p=0.001). Adult tumors form a single
entity, while we observed additional heterogeneity in pediatric
tumors segregating into two subgroups (p=0.01). Initial analyses show that adult PA display an over-representation of factors involved in translation initiation and ciliogenesis according to GeneSet Enrichment Analysis, whereas pediatric PA
show a significant enrichment of pathways involved in glycolysis, signal transmission and AKT signaling.
Conclusions: In all, our proteogenomic approach reveals
clear biological heterogeneity in pediatric and adult PA.
Ongoing drug screening experiments are used to determine
therapeutics with preferential activity against pediatric and
adult PA cultures. These biological insights may improve
biological stratification and reveal novel therapeutic targets
specifically useful for non-resectable tumors with high risk
of progressive disease.
O-043 Genomic Landscape of the First 100
Tumors Registered in the Biological Medicine for
Diffuse Intrinsic Pontine Glioma (BIOMEDE) Trial
J. Grill1 , M.A. Debily2 , D. Castel1 , E. Barret3 , S. Picot3 , A.
Plessier3 , L. Le Dret3 , K. Nysom4 , S. Huybrechts5 , C. Dufour1 , P.
Capolino6 , M.C. Le Deley7 , S. Puget8 , P. Varlet9 , G. Vassal6
1 Institut
Gustave Roussy, Pediatric and Adolescent Oncology & CNRS
UMR 8203, Paris, France; 2 Gustave Roussy & Université d'Evry Val
d'Essone, CNRS UMR 8203, Villejuif, France; 3 Institut Gustave Roussy,
CNRS UMR 8203, Paris, France; 4 Rigshospitalet, Pediatric and Adlescent
Medicine, Copenhagen, Denmark; 5 Hôpital de la Reine Fabiola, Oncologie
Pédiatrique, Bruxelles, Belgium; 6 Gustave Roussy, Clinical Research
Direction, Villejuif, France; 7 Gustave Roussy & Centre Oscar Lambret,
Biostatistiques, Villejuif, France; 8 Hôpital necker Enfants Malades,
Neurochirurgie, Paris, France; 9 Hôpital Sainte-Anne, Neuropathologie,
Paris, France
Background/Objectives: DIPG genomics has been so far
mostly done on autopsy samples and in restrospective studies. In the frame of the BIOMEDE randomized trial of three
targeted therapies (erlotinib, everolimus, dasatinib) based on
three biomarkers identification (EGFR, PTEN, PDGFRA), a
systematic whole exome and RNA sequencing of stereotactic
biopsies performed at diagnosis was implemented to inform
the results of the trial and define additional targets that could
be used to guide therapy at relapse.
Design/Methods: The results of the first 100 patients from
France, Danemark and Belgium are presented. Seventy-five
percents of the samples could be profiled for DNA & RNA,
no frozen material was available for 6% of the tumors and only
one sample was not contributive.
Results: All tumor samples but one included in the study on
the basis of histology showed a loss of H3-K27 trimethylation.
With respect to histone H3-K27M mutation, 75% of the samples were mutated in the H3F3A gene, 17% in the HIST1H3B
gene and 8% were wild-type. Structural copy number aberrations were only found in TP53 mutated samples. Gain of chromosome 1q and whole chromosome 2 were more frequent in
the HIST1H3B-K27M mutated samples. Translocations were
rarely identified and none was recurrent. ACVR1 mutations
were almost exclusively found in HIST1H3B-K27M mutated
samples but two in histone H3 wt samples and one in a
H3F3A-K27M mutated sample. 75% of H3F3A-K27M DIPG
had either a TP53 or a PPM1D mutation while no of the
HIST1H3B-K27M DIPG had a mutation in the TP53 pathway.
Recetors Tyrosine-Kinase mutations or amplifications were
only found in H3F3A-K27M DIPG.
Conclusions: This study refines the description of the differences in the subtypes of DIPG and may support specific treatment adaptations with respect to potential biomarkers. (Supports: INCa PHRC and Imagine for Margo).
O-044 The Clinical and Molecular Landscape of
Infantile Medulloblastoma
G. Robinson1 , V. Rudneva2 , I. Buchhalter3 , D. Bowers4 , A.
Bendel5 , P. Fisher6 , J. Crawford7 , T. Hassall8 , C. Billups9 , A.
SIOP ABSTRACTS
Onar9 , V. Ramamswamy10 , M. Taylor11 , T. Merchant12 , M. Kool13 ,
B. Orr14 , D. Ellison14 , S. Pfister13 , A. Gajjar1 , P. Northcott2
Jude Children's Research Hospital, Oncology, Memphis, USA; 2 St.
Jude Children's Research Hospital, Developmental Neurobiology, Memphis,
USA; 3 German Cancer Research Center DKFZ, Applied Bioinformatics,
Heidelberg, Germany; 4 University of Southwestern Medical Center at
Dallas, Pediatric Hematology and Oncology, Dallas, USA; 5 Children's
Hospitals and Clinics of Minnesota, Pediatric Hematology and Oncology,
Minneapolis, USA; 6 Stanford University, Neurology, Palo Alto, USA; 7 UC
San Diego - Rady Children's Hospital, Neurosciences, San Diego, USA;
8 Lady Cilento Children's Hospital, Paediatric Oncology, Brisbane,
Australia; 9 St. Jude Children's Research Hospital, Biostatistics, Memphis,
USA; 10 The Hospital for Sick Children, Haematology and Oncology,
Toronto, Canada; 11 The Hospital for Sick Children, Neurosurgery, Toronto,
Canada; 12 St. Jude Children's Research Hospital, Radiation Oncology,
Memphis, USA; 13 German Cancer Research Center DKFZ, Pediatric
Neurooncology, Heidelberg, Germany; 14 St. Jude Children's Research
Hospital, Pathology, Memphis, USA
S29 of S518
while a paradigm shift in therapy for infant non-SHH-MB is
necessary.
1 St.
Background/Objectives: Survival of children ≤ 5 years-old
(called “infants”) with medulloblastoma (MB) is vastly inferior to that of older children with MB. The difference is principally due to radiation-sparing therapy, however, radiation
is not a requisite for survival in all. Therefore it is imperative to understand which infants benefit and which fail current
approaches. Herein we comprehensively describe the molecular landscape of the infantile medulloblastoma (iMB) and
show that differences in molecular makeup translate to major
differences in outcome.
Design/Methods: We amassed a discovery cohort of 165 and
a validation cohort of 73 iMB. All were analyzed on 450K
DNA methylation arrays and sequenced against matched normal. The discovery cohort came from a pooled international series and the validation from the SJYC07 clinical trial
(NCT00602667).
Results: iMB divides into three subgroups; SHH, G3, G4. No
WNT MB was observed. Distribution between the 2 cohorts
were similar – Discovery - 31% SHH-MB, 44% G3 and 25%
G4: Validation - 56% SHH-MB, 30% G3 and 14% G4. The
most frequent mutations in SHH-MB are PTCH1 (51% discovery cohort; 29% validation), SUFU (14% and 16%),
KMT2D (12% and 27%). MYCN amplification (6% and 2%)
and TP53 mutations (5% and 2%) are rare. Non-SHH-MB displayed relatively few recurrent mutations but exhibited multiple large copy number aberrations. In the validation cohort,
four-year progression free survival (PFS) of SHH-MB is superior to non-SHH-MB (54%±9 vs 10%±10 p value <0.0001).
Histology and metastatic disease within subgroups were not
prognostic for PFS. Ongoing analysis is occurring to determine if any molecular heterogeneity within subgroups is prognostic.
Conclusions: Infant SHH-MB benefits more from radiationsparing therapy than non-SHH-MB. Future clinical trials
need to prospectively divide into SHH-MB and non-SHHMB. The therapeutic goals need to shift towards optimizing the current chemotherapeutic backbone for SHH-MB,
O-045 Who is Who? Ex-CNS-PNETS and New
Entities: Clinical Consequences of Confined
Diagnostic Groups
K. von Hoff1 , C. Haberler2 , G. Robinson3 , D. Sumerauer4 , J. Cho5 ,
M. Mynarek1 , P. Hauser6 , M. Lastowska7 , A. Korshunov8 , T.
Jacques9 , F. Giangaspero10,11 , C. Hawkins12 , D.
Figarella-Branger13 , P. Burger14 , M. Gessi15 , B. Orr16 , D.
Sturm17,18 , S.M. Pfister17,18 , T. Pietsch15 , M. Kool17
1 University
Medical Center Hamburg-Eppendorf, Pediatric Hematology
and Oncology, Hamburg, Germany; 2 Medical University of Vienna,
Institute of Neurology, Vienna, Austria; 3 St Jude Children's Research
Hospital, Department of Oncology, Memphis, USA; 4 University Hospital
Motol, Department of Pediatric Hematology and Oncology, Prague, Czech
Republic; 5 Yonsei Cancer Center- Yonsei University College of Medicine,
Dept. of Radiation Oncology, Seoul, Republic of Korea; 6 Semmelweis
University, 2nd Department of Pediatrics, Budapest, Hungary; 7 Children's
Memorial Health Institute, Department of Pathology, Warsaw, Poland;
8 German Cancer Research Center DKFZ, Division of Clinical Cooperation
Unit Neuropathology, Heidelberg, Germany; 9 University College London,
Institute of Child Health, London, United Kingdom; 10 Sapienza University
of Rome, Department of Radiological- Oncological and
Anatomopathological Sciences, Rome, Italy; 11 IRCCS, Neuromed Institute,
Pozzilli IS, Italy; 12 The Hospital for Sick Children, Division of Pathology,
Toronto, Canada; 13 La Timone Hospital- Aix Marseille University,
Department of Pathology and Neuropathology, Marseille, France; 14 Johns
Hopkins University, Department of Pathology, Baltimore, USA;
15 University of Bonn, Department of Neuropathology, Bonn, Germany; 16 St
Jude Children's Research Hospital, Department of Pathology, Memphis,
USA; 17 German Cancer Research Center DKFZ, Division of Pediatric
Neurooncology, Heidelberg, Germany; 18 University Hospital, Department
of Pediatric Hematology and Oncology, Heidelberg, Germany
Background/Objectives: The diagnosis “CNS primitive neuroectodermal tumor” (CNS-PNET) was removed from the
updated 2016 WHO classification of CNS tumors. In a cohort
of patients with a previous diagnosis of CNS-PNET, new entities with recurrent genetic alterations were delineated, which
were then also identified in patients with previous other diagnoses (Sturm,2016). Utility of current treatment paradigms in
confined diagnostic groups is not known.
Design/Methods: Through an international collaboration,
additional tumor samples of patients with a previous diagnosis
of CNS-PNET were re-evaluated by DNA methylation profiling and blinded neuropathological panel review. Clinical data
to the newly re-evaluated cases and to previously published
cases, irrespective of historic diagnosis, were pooled and
analyzed.
Results: The given numbers represent preliminary data of
the ongoing project. DNA methylation profile classified 173
newly re-evaluated tumors with historic CNS-PNET diagnosis as: other defined non CNS-embryonal-tumor entity (60%,
n=104), ETMR (21%, n=37), CNS-NB-FOXR2 (9%, n=16),
CNS-HGNET-BCOR (3%, n=5), CNS-HGNET-MN1 (4%,
n=6), and CNS-EFT-CIC (3%, n=5). Blinded neuropathology
SIOP ABSTRACTS
S30 of S518
panel diagnosis fully overlapped with methylation result for
18 correspondingly analyzed ETMR, and a group of embryonal tumors displaying varying degrees of neuronal and ganglionic differentiation corresponded to 12 CNS-NB-FOXR2.
In the combined data set, historic diagnosis other than CNSPNET was uncommon in CNS-NB-FOXR2 (1 of 59, 2%), but
was common in CNS-HGNET-BCOR (28 of 48, 58%), CNSHGNET-MN1 (34 of 51, 67%, mostly diagnosed as astroblastoma, or ependymoma), and CNS-EFT-CIC (5 of 22, 23%).
Five-year PFS and OS was 60% and 95%, respectively, for 31
patients with CNS-NB-FOXR2, 0% and 40% for 16 patients
with CNS-HGNET-BCOR, 27% and 94% for 21 patients with
CNS-HGNET-MN1, and 50% and 51% for 11 patients with
CNS-EFT-CIC methylation profile.
Conclusions: Consensus on diagnostic criteria and treatment
strategy is needed. International collaboration will aim for
prospective molecular and clinical data collection to inform
the development of specific trials e.g. for controlled deescalation of treatment for CNS-NB-FOXR2.
O-046 Molecular Subgrouping of Pineal Tumors
Reveals Distinct Classes Correlated with Clinical
Parameters and Genetic Alterations
E. Pfaff1,2 , M. Snuderl3,4,5 , M.A. Karajannis6 , L. Chavez1 , S.M.
Pfister1,2 , D.T.W. Jones1
1 German
Cancer Research Center DKFZ, Pediatric Neurooncology,
Heidelberg, Germany; 2 Heidelberg University Hospital, Department of
Pediatric Oncology- Hematology & Immunology, Heidelberg, Germany;
3 NYU Langone Medical Center, Division of Neuropathology, New York,
USA; 4 NYU Langone Medical Center, Department of Neurology, New York,
USA; 5 NYU Langone Medical Center, Laura and Isaac Perlmutter Cancer
Center, New York, USA; 6 Memorial Sloan Kettering Cancer Center,
Department of Pediatrics, New York, USA
Background/Objectives: Tumors of the pineal region comprise several different entities with distinct clinical and
histopathological features.
Pineocytoma (PC, WHO grade I), pineal parenchymal tumors
of intermediate differentiation (PPTID) and papillary tumors
of the pineal region (PTPR) (WHO grade II-III), predominantly affect adults and are associated with a favorable prognosis.
Pineoblastoma (PB) is a highly aggressive tumor (WHO grade
IV) in the family of primitive embryonal tumors/PNET occurring in infants, children and adolescents. Especially for infants
and patients with metastatic disease, the outcome is poor
despite aggressive multimodal treatment, and no therapeutically actionable molecular targets have been identified to
date. Whereas most PB arise sporadically, cancer predisposition syndromes including DICER1 or RB1 germline mutations
are associated with PB, the latter in the context of trilateral
retinoblastoma (PB-RB).
We investigated the biological relationships between clinicopathological entities of pineal tumors based on DNA methylation and copy number analysis.
Design/Methods: We performed genome-wide DNA methylation profiling in 230 pineal tumors and normal pineal tissue
controls, including copy-number analysis.
Results: Unsupervised clustering revealed clear separation of
the known entities (PC, PTPR, PPTID and PB-RB). Within
these groups, distinct subgroups could be distinguished,
including the previously hypothesized PTPR-A and PTPR-B
groups. Interestingly, the tumors initially diagnosed as either
PB or pineal PNET formed a number of biologically discrete subgroups, which are now being further characterized.
One group harbored recurrent alterations of DROSHA, an
endoribonuclease involved in miRNA processing upstream of
DICER1, implicating a central role of altered miRNA biogenesis in the development of PB.
Conclusions: Using methylation profiling, we identified biologically distinct subgroups of pineal tumors, including novel
sub-clusters. Our findings provide a foundation for further
molecular and functional characterization, including the role
of miRNA processing defects in oncogenesis.
O-047 Improved Survival and Decreasing
Neurocognitive Function Over Time in Posterior
Fossa Ependymoma
M. Zapotocky1 , J. Adamski1 , A. Lassaletta1 , P. Dirks1 , S.
Laughlin1 , C. Hawkins1 , N. Laperriere2 , U. Tabori1 , U. Bartels1 , D.
Mabbott1 , E. Bouffet1 , V. Ramaswamy1
1 The
Hospital for Sick Children, Pediatrics/ Division of
Hematology/Oncology, Toronto, Canada; 2 Princess Margaret Hospital,
Radiation Oncology, Toronto, Canada
Background/Objectives: Intracranial ependymoma is third
most frequent pediatric brain tumor comprising of distinct
biological entities arising in posterior fossa (PF) or supratentorial (ST) region. We aimed to identify predictors of survival
and neurocognitive outcome in a large consecutive cohort
over three decades.
Design/Methods: Data on demographics, treatment, survival
and neurocognitive functioning were collected in 102 consecutive patients with intracranial ependymoma diagnosed at
SickKids from 1985-2014.
Results: No significant difference between survival of PF
and ST ependymoma was observed (PF 5-year PFS 47.8%
(95%CI, 37.2-61.5%), PF 5-year OS 71.5% (95%CI, 61.383.4%); ST 5-year PFS 56.6% (95%CI, 40.6-79%), ST 5year OS 76.9% (95%CI, 62.2-95.1%)). Independent predictors of favourable outcome in PF ependymoma include gross
total resection (GTR) (p=0.037) and upfront radiotherapy
(p<0.0001). Analysis of consecutive 10 year epochs revealed
SIOP ABSTRACTS
a significant improvement in PFS and OS over time (20052014 compared to 1985-1994 and 1995-2004). This pertains
to the rate of GTR increased from 35% to 77% and use of
upfront radiation increased from 65% to 96% over observed
period in PF ependymoma. None of observed variables were
prognostic in ST ependymoma. The proportion of patients
with recurrent ependymoma who can be salvaged with reirradiation increases 5-year PFS post-recurrence from 0% to
28% (p<0.0001). Complete resection at recurrence is a strong
favourable predictor of survival (p=0.005). Upfront radiation
in primary diagnosis or re-irradiation at recurrence significantly influences neurocognitive outcome, especially in very
young children.
Conclusions: Data from our large homogeneously treated
cohort clearly indicate improved survival of posterior fossa
ependymoma over time, related to more aggressive surgery
and upfront radiation. However for the first time in a large consecutive cohort, we show that this approach results in reduced
neurocognitive outcomes over time. Our data suggests that
all children with posterior fossa ependymoma should receive
upfront radiation and be concomitantly prioritized for early
neuropsychological testing and intervention.
FREE PA PER SESSION:
LEUKEMIA - BIOLOGY
O-048 Integrated Genetic and Epigenetic
Analysis in Pediatric T-Cell Acute Lymphoblastic
Leukemia (T-ALL)
S. Kimura1,2 , M. Seki1 , T. Kawai3 , K. Yoshida4 , T. Isobe1 , H.
Ueno4 , H. Suzuki4 , K. Oki5 , T. Imamura6 , N. Kiyokawa5 , M.
Kobayashi2 , K. Koh7 , A. Manabe8 , A. Ohara9 , M. Sanada10 , Y.
Hayashi11 , K. Hata3 , S. Miyano12 , S. Ogawa4 , J. Takita1
Univesity, Pediatrics, Tokyo, Japan; 2 Hiroshima University
Graduate School of Biomedical Sciences, Pediatrics, Hiroshima, Japan;
3 National Center for Child Health and Development, Maternal-Fetal
Biology, Tokyo, Japan; 4 Graduate School of Medicine- Kyoto University,
Pathology and Tumor Biology, Kyoto, Japan; 5 National Center for Child
Health and Development, Pediatric Hematology and Oncology, Tokyo,
Japan; 6 Kyoto Prefectural University of Medicine- Graduate School of
Medical Science, Pediatrics, Kyoto, Japan; 7 Saitama Children's Medical
Center, Hematology/Oncology, Saitama, Japan; 8 St. Luke's International
Hospital, Pediatrics, Tokyo, Japan; 9 Toho University, Pediatrics, Tokyo,
Japan; 10 National Hospital Organization Nagoya Medical Center, Clinical
Research Center, Nagoya, Japan; 11 Gunma Children's Medical Center,
Hematology/Oncology, Shibukawa, Japan; 12 Institute of Medical ScienceThe University of Tokyo, Laboratory of DNA Information Analysis- Human
Genome Center, Tokyo, Japan
S31 of S518
epigenetic profiles and their potential contribution to clinicopathological features of T-ALL.
Design/Methods: To describe epigenetic landscape of TALL, we conducted methylation array analysis using Illumina HumanMethylationEPIC array, whole transcriptome
sequencing (WTS), and targeted-capture sequencing for 158
ALL-related genes in a cohort of 49 cases with T-ALL. Following analyses were performed using R (v3.3.0).
Results: After normalization, 2975 probes were selected
to identify the most variable methylated probes, when a
standard deviation of the beta-values across the samples
was above 0.35. Unsupervised consensus clustering using
selected 2975 probes clearly identified 3 distinct sample clusters. Combined analyses with expression and fusion data
from WTS revealed that these 3 clusters were characterized by TAL1 fusions/high-expression (M1 cluster; lowmethylation), high TLX1/TLX3 expression (M2 cluster; highmethylation), and PU.1 fusions/high expression (M3 cluster;
intermediate-methylation), respectively. Although the number of frequently affected genes (>15%) was relatively low in
M3 cluster, PTEN and USP7 abnormalities were particularly
enriched in M1 cluster and PHF6, DNM2, and EZH2 mutations were frequently observed in M2 cluster. Furthermore, it
should be noted that, patients in M3 cluster displayed adverse
prognosis, whereas patients in M2 cluster showed excellent
clinical outcome (Log-Rank p = 0.02).
Conclusions: Based on the DNA methylation profiles, pediatric T-ALL is clustered into 3 distinct subtypes, which exhibited remarkable correlation with fusion gene status, gene
expression patterns, genetic signatures, and clinical outcomes.
Although our cohort in the current study is very limited, our
results suggested that the biological phenotype of T-ALL is
mediated by both genetic and epigenetic regulations. Therefore, explorations for aberrant DNA methylation along with
genetic alterations might be helpful for development a new
therapeutic strategy for T-ALL.
1 Tokyo
Background/Objectives: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic-cancer.
Although genetic basis of pediatric T-ALL has been well
characterized, no comprehensive study has yet explored the
O-049 Genomic Breakpoint and Fusion
Transcript Analysis of KMT2A Rearrangement in
Infant Acute Lymphoblastic Leukemia
E. Guest1 , B. Yoo2 , M. Farooqi2 , N. Miller2 , J. Johnston2 , R.
Kostadinov3 , E. Farrow2 , S. Kelley4 , M. Gibson2 , P. Brown4
1 Children's
Mercy Hospital, Hematology/Oncology/Bone Marrow
Transplantation, Kansas City, USA; 2 Children's Mercy Hospital, Center for
Pediatric Genomic Medicine, Kansas City, USA; 3 Johns Hopkins University
School of Medicine, Biostatistics, Baltimore, USA; 4 Johns Hopkins
University School of Medicine, Pediatric Oncology, Baltimore, USA
Background/Objectives: Rearrangement of KMT2A
(KMT2A-R) is a high risk, recurrent molecular driver of
acute lymphoblastic leukemia (ALL) among infants less
than 1 year of age. We sought to determine if variation in
SIOP ABSTRACTS
S32 of S518
the genomic breakpoints of KMT2A and its partner genes
correlates with risk of treatment failure for infants with ALL.
frequent partners [MLLT1, MLLT3, MLLT4, MLLT10, AFF1
and partial tandem duplication (PTD)] of the KMT2A gene.
Design/Methods: We performed whole genome sequencing
(WGS) to an average depth of 30x, and mRNA sequencing on
47 blood and marrow samples from 32 infants with KMT2AR ALL. The infants were enrolled on the Children's Oncology Group trial AALL0631. Cases with the partner genes
AF4 (n=19)or ENL (n=13) were selected for study. Twentyone infants had experienced treatment failure, and 13 had
paired relapse samples. Alignment of sequencing data was
done using BWA. Translocation detection (WGS) was done
using Manta, and fusion transcript detection (RNAseq) was
performed using FusionCatcher.
Design/Methods: It was analyzed 241 cases of de novo pAML, for the identification of KMT2A-r through the mRTPCR identifying all partners studied in the same PCR reaction.
In order to standardized the method described by Burmeister et al, 2014 some modification was necessary, as reagent
changes were performed, including tests of Taq DNA Polymerase and changes in cycles program. Sanger sequencing
was performed to confirm the results.
Results: Whole genome sequencing detected the KMT2A
translocation in 100% of samples and the precise nucleotide
breakpoint in 82% of samples. The location of KMT2A breakage was within introns 8, 9, or 10, or exons 10 or 11 in all
cases. In contrast, the breakpoint locations within AF4 and
ENL were more variable. Relapses were observed in both AF4
and ENL groups and the breakpoints were unchanged in paired
samples at relapse.
Known fusion transcripts were detected in 76% of samples and were biologically consistent with identified DNA
breakpoints. Exon skipping and alternative splice sites were
observed. The reciprocal fusion transcript was frequently
detected for AF4, but never detected for ENL. Fusion of
KMT2A-exon-9 was dominant, detected in 17 cases with
relapse and only 3 without relapse.
Conclusions: The breakpoints of KMT2A in infant ALL are
conserved within a narrow genomic window, in contrast to
the breakpoints of partner genes AF4 and ENL. Fusion of
KMT2A-exon-9 is common among cases with relapse.
O-050 Identification by RT-PCR Multiplex of
Key Partners of KMT2A in Pediatric Patients with
Acute Myeloid Leukemia
I. Cezar1 , F. Andrade1 , M. Pombo-de-Oliveira1
1 Instituto
Nacional do Cancer, Paediatric Haematology-Oncology
Program, RIO DE JANEIRO, Brazil
Background/Objectives: Pediatric acute myeloid leukemia
(p-AML) is a phenotypic and genetically heterogeneous disease. The identification of gene fusion allows the definition of
molecular subtypes in p-AML, with an important role in the
prognosis and follow-up of the treatment response. In earlyage AML the majority of genomic abnormality is characterized by KMT2A rearrangements (KMT2A-r) identified by
FISH MLL break apart. The KMT2A partners gene defines
the prognosis outcome. In this context, we standardized the
multiplex RT-PCR (mRT-PCR) technique to identify the most
Results: Two hundred and forty-one AML cases were
included in the study and about 22% were infants (52 cases);
The most frequent morphological subtype was myelomonocytic (FAB-M4) (36,1%). Thirty-three cases with KMT2Ar were identified by mRT-PCR. Partners were identified
in the following frequencies: 5/33(15.2%) with KMT2AMLLT1 fusion, 12/33(36.4%) positive for KMT2A-MLLT3,
3/33(9.1%) with KMT2A-MLLT4 fusion, 8/33 (24.2%) were
identified with KMT2A -MLLT10, 2/33(6.1%) were positive
for KMT2A-AFF1 and 3/33 (9.1%) presented KMT2A-PTD.
Conclusions: The proposed technique was successfully standardized in our laboratory and it is possible reliable in the
identification of KMT2A with the partner gene and with less
cost compared with FISH.
O-051 Identification of Genetic Aberrations
Predisposing to Familial Burkitt Lymphoma Using
Whole Genome Sequencing
R. Van Paemel1 , C. Derpoorter1 , R. Demuynck1 , E. Terras1 , B. De
Wilde1 , T. Lammens1 , G. Laureys1
1 Ghent
University Hospital, Department of Pediatric Hematology-Oncology
and Stem Cell Transplantation, Ghent, Belgium
Background/Objectives: Burkitt lymphoma (BL) is a rare
pediatric tumor characterized by the translocation of MYC on
chromosome 8 to one of the immunoglobulin loci. Since exposure time to carcinogenics is shorter in children, genetic factors are assumed to be more important in tumor development.
At our department, 2 related children were diagnosed with BL,
strongly suggesting a predisposing factor.
Design/Methods: Whole genome sequencing was performed
on constitutional material from both patients, parents and
grandparents (n=10). Variant calling using genome analysis
toolkit (GATK) was followed by prioritization filtering with
GEMINI (Paila et al., 2013).
Results: At first, data reduction was done through selecting rare variants (< 1% in 1000G_EUR) shared by the
patients and the related parents and absent in spousal controls. Three deleterious variants were identified including 1
in USP28 (rs45570432) and 2 in MAP2K3 (rs56067280 and
rs55796947). Data reduction based on inheritance modeling
SIOP ABSTRACTS
revealed a compound heterozygous variation in C4orf33. In
addition, 13 mutations followed a de novo model of which,
based on the probability of mendelian error, the non-coding
mutations in USP32 and DRD3 seem most plausible. In a third
approach, using a published cancer gene panel (Zhang et al.,
2015), 14 non-coding variants were found segregating in the
family.
Conclusions: Collectively, these data show that multiple candidate BL predisposing variants can be found in the family
under investigation. It is becoming more apparent that noncoding variants play a major role in the development of cancer through up- or downregulating expression, altering splicesites and gene silencing. The identified variants, however,
need functional validation and further examination in large
populations and other families. Importantly, this approach can
be expanded to other pediatric cancer entities to improve our
understanding of tumorigenesis, to enable genetic counseling
and to contribute to novel diagnostic applications and therapeutic options.
* TL and GL are shared senior authors
FREE PA PER SESSION:
NEUROBLASTOMA - CLINICA L
O-052 Neuroblastoma Stage 4S: Regression Rate
and Patients at Risk
M. Tas1 , M. Nagtegaal2 , K. Kraal1 , G. Tytgat1,2 , N. Abeling3 , S.
Pluijm1,4 , M. Zwaan4 , J. Molenaar5 , M. van Noesel1
1 Princess
Máxima Center for Pediatric Oncology, Pediatric Oncology,
Utrecht, The Netherlands; 2 Emma Children's Hospital/Academic Medical
Center, Pediatric Oncology, Amsterdam, The Netherlands; 3 Academic
Medical Center, Laboratory for Genetic Metabolic Diseases, Amsterdam,
The Netherlands; 4 Erasmus MC-Sophia Children's Hospital, Pediatric
Oncology, Rotterdam, The Netherlands; 5 Princess Máxima Center for
Pediatric Oncology, Translational Research, Utrecht, The Netherlands
Background/Objectives: Neuroblastoma stage 4S/MS is a
low risk tumor with an overall survival of 65-92%. The natural course consists of initial growth of multifocal disease followed by regression. However, the precise clinical course of
the initial growth and regressive phase is poorly described. We
performed a retrospective cohort study to describe the clinical course, to identify patients at risk of an adverse outcome
and to compare regression rate between treated and untreated
patients.
Design/Methods: Charts of all patients diagnosed with neuroblastoma stage 4S/MS between 1972 and 2012 in two Dutch
oncology centers were evaluated for therapy, response, outcome and for clinical, metabolic and radiological regression
of tumor and liver metastases. Patients with high risk criteria
were excluded.
S33 of S518
Results: We identified 31 patients. The 5 year overall survival was 84% (median follow up 193.5 months, range 40468). Treatment was given to 55% of the patients. In the first
3 weeks after diagnosis 4 patients died of rapid liver growth
and compression. Neonates were at highest risk of dying: 4/7
(58%) neonates died, while none of the older patients died.
During the regressive phase, the primary tumor completely
regressed in 69% of the patients after a median of 13 months
(range 6-73); liver size normalized in 91% after a median
of 2 months (range 0-131), and architecture normalized in
52% after a median of 14.5 months (range 5-131). No differences in regression rate were seen between the treated and
untreated patients. Late progression to stage 4 was observed
in 3 patients, all had persistent elevated catecholamines. Two
of three are currently in complete remission.
Conclusions: Neonates are at risk of dying of rapid liver
growth. Patients with persistent elevated catecholamines are
at risk of progression to stage 4. Radiological regression of
primary tumor and liver architecture is slow and takes over
12 months.
O-053 I-131-Meta-Iodobenzylguanidine (MIBG)
Therapy Improves Survival in High-Risk
Neuroblastoma Patients with MIBG Positive
Residual Metastatic Disease
T. Simon1 , M. Schmidt2 , B. Decarolis1 , A. Eggert3 , F. Berthold1 , B.
Hero1
1 University
of Cologne, Pediatric Oncology and Hematology, Cologne,
Germany; 2 University of Cologne, Nuclear Medicine, Cologne, Germany;
3 Charite Univeristy Hospital, Pediatric Oncology and Hematology, Berlin,
Germany
Background/Objectives: Randomized trials on mIBG therapy in the first-line treatment of high-risk neuroblastoma
are not available. Therefore, we analyzed the national
neuroblastoma data base on the impact of I-131-metaiodobenzylguanidine (mIBG) therapy, local radiotherapy, and
single agent ch14.18 immunotherapy in the first-line therapy
of high-risk neuroblastoma.
Design/Methods: Patients of two consecutive national neuroblastoma trials were included if they met all key criteria:
(1) stage 4 neuroblastoma, (2) age at diagnosis >18 months,
(3) N5/N6 induction chemotherapy, (4) diagnosis between
1997 and 2014. mIBG therapy prior to the myeloablative
chemotherapy was scheduled for non-progressing mIBG positive lesions. Local radiotherapy 36-40 Gy was delivered to
unresectable mIBG positive residual at the primary site. Single agent ch14.18 immunotherapy was stratified according to
open trials.
Results: A total of 264 patients were included. The median
observation time was 8.9 years. The presence of mIBG
SIOP ABSTRACTS
S34 of S518
positive metastases at the end of induction chemotherapy was
associated with inferior EFS (5yEFS 29.0+/-4.5% vs 41.3+/4.1%, p=0.049). It had no impact on OS (5yOS 49.7+/-5.1%
vs 51.2+/-4.2%, p=0.655). Among 108 patients with residual MIBG positive metastatic disease the EFS was similar between patients who underwent mIBG therapy (5yEFS
31.8+/-6.3%) and patients who did not (5yEFS 25.2+/-6.4%,
p=0.238). The OS was better after mIBG therapy (61.2+/6.6%) compared to no mIBG therapy (5yEFS 37.7+/-7.2%,
p=0.038). Multivariable analysis of all 264 patients including
the variables MYCN, mIBG therapy, local radiotherapy, and
immunotherapy with ch14.18 revealed an independent impact
of MYCN amplification (p=0.034, hr 1.445) and ch14.18
treatment (p<0.001, hr 0.455) on EFS, and MYCN amplification (p=0.001, hr 1.894) and ch14.18 treatment (p=0.001,
hr 0.475) on OS.
Conclusions: mIBG therapy can improve the outcome of
high-risk neuroblastoma patients with incomplete metastatic
response to induction chemotherapy. These results warrant a
prospective multicenter trial on mIBG therapy. In addition,
this analysis confirmed the long term effect of immunotherapy with ch14.18.
O-054 Thrombocytopenia in MIBG-Treated
Patients May be Prevented by the Concomitant
Administration of a Selective Serotonin Reuptake
Inhibitor
T. Blom1 , M. Hansen2 , A. Van Kuilenburg3 , E. Van der Schoot4 , L.
Tytgat5
1 Princess
Máxima Center for Pediatric Oncology, Research, Utrecht, The
Netherlands; 2 Sanquin Research, Hematopoiesis, Amsterdam, The
Netherlands; 3 Academisch Medisch Centrum, Laboratory Genetic
Metabolic Diseases, Amsterdam, The Netherlands; 4 Sanquin Research,
Experimental Immunohematology, Amsterdam, The Netherlands; 5 Princess
Máxima Center for Pediatric Oncology, Pediatric oncology, Utrecht, The
Netherlands
Background/Objectives: Thrombocytopenia is the major
toxicity of metaiodobenzylguanidine (MIBG)-therapy.
Whether this is caused by the whole-body-absorbed radiation
dose or by other mechanisms is not clear. We previously
showed that MIBG is transported via the serotonin transporter (SERT) in platelets and via the NET in neuroblastoma.
We tested if selective serotonin reuptake inhibitors (SSRIs)
inhibit MIBG accumulation in platelets, with no effect on
MIBG accumulation in neuroblastoma in a mouse model.
Design/Methods: The uptake of [125 I]MIBG and
[3 H]serotonin in isolated human platelets was inhibited
by a panel of SSRIs. MIBG uptake in platelets (presumably via SERT) was compared to uptake in SK-N-SH
neuroblastoma cells (via NET). The IC50 (i.e. the inhibitor
concentration that reduces the uptake by 50%) and the
selectivity (IC50 ratio of MIBG uptake in neuroblastoma
cells over that in platelets) were calculated. MIBG tumor
accumulation with and without SSRI's and NET inhibitors
was studied in neuroblastoma xenografts. SSRI containing
plasma of nude mice was used to test the inhibitory potency
on MIBG uptake in human platelets (ex vivo).
Results: Inhibition of serotonin and MIBG uptake in platelets
appeared comparable for the SSRIs suggesting that both substrates share the same transport system. SSRIs were 40100 times more potent in inhibiting platelet MIBG uptake
than in neuroblastoma cells. Imipramine, a classical tricyclic
antidepressant, showed no selectivity and inhibited the MIBG
platelet and MIBG neuroblastoma uptake to the same extent.
MIBG accumulation in neuroblastoma xenografts was not
significantly affected by SSRI administration, but was 60%
diminished in mice treated with desipramine (NET inhibitor).
SSRI drug levels in the murine circulation highly exceeded
those required for effective inhibition of platelet MIBG
uptake.
Conclusions: SSRIs are effective in reducing MIBG uptake in
platelets while leaving the tumor loading unaffected. Administration of SSRIs may prevent MIBG related thrombocytopenia if similar mechanisms are involved in megakaryocytes.
O-055 Feasibility and Toxicity of Busulfan and
Melphalan Conditioning Regimen in the Context of
the German Induction Chemotherapy
B. Hero1 , T. Simon1 , H. Lode2 , A. Eggert3 , F. Berthold1
1 University
of Cologne, Pediatric Oncology and Hematology, Cologne,
Germany; 2 University Medicine Greifswald, Pediatric Hematology and
Oncology, Greifswald, Germany; 3 Charité - Universitätsmedizin Berlin,
Pediatric Oncology and Hematology, Berlin, Germany
Background/Objectives: High-dose chemotherapy with
autologous stem-cell rescue is considered standard in the
treatment of high risk neuroblastoma patients. A randomized
trial recently showed improved outcome with a regimen
using busulfan and melphalan (Ladenstein et al., Lancet
Oncol, 2017). Per protocol, high-dose chemotherapy in trials
of the German neuroblastoma group (GPOH) consisted of
melphalan, etoposide, and carboplatin (MEC). However, in
patients with contra-indications (e.g. ototoxicity), busulfan
and melphalan was recommended as an alternative. Here,
we evaluated the feasibility and toxicity of busulfan and
melphalan in patients treated with the GPOH induction
treatment using long-time infusion of cisplatin, etoposide,
and ifosfamid.
Design/Methods: Data of high risk neuroblastoma patients
registered in the German neuroblastoma trials NB97 and
NB2004-HR and receiving high-dose chemotherapy with
autologous stem-cell rescue in first line treatment were
analyzed.
SIOP ABSTRACTS
Results: High-dose chemotherapy with melphalan, etoposide,
and carboplatin (MEC) was given to 459 patients, while 79
patients received busulfan and melphalan (Bu-Mel). mIBG
therapy was applied to 135 patients receiving MEC and to
nine patients receiving Bu-Mel in median 17 resp. 19 days
prior to high dose chemotherapy. Hematologic recovery was
not different between groups (median leukocyte take in both
cohorts: 11 days, platelet take: 17 (MEC) vs. 18 days (Bu-Mel,
n.s.)).
Detailed toxicity data were available in 371 patients (MEC:
n=322; Bu-Mel: n=49) revealing no significant difference
in toxicity grade 3 or 4 for fever, infection, stomatitis, or
liver enzymes. Veno-occlusive disease (VOD) was reported
in 4.8% after MEC, but in 21.5% after Bu-Mel.
Sixteen out of 459 patients (3.5%) receiving MEC and three
out of 79 (3.8%) receiving Bu-Mel died from high dose
chemotherapy related complications (n.s.) including VOD in
six patients (MEC: n=4; Bu-Mel: n=2).
Conclusions: High-dose chemotherapy with busulfan and
melphalan was feasible after the GPOH induction treatment.
As expected, VOD was observed more often, but otherwise,
the toxicity was comparable.
FREE PA PER SESSION: BONE
T U M O U R S - NO L L E N B U RG PR I Z E
O-056 Pathological Fractures and Prognosis of
High-Grade Osteosarcoma of the Extremities in
Adoloscents and Young Adults. An Analysis of 1,299
Cooperative Osteosarcoma Study Group (COSS)
Patients
L. Kelley1 , M. Schlegel1 , S. Hecker-Nolting2 , C. Rössig3 , P.
Reichardt4 , L. Kager5 , T. Kühne6 , G. Gosheger7 , R. Windhager8 , K.
Specht9 , M. Kevric2 , H. Rechl10 , P.U. Tunn11 , D. Baumhoer12 , M.
Werner11 , T. von Kalle13 , M. Nathrath14 , S. Burdach1 , S. Bielack2 ,
I. von Luettichau1
1 Klinikum
Rechts der Isar- Technische Universität München- CCCM
Munich - Comprehensive Cancer Center- and German Translational
Cancer Research Consortium DKTK, Department of Paediatrics, München,
Germany; 2 Klinikum Stuttgart - Olgahospital, Paediatrics 5 – OncologyHematology- Immunology, Stuttgart, Germany; 3 Klinik für Kinder- und
Jugendmedizin- Universitätsklinikum Münster, Pediatric Hematology and
Oncology, Münster, Germany; 4 Onkologisches Zentrum Berlin-Buch, Klinik
für Interdisziplinäre Onkologie, Berlin, Germany; 5 St. Anna Kinderspital,
Department for Hematology and Oncology, Vienna, Austria;
6 Universitäts-Kinderspital beider Basel, Pediatric Oncology and
Hematology, Basel, Switzerland; 7 Universitätsklinikum Münster, Klinik für
Allgemeine Orthopädie und Tumororthopädie, Münster, Germany;
8 Allgemeines Krankenhaus der Stadt Wien, Universitätsklinik für
Orthopädie der Medizinischen Universität Wien, Vienna, Austria; 9 Klinikum
rechts der Isar - Technische Universität München, Institut für Allgemeine
Pathologie und Pathologische Anatomie, Munich, Germany; 10 Klinikum
Rechts der Isar, Klinik und Poliklinik für Orthopädie und Sportorthopädie,
S35 of S518
München, Germany; 11 HELIOS Klinikum Berlin-Buch, Zentrum für
Orthopädie und Unfallchirurgie - Department Tumororthopädie, Berlin,
Germany; 12 Universitätsspital Basel, Institut für Pathologie Knochentumor-Referenzzentrum, Basel, Switzerland; 13 Klinikum Stuttgart Olgahospital, Radiologisches Institut, Stuttgart, Germany; 14 Klinikum
Kassel, Pediatric Hematology and Oncology, Kassel, Germany
Background/Objectives: The objective of this study was to
investigate the age group of Adolescents and Young Adults
(AYAs) regarding correlations between pathological fractures
(PFs) and prognosis of patients with primary central highgrade osteosarcoma of the extremities.
Design/Methods: We retrospectively analyzed 1,299 patients
ages 15 to 29 with localized or metastatic primary central high-grade osteosarcoma of the extremities, treated
between 1980 and 2010 and registered into the COSSdatabase. Intended treatment included pre- and postoperative
chemotherapy and surgery. Univariate survival analysis was
performed with Kaplan-Meier-Analysis and compared with
Log-Rank-Test. Multivariate survival analysis was conducted
with Cox's proportional hazards model.
Results: Out of 1,299 patients, 97 (7.5%) had documented
PFs. Presence of PF correlated with younger age (P=0.040),
tumor site (P<0.001), localization within the affected bone
(P<0.001), histological subtype (P<0.001) and relative tumor
size (P=0.001), but not with sex, body mass index, primary metastases, type of operation, local surgical remission
or response to chemotherapy. In univariate survival analysis, 5-year overall survival (OAS) of patients with and without PF was 61% vs. 71%, respectively (P=0.025), 5-year
event-free survival (EFS) was 53% vs. 59% (P=0.158) and 5year local recurrence-free survival (LRFS) was 60% vs. 69%
(P=0.049). In multivariate Cox analysis, PF resulted as an
independent prognostic factor for overall survival (P=0.028)
with a hazard ratio of 1.539 (95%CI: 1.048–2.260) and 5-year
LRFS (P=0.023; HR=1.556, 95%CI:1.062–2.278); however,
it did not result as an independent prognostic factor for EFS
(P=0.646; HR=1.090, 95%CI: 0.755–1.572).
Conclusions: We observed the presence of PF to correlate
with inferior OAS and LRFS, with PF remaining as an independent prognostic factor in multivariable analysis. Our survival analyses suggest that local recurrence might be more
common in patients with PF. Therefore further analysis is
needed to exclude other influencing factors. However, the
presence of PF does not seem to influence the type of operation performed.
O-057 Development of a Standardized System for
Measuring Value-Based Healthcare in
Osteosarcoma at Children's Cancer Hospital Egypt
R. Soliman1 , M. Zamzam2 , W. Eweida3 , S. Abouelnaga4
SIOP ABSTRACTS
S36 of S518
1 Children's
Cancer Hospital - 57357 Egypt, Health Economics and
Outcomes, Cairo, Egypt; 2 Children's Cancer Hospital - 57357 Egypt,
Pediatric Oncology, Cairo, Egypt; 3 Children's Cancer Hospital - 57357
Egypt, Chief Operating Office, Cairo, Egypt; 4 Children's Cancer Hospital
Egypt, Chief Executive Office, Cairo, Egypt
Background/Objectives: Value-based healthcare is crucial
for medical conditions that have failed to improve outcomes
such as Osteosarcoma. Aim of work was to develop a standardized system to measure the value of health care delivered
to Osteosarcoma patients, through developing a uniform set
of health outcomes for Osteosarcoma and using a consistent
approach to measure the costs of care delivery.
Design/Methods: The Porter's Outcomes Measurement Hierarchy was used to define the domains of health outcomes for
Osteosarcoma. Time-driven activity-based costing (TDABC)
method was used to determine the total costs of care delivered
to Osteosarcoma patients throughout their journey of cure.
Results: A standardized health outcomes reporting system
was developed for Osteosarcoma based on the outcomes that
mattered most to the patients. The degree of health was measured by the remission status as defined by EURAMOS-1 protocol criteria, response to neo-adjuvant treatment was defined
as poor or good response pathologically, functional outcome
was defined using the MSTS system, and return to normal
activities was measured by the AMPS tool. Process of recovery was measured by evaluating the adverse events using
CTCAE v.4.0, determining the delay in care cycles, reporting any medical or medication errors, and assessing the time
to recovery. Sustainability of health was defined by measuring the quality of life using PedsQL questionnaire, palliative
care at end-of-life using POS survey, and measuring the longterm sequelae of treatment. Process mapping was done for
Osteosarcoma care cycles, which included a total of twentyfive process maps to cover all the activities of care delivery.
The costs were calculated based on the TDABC method for
each process map.
Conclusions: Developing a standardized system for measuring Osteosarcoma outcomes and the total costs for care is fundamental to improving the value of health care delivered to
Osteosarcoma patients and for value-based decision-making.
O-058 Outcomes and Prognostic Variables in
Relapsed Primitive Neuroectodermal Tumors
(PNET) Treated with a Hybrid Salvage
Chemotherapy Regimen
K. Vijaysekharan1 , S. Ramanathan1 , M. Prasad1 , T. Vora1 , G.
Chinnaswamy1 , A. Gulia2 , A. Janu3 , B. Rekhi4 , M. Ramadwar4 , N.
Khanna5 , S. Laskar5 , N. Purandare6 , A. Puri2 , S. Banavali1
1 Tata
Memorial Hospital, Medical Oncology - Pediatric, Mumbai, India;
Memorial Hospital, Surgical oncology - Bone and Soft Tissue Tumor,
Mumbai, India; 3 Tata Memorial Hospital, Radiodiagnosis, Mumbai, India;
4 Tata Memorial Hospital, Pathology, Mumbai, India; 5 Tata Memorial
2 Tata
Hospital, Radiation Oncology, Mumbai, India; 6 Tata Memorial Hospital,
Nuclear Medicine, Mumbai, India
Background/Objectives: Survival in relapsed PNET continues to be suboptimal (5 year survival:10-20%). Considering that 30% patients with initially non-metastatic PNET
and a larger proportion of primary metastatic disease relapse,
factors that determine outcome of relapsed patients needs
clarity. This is an analysis of patients with relapsed PNET
treated on a hybrid salvage regimen consisting of Topotecan/cyclophosphamide and Irinotecan/Temozolomide.
Design/Methods: Retrospective analysis of patients with
relapsed PNET treated with curative intent from Jan’ 2012
to Dec’2016. All patients received a total of 12 cycles of
chemotherapy and local therapy (surgery/radiotherapy after
initial 4 cycles). A subset of patients also received oral metronomic maintenance therapy for 12 months.
Results: The salvage regimen was employed in a total of
53/108 relapsed patients with the rest having opted for palliation upfront. The median age of the treated patients is
19 years(4-40); male:female-2.7:1. The median time to first
relapse was 18.8 months from end of primary treatment.
While 41/53 patients(77%)completed the salvage therapy, 6
patients(11.3%) progressed and 6(11.3%) abandoned treatment. The median follow up of the study cohort is 23.6
months. Of the analyzable cohort(n=47),18(47%)had a second relapse. At time of last follow up, 17 patients had died
(including one due to toxicity) and 30 patients were alive (22
with no active disease and 8 with disease). The 4 year-EFS
and OS is 29.7% and 43% respectively for the entire cohort.
While older patients (>17 years) had a better EFS (p=0.013),
time to first relapse, site of primary disease, metastatic status
at primary diagnosis, type of relapse (local vs metastatic), and
gender had no impact on outcome.
Conclusions: Salvage chemotherapy in relapsed PNET have
been shown to have encouraging results in early phase and
retrospective studies. This reasonably well tolerated regimen
produced promising results in a tumor with otherwise poor
outcome.
O-059 Treatment of Localized Ewing Sarcomas
of the Rib: Euro-EWING99 Analysis of French
Patients
A. Claren1 , J. Doyen1 , M. Eric2 , A. Jouin3 , S. Bolle4 , A. Laprie5 , N.
Corradini6 , C. Vérité7 , P.Y. Bondiau1 , P. Marec-Bérard6 , M.C. Le
Deley8 , N. Gaspar9 , L. Claude10
1 Centre
Antoine Lacassagne, Radiotherapy, Nice, France; 2 Hôpital Necker,
Chirurgie orthopédique et traumatologique pédiatrique, Paris, France;
3 Centre Oscar Lambret, Radiotherapy, Lille, France; 4 Gustave Roussy,
Radiotherapy, Villejuif, France; 5 Institut Universitaire du Cancer de
Toulouse, Radiotherapy, Toulouse, France; 6 Institut d'hématologie et
d'Oncologie Pédiatrique Centre Léon Bérard, Pediatry, Lyon, France;
7 CHU de Bordeaux, Radiotherapy, Bordeaux, France; 8 Centre Oscar
SIOP ABSTRACTS
Lambret, Public health, Lille, France; 9 Gustave Roussy, Pediatry, Villejuif,
France; 10 Centre Léon Bérard, Radiotherapy, Lyon, France
Background/Objectives: Primary Ewing sarcoma (ES) of
the rib represents the most frequent thoracic tumor in children
and young adults, but specific data published remain scarce.
The main objectives of this study were to evaluate survivals
according to local treatment and to define precisely prognostic
factors of these tumors.
Design/Methods: French patients included in EuroEWING99 study (EE99) for localized ES of the rib, with or
without pleural effusion, were eligible. Data were collected
from the prospective EE99 database. In addition, a systematic
retrospective review of all patient records was performed, to
obtain more precise clinical, radiological or therapeutic data,
which were not included in the EE99 database.
Results: Eighty-two patients, median age 13.6 years, were
treated between 12/1999 and 04/2013. Median follow-up was
8.4 years. Fifty-one percent had initial pleural effusion. Local
treatment included surgery in 81/82 patients, mostly after
induction chemotherapy. Sixty patients (73%) were irradiated:
28% on the tumor bed, 13% on the hemithorax (HRT), and
32% on both. Five-year disease free survival (DFS) and overall survival (OS) were 69% and 71% respectively. Twenty-six
patients (31%) relapsed, with a median time of 19 months after
diagnosis. Pleural effusion and incomplete surgical resection (R1 or R2) have proven to be independent prognostic
factors for DFS and OS. In case of initial pleural effusion,
documented or not, OS was 27% without HRT versus 68%
after HRT (p=0.01). Delivering radiation on the tumor bed
increased significantly the OS only in case of poor histological response.
Conclusions: Pleural effusion at diagnosis and incomplete
resection are two independent risk factors for survival in localized ES of the rib. Hemithoracic irradiation increases significantly overall survival in case of pleural effusion, proven or
not. The impact of the boost on tumor bed according to the histological response and quality of surgery should be confirmed
on more patients.
FREE PA PER SESSION: PODC
O-060 Developing a Clinical Diagnostic
Algorithm for Pediatric Burkitt Lymphoma in
Malawi
K. Westmoreland1,2 , N. Montgomery3 , T. van der Gronde4 , S.
Itimu4 , A. Salima4 , T. Tomoka5,6 , B. Dhungel5 , C. Kampani5 , M.
Sanders7 , D. Dittmer7 , G. Fedoriw8 , G. Satish4,9,10
1 UNC
Project-Malawi, Pediatric Hematology Oncology, Lilongwe,
Malawi; 2 University of North Carolina, Pediatric Hematology Oncology,
Chapel Hill, USA; 3 University of North Carolina, Pathology, Chapel Hill,
USA; 4 UNC Project-Malawi, Oncology, Lilongwe, Malawi; 5 UNC
S37 of S518
Project-Malawi, Pathology, Lilongwe, Malawi; 6 University of Malawi
School of Medicine, Pathology, Lilongwe, Malawi; 7 University of North
Carolina, Microbiology and Immunology, Chapel Hill, USA; 8 University of
North Carolina, Pathology, Chapell Hill, USA; 9 University of North
Carolina, Oncology and Infectious Disease, Chapel Hill, USA; 10 University
of Malawi School of Medicine, Oncology, Lilongwe, Malawi
Background/Objectives: Burkitt lymphoma (BL) is the commonest pediatric cancer in sub-Saharan Africa (SSA). Tissuebased molecular confirmation of pediatric BL is standard in
resource-rich settings, but is often impossible in SSA settings
due to limited pathology, absent molecular diagnostic tools,
and difficulty obtaining diagnostic tissue particularly from
visceral sites.
Design/Methods: We prospectively enrolled pediatric
patients <18 years of age with possible lymphoma at Kamuzu
Central Hospital in Lilongwe. Based on hematopathologist
review of diagnostic specimens in the United States, cases
were categorized as gold standard BL, possible but not
confirmed BL, and non-BL. Gold standard BL was defined
histologically based on classic morphology and immunophenotype (CD20+, CD10+, BCL2-, TdT-, Ki-67 >90%).
Plasma Epstein-Barr virus load (EBV-VL) was measured
at baseline by quantitative polymerase chain reaction. Gold
standard BL was compared to non-BL using a t-test.
Results: We identified 17 gold standard BL cases and 23
non-BL cases for analysis. Fifty-seven cases of possible BL
were excluded, most due to cytologic specimen only prohibiting detailed immunophenotyping. Median age of BL
cases was 11.7 years (IQR 7.8-14.2) and non-BL was 12.3
years (IQR 10.0-14.3, p=0.66). Median lactate dehydrogenase (LDH) level at diagnosis was 642 IU/L (IQR 418-1465)
for BL and 295 IU/L (IQR 254-410, p=0.053) for non-BL.
Median plasma EBV-VL at diagnosis was 6.5 log10 copies/mL
(IQR 4.9-7.1) for BL and 4.7 log10 copies/mL (IQR 2.8-5.5,
p=0.039) for non-BL. The positive predictive value of LDH
>1.25x the upper limit of normal (ULN) and EBV-VL >3.0
for BL was 71% (10/14 cases). The negative predictive value
of LDH < 1.25x ULN or EBV-VL <3.0 was 92% (12/13
cases).
Conclusions: LDH and EBV-VL are implementable diagnostic tools that can assist with confirming pediatric BL in SSA.
Ongoing work includes developing and validating a clinical
diagnostic algorithm for molecularly confirmed pediatric BL
in a larger cohort of Malawian children.
O-061 Clinical Profile and Outcome of
Intermediate and High Risk Classical Hodgkin
Lymphoma Treated in a Tertiary Care Cancer
Centre
B. Cheriyalinkal Parambil1 , G. Narula1 , M. Prasad1 , B. Arora1 , S.
Banavali1
SIOP ABSTRACTS
S38 of S518
1 Tata
Memorial Hospital, Pediatric Oncology, Mumbai, India
Background/Objectives:
Classical
Hodgkin
lymphoma(cHL) has excellent 5-year OS, though long term
survival declines after 5 years due to relapse and late effects
of therapy. Recent strategies seek to limit anthracyclines,
alkylating agents, bleomycin and radiation therapy. We studied clinical profile and outcome of children with advanced
cHL on this strategy.
Design/Methods: Children(<15years) with cHL from
February 2013 to December 2016 were retrospectively
analyzed. Staging was by Positron emission computerized
tomography(PET-CT) in all. Bulky sites(X) at baseline
received involved field radiation(IFRT) post-chemotherapy.
IAX,IBX,IIAX,IIE,IIIA were Intermediate-risk(IR) and
IIBX,IIBE,IIIX,IIIE,IIIB,IV High risk(HR). Patients
received 2 cycles OEPA(vincristine,etoposide,prednisolone,
doxorubicin) followed by early PET-CT. Complete
metabolic responses(CMR) received 2 cycles COPDac(cyclophosphamide,vincristine,prednisolone,dacarbazine)
for IR,4 for HR. Partial Responses(PR) were re-evaluated
after 2 or 4 cycles COPDac. Refractory at end treatment or
progressive disease at any time were considered for salvage
options.
Results: Hundred and seventeen children(IR-12, HR-105)
were eligible. Median age was 9 years,M:F-4.5:1,Bsymptoms-70.6%,Bulky disease-86%. Median LDH was
273IU/L(range,24-986), and median B2-microglobulin2.68mg/l(range,1.58-8.58).
Sixty-four(55.3%)
had
Hemoglobin<10.5 g/dl,and 78(66.4%) serum albumin</=4
gm/dl. Of 115 patients evaluable for early response,94(81.7%)
had CMR,while 1(0.8%) progressed. Seventeen among 20
PR cases had second PET and 13(76.4%) achieved CMR by
end-treatment. Eighty-eight(75%) received IFRT(19.8-25.2
to 30.6Gy),81(91%) for bulky disease,and 8(9%) for delayed
CMR. At a median follow-up of 23 months(range,9-43),3year OS was 92%,EFS 91% for all,86% and 86% for IR,and
92.3%, 92% for HR. Grade-3 and higher toxicities were
Gastro-intestinal 8.5%,Febrile neutropenia-8.5%,Severe viral
infections-8.5%,and Hemophagocytic-lymphohistiocytosis5%. Hypothyroidism post-IFRT occurred in 3.4%. Nonrelapse mortality was 4.2%. Gender,bulky disease,Bsymptoms,albumin<4gm/dl or early PET response had no
significant impact on OS and EFS,though a trend towards
improved EFS was seen in patients with Hb>10.5g/dl.
Conclusions:
Primary
chemotherapy
based
on
OEPA+COPDac with IFRT in advanced cHL has good
3-year OS and EFS with manageable toxicities,but
long-term effects needs further follow-up. Intensifying
primary chemotherapy in advanced cHL attains better
disease control,while avoiding therapies with known late
toxicities.
O-062 Improvement in Compliance of Patients
with Non-Metastatic Retinoblastoma with Low-Cost
Prospective Database and Patient Tracking System:
A Study from Tertiary Care Centre in India
A. Batra1 , D. Dhawan1 , R. Paul1 , M. Kumari1 , S. Bakhshi1
1 All
India Institute of Medical Sciences, Medical Oncology, New Delhi,
India
Background/Objectives: Poor compliance has been reported
in retinoblastoma (RB) from resource constraint settings.
Prospective database and patient tracking system (PDPTS)
may improve compliance and hence treatment outcomes in
RB.
Design/Methods: PDPTS was introduced in January 2008 at
our centre, wherein patients were contacted telephonically on
missing their outpatient visit and were encouraged to complete the treatment; and contact information was updated at
each visit. We compared compliance of patients with nonmetastatic RB treated prior to and after PDPTS. ‘Adequate
therapy’ and ‘Effective therapy’ defined compliance during
treatment period (Stage 0: 4 cycles chemotherapy and 1
EUA; Stage 1: Enucleation; Stage 2: Enucleation and 4 cycles
chemotherapy; Stage 3: Enucleation, 4 cycles chemotherapy
and radiation) and follow-up (1 year follow-up or recurrence,
in addition to adequate therapy), respectively.
Results: Two hundred fourteen and 298 patients with RB
were treated during June 2003 to December 2007 (phase 1)
and January 2008 to December 2014 (phase 2), respectively.
Median age (36 months) and sex distribution (male: female2:1) were similar in both phases. Patients with stage III RB
had lowest compliance. Proportion of patients receiving adequate (All stages: 63% vs 77%, p=0.001; Stage 0: 30% vs
100%, p=0.001; Stage 1: 78% vs 90%, p=0.002; Stage 2: 58%
vs 75%, p=0.39; Stage 3: 26% vs 47%, p=0.03) and effective
therapies (All stages: 62% vs 75%, p=0.001; Stage 0: 26% vs
100%, p<0.001; Stage 1: 78% vs 90%, p=0.002; Stage 2: 50%
vs 62%, p=0.58; Stage 3: 24% vs 42%, p=0.06) was significantly higher in phase 2. Annual cost was 7USD per patient
and 350 USD per extra effectively treated patient.
Conclusions: PDPTS has significantly improved compliance
in patients with RB with minimal added cost. Improvement
was seen even in stage III disease with lowest compliance.
O-063 Impact of a Patient Navigator Program on
Pediatric Cancer Outcomes in a Low Resource
Setting
F. Alvi1 , J. Mafwimbo2 , N. Masalu2 , K. Schroeder3,4
1 Washington
University, School of Medicine, St. Louis, USA; 2 Bugando
Medical Centre, Oncology, Mwanza, Tanzania; 3 Duke University, Pediatric
Hematology/ Oncology, Durham, USA; 4 Duke University, Global Health,
Durham, USA
SIOP ABSTRACTS
Background/Objectives: Oncology patient navigation programs have been successfully implemented at hospitals
throughout the U.S., enhancing the quality of care through
financial guidance, treatment coordination, and psychosocial
support. In low resource settings, the barriers to receiving cancer care are increased and a patient navigator in this setting has
the potential to significantly impact outcomes. However, there
is limited research on the efficacy of such programs in these
settings. At Bugando Medical Centre (BMC) in Mwanza, Tanzania, a patient navigation program was established to identify
potential pediatric oncology patients, then assist patients and
their families throughout the diagnosis and treatment process,
with the goals of reducing time to oncology evaluation and
diagnosis, and ultimately improving survival outcomes.
Design/Methods: A retrospective analysis of hospital records
was conducted of all pediatric oncology patients seen at BMC
from 2010-2016, separated by presentation date before or after
establishment of navigation program. Collected data includes
demographics, diagnosis, time from presentation to oncology
evaluation and diagnosis, treatment completion and 1 year survival outcomes.
Results: A total of 238 patient files were reviewed, with
169 pre- and 69 post- program initiation. Patient groups did
not differ by age or gender (p=0.329 and 0.744), or diagnosis distribution. After establishing a patient navigator program, the average time to oncology evaluation decreased from
49.7 to 16.6 days (p=0.015), and time to diagnosis decreased
from 49.1 to 23.6 days (p=0.07). Treatment abandonment
decreased from 50% to 38% (p<0.001) and 1 year survival
increased from 27% to 53% (p<0.001).
Conclusions: In pediatric cancer, early diagnosis is critical
to the initiation of chemotherapy and improving outcomes.
This study has shown that a patient navigation program has the
potential to significantly impact patient outcomes, and should
be included in comprehensive pediatric cancer care programs.
O-064 Cost Effectiveness of Implementing a
Pediatric Early Warning System (PEWS) At a
Pediatric Oncology Hospital in a Low-Middle
Income Country
A. Agulnik1 , F. Antillon-Klussmann2 , D.J. Soberanis Vasquez2 ,
R.H. Arango2 , E. Moran2 , V. Lopez2 , C. Rodriguez-Galindo1 , N.
Bhakta1
1 St
Jude Children's Research Hospital, Department of Global Pediatric
Medicine, Memphis, USA; 2 Unidad Nacional de Oncología Pediátrica,
Hematology/Oncology, Guatemala, Guatemala
Background/Objectives: Hospitalized pediatric oncology
patients are at high risk for clinical decline and mortality, particularly in low- and middle-income countries. Pediatric Early
Warning Systems (PEWS) are nursing-administered clinical
S39 of S518
assessment tools that aid with early identification of deterioration. In 2014, a multidisciplinary team implemented a
modified PEWS at Unidad Nacional de Oncología Pediátrica
(UNOP), a pediatric oncology hospital in Guatemala. Published data demonstrated this intervention reduced clinical
deterioration events and PICU utilization. In this study, we
investigate the cost and cost-effectiveness of PEWS implementation at UNOP.
Design/Methods: The variable costs of running and maintaining the PICU and floor wards at UNOP were calculated for
2013 (pre-implementation) and 2015 (post-implementation)
using hospital administrative data. PEWS implementation
costs were based on study expenditures in 2014. The
number of PICU inpatient-days averted due to reduced
unplanned PICU transfers (clinical deterioration events) postimplementation was calculated after adjusting for changes in
total hospital inpatient-days. Hospital savings per inpatientday due to reduced variable cost expenditures from unplanned
PICU transfers were calculated. All costs were adjusted for
inflation and standardized using 2013 international dollars
(I$).
Results: There were 457 fewer PICU inpatient-days due
to unplanned transfers after PEWS implementation in 2015
compared to 2013. The difference in variable costs of an
unplanned PICU transfer was I$597.36 per day (PICU minus
ward). The total cost of implementing PEWS at UNOP
was I$20,706.08, representing a cost I$10.08 per hospital
inpatient-day. Through reductions in variable PICU costs such
as supportive care measures, UNOP was able to save a net
I$122.77 per inpatient admission (I$252,176.31 annual net
savings) as a result of PEWS implementation.
Conclusions: Implementation of PEWS at UNOP, a pediatric
oncology hospital located in a low-middle income country,
resulted in net cost-savings. This work demonstrates that hospital investment in a PEWS program can both improve the
quality pediatric cancer care and reduce hospital costs.
O-065 Participatory Action Research in
Lilongwe, Malawi: Identification of Five Pediatric
Palliative Care Interventions That Address Total
Pain for Pediatric Oncology Patients and Their
Families
M. Butia Mutai1,2 , I. Mtete Kumwenda1,2 , M. Chasela1,2 , A.
Mpasa1,2 , S. Wachepa1,2 , P. Ward1 , P. Musiwa1 , P. Wasswa1 , P.
Mehta3 , N.K. El-Mallawany3 , P. Kazembe1 , D. Mahoney4 , J.
Casas3,5
1 Kamuzu
Central Hospital, Pediatric Oncology, Lilongwe, Malawi; 2 Baylor
College of Medicine Children's Foundation Malawi, Pediatric Oncology,
Lilongwe, Malawi; 3 Baylor College of Medicine, Texas Children's Cancer
and Hematology Centers, Houston, USA; 4 Baylor College of Medicine,
Texas Children's Hospital Pediatric Palliative Care, Houston, USA; 5 Baylor
SIOP ABSTRACTS
S40 of S518
College of Medicine, Texas Children's Hospital Section of Palliative Care,
Houston, USA
Background/Objectives: The World Health Organization
defines effective pediatric palliative care (PPC) as the total
care of a child's body, mind and spirit involving interdisciplinary support to the entire family using community
resources. While assessment and management of children's
pain remains a global priority, the International Children's
Palliative Care Network has also identified creation of interventions and models of care for PPC as a top global research
priority. Additional literature demonstrates that participatory
action research (PAR) results in sustainable health care delivery models. A program that maximizes community involvement to establish interventions and models of care for PPC
and treatment of total pain in Malawi is needed.
T.F. Eleveld1,2 , L. Schild1 , J. Koster2 , D.A. Zwijnenburg2 , L. Alles1 ,
M.E. Ebus1 , R. Volckmann2 , G.A. Tijtgat3 , P. van Sluis2 , H.N.
Caron3 , R. Versteeg2 , J.J. Molenaar1
1 Department
of Translational Research, Princess Maxima Centre for
Childhood Oncology, Utrecht, the Netherlands; 2 Department of
Oncogenomics, AMC Amsterdam, Amsterdam, the Netherlands;
3 Department of Pediatric Oncology, Emma Children′ s Hospital, AMC
Amsterdam, Amsterdam, the Netherlands
Background/Objectives: We recently showed that mutations
affecting the RAS-MAPK pathway occur frequently in neuroblastoma relapse tumors. We hypothesized that activation
of this pathway is associated with poor prognosis and tumor
progression. Hence the objectives were to detect the activation
state of the RAS-MAPK pathway in tumors, correlate this to
prognosis and find mutations that can serve as biomarkers for
pathway activation.
Design/Methods: Qualitative data obtained through semistructured interviews were collected and analyzed to identify methods to address patients’ total pain. Participants
included bereaved parents of children with incurable hematologic/oncologic diagnoses (n=5) and medical providers from
a tertiary care public hospital oncology unit (n=5). Two independent reviewers conducted thematic data analyses.
Design/Methods: We generated a gene signature that can
identify the activation state of the RAS-MAPK pathway in
cell lines and tumors. These data were correlated to Whole
Genome Sequencing data to identify novel mutations that activate this pathway. Candidate mutations were induced in cell
lines using gene editing and characterized both in vitro and in
vivo.
Results: Five interventions to mitigate total pain were identified. All participants described parents’ “abandonment from
their spiritual community” and expressed urgent need for spiritual support. All participants cited need for financial support
for food security. Supportive home visits and enhanced community education to minimize stigma were universally suggested. All parents recommended support groups to address
emotional/psychological distress. Four medical providers
advocated for play therapy to address patients’ stress and pain,
and all providers cited the need for ongoing psychosocial support training.
Results: In primary neuroblastoma tumors activation of the
RAS-MAPK pathway correlates with poor survival and is
associated with mutations in ALK and other known RASMAPK genes. From integrative analysis we identify mutations in PHOX2B, CIC and DMD that activate the RASMAPK pathway in vitro and we show that activation of this
pathway causes tumor progression in vivo.
Conclusions: Using PAR to promote community involvement
in the creation of a PPC program to treat total pain in Malawi
is feasible and enlightened areas of focus. Financial support,
spiritual support, play therapy, home visits, and parental support groups were identified as the most immediate needs and
will guide next steps in developing a novel PPC program in
this population.
Conclusion: We identify novel biomarkers of RAS-MAPK
activation and reinforce this pathway as a promising target
in neuroblastoma. Further research should determine whether
the identified mutations also function as biomarkers for sensitivity to MEK inhibition.
O-067 Primary Site of Origin Predicts
Differential Genomics in Thoracic Versus Adrenal
Neuroblastoma
B. Truong1 , D. Oldridge2 , D. Russ2 , Z. Vaksman2 , S. Diskin2 , Y.
Mosse2 , S. DuBois3 , J. Maris2 , K. Matthay1
1 University
FREE PA PER SESSION:
NEUROBLASTOMA - BIOLOGY
O-066 Mutations in CIC, DMD and PHOX2B
Activate the RAS-MAPK Pathway in
Neuroblastoma and Activation of this Pathway
Causes Tumor Progression
of California- San Francisco, Pediatrics, San Francisco, USA;
of Pennsylvania School of Medicine, Pediatrics, Philadelphia,
USA; 3 Harvard Medical School, Dana-Farber / Boston Children's Cancer
and Blood Disorders Center, Boston, USA
2 University
Background/Objectives: Neuroblastoma is the second most
common extracranial malignancy of childhood, and has long
been recognized as a biologically and clinically heterogeneous disease. Based on recent studies demonstrating a significant relationship between the primary tumor site, prognosis,
and tumor biological features, we hypothesized that thoracic
SIOP ABSTRACTS
and adrenal neuroblastoma represent different disease subsets
with different genomic features.
Design/Methods: We utilized the TARGET dataset to evaluate the genetic profiles of adrenal (N=646) versus thoracic
(N=118) primary tumors. We also evaluated for association
of common germline variation with primary site in a separate European-American cohort of adrenal (N=707) or thoracic (N=320) primary tumors. Appropriate platforms were
employed to evaluate differences in copy number alterations,
mutations, RNA expression, pathway enrichment, and common germline variation between primary sites. Binary variable associations were evaluated by Fisher-exact test. Prior
evidence of in vitro transforming capability were applied to
call high-likelihood driver mutations in ALK prior to association testing.
Results: We observed higher rates of MYCN amplification,
chromosome 1q gain, and chromosome 11q deletion among
adrenal tumors, which were highly predictive of functional
signatures observed in RNA data. Adrenal neuroblastomas
were less likely to harbor ALK driver mutations than thoracic cases among all cases (OR 0.53, 95% CI 0.29-0.97) and
among cases without MYCN amplification (OR 0.35, 95% CI
0.18-0.65). Common germline SNPs in BARD1 (previously
associated with high-risk neuroblastoma) were found to be
strongly associated with predisposition for origin at adrenal,
rather than thoracic, sites.
Conclusions: Genomic features differ between adrenal and
thoracic neuroblastoma. Most unfavorable somatic features
(MYCN amplification and segmental chromosomal aberrations) were more common among adrenal tumors, though
ALK driver mutations were more common among thoracic
tumors. The presence of specific germline variants increase
the likelihood of adrenal over thoracic site of origin, reinforcing the differences between these two subgroups of this
disease.
O-068 Liquid Biopsies of Patients with
HIGH-RISK Neuroblastoma Disclose Exosomal
miRNA Modulation after the Induction Therapy
M. Morini1 , D. Cangelosi1 , D. Segalerba1 , R. Luksch2 , A.
Castellano3 , D. Fruci3 , J. Font de Mora4 , V. Castel5 , A. Canete5 , Y.
Yanez5 , S. Burchill6 , V.F. Viprey6 , A. Garaventa7 , A.R. Sementa8 ,
M.V. Corrias9 , A. Pezzolo9 , B. Carlini9 , G. Schleiermacher10 , A.
Eggert11 , L. Varesio1
1 G.
Gaslini Children's Hospital, Laboratory of Molecular Biology, Genoa,
Italy; 2 Istituto Nazionale Tumori, Pediatric Oncology, Milan, Italy;
3 Bambino Gesù Children's Hospital, Paediatric Haematology/Oncology,
Rome, Italy; 4 Instituto de Investigación Sanitaria La Fe, Laboratory of
Cellular and Molecular Biology, Valencia, Spain; 5 Hospital Universitario y
Politécnico La Fe, Pediatric Oncology, Valencia, Spain; 6 Leeds Institute of
Cancer and Pathology, Children's Cancer Research Group, Leeds, United
Kingdom; 7 G. Gaslini Children's Hospital, Pediatric Oncology, Genoa,
Italy; 8 G. Gaslini Children's Hospital, Pathology, Genoa, Italy; 9 G. Gaslini
S41 of S518
Children's Hospital, Laboratory of Oncology, Genoa, Italy; 10 Curie
Institute, Pediatric Oncology, Paris, France; 11 Charité Universitätsmedizin,
Pediatric Oncology and Hematology, Berlin, Germany
Background/Objectives: The response of patients with
High-risk (HR) neuroblastoma (NB) to the front line induction chemotherapy is crucial to determine the subsequent
treatment. The absence of early molecular markers predictive
of sensitivity/resistance to treatment led us to the study of exosomes, small vesicles considered the bioprint of tumor cells
in liquid biopsies. We investigated whether exosomal miRNA
(exo-miRs) can be early biomarkers of the response to the
induction-chemotherapy.
Design/Methods: We collected exosomes from plasma samples of 50 patients with HR-NB before and after the induction chemotherapy. Exo-miR expression was evaluated with
RTqPCR on a 381 target panel. Data analyses included feature selection and pathway analysis.
Results: The expression of 20 exo-miRs was significantly
modulated in response to chemotherapy, providing the first
evidence that exo-miRs may serve as biomarkers of the
chemotherapic response. Cluster analysis distinguished two
groups of patients, effectively dividing very good partial responders and minor responders. The correlation of
the two groups with other clinical and biological features is under investigation. Pathway analysis determined
whether chemotherapy influenced the expression of miRNAs
known to be involved in sensitivity/resistance to drugs commonly employed in the induction-chemotherapy. The analysis
revealed that 42% of the 20 differentially expressed exo-miRs
were associated with sensitivity/resistance to drug response.
Mapping the results to individual patients, we identified distinct groups of subjects potentially unresponsive/resistant to
the induction drugs. The exo-miR profile in the middle phase
of the induction therapy is under investigation to find miRNAs
predictors of the response, which may allow a timely change
in the induction protocol for those unresponsive patients.
Conclusions: We demonstrated that exo-miR can represent
biomarkers of the response to induction-chemotherapy and
potential indicators of sensitivity/resistance to specific drugs
for patients with HR-NB. These results pave the way to a
broad application of exo-miRs in liquid biopsies applied to
neuroblastoma targeted treatment.
O-069 Circulating Tumor DNA for Disease
Monitoring in Neuroblastoma
L. van Zogchel1,2 , E. van Wezel2 , J. van Wijk2 , W.C. Bruins2,3 , L.
Zappeij-Kannegieter2 , T.J. Slager3 , I. Verly3 , M.M. van Noesel1 ,
H.N. Caron3 , C.E. van der Schoot2 , G.A.M. Tytgat1,3
1 Princess
Máxima Center for Pediatric Oncology, Pediatric Oncology,
Utrecht, The Netherlands; 2 Sanquin Research- Amsterdam- The Netherlands
and Landsteiner Laboratory of the AMC- University of Amsterdam,
SIOP ABSTRACTS
S42 of S518
Department of Experimental Immunohematology, Amsterdam, The
Netherlands; 3 Emma Childrens Hospital- Academical Medical Center,
Department of Pediatric Oncology, Amsterdam, The Netherlands
Background/Objectives: Circulating tumor DNA (ctDNA)
has been used for disease monitoring in several types of cancer. The aim of our study was to investigate whether ctDNA
can be used for response monitoring in neuroblastoma.
Design/Methods: 162 plasma samples from 63 patients were
analyzed for detection of hypermethylated RASSF1A DNA.
DNA was isolated and total cell free DNA (cfDNA) was determined by qPCR for albumin and the amount of ctDNA was
determined by qPCR for methylated RASSF1A after bisulfite
conversion. Detection of ctDNA was compared with clinicbiological patient characteristics, such as BM and PB MRD
(qPCR), MIBG scans and urinary catecholamines.
Results: In 17/26 (65%) diagnostic samples ctDNA was
detected, including 4/10 (40%) patients with Iocalized disease. During induction chemotherapy (stage 4 patients only)
in 15/45 samples ctDNA was detected (33%). At (suspected)
relapse in 11 out of 18 samples ctDNA was detected (61%).
The amount of cfDNA was significantly higher in patients
with neuroblastoma at time of diagnosis and relapse compared
to healthy controls, with the highest amount in patients with
stage 4. There was significant correlation between ctDNA and
PB or BM MRD, when tumor levels were high or no tumor
was detected. Discrepancies were observed in 20 samples and
were studied in detail. The discrepancies indicated either low
tumor burden (ctDNA-/MRD+) or tumor (and metastases)
without or with minimal BM involvement (ctDNA+/MRD-).
Conclusions: Hypermethylated RASSF1A can be used for
monitoring of ctDNA in patients with neuroblastoma and
highly correlates with the disease status at diagnosis. Our
data indicate that there is a poorer correlation when tumor
load is very low, with both samples with ctDNA+/MRD- and
ctDNA-/MRD+. It is likely that ctDNA can originate from
both primary tumor and metastases and may be of special
interest for disease monitoring in patients relapsing in other
organs than the BM.
O-070 Efficacy of ANTI-GD2 Antibody
CH14.18/CHO and PD1/PD-L1 Checkpoint
Blockade in Neuroblastoma
H. Lode1 , M. Zumpe1 , M. Jüttner1 , S. Troschke-Meurer1 , H.
Loibner2 , N. Siebert1
1 University
Medicine Greifswald, Pediatric Hematology and Oncology,
Greifswald, Germany; 2 Apeiron Biologics, Apeiron Biologics, Vienna,
Austria
Background/Objectives:
Anti-GD2
antibody
(Ab)
ch14.18/CHO is effective for treatment of high-risk neuroblastoma (NB) patients and was approved by EMA with
and without IL2 co-medication. The mechanism of action is
induction of GD2 -specific Ab-dependent cellular cytotoxicity
(ADCC). Programmed death-1 (PD-1) is an inhibitory
receptor expressed by activated T- and NK-cells, and cancer
cells express PD-1 ligand (PD-L1). Here, we report for the
first time effect and mechanism of PD-1/PD-L1 blockade in
the context of ch14.18/CHO therapy in preclinical models.
Design/Methods: Expression of PD-L1 and PD-1 on NB cells
and leukocytes was analyzed by RT-PCR and flow cytometry
in the presence of ch14.18/CHO with and without IL-2. Mechanism of PD-L1 induction was analyzed with anti-CD11b
Ab. The effect of PD-1/PD-L1 blockade on ch14.18/CHOmediated anti-NB immune response was evaluated using antiPD-1 Ab both in vitro (Nivolumab) and in the syngeneic
GD2 + /PD-L1+ NB mouse model (anti-mouse PD-1). Mice
(n=10) were treated with ch14.18/CHO (5x300 �g, i.p.) in
combination with anti-PD-1 (8x250 �g, i.p.), and compared
to controls.
Results: Culture of LAN-1 NB cells with leukocytes
(E/T 10:1), sub-therapeutic ch14.18/CHO concentrations (10
ng/ml), without and with IL2 (100 IU/ml) induced a 2 and 3
fold upregulation of PD-L1, respectively, and inhibited GD2
specific ADCC. Co-incubation with anti-CD11b abrogated
this PD-L1 upregulation and increased ADCC. Importantly,
blockade with Nivolumab reversed the PD-L1-dependent
inhibition of ADCC. Finally, mice treated with ch14.18/CHO
in combination with PD-1 blockade showed strongest reduction of tumor growth, longest survival rate as well as the highest level of NB cell lysis mediated by serum and leukocytes
of treated mice compared to controls.
Conclusions: Ch14.18/CHO and IL2 upregulate the
inhibitory checkpoint PD-1/PD-L1 and combination of
ch14.18/CHO with PD-1/PD-L1 blockade results in synergistic treatment effects in preclinical models. This suggests
clinical evaluation of ch14.18/CHO in combination with
PD-1/PD-L1 checkpoint inhibition.
O-071 Targeted Combination Strategies to
Improve the Clinical Implementation of Venetoclax
for Neuroblastoma Treatment
E. Dolman1 , L.T. Bate-Eya1 , T.E. Eleveld1 , N.A. Schubert1 , B.
Koopmans1 , L.A. Alles1 , L. Schild1 , D. Lelieveld2 , D.A. Egan2 , M.
Kerstjens3 , R.W. Stam1 , J. Koster4 , H.N. Caron5 , J.J. Molenaar1
1 Princess
Máxima Center for Pediatric Oncology, Translational Research,
Utrecht, The Netherlands; 2 University Medical Center Utrecht, Cell
Biology, Utrecht, The Netherlands; 3 Erasmus MC- Sophia Children's
Hospital, Pediatric Oncology and Hematology, Rotterdam, The
Netherlands; 4 Amsterdam Medical Center- University of Amsterdam,
Oncogenomics, Amsterdam, The Netherlands; 5 Emma Children's HospitalAmsterdam Medical Center- University of Amsterdam, Pediatric Oncology,
Amsterdam, The Netherlands
SIOP ABSTRACTS
Background/Objectives: The anti-apoptotic protein B cell
lymphoma/leukaemia 2 (BCL-2) is highly expressed in the
majority of all neuroblastoma. In previous preclinical studies,
we have shown that treatment of BCL-2-dependent neuroblastoma with BCL-2 inhibitors leads to programmed cell death.
These results have contributed to the initiation of a phase I
trial to study the safety and pharmacokinetics of venetoclax
in children with relapsed or refractory neuroblastoma. The
current study focused on the identification and validation of
targeted combination strategies to prevent or overcome neuroblastoma resistance to venetoclax.
Design/Methods: Targeted drugs for combination treatment
with venetoclax were identified by compound-wide screens
with >200 compounds using normal neuroblastoma cell lines
and neuroblastoma cell lines made resistant to venetoclax.
Top hits were subsequently tested more extensively in vitro
and in vivo to validate the screening results.
Results: High-throughput drug screens identified MDM2
inhibitor idasanutlin as one of the strongest re-sensitizers for
venetoclax in venetoclax-resistant BCL-2-dependent neuroblastoma cells with wild-type p53 cellular tumor antigen. Subsequent in vitro validation showed that idasanutlin caused
cyclin dependent kinase inhibitor 1 (p21)-mediated growth
arrest in non-resistant neuroblastoma cells, while inducing
a BCL-2-associated X protein (BAX)-mediated apoptotic
response in venetoclax-resistant neuroblastoma cells in the
presence of venetoclax. In vivo combination of venetoclax
with idasanultin resulted in a remarkably improved anticancer
effect compared to single agent therapy, with almost complete
regression of BCL-2-dependent neuroblastoma xenografts.
Combination screens additionally revealed that inhibitors of
mitogen-activated protein kinase kinase (MEK), anaplastic
lymphoma kinase (ALK) and histone deacetylases (HDACs)
synergize with venetoclax, depending on the genomic background of the neuroblastoma tumors.
Conclusions: Our findings indicate that the clinical use
of venetoclax for the treatment of children with BCL-2dependent neuroblastoma tumors can be improved by combination therapy with targeted inhibitors. Optimal targeted
combination strategies depend on the presence of additional
genomic events driving neuroblastoma tumors.
FR EE PA PER SE SSI O N : R E NA L
TUMOURS
O-072 Impact OF 1Q Status on Outcomes of
Stage IV Favorable Histology Wilms Tumor
(FHWT) Patients Treated on the Children's
Oncology Group (COG) Study AREN0533
S43 of S518
E. Mullen1 , E. Perlman2 , Y.Y. Chi3 , D. Dix4 , G. Eric5 , J.
Gastier-Foster6 , G. Khanna7 , P. Ehrlich8 , J. Geller9 , J.
Kalapurakal10 , C. Fernandez11 , J. Dome12
1 Dana-Farber/Boston
Children's Cancer and Blood Disorders Center,
Pediatric Oncology, Boston, USA; 2 Ann & Robert H. Lurie Children's
Hospital of Chicago, Pathology, Chicago, USA; 3 University of Florida,
Biostatistics, Gainsville, USA; 4 University of British Columbia, Hematology
and Oncology, Vancouver, Canada; 5 University of Tennessee College of
Medicine, Pediatric Oncology, Chattanooga, USA; 6 Nationwide Children's
Hospital and The Ohio State University Medical Center, Biopathology
Center, Columbus, USA; 7 Washington University School of Medicine,
Pediatric Radiology, Saint Louis, USA; 8 University of Michigan, Pediatric
Surgery, Ann Arbor, USA; 9 Cincinnati Children's Hospital, Pediatric
Oncology, Cincinnati, USA; 10 Northwestern University, Radiation
Oncology, Chicago, USA; 11 IWK Health Centre and Dalhousie University,
Pediatric Hematology and Oncology, Halifax, Canada; 12 Children's
National Health System, Pediatric Hematology and Oncology, WashingtonDC, USA
Background/Objectives: 1q gain has been found to be
a negative prognostic marker in multiple retrospective
European and North American studies. Following 6 weeks
of vincristine/dactinomycin/doxorubicin (DD4A), protocol AREN0533 stratified Stage IV FHWT patients to
intensified five drug therapy with addition of cyclophosphamide/etoposide (regimen M) for slow incomplete
response (SIR) of pulmonary metastasis, extrapulmonary
metastasis (EPM), and/or gain of combined LOH 1p and
16q. DD4A was continued and pulmonary radiation withheld for those with rapid complete response (RCR). We
analyzed the impact of 1q status in this novel treatment
algorithm.
Design/Methods: 1q status was successfully analyzed in
248 evaluable patients by multiplex ligation-dependent probe
amplification. Event free survival (EFS) and overall survival
(OS) were summarized at year 4 and compared using the logrank test.
Results: 30% (75/248) had gain of 1q. Overall, those with 1q
gain (N= 75) had an EFS of 75% (95% CI: 62%, 87%) and OS:
91% (95% CI: 84%, 99%); those without 1q gain (N= 173) had
an EFS of 89% (95% CI: 83%, 94%) and OS of 96% (95% CI:
92%, 99%). Patients with SIR and 1q gain (42/116=36%) had
an EFS of 86%, compared to 92% with SR without 1q gain
(p=0.15); OS was 93% and 96% (p=0.45). Patients with RCR
and 1q gain (21/96=22%) had worse outcome than those with
RCR without 1q gain (EFS 57% vs 86%, p=0.0013; OS 89%
vs 97%, p=0.16). Relapse in RCR with 1q gain was predominantly (9/11) pulmonary. For patients with EPM (n=36), 33%
(N=12) had 1q gain (EFS 67%) and 67% (N=24) had no 1q
gain (EFS 88%) [p=0.15].
Conclusions: 1q gain was associated with inferior EFS
for RCR Stage IV FHWT patients with isolated pulmonary metastasis; these patients are not appropriate candidates for radiation omission. Regimen M may mitigate adverse impact of 1q gain in other stage IV risk
categories.
SIOP ABSTRACTS
S44 of S518
O-073 Effect of Chemotherapy Dosage on
Outcome of Patients with Stage II-IV Diffuse
Anaplastic Wilms Tumor: Results from the
Children's Oncology Group AREN0321 Study
N. Daw1 , Y.Y. Chi2 , Y. Kim2 , J.A. Kalapurakal3 , F. Hoffer4 , J.
Geller5 , E. Perlman6 , P. Ehrlich7 , K. Gow8 , E. Mullen9 , A.
Warwick10 , P. Grundy11 , E.J. Gratias12 , D. Ward13 , J.R. Anderson14 ,
A.D.C. Paulino15 , Z. Tochner16 , R. Venkatramani17 , C.
Fernandez18 , J. Dome19
1 The
University of Texas MD Anderson Cancer Center, Division of
Pediatrics, Houston, USA; 2 University of Florida, Statistics, Gainsville,
USA; 3 Ann and Robert H Lurie Children's Hospital of Chicago, Radiation
Oncology, Chicago, USA; 4 Quality Assurance Review Ctr, Diagnostic
Imaging, Lincoln, USA; 5 Cincinnati Children's Hospital Medical Center,
Hematology/Oncology, Cincinnati, USA; 6 Ann and Robert H Lurie
Children's Hospital of Chicago, Pathology, Chicago, USA; 7 C S Mott
Children's Hospital, Surgery, Ann Arbor, USA; 8 Seattle Children's Hospital,
Surgery, Seattle, USA; 9 Dana-Farber/Harvard Cancer Center,
Hematology/Oncology, Boston, USA; 10 Walter Reed National Military
Medical Center, Hematology/Oncology, Bethesda, USA; 11 University of
Alberta Hospital, Hematology/Oncology, Edmonton, Canada; 12 eviCore
Healthcare, Hematology/Oncology, Bluffton, USA; 13 Saint Jude Children's
Research Hospital, Pharmaceutical Services, Memphis, USA; 14 Merck
Research Laboratories, Oncology, North Wales, USA; 15 The University of
Texas MD Anderson Cancer Center, Radiation Oncology, Houston, USA;
16 University of Pennsylvania- Perelman School of Medicine, Radiation
Oncology, Philadelphia, USA; 17 Baylor College of Medicine/Dan L Duncan
Comprehensive Cancer Center, Hematology/Oncology, Houston, USA;
18 IWK Health Centre, Pediatrics and Bioethics, Halifax, Canada;
19 Children's National Medical Center, Center for Cancer and Blood
Disorders, Washington, USA
Background/Objectives: In National Wilms Tumor Study5, 4-year relapse-free survival for patients with stages II-IV
diffuse anaplastic Wilms tumor (DAWT) treated with vincristine, doxorubicin, cyclophosphamide, and etoposide, plus
radiotherapy (XRT) (Regimen I) was 58% (95% CI, 48-68%).
AREN0321 evaluated a more intensive regimen containing
carboplatin in addition to adjusted doses of chemotherapy
used in Regimen I (Regimen UH-1). Dosages of chemotherapy were reduced mid-study due to non-hematologic toxicity that exceeded predefined stopping rules. We analyzed the
effect of this dose reduction on event-free survival (EFS),
overall survival (OS) and toxicity.
stage II, III and IV disease were 86% (95% CI, 66-100%),
85% (95% CI, 69-100%) and 54% (95% CI, 30-78%), respectively. The EFS for patients treated with UH-1/UH-2 was 85%
(95% CI, 71-99%) compared to 68% (95% CI, 49-88%) for
patients treated with revised UH-1/UH-2 (p=0.12). There was
one grade 5 toxicity attributed to treatment on UH-1/UH-2
and two on revised UH-1/UH-2. The number of grade 3-4
non-hematologic toxicities per patient was 3.9 for UH-1/UH2 and 3.1 for revised UH-1/UH-2.
Conclusions: For patients with stage II-IV DAWT, Regimens
UH-1/UH-2 showed a trend toward superior EFS compared
to Revised UH-1/UH-2, with comparable rates of grade 3-5
toxicity.
O-074 Epidemiology of Patients with Wilms
Tumour Registered in Successive UK-Trials through
38 Years
K. Nakata1,2 , S. Tugnait1 , M.P. Falcone1 , N. Galea3 , F. Ceroni1,4 , R.
Al-Saadi1 , M. Chagtai1 , R. Williams1 , W. Mifsud1 , J. Brok1,5 , C.
Stiller6 , V. Moroz7 , A. Kelsey8 , G. Vujanic9 , K. Pritchard-Jones1
1 UCL
Great Ormond Street Institute of Child Health, Developmental
Biology and Cancer Programme, London, United Kingdom; 2 Cancer
Control Center- Osaka International Cancer Center, Department of Cancer
Strategy, Osaka, Japan; 3 Mater Dei Hospital, Paediatric and Adolescent
Cancer Unit, Msida, Malta; 4 Watford General Hospital, Paediatric
Department, Watford, United Kingdom; 5 Rigshospitalet, Dept. of Paediatric
Oncology and Haematology, Copenhagen, Denmark; 6 Public Health
England, National Cancer Registration and Analysis Service, Oxford,
United Kingdom; 7 Institute of Cancer and Genomic Sciences- University of
Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham,
United Kingdom; 8 Royal Manchester Children's Hospital, Department of
Paediatric Histopathology, Manchester, United Kingdom; 9 University
Hospital of Wales, Department of Cellular Pathology, Cardiff, United
Kingdom
Background/Objectives: Since 1979, 2,510 patients with
Wilms tumour (WT) have been registered in five consecutive
UK clinical trials (UKW1-3, SIOP-2001, and IMPORT). We
reviewed all trial data with focus on congenital abnormalities
(CA) and laterality.
Design/Methods: Patients with stages II-IV DAWT without
measurable disease received Regimen UH-1. Patients with
stage IV measurable disease had the option to receive vincristine in combination with irinotecan (VI) in an upfront
window; those with partial response had VI incorporated
into Regimen UH-1 (Regimen UH-2). Cumulative doses of
doxorubicin, cyclophosphamide and etoposide were reduced
by 20-40% in “revised” Regimens UH1/UH2 due to nonhematologic toxicity.
Design/Methods: We categorised patients with WT into five
mutually exclusive groups; WT and aniridia with/without urogenital malformations (WA), urogenital/renal malformations
including Denys-Drash syndrome (UM), hemi-hypertrophy
including Beckwith-Wiedemann syndrome (HH), other congenital abnormalities (other-CA), and without CA (non-CA).
We compared distribution of sex, age at diagnosis, stage, histology and 5-year overall survival (OS) of each group to those
of non-CA. Bilateral vs unilateral tumours were compared for
similar outcomes.
Results: Of 66 eligible patients, 23 were treated with UH1, 32 with revised UH-1, and 5 each with UH-2 and revised
UH-2. Four-year EFS for all patients was 75% (95% CI, 6287%); OS was 76% (95% CI, 64-88%). Four-year EFS for
Results: Numbers and proportions in each group were: WA
(n=24, 1%); UM (n=79, 3%); HH (n=65, 3%); other-CA
(n=116, 5%); non-CA (n=2,226, 88%). Bilateral (n=181,
7%); unilateral (n=2,309, 92%).
SIOP ABSTRACTS
S45 of S518
Patients in WA, UM and other-CA groups had younger
median age of diagnosis and higher proportion of bilateral disease compared to non-CA (20m, 21m and 30m vs 39m, and
33%, 19%, 17% vs 6%, respectively). HH patients showed no
significant difference compared to non-CA group (41m and
11%). UM had male predominance (M/F ratio 1.72 vs 0.88 in
non-CA). There were no significant differences in 5-year OS
for each group compared to non-CA [83% (WA), 88% (UM),
91% (HH), 87% (other-CA), vs 88% (non-CA)].
Compared to unilateral disease, the bilateral group had female
excess (M/F ratio 0.62 vs 0.93), younger age at diagnosis (24m
vs 39m) and poorer 5-year OS (82% vs 89%, p=0.003) that
had improved to 90% for cases diagnosed since 2002.
Conclusions: About one in nine patients with WT had congenital abnormalities. These patients are diagnosed at earlier
age, have more frequent bilateral tumours but 5-year survival
rate seems very similar. Compared to unilateral, bilateral WT
were younger and had poorer survival.
O-075 Prognostic Value of Age in Patients with
Wilms Tumour Treated According to International
Society of Paediatric Oncology (SIOP) 93-01 and
SIOP 2001 Protocols
1
2
1
3
J. Hol , M. Lopez , M. Van Grotel , K. Pritchard-Jones , B. De
Camargo4 , T. Acha5 , H. Van Tinteren2 , C. Bergeron6 , N. Graf7 , M.
Van den Heuvel-Eibrink1
1 Princess
Máxima Center for Paediatric Oncology, Paediatric Oncology,
Utrecht, The Netherlands; 2 Netherlands Cancer Institute, Biostatistics,
Amsterdam, The Netherlands; 3 UCL Great Ormond Street Institute of Child
Health, Paediatric Oncology, London, United Kingdom; 4 Instituto Nacional
de Cancer INCA, Paediatric Haematology-Oncology Program, Rio de
Janeiro, Brazil; 5 Hospital Materno-Infantil Carlos Haya, Paediatric
Oncology, Málaga, Spain; 6 Institut d'Hematologie et d'Oncologie
Pédiatrique- Centre Léon Bérard, Paediatric Oncology, Lyon, France;
7 Saarland University Medical Center, Paediatric Oncology and
Haematology, Homburg, Germany
Background/Objectives: Age has been suggested to be a
prognostic factor for recurrence and mortality in patients with
Wilms tumour (WT). In this study, we assess the prognostic value of age and cutoffs for risk stratification in paediatric
patients with unilateral WT treated according to recent International Society of Paediatric Oncology(SIOP) protocols.
Design/Methods: Patients (6 months-18 years) with stage
I-IV WT were derived from the SIOP93-01 and SIOP2001
database. Only patients who received preoperative chemotherapy were included. The prognostic value of age at diagnosis,
per year/categorized, for 5-year event-free survival (EFS) and
overall survival (OS) was assessed using the Kaplan Meier
method, log-rank test and multivariable Cox regression models. Martingale residual plots were used to assess the functional form of age. The multivariable analysis was adjusted
for gender, biopsy (yes/no), pathological stage, histological
classification and tumour volume at surgery.
Results: 5386/7880 patients met the inclusion criteria; stage
I: 46%, stage II: 23%, stage III: 17%, stage IV: 15%. Median
age at diagnosis was 3.4 years (interquartile range, IQR: 2.0–
5.1) and median follow-up was 6.3 years (IQR: 3.0-8.6). Estimated 5-year EFS and OS were 84% (95%CI 83.3-85.3) and
93% (95%CI 91.9-93.4), respectively. Assessment of martingale residual plots suggested a linear trend for age in both EFS
and OS. Significant differences in EFS and OS were found
between ages <2, 2-4, 4-10 and ≥10 (log-rank p<0.0001).
In multivariable analyses, increasing age was associated with
poorer EFS (linear trend p<0.0001). OS was lower in patients
≥4 years compared to patients <2 years (HR=1.32, 95%CI
1.13-2.57). No linear trend was found. Higher stage, histological risk group and volume were associated with poorer OS
and EFS in univariable and multivariable analyses.
Conclusions: Survival worsens with increasing age in
patients with WT. However, our results do not seem to justify the use of age cutoffs for risk stratification in pretreated
patients.
O-076 Mode of Presentation of Renal Tumours of
Childhood: First Analysis of Data from the
Prospective “IMPORT” Study in the UK and
Republic of Ireland
K. Pritchard-Jones1 , J. Brok1
1 University
College London, UCL Great Ormond Street Institute of Child
Health, London, United Kingdom
Background/Objectives: The Improving Population Outcomes for Renal Tumours of childhood (IMPORT) study collects data on the mode of presentation to facilitate international benchmarking of Wilms tumour (WT) survival rates in
relation to patient/tumour demographics and different models
of primary care.
Design/Methods: Data were extracted from case report forms
submitted by all 20 UK and Republic of Ireland principal treatment centres for childhood cancer. All cases had
central pathology review. The registration form had 4 categories of mode of tumour presentation: route1:routine child
health examination; route2:congenital abnormality screening; route3:non-specific symptoms; route4:tumour-specific
symptoms.
Results: 331 patients were registered with WT from Q4/2012Q4/2016. Diagnosis was through routes 1&2 in twenty (6 %)
patients, route 3 in 53 (16%) and route 4 in 258 (78%). Median
age at diagnosis of WT was 1.8y, 3.3y & 3.6y, respectively.
Stage distribution was:
SIOP ABSTRACTS
S46 of S518
Routes 1&2:stage I:11 (55%), II:1 (5%), III:2 (10%), IV:1
(5%), V:5 (25%)
Route 3:stage I:19 (36%), II:9 (17%), III:7 (13%), IV:13
(24%), V:5 (9%)
Route 4:stage I:96 (37%), II:36 (14%), III:53 (21%), IV:52
(20%), V:19 (7%)
There was no difference in the proportion with high risk
histology (15%; 13%; 10.5%) versus low+intermediate risk
(85%; 87%; 89.5%) by routes 1+2; 3; 4, respectively. Median
tumour volume at diagnosis was 623ml for 306 patients with
3D measurements; 59ml for routes 1&2; 522ml for route 3;
665ml for route 4.
Conclusions: Majority of patients presented with tumourspecific symptoms. Patients diagnosed by screening or child
health checks were younger, with less metastatic disease.
Stage III disease was more frequent in children presenting
with tumour-specific symptoms who also had the highest
median tumour volume. This ongoing data collection on mode
of presentation is now being extended across Europe and will
allow benchmarking, including tumour size and stage at diagnosis, to offer evidence regarding need for paediatric expertise
in the primary care of symptomatic children
O-077 Long-Term Renal Function in Children
with Wilms Tumour and Constitutional WT1
Mutation
M.P. Falcone1,2 , J. Brok1 , W. Mifsud1 , R. Williams1 , K. Nakata1 , S.
Tugnait1 , R. Al-Saadi1 , L. Side3 , J. Anderson1 , T. Chowdhury1 , C.
Duncan1 , D. Böckenhauer4 , K. Pritchard-Jones1
1 UCL
Great Ormond Street Institute of Child Health, University College
London, London, United Kingdom; 2 Paediatric Residency Program,
University of Foggia, Foggia, Italy; 3 Dept. of Clinical Genetics, Great
Ormond Street Hospital for Children NHS Foundation Trust, London,
United Kingdom; 4 Dept. of Paediatric Nephrology, Great Ormond Street
Hospital for Children NHS Foundation Trust, London, United Kingdom
Background/Objectives: Wilms Tumour (WT) survivors,
especially patients with associated syndromes or genitourinary anomalies due to constitutional WT1 mutation, have
increased risk of end-stage renal disease. We described the
long-term renal function in children with WT and WT1 mutation to guide their challenging oncological management.
Design/Methods: Retrospective analysis of patients with WT
and WT1 mutation treated 1993-2016 at Great Ormond Street
Hospital,UK, reviewing genotype, phenotype, tumour histology, laterality, treatment and renal outcome.
Results: We identified 23 patients with WT1 mutation; deletion (4), missense (2), nonsense (7), frameshift (6), splice site
(4). Males 61%, bilateral disease 48%, median age at diagnosis 14m (4-74m). Three (13%) patients had WT-aniridia,
10(43%) genitourinary malformation, 10(43%) no phenotypic
anomalies.
Two patients underwent bilateral nephrectomy, 9 unilateral
nephrectomy, 5 bilateral/unilateral nephron-sparing-surgery
(NSS), 7 unilateral nephrectomy with contralateral NSS. Histological subtype for 32 tumours/22 patients (10 bilateral)
showed 13 mixed, 14 stromal, 2 regressive, 1 blastemal, 2 only
intralobar-nephrogenic rest. Twenty-three tumours had associated nephrogenic rests (17 intralobar) and none had anaplasia.
At median 6y duration follow-up, all patients were alive, 3
in remission after relapse. Six patients (26%) required longterm dialysis; 4 due to chronic kidney disease 2 due to bilateral nephrectomy (one upfront, one relapse). Of these, 4 had
renal transplants and 2 are listed. Two patients developed
chronic kidney disease stage≥3 (e-GFR <60ml/min/1.73m2 ),
15 retained normal e-GFR, but 11 had increased albuminuria
(9 on ACE-inhibitors). Four patients (3 frameshift; 1 WT1
deletion) had normal kidney parameters (follow-up 11, 8, 1.5,
0.5 years).
Conclusions: Despite the known high frequency of chronic
kidney disease in patients with WT and constitutional WT1
mutation, 2/3 patients had sustained normal e-GFR. This
should guide oncology management regarding the balanced
decision about NSS without compromising oncological risk.
Larger international studies are needed to further refine the
prediction of WT1 genotype for longevity of renal function.
FREE PA PER SESSION:
S UP P O RT IVE CARE AND
PA L L I AT I V E CA R E
O-078 Safety Profile of High-Dose Thiotepa with
Autologous Stem Cells Rescue in Children and
Adolescents Treated for a Solid Tumor: A
Single-Institution Report on 465 Courses
C. Pasqualini1 , C. Dufour1 , I. Hezam2 , Y. Oubouzar1 , G. Goma3 , V.
Lapierre4 , D. Valteau-Couanet1
1 Gustave
Roussy, Children and Adolescent Oncology Unit, Villejuif,
France; 2 Gustave Roussy, Clinical Research Operations Department,
Villejuif, France; 3 Gustave Roussy, Biostatistic and Epidemiology Unit,
Villejuif, France; 4 Gustave Roussy, Cell Therapy Unit, Villejuif, France
Background/Objectives: Reported data on high-dose
Thiotepa (HD-Thio) followed by autologous stem cell rescue
(ASCR) in pediatric settings are very few. We aim to define
the safety profile of HD-Thio with ASCR in a large pediatric
cohort of solid tumors.
Design/Methods: We analysed data prospectively recorded
from patients with a solid tumor treated with HD-Thio followed by ASCR from 1986 to January 2016 in the Children and Adolescents Oncology Unit at Gustave Roussy. No
SIOP ABSTRACTS
S47 of S518
sinusoidal obstruction syndrome (SOS) prophylaxis was performed. Toxicity is reported according to CTCAE v4.0.
Decision framework, the panel formulated evidence summaries and recommendations.
Results: HD-Thio was administered to 354 patients, as a tandem HD-chemotherapy (HDC) in 111 patients. The median
age at diagnosis was 6.4 years (0.2-24.1). The most represented diseases were medulloblastoma (n=114), osteosarcoma (n=63), neuroblastoma (n=49), Ewing sarcoma (n=26)
and rhabdomyosarcoma (n=20). HD-Thio was delivered at
relapse for 135/355 patients (38%). In total, 465 courses were
performed, at the dose of 600, 720, 900 mg/m2 for 165, 84
and 216 patients, respectively. The most common toxicity
was digestive, as grade ≥ 3 mucositis and diarrhoea in 102
(22%) and 50 (11%) patients, respectively. Neurological toxicity grade ≥ 3 was reported in 42 patients (9%). Three patients
experienced SOS, mild for 2 of them. The median days to
neutrophils and platelets recovery was 8 days (2-37 and 0377, respectively), and the median duration of hospitalisation
was 22 days (14-70). A toxic mortality rate of 2% (n=7) was
observed, directly related to HD-Thio in 1 patient (SOS). Toxicity profile was not different between single and tandem HDThio and between relapse and first-line treatment.
Results: 7 studies (4 adult, 3 pediatric) were included, with
a low to very low quality of evidence. Regarding outcomes,
overall survival, clinical heart failure, progression free survival and subclinical heart failure were unanimously categorized as critical for decision-making. The panel agreed on a
weak recommendation against a push infusion of anthracycline chemotherapy. A recommendation defining a more precise infusion time period was currently not possible. Research
recommendations were formulated, calling for large randomized trials and pharmacokinetic studies.
Conclusions: HD-Thio with ASCR is globally well tolerated
in children and adolescents with solid tumors, even as a tandem HDC and in heavily pre-treated patients. Prophylaxis for
SOS is not mandatory. Digestive and neurological toxicities
need a careful supportive care management.
O-079 Guideline for the Infusion Duration of
Anthracycline Chemotherapy Agents in Children
with Cancer
E.A.H. Loeffen1 , E.C. Van Dalen2 , R.L. Mulder2 , L.C.M. Kremer2 ,
M.D. Van de Wetering2 , W.J.E. Tissing1 , O.B.O.T. Anthracycline
Cardiotoxicity Working Group1
1 Beatrix
Children's Hospital- University Medical Center GroningenUniversity of Groningen, Department of Pediatric Oncology/Hematology,
Groningen, The Netherlands; 2 Emma Children's Hospital- Academic
Medical Center, Department of Pediatric Oncology, Amsterdam, The
Netherlands
Background/Objectives: One of the established side effects
of anthracycline chemotherapy agents, which are used in various pediatric oncology treatment protocols, is short- and longterm cardiotoxicity. A proposed strategy to minimise this cardiotoxicity is to lengthen the infusion duration. We aimed to
develop recommendations for the infusion duration of anthracycline chemotherapy agents in children with cancer.
Design/Methods: Using an existing Cochrane sytematic
review as starting point, first a top-up search was performed.
A national, multidisciplinary panel (16 persons) was formed,
representing all relevant fields and including patient representatives. With use of the established GRADE system
for evidence appraisal and their more recent Evidence to
Conclusions: In this guideline we provide recommendations
regarding infusion duration of anthracycline chemotherapy in
children with cancer. Given the evidence shortage of highquality studies that address this question, further research is
needed.
O-080 Anesthetic Management of Superselective
Ophtalmic Arterial Chemotherapy for
Retinoblastoma in Children
L. Martynov1 , N. Matinyan1 , A. Sotnikov1 , I. Letyagin1 , N.
Milaschenko1 , Y. Buidenok1 , T. Ushakova2 , I. Trofimov3 , V.
Polyakov2
1 Pediatric
Oncology and Hematology Institute- Blokhin Russian
Oncological Research Center, Anesthesiology, Moscow, Russia; 2 Pediatric
Oncology and Hematology Institute- Blokhin Russian Oncological Research
Center, Oncology department, Moscow, Russia; 3 Pediatric Oncology and
Hematology Institute- Blokhin Russian Oncological Research Center,
Endovascular surgery department, Moscow, Russia
Background/Objectives: Superselective ophthalmic artery
chemotherapy (SOAC) with melphalan has significantly
reduced the need of enucleation in patients with retinoblastoma. Life-threatening complication of the SOAC procedure,
which is expressed in hemodynamic instability and bronchospasm (presumably due to oculo-cardiac reflex), significantly limits the wider implementation of this technique
in children. Our experience of SOAC and life-threatening
adverse cardio-respiratory reactions we have observed are
described.
Design/Methods: Between February 2011 and February
2017 in Pediatric Oncology and Hematology Institute 229
SOAC procedures were performed under general anesthesia, patients aged 17 +/- 5.1 months. After a. carotis interna
catheterization continuous iv infusion of Epinephrine 0.05
– 0.1 mcg/kg/min was started. If the signs of oculo-cardiac
reflex were observed, bolus of Epinephrine 0.5 mcg/kg was
administered.
Results: There were no deaths or major complications.
Oculo-cardiac reflex was triggered during 74 procedures
(32%). All reactions occurred during second or subsequent
SIOP ABSTRACTS
S48 of S518
procedures and were characterized by hypoxia, reduced lung
compliance (bronchospasm) followed by a subsequent deterioration in the oxygen saturation(Sp02) to 70%. Ventilation with 100% oxygen was initiated. Adverse reactions were
successfully treated during 5-10 min in all patients with
Epinephrine (0.5 mcg/kg bolus). One procedure was interrupted due to prolonged hemodynamic instability. 10 patients
required prolonged vasopressor support in early postoperative
period. In 3 cases children had an acute ishemic stroke, which
was confirmed by MRI.
in order to replace the transposed ovary(ies) in their original
position. The incidence of amenorrhea after the end of treatment was 47%. All prepubertal patients at the time of the OT
had a spontaneous menarche. Among 10 patients who have
attempted, 6 obtained a pregnancy, 2 of them after an OT performed in the peri-pubertal period and after pelvic irradiation
> 20 Gy for 3. The rate of spontaneous abortion was 33%.
Endocrine function was preserved in 82% of the 13 nulligeste
evaluated patients but the ovarian reserve was altered in two
thirds of the cases.
Conclusions: Adverse cardio-respiratory reactions are commonly observed in SOAC for retinoblastoma. We believe
that the adverse clinical signs represent an autonomic reflex
response and all patients should be considered at-risk. Reactions occur only during second or subsequent procedures and
can be life-threatening. Anesthesiologists must be vigilant for
adverse reactions and deal with them quickly and effectively.
However, further investigations are needed to improve the
understanding of the manifestations, management, and clinical significance of the described oculo-cardiac reflex.
Conclusions: These results show that OT during cancer treatment is possible and safe in young females including prepubertal, to preserve ovarian function even in younger patients.
Pregnancies can occur spontaneously, even without resorting
to detransposition. Further studies are needed to evaluate fertility after OT performed in pre-pubertal period, in order to
elaborate recommendations concerning the indications of this
technique.
O-082 Pain in Pediatric Cancer Patients
Receiving Chemotherapy in an Outpatient Setting
O-081 Fertility Preservation After Ovarian
Transposition in Pediatric, Adolescent and Young
Adult Female Cancer Patient
J. VALDUGA1 , L. CLAUDE2 , C. ROUSSET-JABLONSKI2 , V.
BERNIER-CHASTAGNER3 , A. LUC4 , P. CHASTAGNER1 , P.
MAREC-BERARD5
1 Centre
Hospitalier Universitaire de Nancy-Brabois, Oncologie et
hématologie pédiatrique, Nancy, France; 2 Centre Léon BERARD,
Radiothérapie, Lyon, France; 3 Institut de Cancérologie de Lorraine,
Radiothérapie, Nancy, France; 4 Centre Hospitalier Universitaire de
Nancy-Brabois, Plateforme d'Aide à la Recherche Clinique PARC, Nancy,
France; 5 Institut d'Hématologie et Oncologie Pédiatrique Européen IHOPe,
Oncologie et hématologie pédiatrique, Lyon, France
E. Michiels1 , F. Van Loon1 , J. Van Amstel1 , G. Elmont1 , M. Zwaan1
1 ErasmusMC/Sophia
Children's Hospital, Pediatric Oncology, Rotterdam,
The Netherlands
Background/Objectives: Pediatric cancer patients currently
spend more time at home. Only a few studies have studied
pain in children receiving chemotherapy in outpatient clinics.Therefore, the objective of this study was to explore if children experience pain when receiving chemotherapy at the outpatient clinic, the severity of the pain and its effect on quality
of life (QoL).
Design/Methods: A retrospective analysis of women who
underwent an OT before the age of 26 yrs between 1990 and
2015 was perfomed. Data on puberty, menstruations, pregnancies and ovarian reserve were collected.
Design/Methods: In this longitudinal observational study,
children visiting the outpatient clinic received 4 pain questionnaires, covering the last day before and the first 3 days following the outpatient chemotherapy administration. Children
were asked to complete at least 3 times the set of 4 questionnaires. Minimum time between 2 sets of questionnaires was
one week. The validated Brief Pain Inventory, Dutch Version
was used. For children aged 0-4 years (for which parents completed the questionnaire) and 9-18 years the numeric rating
scale was used to measure pain intensity. Children aged 4-9
years used the Faces Pain Scale-Revised. Demographic data,
use of pain medication and effect of the pain on QoL were
documented.
Results: An OT was performed in 32 patients before a pelvic
or craniospinal irradiation, associated to chemotherapy in 28
cases. Mean age at the time of the analysis was 24.4 yrs.
Median follow-up was 7.1 yrs. The mean age at the time of
the OT was 15.6 years (95% CI = [14.0-17.2]) and 9 were
prepurbetal. Only 3 patients underwent a second procedure
Results: Seventy-five participants completed 1,028 questionnaires. Diagnoses included ALL (52%), lymphoma (16%),
brain tumor (20%) and other malignancies (12%). In 40.3%
of the questionnaires pain was reported by 82.6% of the children. Clinically significant pain, defined as a score of > 4 on
‘average’ pain or a score > 7 on ‘worst’ pain, was noticed in 45
Background/Objectives: With increasing survival rates, preserve fertility of young patients treated for cancer is essential.
Ovarian transposition (OT) can preserve the ovarian function
from radiotherapy-related damage in pubertal women. However, little data are available about the possibilities of pregnancy after OT, especially when performed in pre or peripubertal period.
SIOP ABSTRACTS
patients (60.0%) and in 21.0% of the questionnaires. Twentyone percent of children experienced pain at least 50% of the
measurements. In 32.4% of the questionnaires in which clinically significant pain was reported, no analgesic medication
was used. The higher the pain scores, the more pronounced its
effect on QoL.
Conclusions: Pain is still very prevalent in children being
treated in an outpatient setting, and the effect on their QoL
is significant. Pain treatment is still suboptimal.
O-083 Predictors of Specialized Pediatric
Palliative Care Involvement and Impact on Patterns
of End-of-Life Care in Children with Cancer: A
Population-Based Study
S. Gupta1 , S. Rinku2 , R. Adam3 , K. Nelson3 , Y. Liu2 , C.
Vadeboncouer4 , S. Zelcer5 , A. Kassam6 , J. Pole7 , C. Earle8 , J.
Wolfe9 , K. Widger3
1 The
Hospital for Sick Children, Haematology/Oncology, Toronto, Canada;
for Clinical Evaluative Sciences, Cancer Research Program,
Toronto, Canada; 3 The Hospital for Sick Children, Paediatric Advanced
Care Team, Toronto, Canada; 4 Children's Hospital of Eastern Ontario,
Pediatric Palliative Care Outreach Team, Ottawa, Canada; 5 London Health
Sciences Centre, Paediatric Haematology/Oncology, London, Canada;
6 Southlake Regional Health Centre, Paediatric Oncology, Newmarket,
Canada; 7 Pediatric Oncology Group of Ontario, POGO Research Unit,
Toronto, Canada; 8 Ontario Institute for Cancer Research, Health Services
Research Program, Toronto, Canada; 9 Dana-Farber Cancer Institute,
Pediatric Palliative Care, Boston, USA
S49 of S518
hematologic cancers [odds ratio (OR) 0.33, 95th confidence
interval (CI) 0.30-0.37; p<0.001)], lowest income quintile
(OR 0.44, 95CI 0.23-0.81; p=0.009), and increased distance
from treatment centers (OR 0.46, 95CI 0.40-0.52; p<0.0001).
In multivariate analysis, SPPC was associated with a 3-fold
decrease in the odds of an EOL ICU admission (OR 0.32,
95CI 0.18-0.57), while GPC had no impact. Similar associations were seen with all other HI-EOL indicators. Excluding
TRM had little impact.
Conclusions: SPPC, but not GPC, is associated with lower
intensity care at EOL. Access to SPPC remains uneven. Without randomized trials, these results provide the strongest evidence to date supporting the creation of SPPC teams, and can
be used to support advocacy and policy efforts.
FREE PA PER SESSION: SOFT
TIS S UE SARCOM AS
2 Institute
Background/Objectives: Children with cancer are at risk
of receiving high-intensity (HI) end-of-life (EOL) care with
associated high symptom burden. The impact of palliative
care (PC) delivered by generalists or of specialized pediatric
palliative care (SPPC) on EOL care patterns is unknown, with
previous studies limited by small sample sizes or low response
rates.
Design/Methods: We assembled a retrospective cohort of all
Ontario children with cancer who died between 2000-2012
and who received care through a pediatric institution with a
SPPC team and a clinical PC database. Patients were linked
to population-based healthcare data capturing inpatient, outpatient, and emergency visits. Clinical PC databases identified patients receiving SPPC. Remaining patients were categorized as having received either general PC (GPC) or no
PC depending on the presence of PC-associated physician
billing or inpatient codes. We determined predictors of SPPC
involvement, and whether either SPPC or GPC was associated
with HI-EOL outcomes: ICU admission <30 days from death,
mechanical ventilation <14 days from death, or in hospital
death. Sensitivity analyses excluded treatment-related mortality (TRM) cases.
Results: 572 patients met inclusion criteria. Children
less likely to receive SPPC services included those with
O-084 Revisiting Risk Stratification in Patients
with Localized Rhabdomyosarcoma (RMS): A
Report from the European Paediatric Soft Tissue
Sarcoma Study Group (EPSSG)
G. Bisogno1 , M. Jenney2 , S. Gallego3 , C. Bergeron4 , J.H. Merks5 ,
C. Julia6 , A. Ferrari7 , Z. Angelica8 , H. Martelli9 , A. Kelsey10 , H.
Glosli11 , V. Minard Colin12 , M. Ben-Arush13 , I. Zanetti14 , G.L. De
Salvo15
1 University
of Padua, Department of Pediatrics, Padova, Italy; 2 Children's
Hospital for Wales Heath Park, Department of Pediatric Oncology, Cardiff,
United Kingdom; 3 Hospital Universitari Vall d'Hebron, Department of
Pediatric Oncology, Barcelona, Spain; 4 Centre Léon Bérard, Institut
d'hématologie et d'Oncologie Pédiatrique, Lyon, France; 5 Emma Children's
Hospital-Academic Medical Center, Department of Pediatric Oncology,
Amsterdam, The Netherlands; 6 Royal Marsden Hospital, Department of
Paediatric Oncology, London, United Kingdom; 7 Istituto Nazionale dei
Tumori, Pediatric Oncology Unit, Milano, Italy; 8 Istituto Fondazione Città
della Speranza, Solid Tumor Laboratory, Padova, Italy; 9 Hôpital Bicêtre,
Chirurgie Pédiatrique, Paris, France; 10 Royal Manchester Children's
Hospital, Department of Pediatric Histopathology, Manchester, United
Kingdom; 11 Rikshospitalet, Department of paediatric haematology and
oncology, Oslo, Norway; 12 Institut Gustave Roussy, Departement
d'Oncologie de l'Enfant et l'Adolescent, Villejuif, France; 13 Ruth Rappaport
Children's Hospital, Pediatric Hematology Oncology and Bone Marrow
Transplantation Division, Haifa, Israel; 14 Azienda Ospedaliera di Padova,
Department of Woman's and Child's Health, Padova, Italy; 15 Istituto
Oncologico Veneto, UOS Sperimentazioni Cliniche- Biostatistica e Nucleo
Ricerca Clinica, Padova, Italy
Background/Objectives: In the stratification system of the
recently closed RMS2005 protocol, 6 factors were used to
define the risk group of children with localized RMS and
assign treatment: histology, IRS Group, nodal involvement,
patients age, tumor site and size. We re-evaluated the value of
this stratification, adding FOXO1 fusion status, in preparation
of the next EpSSG protocol.
SIOP ABSTRACTS
S50 of S518
Design/Methods: A total of 991 patients enrolled from
10/2005 to 6/2013 with >3 yrs follow up were included in the
analysis. The initial step was a validation of the current system, examining its accuracy to discriminate groups of patients
with different prognosis. This was followed by a multivariable analysis in order to select independent prognostic variables. Finally the role of PAX3/PAX7-FOXO1 fusion status
was evaluated in a cohort of 660 patients with the available
data.
Results: 3-yrs EFS was 94.3, 75.8, 66.8 and 52.8 for low,
standard, high and very high risk groups, respectively and
all risk factors within the stratification system had prognostic
value within the univariate analysis. On multivariable analysis IRS group and tumor site were identified as independent
risk factors. An interaction between tumor size (>5cm) and
patient age (>10yrs) emerged discriminating patients with
worst prognosis When fusion status was included in the model
a better risk determination was evident.
Conclusions: the current stratification system has demonstrated good discrimination and calibration in a new cohort of
patients. It will be adopted in the next EpSSG protocol with
the inclusion of FOXO1 status instead of histology.
Variable
HR (95% CI)
(HR) p-value
IRS
I
1
II
1.8 (0.8;4.0)
0.1758
III
2.9 (1.4;6.0)
0.0043
Site
Fav
1
Unfav
1.7 (1.2;2.4)
Size (cm)
0.0018
Age (yrs)
<=5
<10
1
<=5
>=10
0.7 (0.4;1.2)
>5
<10
0.8 (0.4;1.2)
0.3237
>5
>=10
1.6 (1.1;2.3)
0.0111
0.2161
Fusion status
Negative
1
Positive
1.4 (1.0;1.9)
0.0310
O-085 Does Early Detection with off-Therapy
Surveillance Imaging Improve Survival in Pediatric
Rhabdomyosarcoma Patients? The European
Experience
B. Vaarwerk1 , C. Mallebranche2 , M. Adams3 , M.C. Affinita4 , M.
Jenney3 , G. Bisogno4 , K. McHugh5 , R.R. van Rijn6 , D. Orbach2 ,
J.H.M. Merks1
1 Emma
Children's Hospital - Academic Medical Centre, Pediatric
Oncology, Amsterdam, The Netherlands; 2 Institut Curie, Department of
Pediatric adolescent young adult Oncology, Paris, France; 3 Children's
Hospital for Wales, Department of Pediatric Oncology, Cardiff, United
Kingdom; 4 Padova University, Pediatric Hematology and Oncology
Division, Padova, Italy; 5 Great Ormond Street Hospital for Children,
Department of Radiology, London, United Kingdom; 6 Emma Children's
Hospital - Academic Medical Centre, Pediatric Radiology, Amsterdam, The
Netherlands
Background/Objectives: After completion of treatment
patients with localized rhabdomyosarcoma (RMS) are subject
to intensive radiologic tumor surveillance, however the clinical significance of surveillance is unclear. We retrospectively
analyzed the value of off-therapy surveillance, by comparing
survival of patients in whom relapse was detected by routine
imaging to patients in whom relapse was first suspected by
symptoms.
Design/Methods: We studied patients with relapsed RMS,
after completion of treatment for localized RMS, treated in
large pediatric oncology hospitals in France, the Netherlands,
United Kingdom and Italy and enrolled in the SIOP-MMT95 (1995-2004), ICG-RMS96 (1996-2004) or EpSSG-RMS2005 (2005-2013) studies. Survival time after relapse was
compared by log-rank test between patients in whom relapse
was detected by routine imaging (imaging group) and patients
in whom relapse was first suspected by clinical symptoms
(symptoms group).
Results: Preliminary data of 139 patients with relapsed RMS
(treated in France and the Netherlands) revealed 52 patients
(37.4%) in the imaging group and 86 patients (61.9%) in the
symptoms group (1 patient missing). Median follow-up time
after relapse was 7.3 years for survivors (n=66); 5-year postrelapse survival [95% CI] was 45.2% [30.5-59.9%] for patients
in the imaging group and 50.1% [39.1-61.1%] for patients in
the symptoms group (p=0.93).
Conclusions: Although systematic routine imaging is standard of care after treatment for RMS, these analyses indicate that the majority of patients with relapsed RMS are
detected because of clinical symptoms. Furthermore, no survival advantage was observed for patients in whom relapse
was detected before the emergence of clinical symptoms.
These preliminary results show that the value off-therapy
surveillance is controversial, particularly since repeated imaging also entails potential harm (psychological impact, risk of
anesthesia). Final results, including data of patients from the
United Kingdom and Italy, will be presented.
O-086 Outcome of Patients with Group I
Embryonal Rhabdomyosarcoma in the EPSSG
RMS 2005 Study
C. Bergeron1 , M. Jenney2 , S. Gallego3 , J.H.M. Merks4 , H. Glosli5 ,
A. Ferrari6 , D. Ranchère -Vince7 , T. Rogers8 , V. Minard-Colin9 , J.
Chisholm10 , D.S. Gian Luca11 , B. Gianni12
SIOP ABSTRACTS
1 Centre
Léon Bérard, Institut d'hématologie et d'Oncologie Pédiatrique,
Lyon, France; 2 Children's Hospital for Wales, Department of haematology
and oncology, Cardiff, United Kingdom; 3 Hospital Universitari Vall
d'Hebron-, Department of Pediatric Oncology-, Barcelona-, Spain; 4 Emma
Children's Hospital–Academic Medical Center- University of Amsterdam-,
Department of Pediatric Oncology, Amsterdam, The Netherlands; 5 Oslo
University Hospital, Department for Pediatric and Adolescent Medicine,
Oslo, Norway; 6 Fondazione IRCCS Istituto Nazionale Tumori, Pediatric
Oncology Unit, Milano, Italy; 7 Centre Léon Bérard, Bio-pathology
department, Lyon, France; 8 University Hospitals Bristol NHS Foundation
Trust, Department of Paediatric Surgery, Bristol, United Kingdom; 9 Institut
Gustave Roussy, Département d'Oncologie de l'Enfant et l'Adolescent,
Villejuif, France; 10 Royal Marsden NHS Foundation Trust, Children and
Young People's Unit, London, United Kingdom; 11 Istituto Oncologico
Veneto IRCCS, Clinical Trials and Biostatistics Unit, Padova, Italy;
12 University of Padova, Pediatric Oncology Division, Padova, Italy
Background/Objectives: To evaluate the reduction of
the burden of treatment in patients enrolled in the
EpSSG RMS 2005 protocol after initial microscopic
complete surgery for embryonal rhabdomyosarcoma
(ERMS).
Design/Methods: All patients with ERMS with initial microscopic complete resection (group I), lymp-node (LN) negative, were prospectively enrolled in low-risk group A (age <10
years and tumour size < 5 cm) or in standard-risk group B
(age > 10 year or tumour size >5 cm). Regional LN were
investigated with imaging without systematic surgical sampling. Group A patients received 8 courses of vincristin and
actinomycin-D (VA) for 22 weeks while group B received 4
courses of ifosfamide, vincristin and actinomycine-D (IVA)
plus 5 VA for a total of 25 weeks. No radiotherapy was
planned. OS and EFS were calculated using the Kaplan-Meier
method.
Results: From December 2005 to April 2015, 149 patients
(139 males) were enrolled in the study, 59 (39%) in group
A and 90 (61%) in group B. Tumour location was 134
genito-urinary non bladder-prostate (129 para-testicular, 3
uterus, 1 vagina, 1 vulva), 7 extremities, 3 bladder-prostate,
1 head&neck, 1 orbit and 3 others. After pathological
review, one case of nodular fasciitis was excluded from
the analysis. Median follow-up was 44 months. Eight of
the 9 relapses occurred in group B patients and 7 were
older than 10 years and had paratesticular tumour. Three
died of the disease. The 3 yrs EFS and OS were 91%
(95% CI 83.9-95.1) and 97% ( 95% CI91.1-99), respectively
95.3% and 100% for group A, and 88.2% and 95.2% for
group B.
Conclusions: Low-risk ERMS patient treated without alkylating agents and radiotherapy have excellent survivals.
The place of systematic RPLND and/or modern imaging to evaluate regional nodal involvement in patients
> 10 years with paratesticular ERMS requires further
discussion.
S51 of S518
O-087 Malignant Peripheral Nerve Sheet Tumors
(MPNST) in Children and Adolescents: Report of
the European Pediatric Soft Tissue Sarcoma Group
(EPSSG) NRSTS-2005 Study
M. van Noesel1 , D. Orbach2 , B. Brennan3 , G.L. de Salvo4 , I.
Zanetti5 , N. Francotte6 , R. Alaggio7 , A. Kelsey8 , G. Bisogno9 , M.
Casanova10 , A. Ferrari10
1 Princess
Máxima Center for Pediatric Oncology, Dept of Solid tumors,
Utrecht, The Netherlands; 2 Institut Curie, Pediatric Adolescent Young Adult
Department, Paris, France; 3 Royal Manchester Children's Hospital,
Pediatric Oncology, Manchester, United Kingdom; 4 EpSSG Data Centre
Istituto Oncologico Veneto IRCCS, Data Centre, Padova, Italy; 5 EpSSG
Data Centre Istituto Oncologico Veneto IRCCS, EpSSG Data Centre,
Padova, Italy; 6 CHC-Clinique Esperance, Department of Pediatrics,
Montegnée, Belgium; 7 Padova University, Pathology Department, Padova,
Italy; 8 Royal Manchester Children's Hospital, Department of Pathology,
Manchester, United Kingdom; 9 Padova University, Pediatric Hematology
and Oncology Division, Padova, Italy; 10 Fondazione IRCCS Istituto
Nazionale Tumori, Pediatric Oncology, Milan, Italy
Background/Objectives: MPNST are the third most frequent
pediatric soft tissue sarcoma. In 50% MPNST is associated
with Neurofibromatosis type 1. Retrospective studies showed
poor outcome and poor response to conventional chemotherapy. Here, we present the results for patients with localized
MPNST enrolled in the prospective EpSSG NRSTS-2005
study with a risk adapted strategy.
Design/Methods: A cohort of 59 localized MPNST patients
from 8 European countries were treated in 3 treatment groups:
1. Surgical group (R0 ≤5 cm; R0 >5cm and R1/N0) (n=14). 2.
Radiotherapy group (R0 >5cm G2 and R1/N0 G2-G3 ≤5cm
and R1/N0 G2 >5cm) (n=4) with 50.4 Gy for R0 tumors and
54.0 Gy for R1 tumors. 3. Perioperative chemotherapy group
(R0-1/N0 G3 >5cm; n=8) and (R2 + N1; n=33). Chemotherapy: 6 courses ifosfamide 3 g/m2 /day, 3 days + doxorubicin
37.5 mg/m2 /day, 2 days.
Results: Post-surgical staging of all tumors: 24% R0 resection ; 20% R1 resection, 56% R2 resection. In 28/33 evaluable
neo-adjuvant patients, chemotherapy response was complete
(CR) in 6.9%; partial (PR) in 10.3%; minor (MR) in 31.0%; no
progression in 34.5%. Total response to chemotherapy (CR +
PR + MR) is 47.2%. The 3-yrs EFS for the surgical group was
100%; radiation group 67%; Perioperative group <40%. Outcome of 55/59 evaluable patients with a median follow-up of
39.5 months: 27 alive in 1st CR, 9 alive with disease and 19
died. The 3-yrs EFS was 56.1 (95%CI 41.0-68.7) and 3-yrs
OS 66.5 (95%CI 50.9-78.2). NF1 was diagnosed in 47% of
patients.
Conclusions: Outcome of pediatric MPNST patients is poor
and the results of this prospective, interational treatment protocols is comparable or slightly better to historic, retrospective
studies. Novel treatment strategies are necessary to improve
outcome in MPNST.
SIOP ABSTRACTS
S52 of S518
O-088 Intraperitoneal Radioimmunotherapy for
Desmoplastic Small Round Cell Tumor: Results of a
PHASE I Study (Clinicaltrials.Gov Identifier
NCT01099644)
O-089 Genomic Index in Pediatric Synovial
Sarcoma (Synobio Study), Final Results the
European Pediatric Soft Tissue Sarcoma Group
(EPSSG) Experience
S. Modak1 , M.P. LaQuaglia1 , N. Pandit-Taskar2 , P. Zanzonico3 , T.
Heaton1 , J. Lewis2 , N.K. Cheung1 , J. Carrasquillo2
1 Memorial
D. Orbach1 , V. Mosseri2 , D. Pissaloux3 , B. Brennan4 , A. Ferrari5 ,
F. Chibon6 , G. Bisogno7 , G.L. De Salvo8 , C. Chakiba6 , N.
Corradini9 , V. Minard-Colin10 , A. Kelsey11 , D. Ranchère-Vince3
2 Memorial
1 Institut
Sloan Kettering Cancer Center, Pediatrics, New York, USA;
Sloan Kettering Cancer Center, Radiology, New York, USA;
3 Memorial Sloan Kettering Cancer Center, Medical Physics, New York,
USA
Background/Objectives: Desmoplastic small round cell
tumor (DSRCT), a rare sarcoma of adolescents and young
adults, has a long-term survival of <20% despite aggressive
multimodality therapy, warranting a search for novel treatments. The murine monoclonal IgG1 antibody 8H9 recognizes cell surface antigen 4Ig-B7H3 and binds to 96% of
DSRCTs with restricted normal tissue reactivity. DSRCT
recurrences often present as multifocal peritoneal implants.
We hypothesized that intraperitoneal (IP) radioimmunotherapy (RIT) by virtue of prolonged residence time and slow
transfer to the circulation, may selectively target IP DSRCT.
Design/Methods: We conducted a phase I study of radioiodinated 8H9 to evaluate toxicity, pharmacokinetics, biodistribution and efficacy. Cohorts of 3-6 patients were treated with
escalated doses of IP 131 I-8H9. A prior dose of 2mCi 124 I-8H9
IP was used to acquire PET images and biodistribution data.
Toxicity was monitored clinically and biochemically. Pharmacokinetics was studied using serial blood draws.
Results: Thirty-seven DSRCT patients were treated at
doses of 30-90mCi/m2 . Maximum tolerated dose was not
reached; there were no dose-limiting toxicities. Adverse
events (n=1 each) were transient: grade 3 transaminitis, neutropenia, and thrombocytopenia. Blood and peritoneal halftimes were 32.5h and 14.6h respectively. Mean projected
absorbed doses to blood, kidney, liver, lung and spleen
were 0.7,1.72,1.92,0.64 and 1.03 rad/mCi 131 I-8H9 respectively (n=12 patients analyzed). Dehalogenation was insignificant: >80% blood 131 I remained protein-bound 66h post-RIT.
Recommended phase II dose was 80mCi/m2 . Progressionfree survival (PFS) for patients undergoing gross total
resection followed by RIT and whole-abdominal radiotherapy was 17.9±3 months. 11/20 patients survive PF at a
median of 29 months post-RIT. In contrast patients with
gross residual disease pre-RIT (n=13) had PFS of 3.3±1.4
months. Overall survival was also better for the former
(p<0.05).
Conclusions: 124 I-8H9-directed radioimmuno-PET successfully determined biodistribution, whole-body and organ exposure. 131 I-8H9 IP RIT had a satisfactory safety profile and
activity against micro-metastatic DSRCT. A phase II trial will
commence shortly.
Curie, Pediatric adolescents young adults department, Paris,
France; 2 Institut Curie, Department of Biostatistics, Paris, France; 3 Institut
d'Hematologie et d'Oncologie Pediatrique- Centre Léon Bérard, Pathology
department, Lyon, France; 4 Royal Manchester Children's Hospital,
Paediatric Oncology, Manchester, United Kingdom; 5 Fondazione IRCCS
Istituto Nazionale Tumori, Pediatric Oncology Unit, Milan, Italy; 6 Institut
Bergonié, Département de Biopathologie, Bordeaux, France; 7 Padova
University, Pediatric Hematology and Oncology Division, Padova, Italy;
8 IRCCS Istituto Oncologico Veneto, Clinical Trials and Biostatistics Unit,
Padova, Italy; 9 Institut d'Hematologie et d'Oncologie Pediatrique- Centre
Léon Bérard, Pediatric oncology, Lyon, France; 10 Gustave Roussy,
Département de Cancérologie de l'Enfant et de l'Adolescent, Villejuif,
France; 11 Royal Manchester Children's Hospital, Department of Diagnostic
Paediatric Histopathology, Manchester, United Kingdom
Background/Objectives: A genomic index (GI) tool using
array comparative genomic hybridization (aCGH) on tumor
cells correlates with genomic instability and has recently been
developed. GI has emerged as independent prognostic factor
associated with the risk of metastatic relapse in adult synovial
sarcoma (SS). The aim is to assess the role of GI in pediatric
patients with SS.
Design/Methods: All pediatric/adolescent/young adults’
(<25 years) with localized SS (central pathological review
or specific fusion transcript (SYT-SSX)) prospectively
included in the European EpSSG-NRSTS-05 protocol
(EUDRACT2005-001139-31) with a contributive aCGH
were selected. Definition of GI was A2 /C, where A is the total
number of alterations (segmental gains and losses) and C is
the number of involved chromosomes on aCGH results. GI1
group corresponds to cases with no alterations (flat profile,
GI=0) and GI2 group cases with many alterations (complex
CGH profile; GI≥1).
Results: Samples were available from 62 patients. The
median age of the cohort was 13 years (range: 4-24). The commonest primary site was extremities (69%). Patients received
either surgery only (23%), adjuvant therapy (16%) or perioperative therapy with surgery and radiotherapy (61%). In
summary, 54.8% were GI1 group, and 45.2% GI2 . After a
median follow up of 60 months (range: 0.1-112), 10 tumor
events occurred and 5 patients died. Respectively for GI1
vs. GI2 groups, 5-year event free survival (EFS) rates were
93.8±4.2% vs. 66.4±9.8% (P<0.007) and 5Y-Metastatic Free
Survival (MFS) 93.8±4.2% vs. 74.1±9.1% (P<0.05). In multivariate analysis, GI status as adjusted for IRS-group, site and
tumor size remains independent prognostic for EFS with a relative risk (RR) of 6.3[1.3-31.3] (p<0.015) and RR for MFS is
4.7 [0.9-25.2] (p=0.051).
SIOP ABSTRACTS
Conclusions: GI may explain aggressive behavior of some
pediatric SS. Although tumor events were rare, high GI
selected patients with a poorer outcome that may require therapy intensification in future protocols.
Founding sources: “Enfant-et-santé/SFCE” “Info-sarcome”
“La-ligue-contre-le-cancer”
FREE PA PER SESSION:
IMMUNOT HE R A P Y
O-090 Encouraging Responses and Survival for
Patients with Replication Repair Deficiency and
Hypermutant Cancers to Immune Checkpoint
Inhibition. A Report from the International
bMMRD Consortium
P. Angelini1 , M. Sabel2 , V. Larouche3 , E. Opocher4 , S. Lindhorst5 ,
D. Ziegler6 , B. George7 , M. Oren8 , P. Tomboc9 , D. Samuel10 , M.
Osborn11 , A. Bronsema12 , K. Cole13 , D. Stearns14 , S. Chiaravalli15 ,
G. Mason16 , G. Thomas17 , M. Vanan18 , E. Bouffet19 , U. Tabori19
1 The
Hospital for Sick Children, Haematology/Oncology, Toronto, Canada;
of Goteborg, Paediatric Haematology and Oncology, Goteborg,
Sweden; 3 Centre Mere-Enfant Soleil du CHU du Quebec, Paediatric
Haematology and Oncology, Sainte-Foy Quebec, Canada; 4 University of
Padua, Paediatric Haematology and Oncology, Padua, Italy; 5 Medical
University of South Carolina, Neuro-Oncology, Charleston, USA;
6 University of New South Wales, Paediatric haematology and Oncology,
Sidney, Australia; 7 Medical College of Winsconsin, Haematology and
Oncology, Milwaukee, USA; 8 Sheba medical Centre, Paediatric
Haematology and Oncology, Sheba, Israel; 9 West Virginia University,
Paediatric Haematology and Oncology, Morgantown, USA; 10 Valley
Children Health Care, Paediatric Haematology and Oncology, Madera,
USA; 11 Women's and Children's Hospital, Department of Clinical
Haematology/Oncology, North Adelaide, Australia; 12 University Medical
Center Hamburg-Eppendorf, Department of Pediatric Hematology and
Oncology, Hamburg, Germany; 13 Children's Hospital of Philadelphia,
Research Institute, Philadelphia, USA; 14 University Hospital Clevelan
Medical Centre, Pediatrics-Hematology and Oncology, Cleveland, USA;
15 National Cancer Institute, Paediatric Oncology, Milan, Italy;
16 Children's Hospital Pittsburgh, Haematology adn Oncology, Pittsburgh,
USA; 17 Oregon Health and Science University, Paediatric Haematology
adn Oncology, Portland, USA; 18 Children's Hospital Research Institute of
Manitoba, Paediatric Haematology and Oncology, Winnipeg, Canada;
19 The Hospital for Sick Children, Neuro-Oncology, Toronto, Canada
2 University
S53 of S518
Tumour mutation analysis and neo-antigen formation
analysis were performed.
Results: Twenty patients (11 males, median age at starting
ICI 11.9 years) with 25 cancers received ICI. All tumors were
hypermutant (>10mut/MB) and 12 were ultra-hypermutant
(>100mut/MB). Nine patients developed acute “flare” symptoms following the first ICI administration. These included 8
patients with brain tumors and heavy burden of disease and
one bone metastasis from colon cancer. All these patients
required steroid use and 6 died within a few days or weeks
after this first administration. Only 2 patients developed
autoimmune phenomena related to ICI. Of patients with evidence of disease, objective responses were observed in 5/11
brain tumors and 4/4 metastatic extra-cranial tumours. One
year survival is 62+/-13% for the whole cohort and 52+/-12%
for gliomas. All 5 patients with extra-CNS solid tumors are
alive and in continuous response. At a median of 7.2 (3-19)
months, 12 patients are still alive and on therapy.
Conclusions: This is the first cohort of prospectively followed
patients with bMMRD and hypermutant cancers treated with
ICI. The encouraging initial responses and prolonged survival
in this cohort warrants a prospective genetic based study of
ICI in children. The role of “flare reactions” following initiation of treatment needs to be further investigated.
O-091 Preclinical Efficacy and Safety Profile of
CD19CAR+ T Cells Engineered with Sleeping
Beauty Gene Transfer for the Treatment of Acute
Lymphoblastic Leukemia
C.F. Magnani1 , C. Cappuzzello1 , F. Benedicenti2 , S. Tettamanti1 ,
E. Montini2 , G. Gaipa1 , B. Andrea1 , E. Biagi1
1 Research
Center "M. Tettamanti", Pediatric Oncology, Monza MB, Italy;
Raffaele Telethon Institute for Gene Therapy HSR-TIGET, Safety of
Gene Therapy and Insertional Mutagenesis Research Unit, Milan, Italy
2 San
Background/Objectives: Biallelic mismatch repair disease
(bMMRD) is the most aggressive cancer predisposition syndrome in which patients succumb to multiple hypermutated
cancers during childhood. Since hypermutated cancers have
responded to immune checkpoint inhibitors (ICI), we treated
patients with recurrent hypermutant cancers with ICI to assess
toxicity, tumour response and survival.
Background/Objectives: Adoptive transfer of autologous
CD19-specific chimeric antigen receptor (CAR)T cells engineered by viral vectors demonstrated unexpected positive
results, achieving durable responseS in relapsed and refractory patients affected by B-lineage leukemias. We recently
established a platform for non-viral gene manipulation of
Cytokine-Induced Killer (CIK) cells, in compliance with
Good Manufacturing Practices (GMP). In this study, we evaluated the feasibility and reproducibility of a GMP-compliant
protocol, and the preclinical efficacy and safety of SB modified CARCIK-CD19 cells.
Design/Methods: As a part of the international bMMRD
consortium collaboration, bMMRD patients with recurrent/progressive cancers received nivolumab or pembrolizumab. Clinical data was prospectively collected.
Design/Methods: With an improved SB transposon platform,
we genetically modified CIK cells to express the CAR specific
for acute lymphoblastic leukemia CD19+ blasts and evaluated
their preclinical efficacy and safety in vitro and in vivo.
SIOP ABSTRACTS
S54 of S518
Results: Large scale manufacturing process was verified
starting from 45 ml of peripheral blood or, alternatively, 3060X10^6 PBMC isolated from Buffy Coats, reaching stable
expression of CD19CAR (62.425%±6.399). Modified cells
displayed a specific and effective cytotoxicity, IL-2 and IFNgamma production and proliferation towards primary tumors.
We manufactured three lots in an academic Cell Factory,
authorized by Agenzia Italiana del Farmaco. The median
expression of CD3+CD19CAR + cells was 46.90% (range
31.27% – 65.45%). CARCIK-CD19 cells showed a dosedependent antitumor response and persisted in a xenograft
mouse model of common BCP-ALL, bearing the feature of
a Ph-like gene rearrangement (PAX5/AUTS2), and in a survival model with Daudi-cell lymphoma. CARCIK-CD19 cells
induced complete eradication of disseminated tumor. Infusion of CARCIK-CD19 cells proved to be safe and well tolerated. The infused cells persisted in time in the hematopoietic
and post-injection perfused organs. Highly polyclonal distribution of Integration Sites in CARCIKCD19 cell product was
demonstrated.
Design/Methods: To target BAFF-R molecule, we developed
anti-BAFFR.CARs that differ for the inversion of the VH and
VL and the length of the spacer domain. Cytokine-induced
Killer (CIK) cells, an heterogeneous population enriched in
highly cytotoxic CD3+CD56+ cells, were engineered with an
improved Sleeping Beauty platform and used as effector population.
Conclusions: CARCIK-CD19 may offer a valid and sustainable alternative to patient-derived viral approach for patients
with r/r B cell malignancies after HSCT. This study provides
the proof-of-concept for designing phase I/II study for relapsing and refractory ALL post Hematopoietic Stem Cell Transplantation.
Conclusions: Taken together, these findings make this receptor a safe and attractive target for a second line immunotherapy in case of CD19-negative relapse or for a double targeted
approach.
O-092 BAFF Receptor (BAFF-R) Car-Redirected
T Cells as a Novel Tool to Treat High Risk B-Cell
Acute Lymphoblastic Leukemia (B-ALL)
N. Turazzi1 , G. Fazio1 , V. Rossi1 , A. Rolink2 , G. Cazzaniga1 , A.
Biondi1 , C.F. Magnani1 , E. Biagi1
1 M.
Tettamanti Reserach Center- University of Milano Bicocca S.Gerardo
Hospital/Fondazione MBBM, Department of Pediatrics, Monza, Italy;
2 University of Basel, Department of Biomedicine, Basel, Switzerland
Background/Objectives: B-cell Acute Lymphoblastic
Leukemia (B-ALL) is the most common malignancy in
children (80%). CD19-targeting approaches paved the way
for the treatment of relapsed/refractory ALL. However, the
emergence of CD19-negative relapses in 10-30% of treated
patients has been reported. Receptor of B-cell Activating
Factor (BAFF-R) is fundamental for B-cell maturation and
survival with an expression restricted to mature B cells
while not on B-cell precursors and plasmablasts. Recent
studies reported the over-expression of BAFF-R in B-cell
malignancies, including B-ALL. Moreover, leukemic cells
express both BAFF and BAFF-R suggesting an autocrine
signaling loop. BAFF is also expressed in leukemic niche
supporting proliferation and survival of B-ALL blasts.
In this study, we aimed to develop a chimeric antigen receptor
(CAR)-mediated approach targeting BAFF-R molecule.
Results: We showed that BAFF-R expression in B-ALL primary samples is maintained at relapse. Anti-BAFFR.CARs
were stably expressed and the shortest VHVL.CAR exerted
the highest anti-leukemic activity (average 60%) and cytokine
release (8.9±2% of IFN-� and 16.4±5.5% of IL-2 producing
cells) towards NALM-6 in vitro. Importantly, we detected specific lysis of primary B-ALL blasts (65.6±4.5%). Combining the INVsh.CAR with CD19.CAR, we detected a superior anti-tumor activity towards NALM-6 and primary blasts
(78.1±6.9% and 72.2±2.9% of lysis respectively) compared
to single population per se. Furthermore, we demonstrated
the ability of the INVsh.CAR to lysate blasts collected from
CD19-negative relapse.
O-093 Specific Targeting of Acute Myeloid
Leukemia by the use of Engineered CIK
(Cytokine-Induced Killer) Cells Expressing the
Anti-CD33 Chimeric Antigen Receptor (CAR)
M.C. Rotiroti1 , S. Arcangeli1 , C.F. Magnani1 , C. Cappuzzello1 , A.
Biondi1 , S. Tettamanti1 , E. Biagi1
1 Research
Center “M. Tettamanti”, Pediatric Clinic, Monza MB, Italy
Background/Objectives: Acute Myeloid Leukemia (AML)
is still associated with a dismal prognosis.
Immunotherapy employing T cells redirected with Chimeric
Antigen Receptors (CARs) could represent a valid alternative
to current strategies.
CD33 is broadly expressed on AML blasts, representing a
suitable antigen to be targeted with CAR-T cells.
The aim of the study is to preclinically evaluate efficacy and
safety profiles of CD33.CAR redirected Cytokine Induced
Killer (CIK) cells alone and in combination with standard
chemotherapeutic agents.
Design/Methods: We generated CD33.CAR-expressing CIK
cells through the non viral Sleeping-Beauty transposon system, starting from healthy mononuclear cells and primary
AML samples.
SIOP ABSTRACTS
The in vitro anti-AML activity of CD33.CAR-CIK cells has
been assessed by cytotoxicity, proliferation and cytokine production assays upon challenge with AML samples.
The in vivo efficacy of CD33.CAR CIK cells is evaluated in
NSG mice transplanted with MA9-NRas AML cells and primary samples. Moreover we investigate the potential benefit of combining CD33.CAR CIK cells with standard AML
induction therapy.
Results: CD33.CAR-CIK cells resulted in a potent antileukemic activity, in terms of specific killing, proliferation
and cytokine production. We observed that the already established “5+3” induction protocol significantly reduced the
leukemic burden from around 20% to 0.1% in the bone marrow of MA9-NRas cell grafted mice. Since the disease was
not totally eradicated, we are currently investigating the efficacy of the CD33.CAR-CIK cells on chemotherapy resistant/residual AML cells. Preliminary data have shown a survival advantage when adding CD33.CAR-CIK cells on the top
of chemotherapy.
Conclusions: Having demonstrated the in vitro anti-leukemic
activity of SB-modified CD33.CAR-CIK cells, we aim to further evaluate their efficacy in vivo against chemotherapy resistant/residual AML cells to corroborate our initial observations. Envisaging a safer clinical translation, transient CAR
expression, by CD33.CAR mRNA, is under investigation,
to limit the potential long-term off-target effect on normal
hematopoietic stem/myeloid progenitor cells.
O-094 Precision Targeting of Acute Myeloid
Leukaemia Using Costimulatory-Only Chimeric
Antigen Receptors Provides Efficacy without
Toxicity
J. Fisher1 , P. Abramowski1 , N.D. Wisidagamage Don1 , J. Anderson1
1 UCL
Institute of Child Health, Cancer section, London, United Kingdom
Background/Objectives: On-target off-tumour toxicity constrains the development of immunotherapies targeting highly
expressed tumour antigens, producing challenging and
sometimes fatal toxicity. The strength of CD3� -containing
chimeric antigen receptors expressed in ��T cells is also a
limitation as it offers no escape to antigen-expressing healthy
cells. V�2+ ��T cells differentiate between healthy and transformed cells in an MHC-independent manner determined by
differing expression of phosphoantigen on stressed versus
healthy cells. Their native TCR is therefore not redundant in
the tumour context and need not be replaced with an artificial
construct. We sought to determine the efficacy and safety of
V�2+ ��T cells expressing ”co-stimulation only” CARs in a
pre-clinical model.
S55 of S518
Design/Methods: To demonstrate the lack of on-target offtumour toxicity, anti-CD33 “co-stimulation only” CARs
expressed in V�2+ ��T cells were compared to a conventional
second generation anti-CD33 CAR (CD33-28� ). Cytotoxicity against CD33+ AML cell lines, healthy myeloid cells and
myeloid progenitors was assessed. Phenotype was assessed by
flow cytometry and secondary expansion potential was determined by co-culture with irradiated target cells. Mechanistic
information was obtained using cell-free systems to determine
cytokine production and signalling profiles by PhosFlow following stimulus of CD3, CAR or both.
Results: ��T cells expressing a “costimulation-only” CAR
retain anti-tumour cytotoxicity but show no activity against
healthy cells which do not engage the ��TCR. Clinically useful numbers of cells can be generated from a 100ml blood
draw. Precise control of cytokine production and activatory
signalling is achievable with selective stimulus of CAR and/or
TCR. “Costimulation-only” CAR expressing ��T cells have a
phenotype favourable for adoptive transfer with significantly
lower exhaustion marker expression than cells expressing a
conventional CD3� -CD28 CAR, and are capable of mounting a secondary expansion following antigen re-challenge.
Conclusions: This approach offers a means of safely recapitulating immunotherapy against tumour antigens previously
rejected on grounds of on-target off-tumour toxicity.
O-095 Resistance Mechanisms of
Rhabdomyosarcomas to
Rhabdomyosarcoma-Directed Chimeric T Cells
K. Simon-Keller1 , A. Seils1 , P.D.A. Marx1
1 University
Hospital Mannheim, Institute of Pathology, Mannheim,
Germany
Background / Objectives: Background: Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy
of childhood and adolescence. Outcome of children with
advanced RMS is still poor. Immunotherapies may offer new
perspectives for high-risk patients.
Design / Methods: Objective: To reveal tumor cell-intrinsic
resistance mechanisms of RMS cell lines, RMS redirected
cytotoxic T cells expressing a chimeric antigen receptor
(CAR) with specificity for the fetal acetylcholine receptor
(fAChR), which is an almost RMS-specific, tumor associated antigen, were used. Futhermore sensitivity of RMS tumor
cells against Cytokine induced killer cells (CIK) and NK cells
were tested.
Methods: RMS-directed chimeric T-cells (cTCs) were generated by retroviral transduction of peripheral blood lymphocytes with fAChR specific CAR. CIK and NK cells
were enriched by cultivation. Killing efficiency of the named
immune cells and survival of RMS cells were determined by
SIOP ABSTRACTS
S56 of S518
apoptosis tests after co-culture. RMS were checked for expression of anti-apoptotic genes and immunosuppressive as well
as co-stimulatory receptors using FACS, Western Blot and
qRT-PCR.
Results: fAChR specific chimeric T-cells showed RMS tumor
cell lysis in vitro and in vivo, but were less efficient. RMS cells
were resistant to IFN�, TNF�, FAS-L and TRAIL. Molecular features associated with resistance of RMS to cTCs are (a)
lack of essential costimulators for tumour - T cell interaction
and expression of inhibitory molecules like B7H1 and B7H3;
(b) over-expression of inhibitor of apoptosis (IAP) family
members in RMS cells and tissue. Inhibition of IAPs through
siRNA or pharmacological substances improved killing efficiency by chimeric T cells in vitro and in vivo. The mentioned resistance mechanisms were ‘spontaneously’ circumvented by CIK and NK cells to which RMS cells were highly
sensitive.
Conclusions: Blockade of anti-apoptotic mechanisms and use
NK and CIK cell-mediated therapeutic strategies as well as
RMS-specific chimeric T cells should be evaluated as therapeutic strategy in RMS.
treatments were used to evaluate the consistency or coherence
of programs.
Results: Ten manualized interventions (24 reports) were
identified and coded. Some programs yielded clinical effects
(e.g. Bright Ideas, SCCIP). An in-depth analysis revealed that
lack of clinical signal may be due to a variety of factors. A
subset of programs (N=4) lack precise concept definition,
explicit model of change and defined target. Social validity
and acceptability was seldom documented prior efficacy testing. Importantly, dosage or treatment intensity was never systematically studied.
Conclusions: Fine methodological design is necessary for
program testing but is not sufficient for appropriate program
development. Systematic psychosocial interventions to help
parents should build on one another and therefore explicitly
refer to sound models of change. Models of change should
also translate more clearly in the format, tools, and interaction style of programs. Future programs should also address
underserved populations (e.g. fathers) and optimize contact
rates (e.g. e-health initiatives).
O-097 Child Versus Parent Perceptions of
Parenting In Childhood Cancer Surivivors and
Healthy Peers
FREE PA PER SESSION: PPO - I
S. Schepers1 , A. Long1 , K. Russell1 , S. Phipps1
1 St
O-096 Interventions to Support Parents Whose
Child is Being Treated for Cancer: Lessons Learned
from Research on Existing Programs
S. Sultan1 , D. Ogez1 , K. Peloquin2 , R. Ribeiro2 , D. Curnier1 , V.
Marcil1 , D. Sinnett1
1 CHU
Sainte-Justine, Hematology-Oncology, Montreal, Canada;
de Montréal, Psychology, Montréal, Canada
2 Université
Background/Objectives: Parents of children treated for cancer are vulnerable to a variety of issues including heightened
distress and lack of control. Distress during treatment has been
identified as a risk factor for future distress and for increased
difficulties for the family and the child in the long run. To
help parents during treatments, manualized interventions have
been developed and applied with this population.This presentation will identify, review and criticize existing manualized
intervention. We concentrate on program development processes and criteria of quality of psychological treatments to
identify previous achievements as well as avenues for future
improvements.
Design/Methods: A systematic search was run in databases
(electronic and manual) to identify existing programs corresponding to inclusion criteria. The ORBIT framework was
used to evaluate and compare program development processes. Criteria from the APA task force on psychological
Jude Children's Research Hospital, Psychology, Memphis, USA
Background/Objectives: A pediatric cancer diagnosis is a
challenging event that may have an impact on how children
and parents perceive parent-child relationships. The aims of
this study were to (a) examine possible differences in child and
parent perceptions of parenting between childhood cancer survivors and healthy peers, and (b) determine the concordance
between child and parent perceptions of parenting.
Design/Methods: Participants were children aged 8-21 years
(N=206 children with a history of cancer, N=119 healthy
peers), and one of their parents. All patients were ≥ 3 years
from diagnosis (M=7.06, SD=4.25). Both children (Parental
Bonding Instrument (PBI)) and parents (Parenting Relationship Questionnaire (PRQ)) reported on their perceptions of
parenting. Two separate MANCOVA's (PBI and PRQ) were
conducted to determine possible differences between the cancer and the comparison group, while controlling for child
age/gender, and parent SES/gender. Concordance between the
PBI scales of parental care and overprotection and the PRQ
scales of involvement, attachment, communication, parenting
confidence, and relational frustration was assessed with Pearson correlation coefficients.
Results: Survivors of childhood cancer (p=.868) and their
parents (p=.202) did not differ in their perceptions of
parenting compared to healthy peers. The magnitude of
SIOP ABSTRACTS
effect between parent-child dyads was not significantly different for childhood cancer survivors and healthy peers.
The child's report of a caring parent-child relationship
was positively and significantly associated with parentreported involvement, attachment, communication, and parenting confidence (r’s ranged from .20 to .30), and negatively associated with relational frustration (r=-.36). Children that perceived their parents as overprotective had parents that reported significantly more relational frustration
(r=.24).
Conclusions: A history of childhood cancer does not appear
to influence parenting behavior, as perceived by both children
and parents. However, children who experienced their parents
to be overprotective had more frustrations in the parent-child
relationship, which might warrant future interventions.
O-098 Parental Functioning after Induction
Treatment of Their Child with Acute
Lymphoblastic Leukemia
L.M.H. Steur1 , N. Rensen1 , M.A. Grootenhuis2,3 , N.K.A. van
Eijkelenburg2 , I.M. van der Sluis2,4 , D.W.M.W. te Loo5 , C. van den
Bos6 , W.J.E. Tissing7 , G.J.L. Kaspers1,2,8 , R.R.L. Litsenburg1,2
1 VU
University medical center, Department of pediatric
oncology/hematology, Amsterdam, The Netherlands; 2 Princess Máxima
Center for pediatric oncology, Utrecht, The Netherlands; 3 Emma Children's
Hospital Academic Medical Center, Psychosocial department, Amsterdam,
The Netherlands; 4 Sophia Children's Hospital Erasmus Medical Center,
Department of pediatric oncology, Rotterdam, The Netherlands; 5 Amalia
Children's Hospital Radboud University Medical Center, Department of
pediatric oncology, Nijmegen, The Netherlands; 6 Emma Children's Hospital
Academic Medical Center, Department of pediatric oncology, Amsterdam,
The Netherlands; 7 Beatrix Children's Hospital University Medical Center
Groningen, Department of pediatric oncology, Groningen, The Netherlands;
8 Dutch Childhood Oncology Group, The Hague, The Netherlands
Background/Objectives: Parental and child quality of life
(QoL) are bidirectionally related. To improve QoL of families, parental functioning should also be addressed. This study
aims to describe parental QoL, sleep and distress and to investigate predictors of parental QoL in childhood ALL.
Design/Methods: Parents of children aged 2-18 years, treated
according to the Dutch Childhood Oncology Group ALL-11
treatment protocol, were included (expected final sample size
n=105).
Parental functioning (QoL, sleep and distress) was assessed
shortly after end of induction treatment with questionnaires
(Short Form-12, Medical Outcome Study Sleep Scale, Distress Thermometer). Scores were compared to healthy norms.
QoL- and sleep scores 1 and 2 standard deviation (SD) different from the norm reflected clinical relevance. A distress
score of 4 or higher indicated clinical distress. Predictors
for parental QoL were selected with backward regression
analyses.
S57 of S518
Results: Ninety parents (mean age 38.4±6.0 years, 77.8%
mothers) of 90 children (mean age 7.0±4.4 years, 43.3%
girls), were included (response rate 66%).
Parents reported significantly lower mental QoL, more overall
sleep problems, and more distress (P<0.001). Physical QoL
was not different from norms. Clinically relevant lower mental QoL was found in 45.6% (SD<-1) and 18.9% (SD<-2) of
the parents and clinically relevant sleep problems in 52.2%
(SD>1) and 24.4% (SD>2), compared to 15.9% and 2.3%
in healthy norms, respectively. Clinical distress was present
in 74.7% of the parents compared to 41.2% in the norm.
Lower child age, higher parental age, more parental sleep
problems and more parental distress predicted lower mental
QoL (explained variance 53%). Male child gender and more
child sleep problems predicted lower physical QoL (explained
variance 10%).
Conclusions: Parents of children with ALL are at risk for a
lower QoL and impaired psychosocial functioning. Aiming to
improve functioning of the whole family, interventions targeting parents at risk are warranted.
Acknowledgements: Grant sponsor: Dutch Cancer Society.
O-099 Improvements in Psychological
Adjustment in Siblings and Parents of Children
with Cancer after Participation in A Sibling Group
Intervention: A Randomized Control Trial
B. Maru1 , E. Atenafu2 , F. Schulte3 , P. Nathan4 , K. Hancock5
1 Hospital
for Sick Children, Psychology, Toronto, Canada; 2 University
Health Network, Biostatistics, Toronto, Canada; 3 Alberta Children's
Hospital, Psychology, Calgary, Canada; 4 Hospital for Sick Children,
Haematology/Oncology, Toronto, Canada; 5 Hospital for Sick Children,
Pscyhology, Toronto, Canada
Background/Objectives: Pediatric cancer diagnosis and
treatment can affect psychological adjustment in parents and
healthy siblings. Systematic, rigorous assessment of interventions targeting the psychosocial needs of these siblings are
rare. Our objective was to assess the effects of a manualized
group intervention, Siblings Coping Together (SCT), on siblings’ and parents’ adjustment and to explore factors related
to intervention effect.
Design/Methods: We conducted blocked randomized controlled trial (RCT) with two arms, the experimental arm (EG)
and an attention control group (CG). 75 healthy siblings (average age 11 years, range 7-18) of children with cancer who
were >3 months from diagnosis participated. Both groups had
eight weekly two-hour sessions. EG followed SCT's educational, social, and therapeutic problem-solving plan through
games and crafts; CG consisted of games and crafts only. Siblings self-reported on symptoms of depression and anxiety;
parent self-reported on symptoms of anxiety, at baseline, after
SIOP ABSTRACTS
S58 of S518
intervention ended, and 3 months later. Multivariable analyses
with a mixed effects model were used to examine the intervention effect over time, controlling for covariates (e.g. gender,
on/off ill child's treatment).
Results: A significant group by gender interaction with the
total depression scores indicated female siblings in the EG
reported significantly lower scores than girls in the CG across
times (p < 0.05, h2 =0.071). This was also the case for the
subscales of ineffectiveness (p < 0.01, h2 =0.096) and anhedonia (p <0.05, h2 =0.064). A significant difference on group
by gender interaction was also found for total anxiety scores
for parents (p =-0.002, h2 =0.159), with parents of females in
the EG reporting lower scores than equivalent parents in the
CG.
Conclusions: A group intervention for siblings of children
with cancer can result in improvements in psychological
adjustment for both siblings and parents, particularly if the
sibling is female. This research was funded by the Canadian
C17 Network.
h2 =0.134 and h2 =0.133. respectively). Siblings in the EG
reported significantly better school PedsQL scores overall
than siblings in the CG (M = 79.51 vs 73.74; p < 0.03, effect
size=5.76). A significant group by gender interaction in the
proxy school PedsQL scores indicated that compared to the
EG, girls in the CG were rated with worse scores (p < 0.003,
h2 =0.126).
Conclusions: Participating in groups with other siblings of
children with cancer can result in improved overall QOL.
However, participating in specific group intervention to
address siblings’ needs can improve school QOL, particularly
in females. Challenges to this research need to be addressed.
This research was funded by Canadian C17 Network.
O-101 Development and Validation of Age
Stratified Paediatric Oncology Distress
Thermometer
L. Edwards1
1 The
O-100 Changes in Quality of Life in Siblings of
Children with Cancer after Group Intervention
Participation: A Randomized Control Trial
M. Barrera1 , E. Atenafu2 , P. Nathan3 , F. Schulte4 , K. Hancock1
1 Hospital
for Sick Children, Psychology, Toronto, Canada; 2 University
Health Network, Biostatistics, Toronto, Canada; 3 Hospital for Sick
Children, Heamatology/Oncology, Toronto, Canada; 4 Alberta Children's
Hospital, Psychology, Calgary, Canada
Background/Objectives: Pediatric cancer diagnosis and
treatment can result in reduced quality of life (QOL) in healthy
siblings. Interventions targeting sibling QOL and the rigorous
examination of these interventions are lacking. Our objective
was to assess the efficacy of a manualized group intervention
(EG), Siblings Coping Together (SCT), on siblings’ quality
of life compared to an Attention Control Group (CG), and to
identify factors related to the intervention effect.
Design/Methods: We conducted a randomized controlled
trial (RCT) with two arms: EG and CG. 75 healthy siblings
(average age 11 years, range 7-18) of children with cancer who
were >3 months from diagnosis participated. EG followed
SCT's educational, social, and therapeutic problem-solving
plan through games and crafts; CG consisted of games and
crafts only. Self- and proxy reported Pediatric Quality of Life
Questionnaires (PedsQL) were completed at baseline, end of
intervention, and 3 months later. Total and subscales scores
were generated. Multivariable analyses with a mixed effects
model were used to examine the intervention effect over time,
controlling for covariates (e.g., gender).
Results: Improvements in PedsQL proxy scores (total and
subscales) were noted over time in both groups (p < 0.001,
Royal Marsden NHS Foundation Trust, Paediatric Psychological
Support, Sutton, United Kingdom
Background/Objectives: The aim of this project is to complete the development and validation of a brief psychosocial
and memory distress thermometer (DT) to be used with paediatric/young adult cancer patients
Design/Methods: Pre-pilot/Development of the tool
Age-appropriate versions of the screening tool were developed: under five, 5-7, 8-12, 13-17 and 18plus . along with an
accompanying parent proxy version.
Pilot
A pilot study was carried out with 45 patients and their parents
to test acceptability and usability of the tool. Amendments
were made to the tools according to the feedback.
Validation
The cross sectional questionnaire project was conducted in
7 collaborating paediatric oncology centres with 549 participants ( child patient and parent proxy) to validate the DT
against the Strengths and Difficulties Questionnaire (SDQ),
the Hospital Anxiety and Depression scale (HADS) for psychological distress, Health Utilities Index (HUI2) for memory and learning validation and Paediatric quality of life scale
(Pedsql)
Results: Using a cut-off of 4, sensitivity against SDQ for
all age groups under 18 was 75.8 (range 65.7–84.2), 18plus
against HADS was 75.8 (65.7–84.2). The specificity was 53.3
(range 47.8–58.7) against the SDQ for the 18 plus specificity against the HADS was 47.1 (34.8–59.6). The sensitivity
against the HUI2 for all age groups was 89.0 (79.5–95.1), sensitivity was 70.3 (65.9–74.4).
SIOP ABSTRACTS
Conclusions: The DT is valid and acceptable for use as a rapid
screening instrument for paediatric cancer patients in the UK.
The results indicate that it can be used to monitor change in
psychological distress and memory problems over time, but
we recommend further work to determine how and when to
use the tool clinically.
The screening tool research project was approved by the Royal
Marsden Research and Development committee and Surrey
Borders Ethics Committee (MREC).
FREE PA PER SESSION: PPO - I I
O-102 Establishing a Paediatric Oncofertility
Program: Uptake of Procedures and Acceptance of
Fertility Decisions in Families at A Tertiary Centre
Y. Jayasinghe1 , M. Kemertzis1 , L. Orme2 , M. Zacharin3 , M. Peate4 ,
C. Ho5 , D. Gook6 , K. Stern6 , H. Bourne6 , G. Clarke7 , Y. Heloury8 ,
M. Sullivan2 , S. Jayasuriya9 , H. Clark9 , F. Agresta10 , P. Downie2 ,
L. Super2 , L. Gillam11
1 Royal
Children's Hospital, Gynaecology, Melbourne, Australia; 2 Royal
Children's Hospital, Children's Cancer Centre, Melbourne, Australia;
3 Royal Children's Hospital, Endocrinology, Melbourne, Australia;
4 University of Melbourne, Obstetrics & Gynaecology, Melbourne,
Australia; 5 National University Hospital, Endocrinology, Singapore,
Singapore; 6 Royal Womens Hospital, Reproductive Services, Melbourne,
Australia; 7 Royal Childrens Hospital, Andrology, Melbourne, Australia;
8 Royal Children's Hospital, Surgery, Melbourne, Australia; 9 Monash
University, Medicine, Melbourne, Australia; 10 Melbourne IVF, Clinical
Research, Melbourne, Australia; 11 Royal Children's Hospital, Clinical
Ethics Service, Melbourne, Australia
Background/Objectives: There is little published data
regarding fertility preservation in the paediatric population,
including data on families feelings of regret or acceptance of
their fertility decision. We aim to describe uptake of fertility preservation procedures at The Royal Childrens Hospital
Melbourne since 1987, and their impact on decision regret in
families.
Design/Methods: Bidirectional cohort study. In August 2013,
we introduced a formalised oncofertility service under three
levels of governance (as a novel technology, with research and
clinical ethics governance). Oncofertility data was recorded
in a fertility preservation database. Families completed a validated decision regret scale regarding the fertility decision with
scores ≥ 30 representing high regret.
Results: Three hundred and ten patients underwent fertility
preservation procedures at a mean age of 13.9 years (range
0.1-23 years), 55% were male, 32% pre-pubertal. Most procedures (65%) occurred between 2013-2016. These included
ovarian tissue preservation [28% (n=88)] with follicle density of 0.3-134/mm2, (where 4 patients had mature oocytes
within the tissue); testicular tissue preservation [28% (n=88)]
(where 8 had mature sperm within the tissue); sperm
S59 of S518
cryopreservation [39% (n=121)]; oocyte collection
[0.9%(n=3)], GnRH analogues alone [1.9% (n=6)]. Invasive
procedures were done for moderate to high risk of infertility.
Minor complications occurred in 3%, with no delays to cancer
treatment. One hundred and thirty eight participants (108
parents, 30 patients) completed a decisional regret survey.
Most (82.5%) reported low regret (mean score 13.7, SD 18.8;
range 0-95). Having a fertility preservation procedure was an
independent predictor of low regret on (p<0.0001, OR=0.11,
CI= 0.03 - 0.37). Expectation of a positive fertility outcome
within the next generation was high.
Conclusions: Paediatric fertility preservation procedures are
safe, and associated with low regret in families. Demand is
steadily increasing. It is important to provide accurate and
transparent and realistic information support to families prior
to diagnosis and throughout survivorship.
O-103 Genetics-Related Beliefs, and Information
and Service Needs, of Childhood Cancer Survivors
and Their Parents
C. Wakefield1,2 , E. Doolan1,2 , C. Signorelli1,2 , K. Tucker3 , A.
Patenaude4 , J. Vetsch1,2 , R. Cohn1,2
1 University
of NSW, School of Women's and Children's Health, Sydney,
Australia; 2 Kids Cancer Centre, Sydney Children's Hospital, Sydney,
Australia; 3 Prince of Wales Hospital, Hereditary Cancer Clinic, Sydney,
Australia; 4 Dana-Farber Cancer Institute, Department of Psychosocial
Oncology and Palliative Care, Boston, USA
Background/Objectives: Despite increasing recognition of
the potential role of genetics risk assessment in childhood cancer survivorship, the genetics-related needs of survivors and
their families are understudied. This mixed-methods study
assessed survivors’ and parents’ beliefs about what caused the
cancer (causal attributions), their genetics-related service use,
future service needs and their unmet genetics-related information needs.
Design/Methods: 596 participants (384 survivors; 211 parents of survivors) completed questionnaires and optional
interviews. We used multiple logistic regression to determine
clinical/demographic associations with perceived importance
of access to a geneticist and with unmet information needs.
Results: 36/49 survivors offered cancer-related genetic testing chose to undergo testing. Of those not offered genetic
testing (n=547, 92% of total sample), 16% of survivors
and parents endorsed genetics (‘it runs in the family’) as
a cause of the cancer. Most participants (survivors=80%,
parents=82%) indicated it was ‘important’/’very important’
to receive genetics-related information in survivorship care,
and 28% of survivors and 35% of parents indicated that it was
important to have access to a genetics specialist. 47% of survivors and 51% of parents indicated they had an unmet need
for genetic information related to their cancer. In survivors,
SIOP ABSTRACTS
S60 of S518
greater fear of cancer recurrence (p=.03) and longer time
since diagnosis (p=.01) was associated with greater likelihood
of indicating access to a genetic counsellor/geneticist was
important. Participants who believed the cancer was genetic
and those with greater fear of recurrence were more likely to
have unmet genetics-related information needs (p≤.03). Survivors satisfied with their follow-up care were less likely to
indicate they had unmet genetics-related information needs
than those who were unsatisfied (p≤.04).
Conclusions: Our findings suggest that survivors and their
parents have needs for genetics-related services and information, which are largely unmet. Meeting such needs using innovative models of care may improve satisfaction with survivorship care.
O-104 Impact of Chronic Pulmonary Deficits and
Cardiac Abnormalities on Neurocognitive Function
in Long-Term Survivors of Childhood Hodgkin
Lymphoma
Y.T. Cheung1 , N.D. Sabin2 , D.A. Mulrooney3 , K.K. Ness1 , M.J.
Krasin4 , T.M. Brinkman1 , P. Banerjee1 , D. Srivastava5 , L.L.
Robison1 , M.M. Hudson3 , K.R. Krull1
1 St.
Jude Children's Research Hospital, Epidemiology and Cancer Control,
Memphis, USA; 2 St. Jude Children's Research Hospital, Diagnostic
Imaging, Memphis, USA; 3 St. Jude Children's Research Hospital,
Oncology, Memphis, USA; 4 St. Jude Children's Research Hospital,
Radiation Oncology, Memphis, USA; 5 St. Jude Children's Research
Hospital, Biostatistics, Memphis, USA
Background/Objectives: To compare neurocognitive function in long-term survivors of Hodgkin lymphoma (HL)
to community controls and examine associations with pulmonary deficits and cardiac abnormalities.
Design/Methods: 158 HL survivors treated with thoracic
radiation (mean[SD] age 37.7[7.8] years, 23.4[8.1] years
post-diagnosis) and 164 age- and sex-matched controls completed neuropsychological testing. Age-adjusted Z-scores
(�=0, �=1.0) were compared between groups. Systematic
grading of pulmonary deficits (obstructive, restrictive, diffusion deficits) and cardiac abnormalities (structural, functional
defects, arrhythmias) was conducted and analyzed as predictors of neurocognitive function using generalized linear modeling, adjusting for age. Analyses were stratified to examine
the effect of smoking on neurocognitive function in survivors
with/without morbidity.
Results: Survivors performed poorer than controls on short(mean[SD] Z-scores: -0.24[1.0] v 0.13[1.0]; P=0.008) and
long-delay recall (-0.29[1.1] v 0.05[1.1]; P=0.02), sustained
attention (-0.60[3.1] v 0.24[0.8]; P=0.005) and visual-motor
processing speed (0.14[1.0] v 0.39[1.0]; P=0.05). Moderate to disabling pulmonary deficits (32%) and cardiac
abnormalities (22%) were present in survivors. Survivors
with pulmonary deficits performed worse than survivors
without any morbidity, on sustained attention (-1.47[3.5]
v -0.09[2.2]; P=0.009), visual processing speed (-0.28[1.0]
v 0.46[1.0]; P=0.003) and visual-motor processing speed
(-0.23[0.8] v 0.30[1.0]; P=0.005). Cardiac abnormalities
were not associated with neurocognitive function. In survivors without pulmonary deficits, current smokers were more
impaired than non-current smokers (P's<0.05) but in survivors with pulmonary deficits, smoking did not contribute
to worse performance.
Conclusions: Roughly 20 years post-treatment, survivors of
HL have worse neurocognitive outcomes than controls. Pulmonary deficits and smoking were associated with worse
outcomes. Future work should evaluate the impact of pulmonary insufficiency on neurocognitive outcomes. HL survivors should be educated on the neurocognitive effects of
smoking.
O-105 The use of Murine Models of
Chemosensitivity to Anticancer Agents in
Childhood Cancer Clinical Care: Survivor, Parent
and Community Acceptability and
Willingness-to-Pay
C. Wakefield1,2 , V. Quinn1,2 , E. Doolan1,2 , J. Fardell1,2 , K. Tucker3 ,
A. Patenaude4 , K. Marshall1,2 , R. Lock1,5 , C. Signorelli1,2 , G.
Georgiou1,2 , R. Cohn1,2
1 University
of NSW, School of Women's and Children's Health, Sydney,
Australia; 2 Kids Cancer Centre, Sydney Children's Hospital, Sydney,
Australia; 3 Prince of Wales Hospital, Department of Medical Oncology,
Sydney, Australia; 4 Dana-Farber Cancer Institute, Department of
Psychosocial Oncology and Palliative Care, Boston, USA; 5 Children's
Cancer Institute, Lowy Cancer Research Centre, Sydney, Australia
Background/Objectives: Using patient-derived xenografts
(PDXs) to assess chemosensitivity to anti-cancer agents
in real-time may improve child cancer care, potentially
enabling individualized clinical decision-making. However, it
is unknown whether this application of a new methodology
to clinical practice will meet with wider community acceptance. Our two-stage study with 491 participants investigated
the acceptability of PDXs in those affected by childhood cancer and the community.
Design/Methods: Stage 1 identified the most commonly perceived advantages/disadvantages of PDXs in 24 individuals affected by childhood cancer (16 survivors, 8 parents).
In Stage 2, we interviewed 68 individuals (26 survivors,
42 parents of survivors), and surveyed 399 matched community members (213 young adults, 186 parents) on the
issues highlighted in Stage 1. We computed regressions to
identify factors influencing willingness-to-use, willingnessto-pay, acceptable wait-times for results, and acceptable number of mice used.
SIOP ABSTRACTS
Results: PDXs were highly acceptable: 90% of those affected
by cancer leaned toward using PDXs (community participants: 65%). Survivors and survivors’ parents were more willing to use PDXs [t(465)=2.39, p=.02], and were willing to pay
more [t(65.47)=5.49, p<.001], wait longer [t(69.61)=2.94,
p=.004], and sacrifice more mice (t(31.90), p=.003) than
community participants. Willingness-to-use remained high
in survivors/survivors’ parents after considering PDX disadvantages [t(66)=0.15, p=.88]. Community participants had
higher willingness-to-use, would pay more, and use more
mice when considering their child rather than themselves.
Better understanding predicted higher willingness-to-use, and
increased willingness-to-wait. Harm to animals was the least
endorsed disadvantage.
Conclusions: Although clinical efficacy of PDXs is not yet
established, consent rates will likely be high when PDXs
are used in clinical practice, especially when the patient is a
child. Willingness-to-pay and maximum acceptable number
of mice aligned well with planned usage, although maximum
acceptable wait-times were lower than is likely to be clinically
achievable.
O-106 Social Outcomes among Adolescent
Long-Term Survivors of Wilms Tumor: A Report
from the Childhood Cancer Survivor Study
R. Foster1,2 , R. Hayashi2 , M. Wang3 , W. Liu3 , C. Mohrmann2 , R.
Howell4 , S. Smith4 , T. Gibson5 , D.K. Srivastava3 , D. Green5 , K.
Oeffinger6 , W. Leisenring7 , L. Robison5 , G. Armstrong5 , K. Krull5 ,
K. Hardy8,9
1 St.
Louis Children's Hospital, Department of Psychology, St. Louis MO,
USA; 2 Washington University School of Medicine, Department of
Pediatrics, St. Louis MO, USA; 3 St. Jude Children's Research Hospital,
Department of Biostatistics, Memphis TN, USA; 4 University of Texas MD
Anderson Cancer Center, Department of Radiation Physics, Houston TX,
USA; 5 St. Jude Children's Research Hospital, Department of Epidemiology
and Cancer Control, Memphis TN, USA; 6 Memorial Sloan Kettering
Cancer Center, Departments of Pediatrics and Internal Medicine, New York
NY, USA; 7 Fred Hutchinson Cancer Research Center, Clinical Research
Division, Seattle- WA, USA; 8 Children's National Health System,
Neuropsychology Division, Washington DC, USA; 9 George Washington
University School of Medicine, Departments of Psychiatry & Behavioral
Sciences and Pediatrics, Washington DC, USA
Background/Objectives: The study aims were to identify
social problems among adolescent long-term survivors of
Wilms tumor (WT) and determine whether treatment exposures, chronic health conditions, or psychological concerns
relate to peer interaction frequency and quality.
Design/Methods: Parent-reports from the Childhood
Cancer Survivor Study (CCSS) were analyzed for
666 survivors of WT diagnosed between 1970-1999
(Median[range] age at diagnosis=2.59[0.01-11.18] years;
time since diagnosis=12.56[5.62-17.44] years; age at
survey=15.42[12.00-17.97] years) and 698 siblings of
S61 of S518
survivors from the overall CCSS cohort (15.49[12.01-18.00]
years). Survivors were compared to siblings on frequency and
quality of parent-reported peer interactions on the Behavior
Problem Inventory (BPI) adjusting for race and household
income. Survivors’ treatment exposures, chronic medical
conditions (CTCAE v4.03), and psychological outcomes
from the BPI were examined via multinomial logistic regression adjusting for sex, race, household income, and age at
diagnosis to calculate adjusted Relative Risk (aRR) and 95%
confidence intervals (CI).
Results: Compared to siblings, fewer survivors were reported
to have zero or one friend (10.10% vs. 7.21%, p=0.04); however, survivors were rated as having greater difficulties getting along with friends (p<0.0001). Survivors with anxiety/depression (aRR=5.27, 95% CI 2.34-11.90), headstrong
behavior (aRR=3.74, CI 1.80-7.74), attention problems
(aRR=3.28, CI 1.56-6.91), or social withdrawal (aRR=8.35,
CI 3.91-17.85) had fewer friends compared to survivors
without these problems. Survivors with antisocial behavior
(aRR=0.31, CI 0.14-0.67), anxiety/depression (aRR=0.41, CI
0.20-0.83), headstrong behavior (aRR=0.36, CI 0.20-0.67),
attention problems (aRR=0.44, CI 0.25-0.80), or social withdrawal (aRR=0.12, CI 0.05-0.30) were described as having greater difficulty getting along with friends compared
to survivors without problems. Treatment exposures (e.g.,
chemotherapy, radiation) and endocrine and cardiovascular
problems did not impact number of friends, time spent with
friends, or ability to get along with friends.
Conclusions: Despite multiple friendships, relationship quality for adolescent survivors of WT appears worse than for siblings. Adolescent survivors require support to develop socialization skills enhancing relationship quality.
O-107 Sleep Problems After Induction Therapy
in Children with Acute Lymphoblastic Leukemia
and their Association with Quality of Life and
Fatigue
L.M.H. Steur1 , M.A. Grootenhuis2,3 , N.K.A. van Eijkelenburg2 ,
I.M. van der Sluis2,4 , D.W.M.W. te Loo5 , C. van den Bos6 , W.J.E.
Tissing7 , G.J.L. Kaspers1,2,8 , R.R.L. Litsenburg1,2
1 VU
University Medical Center, Department of pediatric
oncology/hematology, Amsterdam, The Netherlands; 2 Princess Máxima
Center for pediatric oncology, Utrecht, The Netherlands; 3 Emma Children's
Hospital Academic Medical Center, Psychosocial department, Amsterdam,
The Netherlands; 4 Sophia Children's Hospital Erasmus Medical Center,
Department of pediatric oncology, Rotterdam, The Netherlands; 5 Amalia
Children's Hospital Radboud University Medical Center, Department of
pediatric oncology, Nijmegen, The Netherlands; 6 Emma Children's Hospital
Academic Medical Center, Department of pediatric oncology, Amsterdam,
The Netherlands; 7 Beatrix Children's Hospital University Medical Center
Groningen, Department of pediatric oncology, Groningen, The Netherlands;
8 Dutch Childhood Oncology Group, The Hague, The Netherlands
SIOP ABSTRACTS
S62 of S518
Background/Objectives: Sleep may be a predictor of quality
of life (QoL) and fatigue in children with acute lymphoblastic
leukemia (ALL). This study aims to investigate the extent of
sleep problems and their relation to QoL and fatigue in children during treatment for ALL.
Design/Methods: Patients aged 2-18 years, treated according
to the Dutch Childhood Oncology Group ALL-11 treatment
protocol, were included (expected final sample size n=105).
Sleep, QoL and fatigue were assessed shortly after end of
induction treatment with parent-proxy questionnaires (Children Sleep Habits Questionnaire and Pediatric Quality of
Life Inventory Generic and Multidimensional Fatigue Scale).
Additionally, sleep was objectively measured using actigraphy. Z-scores were calculated for total sleep questionnaire
scores using healthy norms. Scores exceeding Z-scores of
1 and 2 reflected clinically relevance. Actigraphy outcomes
(sleep duration, sleep efficiency and wake after sleep onset
(WASO)) were compared to norms. Regression models were
constructed for the associations between sleep and QoL and
fatigue.
Results: Ninty-nine children (mean age 6.9±4.5 years, 40.8%
girls) were included (response rate 66%). Questionnaires were
assessed in 98 children and actigraphy data were available in
56 children.
Clinically relevant sleep problems were found in 36.8% (Zscore>1) and 14.9% (Z-score>2) of the patients, compared to
15.9% and 2.3% in healthy norms, respectively.
Patients had a longer sleep duration (508.3 versus 412.1
minutes (p<0.001)), a lower sleep efficiency (76.0% versus
78.2% (p=0.03)) and more WASO (134.4 versus 87.0 minutes
(p<0.001)).
Adjusted for pre-existing sleep problems and gender,
sleep problems were significantly associated with lower
physical- (B:-7.25(95%CI:-11.19;-3.30)) and psychosocial QoL (B:-3.98(95%CI:-7.31;-0.66)) and more general(B:-6.55(95%CI:-10.74;-2.36)), sleep/rest- (B:-8.77(95%CI:12.06;-5.48)) and cognitive fatigue (B:-4.55(95%CI:-7.90;1.20)).
Conclusions: Clinically relevant sleep problems are common
during treatment for ALL and were negatively associated with
QoL and fatigue. Intervention studies aiming to improve sleep
are needed to improve QoL and fatigue in children with ALL.
Acknowledgements: Grant sponsor: Dutch Cancer Society.
FREE PA PER SESSION: PODC
SUPPORT IVE CA R E
O-108 Sofosbuvir-Based Therapy for Chronic
Hepatitis C Infection in Children with Malignancies
S. Jayabose1 , A. Palaniappan1 , N. Iyer1 , K. Viswanathan1 , A.
Annamalai1
1 Meenakshi
Mission Hospital & Research Center, Pediatric
Hematology-Oncology, Madurai, India
Background/Objectives: In adults with chronic hepatitis
C virus (HCV) infection, their outcomes have dramatically
improved with directly acting antiviral agents (DAA) like
sofosbuvir. But there are no data or guidelines on the use of
DAA in children under 12 years of age. The objective of our
study is to analyze the efficacy and safety of sofosbuvir-based
therapy in children with malignancies and genoype-1 HCV
infection, refractory to peg-Interferon alfa 2b (pegIFNa2b)
plus ribavirin.
Design/Methods: Our cohort includes 13 children with cancer and genotype 1 HCV infection who had failed standard
treatment with pegIFNa2b plus ribavirin (twelve of them off
all chemotherapy) treated in 2015. All patients received triple
drug combination: fixed dose sofosbuvir-400 mg P.O. once
daily; weekly pegIFNa2b, 1.5 to 2.0 �g/kg, by s/c inj; and ribavirin P.O.,15 mg/kg/day in 2 doses, for 12 weeks. HCV titers
were followed at 12 and 24 weeks from start of treatment.
Results: Thirteen children with chronic HCV infection, all
with genotype 1, were treated: Male,6; female, 7; median age,
9.5 years (range 7 to 21). Underlying malignancies were B
ALL, 9; T-ALL, 1; Burkitt Lymphoma, 1; AML,1; Hodgkin
Lymphoma, 1.. Viral load at diagnosis ranged from 0.1 to 10
million IU/ml. Sustained virologic response ([SVR] defined
as negative HCV RNA at 12 weeks after completion of treatment) was achieved in 10 of 11 patients evaluable for SVR;
one patient died within 3 months due to progressive malignancy; and one was lost to follow-up after 12 weeks. Median
follow-up: 14 months (range, 3-21). One patient had oral aphthous ulcers, requiring interruption of peg-Interferon alone for
2 weeks. No patient had grade 3 or 4 neutropenia or significant
elevation of AST and ALT on therapy.
Conclusions: Sofosbuvir containing triple drug therapy is an
effective and safe treatment for genotype-1 HCV infection in
children with malignancies.
O-109 Infectious Complications in HIV-Infected
and HIV-Uninfected Children Treated for B-Cell
Non-Hodgkins Lymphomas (NHL)
G. Naidu1 , A. Izu2 , R. Wainwright1 , S. Poyiadjis1 , D. MacKinnon1 ,
B. Rowe1 , S.A. Madhi3
1 University
of the Witwatersrand and Chris Hani Baragwanath Academic
Hospital, Paediatrics, Johannesburg, South Africa; 2 Medical Research
Council-, Meningeal and Respiratory Pathogens Research Unit- University
of the Witwatersrand, Johannesburg, South Africa; 3 Medical Research
Council- Department of Science/ National Research Foundation: Vaccine
Preventable Diseases- Faculty of Health Science- National Institute for
Communicable Diseases- a Division of National Health Laboratory
SIOP ABSTRACTS
Service- Sandringham-, Meningeal and Respiratory Pathogens Research
Unit- University of the Witwatersrand, Johannesburg, South Africa
Background/Objectives: INTRODUCTION: Treatment of
cancer in HIV-infected children is challenging as therapy
compromises an already immune-suppressed state.
AIM OF THE STUDY: To establish the infectious complications in HIV-infected and HIV-uninfected children treated for
NHL with the BFM-NHL protocol.
Design/Methods: METHOD: Hospital records for children
with NHL (2000 to 2009) were reviewed. Age, HIV status
(CD4+ count and HIV viral load if HIV-infected), cancer
stage, sex and anthropometry were recorded. The temperature,
duration of fever, white cell count, neutrophil, lymphocyte and
monocyte counts, blood culture and clinical syndromes were
recorded for each septic episode.
Results: 58 children had NHL (51.7% HIV-infected, 80.7%
males, and median age 89.5 months). The microbiologicallyconfirmed septic episodes (100 child years) among HIVinfected children was 122.5 and for HIV-uninfected children
was 48.2 (p<0.001). The incidence of Gram-positive bacteraemia was (121 vs. 35; p<0.001), Gram-negative bacteraemia (101 vs. 31; p<0.001), pneumonia (75 vs. 12; p<0.001),
tuberculosis (25 vs. 2; p<0.001), and invasive fungal infections (28 vs 7; p=0.001) in the HIV-infected compared with
the HIV-uninfected cohort. The mean maximum temperature was higher in the HIV-infected (p=0.022). HIV-infected
children had a longer duration of neutropenia (p<0.001) and
lymphopenia (p<0.001) than HIV-uninfected children. Ten
(33.3%) of the HIV-infected cohort died because of sepsis
(p=0.0006), 60% had Stage 4 disease, 80% had a CD4+
< 15%, and 70% had a HIV-viral load > 200 000 RNA
copies/ml. Multiple pathogens were isolated from children
who died including multi-drug resistant bacteria, and 90% had
pneumonia.
Conclusions: ARVs have reduced the mortality and morbidity of HIV-infected patients; but lymphomas remain a
major issue. The use of chemotherapy in HIV-infected
patients results in further immune-depletion and an increased
rate of infections. As children with HIV survive longer
due to better antiretroviral and supportive therapies, HIVrelated malignancies may become an increasingly common
problem.
S63 of S518
Background/Objectives: Febrile respiratory illness (FRI) is
common in immunocompromised children receiving treatment for malignancy. Data on viral respiratory pathogens as a
cause of febrile neutropenia is limited. Etiologic significance
of respiratory virus detection, its impact on hospital stay and
antibiotic use was evaluated.
Design/Methods: Immunocompromised children (≤18years
of age) receiving treatment at a pediatric oncology unit,
presenting with FRI, were prospectively analysed from
September2015–February2017. Children were evaluated
clinically and respiratory secretions were obtained for detection of 16 viruses and 6 bacteria by real-time polymerase
chain reaction.
Results: A total of 85 episodes were evaluated from 53 eligible children out of 182 being treated. Male:female ratio
was 2.2:1, median age 3.16 years. Cough (92.9%) was the
most common respiratory symptom associated with tachypnoea in 32.9%. Atleast one respiratory pathogen was identified in 70 (82.3%) samples and 17 (20%) of them tested
positive for dual respiratory pathogens. Rhino-virus(24.4%)
was the most common isolate followed by Parainfluenzavirus (18.7%) and Respiratory-Syncytial-virus (17.4%). Others being Coronavirus (7.3%), Bocavirus (7%), Influenzavirus
(4.7%), respiratory bacteria (4.7%) and Adenovirus (1.2%).
Febrile neutropenia (FN) was present in 61.6% of the total FRI
episodes. Viral respiratory pathogen was the only identifiable
etiology of febrile neutropenic episode in 47.3%. Culture positive sepsis (20.7%) or other underlying cause was detected in
11.3% while cause of FN could not be identified in 20.7%.
Duration of hospitalisation was significantly shorter in those
with solely respiratory pathogen as an etiology for FN compared to those with sepsis (P<0.001). These children could
be managed with lesser number of antibiotics compared to
those where no cause of FN was established (P=0.02) and
had no mortality compared to children with co-existent sepsis
(33.3%) or other underlying cause (13.3%).
Conclusions: Respiratory viruses are common in FRI during
febrile neutropenia. Isolation of respiratory virus can minimize antibiotics use and hospital stay.
O-111 Is it Safe to Administer High-Dose
Methotrexate (HD-MTX) without Monitoring Mtx
Levels? Experience with 100 Cycles
K. Vaishnavi1 , D. Bansal1 , A. Trehan1 , R. Jain1 , S. Attri2
O-110 Clinical Impact of Isolating Respiratory
Viruses in Children with Febrile Neutropenia
P. Jain1 , V. Gunasekaran1 , V. Dinand1 , N. Radhakrishnan1 , A.
Sachdeva1
1 Sir
Ganga Ram Hospital- Delhi, Pediatric Hematology Oncology and BMT
unit, Delhi, India
1 Postgraduate
Institute of Medical Education and Research, Pediatric
Hematology-Oncology unit- Dept. of Pediatrics- Advanced Pediatrics
Centre, Chandigarh, India; 2 Postgraduate Institute of Medical Education
and Research, Biochemistry- Dept. of Pediatrics- Advanced Pediatrics
Centre, Chandigarh, India
Background/Objectives: Access to MTX-levels is often
lacking in developing countries. To evaluate if HD-MTX can
SIOP ABSTRACTS
S64 of S518
be administered safely with extended hydration/leucovorin
rescue, with monitoring of serum-creatinine and urinary-pH.
Design/Methods: In the prospective study, 3 and 5 gm/m2
of MTX (24-hour infusion) was administered to patients with
B and T-cell ALL/NHL, respectively. Six doses of leucovorin (15 mg/m2 /dose), instead of recommended 3 (if the levels
were to be optimally reduced) at the standard timing (42-hours
from start of HD-MTX) were administered. Hydration was
continued for 72-hours, instead of recommended 30-hours. If
serum creatinine exceeded 1.25 times the baseline, the volume of hydration was increased. Urinary-pH was measured
at three time points. The study was approved by institution's
ethics committee (NK/1938/MD/2692-93). Informed consent
was obtained.
Results: Study included 100-cycles of HD-MTX in 53
patients: B-lineage ALL: 51, T-lineage ALL: 28, T-NHL: 18
and relapsed-ALL: 3. The mean age was 6.8±3.2 years (range:
1-13). Patients were underweight in 15 (15%) cycles. Patients
in 23 (23%) cycles had a rise in creatinine to >1.25 times
the baseline. Augmentation of alkalinization was not indicated, as urinary-pH was optimal (≥7) in all. Toxicities (NCICTCAE-v4.0) included, mucositis (32%), diarrhea (10%)
and febrile neutropenia (9%). The mean serum-creatinine at
0/24/48 hours of HD-MTX was 0.324±0.105, 0.330±0.114
and 0.342±0.128, respectively (p=0.537). Grade 1/2/3/4 rise
in creatinine was observed in 26/16/1/0 cycles, respectively.
Toxicities at 12-14 days were neutropenia (64%), thrombocytopenia (37%) and anemia (62%). Mucositis was increased
with co-administration of voriconazole (p=0.005). A single mortality was observed from seasonal, dengue-shocksyndrome.
Conclusions: Administration of HD-MTX without measuring MTX-levels, with extended hydration, additional doses of
leucovorin and monitoring of serum creatinine is feasible with
manageable toxicities. The study could be replicated in additional centers for generating evidence, for suggesting guidelines for administration of HD-MTX in numerous centers in
developing countries that lack access to MTX-levels
regimens, increasing life-threatening complications that may
require Pediatric Intensive Care Units (PICU) admission.
Nearly 40% of pediatric cancer patients may require intensive
care services, accounting for approximately 3% of all PICU
admissions.The aim of the current study was to evaluate predictors of outcome among pediatric cancer patients treated at
the PICU, National Cancer Institute (NCI), Cairo University,
and its co-relation to patient's risk factors.
Design/Methods: A retrospective study including 217
patients, for whom 267 PICU admissions was recorded during the period between July 2013 to June 2014. Data analysis included patients’ demographics. Patients were assessed
according to Pediatric Risk of Mortality III (PRISM), as well
as Pediatric Organ Logistic Dysfunction (PELOD) on their 1st
day of PICU admission. Moreover, survival was correlated to
other risk factors including age, diagnosis, disease status, sepsis, the use of mechanical ventilation, and need for inotropes.
Results: Patients age ranged from 6 months to 18 years
(median 6 years), with evident male predominance. Sixty percent of the patients had hematological malignancies. Average
length of stay was 8 days [SD± 6.6], ranging from 1 to 38
days.
Risk factors associated with worse outcome included high
PRISM and PLEOD score; p-value 0.003, and <0.001 respectively. Survival outcome was worse in patients who were
mechanically ventilated, and/or on inotropic support, with a
p-value of <0.001.
Conclusions: high PRISM III as well as PELOD scoring
-rather than type of malignancy and disease status- is the
main predictor of outcome in PICU among pediatric cancer
patients. Early recognition of signs of organ failure, and referral to PICU may shorten the ICU length of stay with its morbid
complication that can worsen the outcome.
O-113 Early Deaths in Pediatric Acute Leukemia;
A Major Challenge in Developing Countries
H. Hafez1,2 , R. Soliaman1 , D. Bilal3 , L. Shalaby1,2
1 National
O-112 Degree of Organ Dysfunction is the Major
Risk Factor for Mortality in Pediatric Cancer
Patients Admitted to Pediatric Intensive Care Unit
H. Abdel Rahman Sayed1 , S. Abdel Hamid2 , H. El Gebaly3 , S.
Hassan4 , N. Hassan5
1 National
Cancer Institute- Cairo University- Egypt, Pediatric Oncology,
Guizah, Egypt; 2 National Cancer Institute- Cairo University- Egypt,
Pediatric Oncology, Cairo, Egypt; 3 Cairo University, Pediatric, Cairo,
Egypt; 4 Nasser Institute, Pediatric Oncology, Cairo, Egypt; 5 National
Cancer Institute- Cairo UIniversity, Medical biostatisics, Cairo, Egypt
Background/Objectives: Improvement of survival in pediatric cancers has been linked to more aggressive treatment
Cancer Institute - Cairo University, pediatric
hematology/oncology, Cairo, Egypt; 2 Children Cancer Hospital Egypt
CCHE 57357, pediatric hematology/oncology, Cairo, Egypt; 3 National
Cancer Institute - Cairo University, Biostatistics, Cairo, Egypt
Background/Objectives: Despite a steady improvement in
supportive care over the last 30 years, treatment related toxicity remains a major challenge in childhood acute leukemia
therapy, especially in middle income countries. The aim of the
study is to describe the incidence and risk factors associated
with early deaths (first 42 days of treatment) among children
with acute leukemia
Design/Methods: This is a retrospective study included
newly diagnosed patients with acute leukemia who presented
SIOP ABSTRACTS
to the National Cancer Institute, Cairo University between
Jan. 2011 to Dec. 2013. Patients’ data were collected and analyzed for the total and early death rates and proposed causes of
death.
Results: The study included 370 patients, 253 with acute lymphoblastic leukemia (ALL), 100 with acute myeloid leukemia
(AML) and 17 with mixed phenotypic acute leukemia. The
total death rate among the whole group was 40.5% (n=150)
and induction death rate was 19.2% (n=71). Patients with
AML had higher total and induction death rates as they were
58% and 25% respectively, compared to 33.6% and 17.4%
in ALL. Most of the early deaths were attributed to infection 64.7% and cerebrovascular accidents 18.3%. Early deaths
were significantly higher in patients below 2 years old (p.
= 0.008), and in those with poor response to therapy (p. =
0.001). Using enhanced supportive care measures with available intensive care unit during 2013 had significantly reduced
the overall and induction mortality rates (27.8% and 13.8%
respectively in 2013 versus 45% and 20.3% in 2011 and 49%
and 25% in 2012)
Conclusions: Induction deaths in pediatric acute leukemia
remain a major challenge in developing countries and constitute an increasing fraction of all deaths. Accordingly, using
well equipped centers with better supportive care guidelines
is essential to improve the survival in this group of patients
FREE PA PER SESSION:
EPIDEMIOLOGY - II
O-114 Pilot Study Identifies CSF Metabolomic
Biomarkers for Symptoms of Cognitive Impairment
during Treatment for Pediatric Acute
Lymphoblastic Leukemia
A.L. Brown1 , K.P. Raghubar2 , O.A. Taylor1 , I.M. Moore3 , C.C.
Rodgers4 , M.C. Hooke5 , W. Pan4 , M.J. Hockenberry4 , M.E.
Scheurer1 , P.J. Lupo1
1 Baylor
College of Medicine, Department of Pediatrics – Oncology,
Houston- TX, USA; 2 Baylor College of Medicine, Department of Pediatrics
– Psychology, Houston- TX, USA; 3 University of Arizona, College of
Nursing, Tucson- AZ, USA; 4 Duke University, School of Nursing, DurhamNC, USA; 5 University of Minnesota, School of Nursing, Minneapolis- MN,
USA
Background/Objectives: While survival rates for pediatric
acute lymphoblastic leukemia (pALL) exceed 90%, many
patients experience treatment-related cognitive impairment.
Because prognostic markers of cognitive impairment are lacking, the purpose of this pilot study was to identify cerebrospinal fluid (CSF) biomarkers for symptoms of cognitive
impairment during pALL chemotherapy.
S65 of S518
Design/Methods: CSF samples were collected at 5-months
post-induction on 96 patients. Untargeted metabolomics
detected 314 metabolites by gas chromatography (GC)-mass
spectrometry (MS) and liquid chromatography (LC)/MS/MS.
Caregiver-perceived cognitive function was evaluated during
the first month of treatment and 12-months post-induction
using a 13-item scale (pedsFACIT-PCF). Mann-Whitney U
test and logistic regression were used to compare metabolite
values between: 1) cases whose ratings declined from the normal range (T-score≥50) during the first month of treatment
to the mild-moderate difficulty range (T-score<50), and 2)
controls with ratings in the normal range at 12-months postinduction. A false discovery rate (FDR) p-value accounted for
multiple comparisons.
Results: In this cohort diagnosed 2012-2014, 24% of patients
displayed symptoms of mild-moderate cognitive impairment at 12-months post-induction. Significant alterations
(FDR<0.05) were observed in six metabolites, including tyrosine (3-(4-hydroxyphenyl)lactate, Fold Change [FC]=0.69,
p=1.7e-4), glutamate (5-hydroxyindoleacetate, FC=0.67,
p=3.6e-4), and histidine (3-methylhistidine, FC=2.29,
p=3.8e-4) metabolites. These associations remained after
adjusting for age, sex, race, and treatment intensity. Notably,
four of the six metabolites identified by this study are
involved in dopamine neurotransmitter metabolism. Compared to patient and treatment factors alone (area under
curve [AUC]=0.71), CSF biomarkers significantly (p=0.01)
improved the ability to distinguish patients with symptoms
of cognitive impairment from those with normal cognitive function (AUC=0.89 for 5-hydroxyindoleacetate and
tyrosine).
Conclusions: We identified novel CSF biomarkers for
caregiver-perceived symptoms of treatment-related cognitive
impairment among patients treated for pALL. These findings
may translate to clinical improvements in the management of
cognitive outcomes by introducing the opportunity to deliver
targeted interventions to high-risk patients prior to irreversible
cognitive impairment.
O-115 TED: A French National Registry for
Childhood Cancers and Congenital Abnormalities
Associations
C. Fouquet1 , M. Semeraro2 , F. Bourdeaut3 , H. Cave4 , L.
Galmiche-Rolland5 , Y. Perel6 , L. Brugières7 , A. Jeanne8 , S.
Sarnacki1
1 Hôpital
Necker Enfants-Malades, Service de chirurgie viscérale
pédiatrique, Paris, France; 2 Imagine, Centre d'Investigation Clinique,
Paris, France; 3 Institut Curie, Laboratoire de Recherche Translationnelle
en Oncologie Pédiatrique, Paris, France; 4 Hôpital Robert Debré,
Département de Génétique, Paris, France; 5 Hôpital Necker
Enfants-Malades, Service Anatomie Pathologique, Paris, France; 6 Hôpital
Pellegrin, Unité d'onco-hématologie pédiatrique, Bordeaux, France;
7 Institut Gustave Roussy, Département de cancérologie de l'enfant et de
SIOP ABSTRACTS
S66 of S518
l'adolescent, Villejuif, France; 8 Imagine, Embryologie et Génétiques des
malformations congénitales, Paris, France
Background/Objectives: Most of the cancers arising in early
childhood result from the embryonic layers and represent,
unlike the adults tumors, developmental and implementation
accidents of various tissues more than accidents bound to ageing or tissue turnover.
Design/Methods: Launched in June 2013, the TED (Tumeur
Et Developpement) study is a national, prospective and retrospective registration of cases combining a paediatric cancer
and congenital abnormalities. A data extraction has been performed and the clinical characteristics of these patients are
here depicted.
Results: From 2013 to March 2017, 628 patients have been
enrolled in the TED database by 27 French medical centres.
The number of cases was slightly higher for boys (sex ratio
1.12) and the most frequent tumors were leukaemias (17%),
brain tumors (16%) and nephroblastomas (15%), which were
different from that that described by the National Registry
of Childhood Cancers. Data concerning both developmental abnormalities and tumors were available for 532 patients.
Among them, about 177 predisposition syndromes (33%)
have been recorded. Despite the evidence of the already
known associations, (type 1 neurofibromatosis and optic
glioma, Beckwith-Wiedemann syndrome and nephroblastoma, Down syndrome and leukaemia, gonosome abnormalities and malignant germinal tumors), new interesting associations were found highlighting common embryonic origin
(ie neuroblastoma and depigmentation phenotype), somatic
mosaicisms (ie bladder rhabdomyosarcoma and hypospadias)
and early cancer diagnoses compared to median age of paediatric cancer occurrence (4.3 vs 5 years old). Only 44.5 % of
the patients recorded in the database benefited from a genetic
counselling.
Conclusions: TED is one of the most important and exhaustive study reporting associations of birth defects with paediatric cancers. It represents a key collection for describing new
mechanisms and genetic pathways involved in tumorigenesis
and malformations. Further efforts are actually deployed to
better identify the clinical and genetic clusters.
Background/Objectives: Approximately 80% of children
and adolescents diagnosed with cancer live in countries with
limited resources were the chances of cure are much lower
than the 80% reported in developed countries. Data from 2004
São Paulo-Brazil population-based cancer registry revealed a
5-years survival (OS) rate of only 41% for children 0-14 years
of age. Objective: to evaluate the characteristics and 5 years
OS of pediatric patients in a single institution.
Design/Methods: In 2010, we established an institutional
cancer registry that is fully organized and mature enough to
provide reliable data of our patient population. The data for
survival estimates were extracted from patients’ charts and by
active search of public records. We excluded from the survival
analysis patients who received only one treatment modality
and then returned to the service of origin.
Results: Of 6126 patients registered from 1991 to 2015, 56%
were boys. Age distribution at diagnosis was as follows: 0-9
years of age 58%, 10-19 years old 37%, over 19 years 5%. The
most common cancer type was brain tumors (18%), leukemia
(17%) and bone tumors (13%). There was a noticeable shift
in the patients’ profile reflecting institutional growth: in the
first decade, malignancies amenable to outpatient treatment
were more common, whereas in the second decade we registered a marked increase of high complexity cases such as brain
tumors. The 5-years OS for patients < 19yrs was 71%. Survival has reached international standards for Hodgkin's lymphoma (95%), Wilms tumor (87%) and B-lineage ALL (80%).
Conclusions: The organization of a registry allowed us to
study the epidemiological profile of our patients and document that our institutional OS is superior to the state of
Sao Paulo. This led us to conclude that an organized, dedicated oncology center is able to narrow the survival gap
between Brazilian patients and their counterpart in the developed world.
O-117 Incidence and Determinants of Lost
Diagnostic Opportunities for Children with Cancer
in Argentina
E. Grynszpancholc1 , V. Pinto1 , A. Ayoroa1 , L. García1 , G. Dran2
1 Fundación
O-116 Narrowing Childhood Cancer Survival
GAP in Brazil: Analisys of 6126 Patients by A
Hospital Based Cancer Registry in 25 Years’
History of a Single Institution
M. Cypriano1 , A. Pires1 , M. Silva1 , E. Caran1 , M.L. Lee1 , A.V.
Sousa1 , N. Silva1 , A. Cappellano1 , F. Luisi1 , C. Macedo1 , C.
Bassioli1 , S. Petrilli1
1 Pediatric
Oncology Institute/GRAACC/Unifesp, Pediatric Oncology, Sao
Paulo, Brazil
Natalie Dafne Flexer- Argentina, Fundación Natalie Dafne
Flexer- Argentina, Buenos Aires, Argentina; 2 National Counsil For
Scientific And Technologic Investigation CONICET, Facultad
Latinoamericana de Ciencias Sociales FLACSO, Buenos Aires, Argentina
Background/Objectives: Disparities in accessing to accurate
and timely childhood cancer diagnosis are usual in developing countries. Failed or delayed diagnoses are major causes
of poor survival and quality of life. The Natali Dafne Flexer
Foundation (FNDF) provides integral assistance to families
facing pediatric cancer in Argentina. This study contains preliminary data from an ongoing study aimed to analyze the
SIOP ABSTRACTS
incidence and modulators of lost diagnostic opportunities
(LDO) in those families assisted by the FNDF along a fiveyear period.
Design/Methods: Retrospective quali-quantitative analysis.
Families with 0-20 y/o children who got cancer diagnoses
between 2011 and 2015 were included. Demographic, disease
and health insurance data, and medical institutions involved in
the diagnoses process, were compared between groups with or
without LDO. Additional data were extracted from parent‘s
narration.
Results: A total of 572 families whose diagnostic trajectory was exhaustively registered were included. 56% of them
reported to have one (36%), two (14%), three (3%) or more
than three (3%) LDO. 91.5% were Argentinian, being the
sample fairly representative of the distribution of childhood
cancer in the Country regarding age, province of residence,
sex and type of cancer. 30% had social/private health insurance and 69%, Public Health coverage. Retinoblastoma and
low age positively correlated with absence of LDO (p<0.01).
The Southern and Northern Regions, with vast provinces of
low socioeconomic index and low population density, exhibited higher proportion of LDO than the mean for the Country. The type of institution (public/private) was independent
of the presence of LDO, while consultations to private centers became more frequent as the number of LDO increased
(p<0.05).
Conclusions: A substantial number of families experience problems for obtaining childhood cancer diagnosis in
Argentina. Disease and demographic determinants may influence the possibility of having LDO. Addressing such problems will help developing evidence-driven, specific and local
interventions to improve diagnoses process.
O-118 Improving Early Referral and Diagnosis of
Brain Tumours in Children- Impact of National
“lHeadSmart” Campaign in west of Scotland
J. Sastry1 , A. Hafez1
1 Royal
Hospital for Children, Haematology and Oncology, Glasgow,
United Kingdom
Background/Objectives: A nation-wide campaign, “HeadSmart: Be Brain Tumour Aware”, was launched in 2011 in
response to a national survey carried out in 2006 which indicated that referral practice in the UK for paediatric brain
tumours ranked poorly in international comparisons. The aim
of the campaign was to raise public and professional awareness in order to reduce the total diagnostic interval (TDI) from
a pre-campaign median of 14 (mean 35.4) weeks to less than
5 weeks so as to match the shortest published TDI. The audit
was carried to evaluate the effectiveness of the campaign 5
S67 of S518
years later and, in addition, to compare how local (Glasgow)
referral practice aligns with national data.
Design/Methods: Data was gathered from 19 patients under
the age of 16 diagnosed with CNS tumours in Glasgow
between May 2014 and March 2015. Data collection was performed by analysis of online patient records accessed through
the NHSGGC clinical portal. TDI was calculated using various patient notes including GP letters and in-patient hospital
records.
Results: Since the initial survey in 2006, there has been a considerable reduction in TDI to a median of 9 (mean 16.3) weeks
in the patients in Glasgow investigated in this study. However,
this is still higher than the national median of 6.7 (mean 21.3)
weeks in 2013. The greatest observed improvement was in the
time taken to diagnose patients after their first presentation
to healthcare, for which the median reduced from 3.3 to 0.5
weeks between 2011 and Glasgow patients in 2014/2015.
Conclusions: The increased public and professional awareness of brain tumours has led to a clear improvement in TDI
nationwide since 2006. However, the data analysed in this
study suggests that continued work and data collection is
required in Glasgow to ensure that TDIs more closely resemble nationwide results.
Acknowledgement: J Ferguson, Data manger
O-119 Factors Influencing Diagnostic Delays of
Pediatric Cancers in Botswana
K. Carpenter1 , A.K. Slone2,3 , P.S. Mehta2,3 , M.E. Scheurer4 , J.S.
Slone2,3
1 Botswana-Baylor
Children's Clinical Centre of Excellence, Adolescent
Services, Gaborone, Botswana; 2 Texas Children's Cancer and Hematology
Centers, Pediatrics, Houstan, USA; 3 Baylor College of Medicine,
Pediatrics, Houston, USA; 4 Texas Children's Cancer and Hematology
Centers, Childhood Cancer Epidemiology and Prevention Program,
Houstan, USA
Background/Objectives: In low-to-middle income countries
(LMICs), timely access to care is a major barrier in treatment
of childhood cancer and may lead to patients presenting with
more extensive disease. This study aims to elucidate factors
influencing diagnostic and treatment delays within Botswana.
Design/Methods: Utilizing the Botswana Pediatric Oncology
Database (BPOD), this study retrospectively analyzed demographic and timeline data from pediatric oncology patients
(ages 0-18) presenting to Princess Marina Hospital (PMH)
between January 2008-December 2015.
Results: Median total diagnostic delay, defined as date
of symptom onset to date of diagnosis, was 10.7 weeks
(IQR=5.1-20.7) (N=69). Of these ten weeks, the time that
it took patients to reach PMH following onset of symptoms
accounted for the majority of the delay (med=9.6 weeks,
IQR=4.1-19.7) (N=66). Once patients presented to the ter-
SIOP ABSTRACTS
S68 of S518
tiary care facility, the median time from biopsy to pathology
result was 3 weeks (IQR=1.1-4.3) (N=89). Presence of metastasis upon diagnosis was significantly correlated with longer
total diagnostic delay (p=0.001). Age, sex, distance to a cancer center, HIV status, medical aid status, and cancer diagnosis did not have a significant effect on diagnostic delays.
Conclusions: Pediatric cancer patients in Botswana experienced significant delays in presenting to PMH for treatment.
The overall diagnostic delay was comparable to that found
in reports from other LMICs. However, diagnostic delay was
correlated with risk for having metastatic disease, a unique
finding compared to existing literature. Further prospective
research is necessary to fully understand factors influencing
diagnostic and treatment delays and to develop strategies to
address these factors.
FREE PA PER SE SSI O N : L E U K E M IA
A ND LYMPHO MA
O-120 Safety and Feasibility of Administration of
OEPA/COPDAC Chemotherapy and PET-CT
Based Strategy for Treating Hodgkin Lymphoma in
a Developing Country
D. Bansal1 , J. Ramamoorthy1 , S. Mohapatra1 , A. Trehan1 , R. Jain1 ,
B. Mittal2 , A. Bhattacharya2 , R. Kapoor3 , R. Srinivasan4 , A.
Rajwanshi4 , N. Kakkar5 , A. Das5
2-13); 39% were underweight. The median observation time
was 39 months (17, 61.5). An inadequate PET-response
was observed in 30/97 (31%) patients. Radiotherapy was
administered to 15/30 patients. There were 36 episodes of
febrile-neutropenia in 22 patients, resulting in 4 deaths. All
4 treatment-related-mortalities and 33/36 (92%) episodes of
febrile-neutropenia were observed following the first-course
of OEPA. Other events included 9 relapses and 1 therapyrelated AML.
The 5-year-OS in TG 1, 2 and 3 was 96.8%, 100% and 91.1%,
respectively. The 5-year-EFS and OS were 86.1% and 96%,
respectively. The outcome compared favorably to the 5-yearEFS (77.7%) and OS (92.7%) of the centers earlier experience
with ABVD/COPP in 206 patients. Relapse was associated
with bulky disease (P=0.001) and ΔSUVmax <7 (P=0.01).
Episodes of febrile-neutropenia had a trend of association
with anemia (P=0.074) and involvement of ≥4 nodal regions
(P=0.095).
Conclusions: Chemotherapy with OEPA/COPDAC and
PET-CT based response permitted reduction of therapy with
a 5-year-EFS (86.1%) that compared favourably with the 5year-EFS (77.7%) of patients who received ABVD/COPP in
the center in the past. Febrile neutropenia and resultant mortality (4%) was concerning, and occurred commonly following the first-course of OEPA. Supportive-care systems should
be well-placed for administration of OEPA in developing
countries.
1 Postgraduate
Institute of Medical Education and Research, Pediatric
Hematology-Oncology unit- Dept. of Pediatrics- Advanced Pediatrics
Centre, Chandigarh, India; 2 Postgraduate Institute of Medical Education
and Research, Nuclear Medicine, Chandigarh, India; 3 Postgraduate
Institute of Medical Education and Research, Radiotherapy, Chandigarh,
India; 4 Postgraduate Institute of Medical Education and Research,
Cytology, Chandigarh, India; 5 Postgraduate Institute of Medical Education
and Research, Histopathology, Chandigarh, India
Background/Objectives:
Protocols
with
reduced
anthracycline/alkylating-agent/bleomycin are currently
favoured for Hodgkin lymphoma (HL). ABVD is popular
in developing countries for ease/convention. There is lack
of data on administration of ‘non-ABVD’ protocols from
developing countries.
Design/Methods: The study was retrospective. Euronet-PHLC1 based protocol was administered in a center in India
from January-2010 to March-2016. A PET-CT was performed at diagnosis and following OEPA-2. Two/four courses
of COPDAC were administered in Treatment Groups (TG)
2/3, respectively. Radiotherapy was indicated for inadequate
(Deauville-score ≥4) PET-response.
Results: One-hundred-and-thirty-five patients with HL were
treated in the 6-year-period; 101 fulfilled the study criteria. The mean-age of 101 patients was 7.6±2.4 years (range:
O-121 Overview and Survival of Pediatric
Advanced Stage Hodgkin Lymphoma Treated in
Developing Countries; Children Cancer Hospital
Egypt Experience
R. Khedr1 , A. Hamouda1 , S. Naguib2 , M. khalaf3 , S. fikry4 , A.
Elsayed5 , H. taha6 , M. zaghloul7 , I. Attia1
1 National
cancer institute - Cairo university / Children's Cancer Hospital
57357, Pediatrics oncology, Cairo, Egypt; 2 Children's Cancer Hospital
57357, Clinical research Department, Cairo, Egypt; 3 National cancer
institute - Cairo university / Children's Cancer Hospital 57357,
Radiodiagnosis Department, Cairo, Egypt; 4 Children's Cancer Hospital
57357, Clinical pharmacy Department, Cairo, Egypt; 5 National cancer
institute - Cairo university / Children's Cancer Hospital 57357, Nuclear
Medicine, Cairo, Egypt; 6 National cancer institute - Cairo university /
Children's Cancer Hospital 57357, Surgical Pathology, Cairo, Egypt;
7 National cancer institute - Cairo university / Children's Cancer Hospital
57357, Radiothaerapy Department, Cairo, Egypt
Background/Objectives: The major challenge in advanced
stage Hodgkin Lymphoma is to optimize the balance between
overall survival and treatment related toxicity. The aim of the
study was to describe the pediatric population with advanced
Hodgkin lymphoma (HL) in our country and their treatment
outcome.
SIOP ABSTRACTS
S69 of S518
Design/Methods: This is a retrospective single center study.
Data analysis for children with advanced stage HL (IIB or IIIB
with bulk disease, or stage IV) as done. Demographic data,
staging, number of cycles (doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)) received and whether or not
consolidation radiotherapy (RTH) was administered. Positron
emission tomography (PET) was performed baseline and after
the second cycle to detect early response without any change
to treatment plan.
Results: Three hundred and eighty-one patients with newly
diagnosed Hodgkin lymphoma were enrolled in the data analysis. Male (283) to female (98) ratio 3:1. B-symptoms was
present in 60% of patients. Ann Arbor staging distribution
was as follows; 68 (17.8%) IIB, 97 (25.5%) IIIA, 96 (25.2%)
IIIB, 55 (14.4%) IVA, 65 (17.1%) IVB. One hundred sixtyfive patients with early unfavorable and 216 with advancedstage disease were treated with ABVD ± RTH. One hundred
twenty- nine (34%) patient did not receive RTH. The Fiveyears Overall survival (OS) and the Event free survival (EFS)
in these patients was 90.7 (95% CI: 85.4-95.9 and 71.9% (95%
CI: 63.6-76.1) (p value 0.006) respectively. The OS and EFS
of patient with advanced stage HL in the whole study population was 94.1 (95% CI: 91.5-96.6) and 79.4 (95% CI 74.384.4) respectively.
Conclusions: More than 90% of patients are cured with riskbased combined-modality therapy, yet these therapies are frequently associated with risks for significant long term toxicities; innovative approaches are needed for those patients who
have a high risk of failure with current therapies.
9 (11%) Stage II, 64 (80 %) Stage III, and 5 (6%) Stage IV.The
median time of follow-up was 25.2 months (range, 7.1 - 74.8
months), 55 patients survived without disease at the last of
follow-up, the 3-year EFS was 65%±6%. Sixty-five patients
(81%) were treated with theCCCG-BNHL-2010regimen and
15cases (19%) treated with other regimens. The 3-year EFS
were 68%±5% vs.65%±20%( P=0.21).(,. The 3-year EFS was
57%±7% and 78%±11% for patients with or without B symptoms (P=0.01). Twenty-four patients experienced disease progression or relapse. The median time from initial diagnosis
to tumor failure was7.0 months (ranged, 1.5 -42.6 months)
(median,). At the last evaluation, there were 5 patients still
aliveafter disease progression and relapse. By univariate analysis, sex (P=0.04) and B symptoms (P=0.00) were identified
as risk factors of disease progression or relapse. Nevertheless, only B symptoms (HR 5.60 95% CI 1.47∼21.27, P≤0.05)
wererisk factors in multivariate analysis.
Conclusions: The presenting features of children and adolescents with ALCL and EFS rates in this study were similar
to those reported by western countries. Refinement of therapeutic strategies to improve survival for patients with disease
progression or relapse should be the priority in future clinical
study.
O-123 Preclinical Efficacy of Daratumumab in
T-Cell Acute Lymphoblastic Leukemia
K.L. Bride1 , T. Vincent1 , L. Im1 , T. Ryan1 , T. Fuller1 , D.M.
Barrett1 , S.L. Maude1 , M.L. Hermiston2 , S.A. Grupp1 , B.L. Wood3 ,
D.T. Teachey1
1 The
O-122 Diagnosis and Treatment of Anaplastic
Large-Cell Lymphoma in Children and Adolescents
in China: A Retrospective Multicenter Survey Study
1
1
1
Q. Mi , G. Yijin , T. Jingyan
1 Shanghai
Children's Medical Center, Hemotology amd Oncology,
Shanghai, China
Background/Objectives: This study was to provide a
description review and improve our understanding of the
treatment outcome of pediatric anaplastic large cell lymphoma (ALCL) in China.
Design/Methods: The clinical data and outcomes of patients
under16 years with newly histopathologically-confirmed
ALCL treated in 10 large single institutions in China between
January 2009 and June 2013, were retrospectively analyzed.
The event-free survival (EFS) was analyzed using the KaplanMeier method. The risk of disease progression or relapse was
evaluated using logistic regression analysis. Significance was
defined as P < 0.05.
Results: Of the 80 eligible patients, the median age was 8.4
years (range, 1.3 - 15.7 years). Two patients (3%) were Stage I,
Children's Hospital of Philadelphia, Pediatrics, Philadelphia, USA;
Medical Center-Mission Bay, Pediatrics, San Francisco, USA;
3 Seattle Children's Hospital, Pathology, Seattle, USA
2 UCSF
Background/Objectives: Targeted immunotherapy has
become critical for the successful treatment of many cancers,
particularly therapeutic antibodies with cytotoxic abilities.
No effective immunotherapies have been developed for T-cell
acute lymphoblastic leukemia (T-ALL). CD38 is found on
the cell surface of activated T cells, terminally differentiated
B cells, but relatively low levels on normal lymphoid and
myeloid cells. Daratumumab (dara) is a human monoclonal
antibody that binds to CD38 and is successfully used in
patients with refractory multiple myeloma.
Design/Methods: To ensure CD38 is a relevant target, we
measured CD38 expression by flow cytometry from 21
patients with T-ALL (10 early T-cell precursor (ETP) and
11 non-ETP) at diagnosis and after induction chemotherapy.
We also xenografted primary ALL blasts from 15 different
patients, 7 with ETP-ALL and 8 with non-ETP T-ALL. Mice
were randomized to dara (200 �g /mouse intraperitoneally
weekly) vs isotype (200 �g/mouse; 5 mice per arm for each
sample) after they developed >1% peripheral blood (pb) blasts
SIOP ABSTRACTS
S70 of S518
by FACS. Disease burden was assessed by FACS enumeration
of pb blasts weekly and splenic blasts at sacrifice.
Results: CD38 was expressed in all 21 patient samples and
surface expression remained unchanged after induction (mean
CD38 MFI at diagnosis vs end-induction: 3.27 vs 3.19 log (p
= 0.25).
All 7 ETP T-ALL samples responded with marked improvement in disease burden. For 5 of 8 of the non-ETP T-ALL
samples, mice with advanced disease died immediately after
exposure to dara, presumably from tumor lysis. We repeated
experiments treating after injection but prior to development
of peripheral blasts with 7 of 8 non-ETP ALL samples demonstrating efficacy to daratumumab (2 responded at high disease
burden, 5 responded at low disease burden but had toxicity
with high disease, and 1 did not respond).
Conclusions: In summary, dara is a highly effective novel
monotherapy for T-ALL in preclinical models.
Results: In TP53mut leukemias, we observed a poor response
to doxorubicin but sensitivity in TP53wt ALL. In contrast,
TP53mut ALL were highly sensitive to APR-246 while
TP53wt leukemias showed insensitivity. APR-246 induced
structural restoration of mutant p53 and functional p53 activation as indicated by p53 wild-type conformation, p53 phosphorylation and increased expression of p53 target molecules
NOXA and PUMA, finally leading to leukemia cell apoptosis. Knockdown of p53 in TP53mut ALL led to abrogation of
cell death, indicating that APR-246 targets mutant p53. Moreover, a strong synergism and re-sensitization to DNA-damage
induced cell death was observed upon combined APR-246
and doxorubicin exposure. Importantly, in a preclinical setting we treated TP53mut ALL bearing recipient mice with
APR-246 and observed a significant reduction in leukemia
load demonstrating clear in vivo activity of APR-246.
Conclusions: In BCP-ALL, APR-246 restores mutant p53 to
wild type conformation and reactivates its tumor suppressor
function leading to apoptosis induction. Targeting mutated
p53 might provide an effective novel strategy for therapeutic
intervention in this high-risk subtype of ALL.
O-124 Therapeutic Targeting of Mutant P53 in
Pediatric Acute Lymphobastic Leukemia
S. Demir1 , Q. Sun1 , E. Tausch2 , S. Stilgenbauer2 , G. te Kronnie3 , C.
Eckert4 , L. Wiesmüller5 , G. Selivanova6 , K.M. Debatin1 , L. Meyer1
1 Ulm
University Medical Center, Department of Pediatrics and Adolescent
Medicine, Ulm, Germany; 2 Ulm University Medical Center, Internal
Medicine III, Ulm, Germany; 3 University of Padova, Department of
Women's and Children's Health, Padova, Italy; 4 Charité University
Medicine, Department of Pediatric Oncology and Hematology, Berlin,
Germany; 5 Ulm University Medical Center, Department of Obstetrics and
Gynecology, Ulm, Germany; 6 Karolinska Institute, Department of
Microbiology- Tumor and Cell Biology, Stockholm, Sweden
Background/Objectives: Mutations in the tumor suppressor
gene TP53 (TP53mut) are infrequent at initial diagnosis of
pediatric acute lymphoblastic leukemia (ALL) but enriched at
relapse and associated with inferior outcome. Here, we evaluate mutated p53 as target for directed therapy and investigate
the effects of the p53-targeting small molecule APR-246.
Design/Methods: Patient, patient-derived xenograft
(NOD/SCID/huALL) and cell line B-cell precursor (BCP)ALL samples were analyzed for TP53mut (high-performance
liquid chromatography, Sanger sequencing). Sensitivities for
the DNA damaging agent doxorubicin and the p53-targeting
small molecule APR-246 (kindly provided by Aprea, Stockholm, Sweden) were investigated. Apoptosis (caspase-3
activation, Annexin-V/propidium iodide positivity), p53
restoration (immunoprecipitation with conformation-specific
antibodies) and activation (p53pSer15, expression of p53
downstream molecules) were analyzed. p53 deficient cells
were generated by lentiviral shRNA mediated knock-down.
Xenograft ALL bearing NOD/SCID mice were treated with
APR-246 or vehicle.
O-125 Treatment-Related Veno-Occlusive
Disease in Children with De Novo Acute
Lymphoblastic Leukemia During Intensification
C. McAtee1 , N. Schneller1 , J. Brackett1 , M.B. Bernhardt2 , S. Eric1
1 Baylor
College of Medicine, Pediatric Hematology-Oncology, Houston,
USA; 2 Texas Children's Hospital, Pharmacology, Houston, USA
Background/Objectives: Veno-occlusive disease (VOD) has
been described following treatment of acute lymphoblastic
leukemia (ALL) with 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy
demonstrated a high incidence of VOD, typically presenting
after prolonged exposures to 6-TG. 6-TG continues to be used
as a single, 14-day burst during intensification, however, VOD
associated with brief courses of 6-TG is poorly described. We
describe our single-institution experience with VOD in this
setting.
Design/Methods: Subjects were identified from de novo
patients with ALL at Texas Children's Cancer Center between
1/1/08 and 10/28/16 through medical record searches for those
diagnosed with VOD within 60 days of receiving 14 days of
6-TG. Subject demographic and clinical data were collected.
Medians and ranges were calculated.
Results: Of 680 new patients with ALL, 10 (1.5%) were identified with VOD. No predominant sex, ethnicity or race was
noted. VOD was diagnosed 16.5 (6-42) days from starting
6-TG. Isolated thrombocytopenia was noted in 9/10 patients
and presented 5 (0-34) days prior to VOD, with 8/10 of these
patients being clinically stable outpatients and 7/10 patients
SIOP ABSTRACTS
S71 of S518
still taking 6-TG. Refractoriness to platelet transfusions was
noted in 8/10 patients, presenting 2 days prior to VOD with
7/8 of these being stable outpatients and 3/8 still taking 6-TG.
Fever was noted in 7/10 patients within 24 hours and 6/10
had documented or suspected infection in the 14 days prior
to VOD. Intermediate thiopurine methyltransferase genotype
was noted in 5/8 patients with data available.
mediate and high risk HB was 59/74% and 38/46%, respectively. Except for 40 cases who underwent primary resection,
complete resection of primary after CITA was performed 98%
of standard risk, 76% of intermediate risk and 86% of high
risk patients. And the late phase complications were 51 cases
with maldevelopment, 20 with cardiac complications, 65 with
ototoxicity and 8 with second malignancies.
Conclusions: VOD generally presents early following initiation of 6-TG in intensification phases of ALL treatment.
Disproportionally severe thrombocytopenia and transfusion
refractoriness typically preceded VOD diagnosis by several
days, occurring in clinically stable outpatients. Identifying
risk factors and early signs and symptoms of VOD in this
population can hasten appropriate diagnosis/treatment, and in
some cases, may allow for discontinuation of the offending
6-TG.
Conclusions: As compared with other multicenter cooperative protocols, CITA regimens achieved similar rates of survival and resectability in standard risk patients. More promising strategies including adequate liver transplantation and
new targeting drugs should be developed for intermediate and
high risk HBs.
FR EE PA PER SE SSI O N : L I V E R
TUMOURS AND RARE TUMOURS
A. O'Neill1 , M. Malogolowkin2 , M.D. Krailo3 , C. Xia4 , M. Qayed5 ,
M.R. Langham Jr6 , R.L. Meyers7 , H.M. Katzenstein8
O-127 AFP as a Biologic Marker and Prognostic
Factor in Newly-Diagnosed Completely Resected
Hepatoblastoma
1 Dana
Farber Cancer Institute, Pediatric Oncology, Boston, USA;
of California Davis Comprehensive Cancer Center, Pediatric
Oncology, Sacramento, USA; 3 University of Southern California Keck
School of Medicine, Research Preventive Medicine, Los Angeles, USA;
4 Statistics and Data Center- Children's Oncology Group, Statistics,
Monrovia, USA; 5 Emory Winship Cancer Institute, Pediatric Oncology,
Atlanta, USA; 6 Le Bonheur Children's Hospital and University of
Tennessee, Department of Surgery, Memphis, USA; 7 Primary Children's
Hospital and University of Utah, Department of Surgery, Salt Lake City,
USA; 8 Vanderbilt University School of Medicine- Monroe Carell Jr.
Children's Hospital, Pediatric Oncology, Nashville, USA
2 University
O-126 Survival and Lates Effects of JPLT
(Japanese Study Group for Rediatric Liver
Tumor)-2 Risk-Stratified Study for Hepatoblastoma
E. Hiyama1 , T. Hishiki2 , K. Ida2 , K. Watanabe2 , Y. Tanaka2 , Y.
Aoki2 , T. iehara2 , T. Kazama2 , K. Kihira2 , T. Taguchi2 , J.
Fujimura2 , K. Hoshino2 , S. Honda2 , K. Matsumoto2 , M. Mori2 , M.
Yano2
1 Hiroshima
2 Japanese
University Hospital, Peditric Surgery, Hiroshima, Japan;
children cancer group, Liver tumor committee, Tokyo, Japan
Background/Objectives: The Japanese Study Group for
Pediatric Liver Tumor (JPLT)-2 study for hepatoblastoma
(HBL) launched in 1999 and closed in 2012. The main
aim of this study launched to evaluate the efficacy of cisplatin/pirarubicin in risk-stratified HB: standard risk HB (a
tumor involving three or fewer sectors of the liver), intermediate risk HB (a tumor involving all sectors of the liver or
invasion into portal or hepatic vein) and high risk HB (a tumor
involving all sectors of the liver or with metastasis).
Design/Methods: Until 2012, 360 HB children who were
younger than 15 years of age were eligible for inclusion in
the JPLT2 study in which the cisplatin/pirarubicin regimen
(CITA) is kept as the first line. In this study, we examined
the outcome and late effects of the HB patients by the riskstratified three groups (standard, intermediate and high risk
groups).
Results: Among 360 cases, PRETEXT I was 25, II was 117,
III was 134, and IV was 84 including 61 cases (17%) with
metastatic tumors. The 5-year EFS/OS of the cases with standard risk HB were 77/92%, while those of the cases with Inter-
Background/Objectives: Hepatoblastoma (HB) is the most
common pediatric liver neoplasm. Greater than 90% of newly
diagnosed patients present with an elevated serum alpha fetoprotein (AFP) level. The decline of AFP levels throughout
therapy is routinely utilized as a marker of response however
the exact relationship between AFP decline and outcome is
not well established.
Design/Methods: Children's Oncology Group (COG) protocol AHEP0731 was designed for patients with newly diagnosed HB and included a stratum for low-risk patients with
disease that was resected at diagnosis and followed by two
adjuvant cycles of cisplain, 5-fluorouracil, and vincristine
(C5V). AFP levels were obtained per protocol at diagnosis, during therapy, and at routine off-therapy followup visits every 6 months. We analyzed AFP levels at diagnosis, and
decline in response to therapy until normal, per institutional
standards indicating “complete remission.“
Results: Fifty-one subjects were enrolled on the low-risk stratum, 49 of whom were eligible for this analysis. Mean AFP
at diagnosis was 70,582 ng/mL, excluding two patients that
lacked baseline values (median: 15,881, range: 104-391,410
ng/mL). AFP values normalized in subjects as follows: 6
SIOP ABSTRACTS
S72 of S518
patients during therapy, 26 patients at the end-of-therapy, and
14 and 1 patient(s) at 6 and 12 months off-therapy, respectively. Two subjects failed to normalize AFP. There was no
difference in outcome based on the timing of normalization
of AFP levels. All patients who recurred had progressive reelevation of successive AFP levels. Minor transient increases
(levels < 100 ng/ml) in AFP were observed and did not necessarily indicate relapse.
Conclusions: In patients with upfront, resected disease, timeto-normalization of AFP levels was not predictive of overall
outcome. AFP as an indicator of relapse is highly sensitive.
O-128 PARP1-Dependent Chromosomal
Domains Determine the Development of Aggressive
Hepatoblastoma by Activating Multiple Pathways of
Cancer
L. Valanejad Kiefer1 , A. Cast1 , M. Wright1 , M. Weirauch2 , N.
Timchenko1
1 Cincinnati
Children's Hospital Medical Center, Division of Pediatric
General and Thoracic Surgery, Cincinnati, USA; 2 Cincinnati Children's
Hospital Medical Center, Center for Autoimmune Genomics and Etiology,
Cincinnati, USA
Background/Objectives: Hepatoblastoma (HBL) is a pediatric liver cancer that affects children under the age of three.
Reduction of tumor suppressor proteins (TSPs) is seen in
many types of liver cancer. Surprisingly, we found that aggressive, chemo-resistant HBLs are characterized by an elevation
of TSPs. Our goals were to determine mechanisms by which
aggressive HBL neutralizes activities of elevated TSPs; elucidate mechanisms that elevate TSPs in aggressive cancer; and
examine if the inhibition of these mechanisms inhibit HBL.
Design/Methods: Using RNA-Seq and biochemical
approaches, we analyzed a large cohort of HBL samples.
Post-translational modifications of 5 TSPs (Rb, p53, C/EBP�,
HNF4� and CUGBP1) and protein-protein complexes of
these TSPs were examined using HPLC-based size exclusion
chromatography, Co-IP, and 2D gel electrophoresis. Changes
in chromatin structure were examined using ChIP assays.
Results: While HBL samples with a mild phenotype have
reduced levels of TSPs, aggressive HBL is characterized by
an elevation of TSPs that underwent post-translational modifications eliminating their tumor suppression activities. We
found that genes of each TSP contain a unique 250 base
pair chromosomal domain (Aggressive Liver Cancer Domains
(ALCDs)). The human genome contains 30 ALCDs located
in chromosomal regions of 5 TSPs and certain cancer related
genes, but ALCDs are not observed in the mouse genome.
ALCDs and corresponding genes are activated by an elevation of PARP1/Ku80/Ku70 complexes, which bind directly
to ALCDs. Inhibition of PARP1 in cultured hepatoblastoma
cells eliminates PARP1/Ku80/Ku70 complexes and inhibits
or normalizes expression of corresponding genes resulting in
an inhibition of proliferation.
Conclusions: Activation of ALCDs by PARP1 is a key
event in the development of aggressive HBL. This phenotype
also involves post-translational modifications that block their
tumor suppression activities. Activation of PARP1 is a mechanism for development of aggressive HBL suggesting that
FDA-approved PARP1 inhibitors might be used for treatment
of chemo-resistant HBL.
O-129 Genetic and Epigenetic Analyses of
Hepatoblastoma Identify Subgroups with Different
Clinical and Biological Features
M. Sekiguchi1 , M. Seki1 , T. Kawai2 , T. Isobe1 , K. Yoshida3 , M.
Yoshida1 , N. Hoshino4 , Y. Shiraishi5 , R. Souzaki6 , K. Watanabe7 ,
Y. Arakawa7 , K. Koh7 , Y. Hayashi8 , T. Taguchi6 , M. Sanada9 , Y.
Tanaka10 , S. Miyano5 , K. Hata2 , S. Ogawa3 , J. Takita1
1 The
University of Tokyo, Department of Pediatrics, Bunkyo-ku, Japan;
Research Institute for Child Health and Development,
Department of Maternal-Fetal Biology, Setagaya-ku, Japan; 3 Kyoto
University, Department of Pathology and Tumor Biology, Kyoto, Japan;
4 The University of Tokyo Hospital, Department of Pediatric Surgery,
Bunkyo-ku, Japan; 5 The Institute of Medical Science- The University of
Tokyo, Human Genome Center, Minato-ku, Japan; 6 Kyushu University,
Department of Pediatric Surgery, Fukuoka, Japan; 7 Saitama Children's
Medical Center, Department of Hematology/Oncology, Saitama, Japan;
8 Japanese Red Cross Gunma Blood Center, Director, Maebashi, Japan;
9 Nagoya Medical Center, Department of Advanced Diagnosis, Nagoya,
Japan; 10 Kanagawa Children's Medical Center, Department of Pathology,
Yokohama, Japan
2 National
Background/Objectives: Hepatoblastoma (HBL) is the most
common liver tumor in children. Despite intensive multimodal therapy, the prognosis of high-risk HBL remains poor,
and this underscores the importance of understanding HBL
pathogenesis and developing novel therapeutic modalities.
However, as the mutation rate in HBL is relatively low and
molecular targets except for Wnt/beta-catenin pathway have
not been established, our understanding of the molecular basis
of HBL is still limited.
Design/Methods: We performed methylation array analysis
and single nucleotide polymorphism (SNP) array-based copy
number (CN) analysis on 38 samples of HBL. A part of
the samples were also subjected to whole-exome sequencing
(WES, 10 samples) and RNA sequencing (RNA-seq, 18 samples).
Results: We identified mutations/deletions of CTNNB1 in
all samples subjected to WES/RNA-seq. No other recurrent mutation or gene fusion was detected. Consensus clustering of 38 samples based on methylation data indicated
the presence of 3 distinct clusters. Cluster 1 was characterized by high expression of LGALS1 associated with the promoter hypomethylation and marked by low diagnostic age.
SIOP ABSTRACTS
Intriguingly, cluster 1 included most of the cases with uniparental disomy/trisomy of chromosome 11p. As for cluster
2, all but one case had 1q/2q gains. Cluster 2 included most
of the cases staged as PRETEXT IV that required liver transplant. Cluster 3 exhibited low expression of NQO1 with the
promoter hypermethylation and less frequent CN alterations.
Patients with relatively low serum AFP levels were enriched
in this cluster. Being consistent with low expression of NQO1,
known as a poor prognostic factor in several kinds of tumors,
patients in cluster 3 showed better event-free survival than the
others (100% vs 56.0%, p = 0.046).
Conclusions: Our integrated genome-wide study of HBL
identified methylation subgroups well correlated with biological and clinical features. It may be useful for clinical risk stratification and searching for new molecular targets.
O-130 Patterns of Care and Treatment Outcomes
of Pancreatic Tumors in Children: an Analysis of
the National Cancer Database
O. Picado1 , J. Tashiro1 , K. Rao1 , J. Sola1 , E. Perez1
1 University
of Miami - Miller School of Medicine, Surgery, Miami, USA
Background/Objectives: Pancreatic tumors are rare in children and limited data is available. We aimed to describe
patient and tumor characteristics and to report on survival of
this disease.
Design/Methods: Data from the National Cancer Database
(2004-2013) on children younger than 18 years with pancreatic tumors were analyzed. The association between treatment
and hazard of death was assessed using Kaplan-Meier method
and Cox regression model.
Results:We identified 86 children with pancreatic tumors;
52% were male, 56% white non-Hispanic, and 90% insured.
Median age at diagnosis was 14 (IQR: 9-16) years. Tumors
were distributed as follows, pseudopapillary neoplasm (27%,
n=23), endocrine tumors (26%, n=22), pancreatoblastoma
(17%, n=15), pancreatic adenocarcinoma (16%, n=14), sarcoma (8%, n=7) and neuroblastoma (6%, n=5). Sixty patients
underwent surgery, 70% (n=42) achieved R0 resection. Most
patients (75%, n=45) had lymph node examination, and 22%
had positive samples. Twenty percent (n=17) received adjuvant therapies; 14% (n=12) chemotherapy and 6% (n=5)
chemoradiation therapy, while 19% (n=16) received palliative treatment. Most pancreatoblastomas (80%, n=12) and
sarcomas (57%, n=4) received chemotherapy and chemoradiation therapy, respectively. Five-year overall survival for
all pancreatic tumors was 61%. Five-year overall survival by
tumor histology were 95%, 75%, 70%, 51%, 43%, and 34%
for pseudopapillary neoplasm, neuroblastoma, pancreatoblastoma, endocrine tumors, sarcoma and pancreatic adenocarcinoma, respectively. On univariate analysis, males (HR: 2.50,
S73 of S518
95%CI: 1.07–5.80, p=0.03), sarcomas (HR: 13.48, 95%CI:
1.51–120.59, p=0.02), endocrine tumors (HR: 10.11, 95%CI:
1.26–80.90, p=0.03), adenocarcinoma (HR: 22.95, 95%CI:
2.81–187.20, p<0.01), and non-surgical management (HR:
4.80, 95%CI: 2.15–10.71, p<0.001) were all significant predictors of worse survival. Though, non-surgical management
(HR: 4.07, 95%CI: 1.56–10.62, p<0.001) remained independent predictor of worse survival on multivariate analysis.
Conclusions: Overall survival of children with pancreatic
tumors is grim, with varying survival rates among different
tumors. Surgical management of pancreatic tumors in children is associated with long-term survival.
O-131 NUT Midline Carcinoma in Children and
Adults: A Multicenter Retrospective Study
L. Lemelle1 , G. Pierron2 , P. Fréneaux3 , S. Huybrechts4 , A.
Spiegel5 , D. Plantaz6 , M. Julieron7 , S. Dumoucel8 , A. Italiano9 , F.
Millot10 , C. Le Tourneau11 , G. Leverger12 , P. Chastagner13 , M.
Carton14 , D. Orbach15
1 Institut
Curie, Department of Pediatric- Adolescent- Young Adults, Paris,
France; 2 Institut Curie, Unité de Génétique somatique, Paris, France;
3 Institut Curie, Département de pathologie, Paris, France; 4 Hôpital
Universitaire des Enfants Reine Fabiola- ULB Université libre de Bruxelles,
Hematology-Oncology Unit, Brussels, Belgium; 5 CHU Hautepierre,
Department of Pediatric Hematology-Oncology, Strasbourg, France;
6 Hôpital de Grenoble, Department of Pediatric Hematology-Oncology,
Grenoble, France; 7 Centre Oscar Lambret, Head and Neck Surgery
department, Lille, France; 8 CHU Sainte Justine- University of Montreal,
Department of Pediatric Hematology-Oncology, Montreal, Canada;
9 Institut Bergonié, Department of Medical Oncology, Bordeaux, France;
10 Centre Hospitalier Universitaire Poitiers, Pediatric oncology
departement, Poitiers, France; 11 Institut Curie, Medical oncology
department- INSERM U900 Research unit- Saint-Cloud, Paris, France;
12 Assistance Publique – Hôpitaux de Paris- Hôpital Armand Trousseau,
12Department of Pediatric Hematology and Oncology, Paris, France;
13 Hôpital d'Enfants de Brabois, Department of Pediatric
Hematology-Oncology, Vandoeuvre Les Nancy, France; 14 INSERM UMS
11, 14Population-based Epidemiological Cohorts Unit, Villejuif, France;
15 Institut Curie, Department of Pediatric- Adolescent- Young AdultsFrench Pediatric Rare Tumor group groupe Fracture, Paris, France
Background/Objectives: NUT midline carcinoma is an
aggressive tumor defined by the presence of NUT rearrangement (BRD3/4-NUT fusion oncogene) with a poor prognosis.
This rare cancer is underdiagnosed and poorly treated.
The primary objective of this study was to describe the clinical, radiologic and biological features of NUT midline carcinoma. The secondary objective was to describe the various
treatments and assess their efficacy.
Design/Methods: This retrospective multicenter study was
based on review of the medical records of children and adults
with NUT midline carcinoma with specific rearrangement or
positive anti-NUT nuclear staining (>50%).
Results: This series of 12 patients had a median age of 18.1
years (ranges: 12.3 – 49.7 years). The primary tumor was
located in the chest in 8 patients, the head and neck in 3
SIOP ABSTRACTS
S74 of S518
patients and 1 patient had a multifocal tumor. Nine patients
presented regional lymph node involvement and 8 distant
metastases. One-half of patients were initially misdiagnosed
and diagnosis of NMC was therefore subsequently corrected
by targeted molecular biology analyses. Specific NUT antibody was positive in all cases tested. The specific BRD4NUT translocation was found in 10/12 patients. A transient
response to chemotherapy was observed in 4/11 patients. Only
2 patients were treated by surgery and 5 received radiotherapy
with curative intent. Three out of 12 patients received targeted
therapy. At the end of follow-up, only one patient was still
in remission more than 12 years after the diagnosis. Median
overall survival was 4.7 months (95%CI: 2.1-17.7).
Conclusions: NUT midline carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by
NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful for diagnosis. It
should lead to propose optimal therapeutic strategy with early
inclusion in targeted therapy studies.
CHILDHOOD CA NCER
I N T E R NAT I O NA L (C C I )
O-132 A Childhood Cancer Parent's Guide to
Transforming Pediatric Cancer Policy in Your State
J. Bloyd1
1 American
Childhood Cancer Organization, Lexington, USA
Background/Objectives: The objective of this presentation
is to empower parents of childhood cancer patients and survivors to effectively engage policy makers to raise awareness
about childhood cancer and the need for additional resources.
The presenter will share about her personal experience in
forming partnerships with state legislators and the Governor to pass legislation making Kentucky a national model for
change.
Mrs. Bloyd is the mother of a Burkitts Lymphoma Leukemia
survivor, Paxton. She worked for KY Governor Ernie Fletcher
as well as U.S. Senate Majority Leader Mitch McConnell in
D.C., and as a grassroots advocacy lobbyist/consultant for
the American Heart Association, Campaign for Tobacco Free
Kids, and Americans for Non-Smokers Rights prior to her
son's diagnosis.
initiative is funded through an innovative approach giving
Kentucky residents the opportunity to donate via their annual
state income tax return. As a result of her leadership, Mrs.
Bloyd was appointed by the Governor to the board and elected
President. Mrs. Bloyd also led the way in changing Kentucky's
Cancer Action Plan to include specific objectives regarding
childhood cancer research and survivorship. To commemorate International Childhood Cancer Day Jamie recently partnered with Governor Matt Bevin and the First Lady in launching KY's first-ever pediatric cancer advocacy day at the State
Capitol.
Conclusions: Although childhood cancer is the number one
cause of death by disease for children, the issue goes largely
unnoticed by state policy makers. Effective advocacy at the
grassroots level has the power to change the political landscape in making childhood cancer a priority issue.
O-133 The Best Interests of the Paediatric
Oncology Patient: A Case Study Where Medical
Professionals and Carers do not Agree
T. Di Lallo1
1 Royal
Children's Hospital, Parent's Advisory Group- Children's Cancer
Centre, Parkville, Australia
Background / Objectives: Background: In December 2015,
Oshin Kiszko was diagnosed with a rare brain tumour, medulloblastoma. Oshin was then six years old. He died in December 2016.
Following surgery in December 2015, curative treatment
comprising intensive chemotherapy and craniospinal radiotherapy was indicated. Oshin's parents were advised accordingly.
Oshin's parents initially opposed the administration of
chemotherapy. They subsequently agreed to limited
chemotherapy, but otherwise preferred to pursue alternative therapies. They declined radiotherapy under any
circumstances.
Litigation took place between Oshin's parents and the treating
Hospital.
Objectives: Consideration of the legal/ethical issues which
emerge when legal guardians seek to limit medical treatment
for the infant patient in the exercise of their parental entitlement to protect their child's welfare.
Design/Methods: Mrs. Bloyd will use her experience as a
case study to reveal pitfalls and pearls for effective grassroots
advocacy.
Identification of how the legal and ethical issues become especially acute where the indicated medical treatment takes the
form of “special medical procedures” as that term is understood by law.
Results: Mrs. Bloyd led the way in Kentucky drafting legislation to create a new pediatric cancer research trust fund. This
Analysis of why the Court ultimately deferred to the wishes
of Oshin's legal guardians concerning on-going medical
SIOP ABSTRACTS
treatment in preference to the recommendations of the child's
treating medical professionals.
Design/Methods: Nil.
Results: Nil.
Conclusions: The ‘bests interests’ approach to the consideration of patient welfare does not offer a specific hierarchy of
values.
The application of the “best interests’ approach in the case of
the individual patient is multifaceted and intricate, especially
in the context of “special medical procedures”.
Best interests are values, not facts. Therefore, complex ethical
and legal issues intrude into otherwise clinical questions.
The wishes of legal guardians are protected by law and cannot
lightly be derogated from.
S75 of S518
Results: During the year 2015-16 Cankids provided medical
assistance to 4531 patients, with total outlay of $551,655. By
using generics for 4 of these 5 drugs we had a cost reduction
of 63%. For native Asparaginase only innovator product was
used. Apart from this, by using above mentioned strategies, a
reduction of 58% in the retail price of final purchased generic
drugs was achieved.
Conclusions: Significant cost reductions can be achieved in
partnership with pharmaceutical industry enabling support
groups to reach out to more patients.
O-135 Increasing Fundraising Capacity for
Parent Run Organizations in LMICs
M. Hamid1 , S. Choudhury1
1 ASHIC
O-134 “Getting More Bang for Your Buck” - The
Perspective of a Not-for Profit on Innovative
Strategies to Get Better value for Money for
Medical Assistance
H. Gupta1 , A. Taluja2 , K. Sawhney1 , P. Bagai1 , A. Mahajan1
1 Cankids...Kidscan,
Medical Projects and Support Service Program, Delhi,
India; 2 Cankids...Kidscan, Quality Control Research and Impact, Delhi,
India
Background/Objectives: Drugs cost is a significant component of the overall financial burden in the management
of childhood cancer. The diverse healthcare dynamics in
India leads to a significant albeit variable part of this burden
being passed on to the families. Cankids is a grassroots level
organization providing holistic support to pediatric oncology
patients at 45 centers in India. Support for medications currently constitutes the biggest outlay in our annual expenditure. It is therefore, vital for us to find ways to cut costs without compromising on the quality of treatment. The aim of this
study was to quantify the cost reduction achieved using various strategies.
Design/Methods: Medical Assistance team of cankids selects
and procures chemotherapy/supportive drugs directly from
pharmaceutical companies for all Cankids supported Hospital
units. Drugs requiring cold-chain are delivered through local
stockists of parent company. As a general principle generics
approved by Drug General Controller of India are procured.
Bulk purchasing facilitates better negotiation in prices and
value additions such as some complimentary vials and diagnostics. Billing centrally leads to avoidance of higher taxes at
state level. Attempt was made for the purpose of this study to
quantify the overall economic benefit using the above strategies for five commonly prescribed, key drugs L-Asparaginase,
Imatinib, Filgrastim, Voriconazole, Meropenem.
Foundation, Pediatric Oncology, Dhaka, Bangladesh
Background/Objectives: LMICs struggle with a multitude
of indigenous socio-economic issues, making it difficult to
raise the fundraising capacity for small parent-run organizations focused on a specific cause such as childhood cancer.
In a country such as Bangladesh, malnutrition, education and
communicable diseases receive the lion's share of public funding and attention. Specialized causes such as childhood cancer are forced to resort to private sources of funding. Unequal
distribution of wealth keeps more than 90% of the country's
wealth in the hands of the select few, who make their own
decisions on what projects to fund. Most have causes in their
own communities or extended families that they choose to
support, and as a result specialized programs such as support
for childhood cancer gets ignored.
Design/Methods: With a track record of swindlers in the
community, individuals are also slow to trust private nongovernmental organizations (NGOs) unless they have a personal connection with the administrators of the organization.
Formed in 1994, ASHIC Foundation got its start with 100%
of its small budget funded by private funds from the founders
of the organization. Maheen Hamid, daughter of the founders
Afzal & Salma Choudhury, will share the family's journey
over the last two decades. This includes relationship building
with the local medical communities, tapping into international
networks/ partners, building credibility of ASHIC Programs
by being consistent and dedicated service providers and many
other factors that have helped to build the trustworthiness of
the organization.
Results: Today, the organization gets about ∼70% of its current ∼$100,000 annual budget from private donations, including those from individuals and institutions.
Conclusions: Several parent run organizations in LMICs may
be able to benefit from the effective strategies employed by
ASHIC Foundation, and the organization's plans to leverage
new marketing tools for increasing fundraising capacity.
SIOP ABSTRACTS
S76 of S518
O-136 Developing an Intelligent Resource
Mobilization Strategy in Response to Rapid Growth
of Programs Focussed on Change for Childhood
Cancer in India
A. Kumar1 , P. Bagai1 , G. Nagar1 , K. Sawhney1
1 CanKids...KidsCan,
Resource Mobilisation Department, New Delhi, India
b. Number of hospitals supported has increased from 27
to 44
2. Previous two year comparison
a. 56% in 2015-16 to 65% in 2016-17 raised through
project funds
b. Increase from previous year funds raised – 33% in
2015-16 to 66% in 2016-17
Background/Objectives: CanKids...KidsCan (CK) – a grassroot level not-for-profit organization works for Change for
Childhood Cancer in India and You Are Not Alone (YANA)
Social Support Protocol; executed through their social support
teams working in 44 cancer centres across India providing
holistic support ( Range of 18 services) to provide best standards of treatment, care and support. Hence, requires fundraising & implementable resource mobilization roadmap.
3. Strong database of continual group/ individual relationships for future
Design/Methods:
3. Multiple fundraising tools helped increase donations and
flexibility to implement programs
1. Adaptive fundraising strategy
a. Evolving corporate atmosphere has brought into limelight the corporate social responsibilities (CSR) of
each organization. Project/programs created developed
according to CSR needs
2. Building expertise by
a. Working with different stakeholders,
b. Developing fundraising roadmap.
c. donor management tools- sales force ( 4616 donors)
d. Building corpus fund
3. Community involvement through
a. Seven Care centers, for cancer children for focused
interventions
b. Donation in kind – involving community through their
time, food and supplies.
4. Events
a. Awareness – through disease based national campaign,
survivor specific campaigns and statewide car rallies
b. Networking through fundraising dinners
5. Other Fundraising tools
a. Crowd & bite sized fundraising
b. Using network's network
c. fundraising target setting
d. Schools /institutional partnerships
Results:
1. Five year trend:
a. Increase in funds raised from USD 460,000 to USD
945,000 to 1,280,000USD to 1,450,000USD to USD
2,000,000
Conclusions:
1. Donor focussed projects led to renewable partnerships,
reducing reliance on foreign funding
2. Team strengthening is essential for sustainability
4. Effective low cost models for fundraising.
5. Community involvement shoulders some burden of
fundraising
O-137 Charity Role in International Paediatric
Cancer Clinical Trials
S. Kennedy1 , D. Ludwinski1 , S. Richards2 , N. Bird2 , L. Knox2 , J.
Rogers2
1 Solving
Kids’ Cancer, Research Programs, New York, USA; 2 Solving Kids’
Cancer Europe, Research Programs, London, United Kingdom
Background/Objectives: International clinical trials are
becoming increasingly important in paediatric cancers to
facilitate faster accrual rates and provide wider access to children for testing new therapies. Challenges of increased design
and monitoring complexities, regulatory burden, and cost
remain significant. This presents an opportunity for charities
to stimulate and support international collaborations between
academia, industry, government agencies, and non-profits.
Design/Methods: Research advocacy by an international
charity based in the US and UK identified unmet needs for
children with neuroblastoma. A call for proposals was issued
to the international research community to submit ideas for
combination immunotherapy. An international panel of scientific reviewers selected a proposal to recommend for the
award. Another clinical trial testing a targeted drug planned
in a US consortium was expanded to include UK and Europe
due to charity support and influence. Seven additional charities in the US and UK are supporting these trials.
Results: Two international clinical trials testing novel therapies in neuroblastoma influenced and supported by charity advocacy are due to open in 2017. One is testing targeted radiotherapy 131I-MIBG with immunotherapy
SIOP ABSTRACTS
combination using anti-GD2 antibody dinutuximab-beta and
anti-PD1 antibody nivolumab and will accrue relapsed and
refractory neuroblastoma patients in US, UK, and Germany
(NCT02914405). The second is a third-generation ALK
inhibitor lorlatinib for children with ALK-positive neuroblastoma that will accrue patients in US, UK, and France.
Conclusions: Charities advocating for and supporting innovative international clinical trials are providing an essential
role in stimulating trials that will accrue in a timely manner
and address the need for more therapeutic options across borders for children with cancer.
O-138 Have A Heart for Children with Cancer: A
Campaign to Raise Awareness of and Funds for
Children living with Cancer
L. Moore1
1 CHOC
Childhood Cancer Foundation SA, Gauteng South Region,
Saxonwold, South Africa
Background/Objectives: The non-profit sector in South
Africa has become increasingly more competitive which has
resulted in a scramble for available funds. CHOC Childhood
Cancer Foundation South Africa (CHOC), the largest childhood cancer NGO operating in the African continent, developed a national awareness and fundraising campaign entitled
“Have a Heart for Children with Cancer” with the primary
aim of raising awareness of childhood cancer and funds for
the organisation.
Design/Methods: The “Have a Heart for Children with Cancer” campaign is linked to ICCD on the 15th February, In 2015
CHOC identified the need to formalize and give structure to
the campaign. The campaign went blue to align with the corporate identity of the organisation and merchandise was developed with the “heart” theme. A round plastic pin that could
be worn on the days leading up to and on the 15th February
was designed, together with a chocolate to fit the Valentine's
day theme. Both items were branded with the “Have a Heart
Children with Cancer” slogan. The campaign encourages people “go blue” on the day and wear their badges and pins –
all in support of childhood cancer and CHOC. Linked to this
was a national media, social media and advertising campaign,
including the lighting up of Table Mountain in Cape Town and
a National Monument in Pretoria in the blue colour theme.
Results: There has been an increase in the number of people
being made aware of CHOC and childhood cancer. This is evident in the number of media articles/interviews, the number
of participants aligning themselves to the campaign and the
increase in sales of “Have a Heart for Children with Cancer”
merchandise.
Conclusions: The “Have a Heart for Children with Cancer”
campaign is an effective awareness and fundraising campaign
S77 of S518
that has seen increased support for both CHOC and childhood
cancer.
O-139 Children Raising Funds for Children:
Implementing an Effective Fundraising Campaign
in Schools in Gauteng, South Africa
L. Moore1
1 CHOC
Childhood Cancer Foundation SA, Gauteng South Region,
Saxonwold, South Africa
Background/Objectives: It is important that non-profit
organisations leverage support from a wide variety of income
sources. An effective way of doing this is implementing
a holistic school giving programme that is mutually beneficial to both the organisation and the school. There is
increased pressure on children today to be effective and
contributing citizens of society. The opportunities for charities to get maximum benefit from this social movement
are enormous and CHOC has been extremely successful in leveraging off these opportunities in its fundraising
efforts.
Design/Methods: This initiative is broken into four key sections: monetary activities, community service opportunities,
social responsibility clubs and collections of in-kind donations. Key activities promoted in schools include: civvies
days, where children pay a donation to wear clothing of
their choice to school (often linked to national/international
awareness campaigns related to childhood cancer); collection of items that are needed to implement core programmes;
opportunities for social responsibility clubs to engage with
CHOC at its operational sites, assisting in various activities such as painting, cleaning, preparing meals and administration tasks and; providing opportunities for individual
learners to gain both passive and active community hours
through assisting with campaigns, events and fundraising
initiatives.
Results: There has been a steady increase in the number of schools and learners getting involved in CHOC
initiatives. Monetary income has increased and currently
accounts for 11% of overall income received. There has
been over a 100% increase in the amount of in-kind
donations received which has a huge impact on reducing
expenditure.
Conclusions: A well planned and implemented schools
fundraising campaign will see steady growth over a period
of time and can comprise a significant portion of an organisations income. It opens opportunities to gain access to other
income sources whilst assisting in shaping future leaders who
will become active members of society contributing to social
change.
SIOP ABSTRACTS
S78 of S518
O-140 Creating and Developing Games
Throughout Interdisciplinarity and Patient
Participation
S. Mozzilli1 , E. Sassi2 , L. Rossi3 , V. Sonaglio4 , F. Francisco4 , A.
Duarte5 , L. Panzoldo4 , G. Yabu2 , D. Costa6 , S. Sredni7
1 Instituto
Beaba, Direction, Sao Paulo, Brazil; 2 Instituto Beaba, Creative,
São Paulo, Brazil; 3 Mukutu Game Studio, Development, Santos, Brazil;
4 A.C. Camargo Cancer Center, Pediatric Oncology, São Paulo, Brazil;
5 Universidade de Brasília, Pediatric Oncology, Brasília, Brazil; 6 Mukutu
Game Design, Development, Santos, Brazil; 7 Children's Memor Rsrch Ctr,
Pediatric Oncology, Chicago, USA
edge with human factors in order to educate, empower
and improve the quality of life of children fighting cancer.
www.beaba.org/games
O-141 A Childhood Cancer Parent's Experience
with CBD (Cannabidiol) HEMP Oil as a Substitute
for Pain Relief and Anxiety
D. Mujagic-Cammett1
1 Parent,
n/a, Bethesda, USA
In this scenario, we decided to bring all stakeholders –
patients, caregivers, healthcare professionals, creatives and
entrepreneurs together to create an application for tablet and
mobile devices that would help children demystify cancer and
its treatment.
Background/Objectives: The objective of this presentation
is to inform and empower the parents of childhood cancer
patients of pain remedy and anxiety alternatives and to raise
awareness among oncologists and researchers of the potential such natural alternatives could provide to patients who do
not respond positively to conventional medicine. The presenter will share her personal experience introducing CBD hemp
oil as a substitute for pain treatment and anxiety during her
daughter Sabrina's treatment for Neuroblastoma.
Design/Methods: 1 - Interdisciplinarity: which involves the
combination of two or more academic disciplines into one
activity;
Mrs. Mujagic-Cammett is the mother of a Neuroblastoma
patient, Sabrina who battled this disease on and off for nine
years before passing in October 2016 at the age of 12.
2 - Design Thinking: a human centered methodology for a
rapid ideation with the ability to visualize and adapt the results
in near real time;
Design/Methods: Mrs. Mujagic-Cammett will present her
experience as a case study of the success she had introducing cannabidiol hemp oil to combat Sabrina's pain and anxiety
in order to inform parents and to spark the interest of doctors
and researchers to explore the potential benefits of substituting
hemp oil or other naturally occurring substances for opioids
to address pain and anxiety during inpatient procedures.
Background/Objectives: In an increasingly technological
world, digital information about childhood cancer that is easily accessible to pediatric patients, their families and healthcare providers is still missing.
3 - Agile UX: a methodology which integrates the user experience design and developer team;
4 - Patient Centered Design;
5 - Project Management Platforms;
6 - Collaboration and Communication Tools.
Results: 1 - Development of an application with 20
minigames for iOS and Android platforms, in a language that
is easily accessible to children with an attractive an colorful interface where the child can identify him/herself with a
custom designed character that guides them through different
steps of the treatment. The initiative was highlighted in the
AppStore and resulted in almost 4 million views.
2 - Acquisition and expansion of interdisciplinarity for all
stakeholders.
3 - And most importantly, development of empathy and compassion for our patients.
Conclusions: The interdisciplinarity and the effective participation of all the stakeholders in the project, allowed an integrated access to information, facilitating the understanding,
identification, codification and availability of information that
resulted in generation of easily accessible knowledge to our
targeted population.
The greatest transformation was not only in the technological advance itself, but in our new way to associate knowl-
Results: While treating Sabrina both at home and in the hospital, Mrs. Mujagic-Cammett confirmed that utilizing a natural
product could produce an equivalent response versus a pharmaceutical in Sabrina's case. During her treatment, Sabrina
did not exhibit nor express discomfort while provided with
CBD to manage pain as her decease progressed.
Conclusions: Mrs. Mujagic-Cammett believes such options
should be added to those presented to parents as an alternative to providing pain relief and reducing anxiety for their
child during treatment. Also, that more studies should be conducted to determine the relative effectiveness of CBD hemp
oil or other naturally occurring medicines as another choice
for parents and doctors.
O-142 Continuity of Oncology Care for Central
American Migrant Children in the US
M. Orjuela-Grimm1 , L. Fu2 , R. Martinez3 , L. Onesi4 , C. Batista5 , J.
Levine4 , M. Barnett6 , C. Urey7 , B. Mejia8 , Y. Gonzalez Cerdeira8 ,
S. Blanco5 , J.P. Medina-Paez9 , P. Satwani10
1 Columbia
University Medical Center, Pediatrics-Oncology &
Epidemiology, New York City NYC, USA; 2 Hospital Escuela, Pediatric
SIOP ABSTRACTS
Oncology, Tegucigalpa, Honduras; 3 Hospital Mario Catarino Rivas,
Pediatric Oncology, San Pedro Sula, Honduras; 4 Columbia University
Medical Center, Pediatrics Oncology, New York CIty, USA; 5 Columbia
University Medical Center, Pediatrics Oncology & Social Work, New York
City, USA; 6 Columbia University Medical Center, Pediatrics Oncology &
Psychology, New York City, USA; 7 Coalicion Mexicana/ Universidad
Centro Americana, Red Jesuita de Servicio a Migrantes en NY, Managua,
Nicaragua; 8 ERIC-SJ, Investigación y Derechos Humanos, Progreso,
Honduras; 9 Columbia University Medical Center, Epidemiology, New York
City, USA; 10 Columbia University Medical Center, Pediatrics BMT, New
York City, USA
Background/Objectives: During the past 4 years the numbers of Central American children migrating overland to the
US has reached unprecedented levels, with > 93,000 migrating during 2016. Some children migrate while undergoing
chemotherapy, interrupting intended care. We report a collaboration between pediatric oncology teams in sending and
receiving countries permitting continuity of care despite complex legal circumstances.
Design/Methods: A 4 year old girl undergoing maintenance
therapy for B cell precursor standard risk ALL in Honduras,
abandoned therapy, traveling overland to the US. After resettling in NYC she ran out of medications, developed fevers
and was admitted in relapse at Columbia. After electronic discussion between NY and Honduran oncologists, she began
relapse therapy, quickly achieving remission. Pre-BMT unrelated donor search yielded only 9/10 HLA matches. Sibling
testing revealed a 10/10 HLA match in one 9 year old brother
living in a remote Honduran village. Because of the nature
of the family's migration to the US, he was ineligible for a
tourist visa, and stem cells from Honduras could not enter the
US. The NY oncologists working closely with a Jesuit human
rights organization, a NY community organization, Honduran
oncologists, and a volunteer immigration lawyer petitioned for
the boy's US entry.
Results: The 10/10 HLA-matched 9 year old was granted
Humanitarian Parole by US Homeland Security within 3
months of HLA testing. Marrow donor assent and preparation for flying was done with video calling. The boy traveled
4 days later. BMT proceeded without complications. The girl
was discharged on day +28. The donor returned to Honduras
complying with his Parole. After day +180 the girl's family
chose to return to Honduras where she is again followed by
her Honduran oncologist, now in close electronic communication with the NY team.
Conclusions: We propose technology facilitated binational
oncologic continuity of care as a model for treatment during
migration.
O-143 UNITE2CURE - Breaking the 18 Year
Age-Limit Dogma
N. Scobie1 , C. Copland2
S79 of S518
1 Unite2Cure,
Zoé4life, Sullens, Switzerland; 2 Unite2Cure, Parent
representative, Sullens, United Kingdom
Background/Objectives: Unite2Cure is partnering with
Accelerate in order to remove the “18 year age-of entry
dogma” within clinical trial designs. Ages of entry to adult trials should be flexible and based on considerations of biology
and safety. Trials specifically for teenagers and young adults
are less common even than for children.Adolescents tend to
be grouped with children and thus are excluded from adult
trials. We contend that inclusion in trials should be based on
medical need rather than arbitrary age limits.
Design/Methods:
1. The age of clinical trial entry should be reduced to 12 years
in adult early phase cancer drug studies unless there are welljustifiable medical/scientific reasons not to do so.
2. No upper or lower age limit criteria for Phase-II and III
trials– when AYA diseases present in both paediatric and adult
populations– and have the same biology.
3. Trials enrolling adolescents should always be conducted in
an age-appropriate setting
4. Adolescents should still be included in paediatric PhaseI, II and III trials– where relevant, to maximise therapeutic
opportunities.
5. Young adults should be permitted to participate in paediatric Phase II-III trials– especially for ‘paediatric’ type cancer.
6. The indication proposed in a regulatory marketing authorisation application for of a given cancer drug should include
adolescents at the same time as the adult authorisation.
Results: 1. Improved access of adolescents to new cancer
drugs
2. Better understanding of biology and response of the MoA
(Explore differences, if they exist, between adolescents and
adults)
3. Positive influence in paediatric drug development (Early
signs of activity in a paediatric disease present in adolescents)
4. Positive influence in adult drug development (Increased
likelihood of achieving proof of concept/proof of principle for
drugs with brand new mechanisms of action)
Conclusions: Is it safe to recruit teenagers in adult early drug
trials? YES, either in adult Phase 1 and Phase 2 trials
O-144 The Promote, Protect and Support
Malnutrition (PPSN) Model for Delivering
Nutritional Support to Childhood Cancer Patients
in India
A. Sharma1 , P. Bagai1 , M. Khurana1 , N. Joshi1
1 Cankids...Kidscan,
Treatment Support Program, NEW DELHI, India
SIOP ABSTRACTS
S80 of S518
Background/Objectives: A survey of nutritional practices
for children with cancer in India in 2014 established that
there is a deficiency of provision of nutritional services and
variability in existing practices of nutritional assessment and
intervention. To address the problem, Cankids, a not for profit
childhood cancer organisation, developed the PPSN model.
Design/Methods: Using the SIOP PODC algorithm as a
starting point for nutritional assessment and intervention, the
PPSN model provides the necessary resources. The resources
include
1. Dietitians and other staff.The dietician managed the nutrition status of the child through prospective assessment, 1
on 1 counselling and risk stratification.The social support
team and a parent support group (PSG) worker work with
the dietician to deliver the program.
2. Information education communication materials on nutrition and hygiene
3. Nutritional supplements,Desired home based and industrial supplementation are provided.
4. In addition, advocacy and stakeholder engagement is promoted through a national group called POSHAN.
Results:
• ⋅6 dieticians were provided and supported in 11 cancer centers in India in the last 12 months.40 PSG workers were
trained for nutritional assessment.
• ⋅144 sessions for awareness generation on nutrition and
288 session on hygiene maintenance were conducted.1
recipe exhibition was organised.15 Focus group discussions
were conducted and equipment for anthropometric measurements were provided. A nutrition management guidebook for families in 3 languages and a snake and ladder
game for child education was developed..
• Feeding program was provided to 218 beneficiaries per
month in 4 centers Supplementation support was provided
to 400 patients based on risk stratification.
• ⋅488 parents and children participated in the nutrition
awareness campaign across India. Nutrition week was celebrated for awareness generation at community level.
Conclusions: The PPSN model is feasible to deliver nutritional support in resource-limited settings. Studies to measure
impact are being planned.
O-145 Enhancing Childhood Cancer Awareness
through Road Show to the Urban Places in
Indonesia
A.U. Sudjoko1
1 Yayasan
Onkologi Anak Indonesia, Secretary, Jakarta Barat, Indonesia
Background/Objectives: To increase public awareness of
children with cancer, the importance of early detection and
subsequent care is the mission of the Indonesian Childhood
Cancer Foundation or Yayasan Onkologi Anak Indonesia
(YOAI). Indonesia is an archipelago of over 17.000 islands
straddling the equator. Many are sparsely inhabited, some not
at all. However, with a population over 250.000.000 there are
very few oncologists or specialists for children with cancer
and those are not found outside urban areas. Many children
with cancer must travel far to find treatment in Jakarta, the
capital of Indonesia. YOAI has taken the initiative to offer outreach by promoting seminars for laymen and professionals in
our far flung communities with our Road Show.
Design/Methods: Our road show gives informative presentations to public on awareness of children with cancer by cooperating with community health centers, schools and other relevant organizations. Scientific seminars are offered to doctors,
nurses and students from academic medical institutions. We
cooperate with hospitals and universities where the presentations are held.
Results: Our Road Shows have helped raised awareness of
children with cancer and their needs in regions outside urban
areas and how to assist them in their forward needs. We also
encourage doctors to become specialists in the field of childhood oncology.
Conclusions: YOAI has been doing the Road Show for the
past two years not only at the hospital in Jakarta but also
in other cities such as Bandung, Jogyakarta, Solo, Surabaya,
Padang, Medan, Garut and Cirebon. Our goal is to move on
until we covered the whole provinces of Indonesia
O-146 Using Thunderclap to Raise Awareness
about #Kidscancerpain Over Social Media
P. Tutelman1 , C. Chambers1 , J. Stinson2 , J. Parker1 , E.K. Drake9 ,
M. Barwick2 , F. Campbell3 , C. Fernandez4 , K. Irwin5 , L. Jibb6 , P.
Nathan7 , H. Witteman8
1 IWK
Health Centre, Centre for Pediatric Pain Research, Halifax, Canada;
Hospital for Sick Children, Child Health Evaluative Sciences, Toronto,
Canada; 3 The Hospital for Sick Children, Anesthesia and Pain Medicine,
Toronto, Canada; 4 IWK Health Centre, Hematology-Oncology, Halifax,
Canada; 5 Multimed Inc., Cancer Knowledge Network, Toronto, Canada;
6 University of Ottawa, Nursing, Ottawa, Canada; 7 The Hospital for Sick
Children, Haematology/Oncology, Toronto, Canada; 8 Université Laval,
Family & Emergency Medicine, Quebec City, Canada; 9 Independent
Healthcare Consultant, Halifax, Canada
2 The
Background/Objectives: Social media is increasingly being
used to disseminate health information, connect experts
with patients, and raise awareness about medical conditions. Funded by the Canadian Cancer Society, #KidsCancerPain is a social media campaign in partnership with the
SIOP ABSTRACTS
Cancer Knowledge Network aimed at delivering evidencebased information on pediatric cancer pain to parents.
This study evaluated the use of Thunderclap, a crowdspeaking social media platform, to raise awareness about
#KidsCancerPain.
Design/Methods: A Thunderclap campaign introducing
#KidsCancerPain was created. A Thunderclap is an organized
social media event where supporters share a similar message
via Twitter and/or Facebook on the same day at the same time.
Supporters were invited via email/newsletter blasts, online
promotion, and targeted invitations. To join, supporters authorized Thunderclap to send a pre-programmed message (“No
parent wants to see their child in pain. Help us in “Making
Cancer Less Painful for Kids”. #KidsCancerPain”) via their
Twitter/Facebook account on the set date/time.
Results: Between July 13-27 2016, 366 unique social media
accounts (Twitter, 61.5%; Facebook, 38.5%) joined the #KidsCancerPain Thunderclap, held July 27, 2016, 9pm ET. This
resulted in a social reach of 1,672,727 people, making it
the largest childhood cancer Thunderclap to date. Supporters were individuals (84.7%) and organizations (15.3%) and
included cancer, health, research/academic, and pain groups
(e.g., Canadian Cancer Society, WEGO Health etc.). The
majority of supporters were from Canada (60.1%), followed
by the United States (24.6%), Australia (8.2%) and the United
Kingdom (3.3%). During the Thunderclap, #KidsCancerPain
trended on Twitter in Canada (i.e., became a viral topic).
Most supporters used the pre-programmed message (55.7%)
and 11.7% modified the message. The content of the posts of
35.4% of supporters were unavailable due to privacy settings
on accounts.
S81 of S518
ing the fifth guideline focusing “Siblings”, whose difficulties
are well known but no enough attention has been given. The
guideline was concluded in Dec. 2016 and published in Feb.
2017.
Design/Methods: A working group was organized of which
members are, a sibling of childhood cancer patient, a mother,
a farther, a survivor, a pediatrician, a nurse, a social worker, a
primary school teacher and a nursery teacher. Started in 2013
in total 13 meetings of WG were held and enthusiastic discussions were made until the conclusion in Dec. 2016. In addition, open discussions were made in the annual open symposium held in conjunction with annual congress of JSPHO
and JSPON from 2013 through 2016, and reflected in the final
draft.
Results: The guideline titled “Siblings of childhood cancer
patients –Things you need to have in main when you are with
them” was published in Feb. 2017. The guideline is written
in the manner addressing to those who care about siblings
describing various situations siblings face during and after the
treatment of patients. The last section is designed to address
to siblings with a key message “you are not alone”. A card for
the siblings to write and exchange messages is also enclosed
as an attachment.
Conclusions: The guideline is expected to be of helps to
deepen understandings between siblings of childhood cancer patients and those who surround them including parents,
and also to serve as a trigger for effective dialogue with
siblings.
Conclusions: Thunderclap was a novel and rapid way to
build widespread awareness about pediatric cancer pain and
the #KidsCancerPain campaign. Challenges and opportunities
will be discussed.
SESSION 1: NEUROBLASTOMA &
F E RT I L I T Y
O-147 Developing and Publishing a Guideline
Titled “Siblings of Childhood Cancer Patients
-Things You Need to Have in Mind When You are
with Them”
M. Jans1 , G. Tytgat2 , S. Zwaveling3,4 , C. van de Ven1,5 , S.
Terwisscha van Scheltinga1,5 , R. van Baren6 , M. Fiocco7 , H. Heij1 ,
M. Wijnen1,8
K. Yamashita1 , M. Ozawa2
1 Children's
2 St.
Cancer Association of Japan, Chairman, Minato-ku, Japan;
Luke's International Hospital, Pediatrics, Cyuo-ku- Tokyo, Japan
Background/Objectives: Development and publication of
various booklets and guidelines to serve the needs of patients
and families is one of very important tasks of Children's
Cancer Association of Japan known as CCAJ. Since 2000,
four guidelines, i.e. “Support to patients and families”, “Educations of patients”, “Supporting survivors” and “Palliative
care” were published. In 2013, a plan was started for develop-
O-148 Analysis of Surgery for Neuroblastoma in
the Netherlands 1998 – 2014
1 Prinsess
Máxima Center, Pediatric Surgery, Utrecht, The Netherlands;
Máxima Center, Pediatric Oncology, Utrecht, The Netherlands;
3 Academic Medical Center, Pediatric Surgery, Amsterdam, The
Netherlands; 4 Vrije Universiteit Medical Center, Pediatric Surgery,
Amsterdam, The Netherlands; 5 Erasmus Medical Center, Pediatric Surgery,
Rotterdam, The Netherlands; 6 University Medical Center, Pediatric
Surgery, Groningen, The Netherlands; 7 Leiden University, Mathematical
Institute, Leiden, The Netherlands; 8 Radboud University Medical Center,
Pediatric Surgery, Nijmegen, The Netherlands
2 Prinsess
Background/Objectives:
1. Establishing surgery related complications, mortality and
long-term sequelae in a large cohort of patients with neuroblastoma (NBL).
SIOP ABSTRACTS
S82 of S518
2. Evaluating impact of extent of resection on survival and
local recurrence in high-risk patients.
Design/Methods: This retrospective multi-center cohort
study included all patients who underwent primary tumor
resection for NBL in The Netherlands between 1998 and
2014, before the start of centralized care. Surgery related
complications, mortality and long-term sequelae were documented. For all high-risk patients, five-year overall survival
(OS), five-year event free survival (EFS), five-year cumulative
incidence of relapse (CIR) and total number of local recurrence (NLR) were estimated for complete, >95% and ≤ 95%
resection.
Results:
1. Surgery was performed in 301 children. Peroperative
complication rate was 42%. Short-term postoperative
complication rate was 43%. PICU support for surgical
complications was necessary in 5%. Secondary surgery
was performed in 8%. Five children (2%) died of surgery
related causes. Long-term complications occurred in 9%
of children, long-term sequelae in 6%.
2. A total of 170 children (57%) were stratified as high-risk
patients. For complete resection, EFS was 25% (15% 35%), OS was 26% (15%-36%), CIR was 72% (61% - 82%),
NLR was 15 (18%). For >95% resection, EFS was 24%
(13% - 34%), OS was 27% (15% - 39%), CIR was 62.7%
(50% - 76%), NLR was 8 (14%). For ≤ 95% resection, EFS
was 33% (16% - 50%), OS was 45% (29% - 64%), CIR was
53% (35% – 72%), NLR was 6 (20%).
Conclusions:
1. A large series of surgery related adverse events in children treated for Neuroblastoma is presented. Surgery for
neuroblastoma is associated with significant morbidity and
mortality.
2. For high-risk patients, no significant difference was found
in overall survival, event free survival, cumulative incidence of relapse or total number of local recurrence for
complete, >95% or ≤ 95% resection.
O-149 Surgical Complications of Kidney and
Urinary Tract in Abdominal Neuroblastoma- A
Retrospective Single-Institutional Review of 521
Cases in 5 Years
H. Wang1
1 Beijing
Children's Hospital- Capital Medical University, Surgical
Oncology, BEIJING, China
Background/Objectives: Gross total resection(GTR)
is survival-beneficial even for advanced neuroblastoma.
Although it is still controversial and may be relevant to higher
rate of complications, GTR has been the goal of surgery
for most cases. So it is important to know better about the
possible complication, particularly the injury of kidney
and urinary tract which is the most common in abdominal
neuroblastoma.
Design/Methods: 521 consecutive patients who underwent
primary tumor resection enrolled hospitalization in our hospital from January 2011 to January 2015. By reviewing the
medical records and follow-up data, 66 cases was identified
to have kidney and urinary tract injury.
Results:
1. Of the 66 cases, patients aged from 6 months to 8 years.
The INSS staging were 3 and 4. All the patients accepted
preoperative chemotherapy.
2. 10 cases underwent intraoperative nephrectomy and seminephrectomy, 3 due to renal vascular encasement and 7
due to invasion to parenchyma. Nephrectomy were planed
before operation.
3. 21 cases were found in the following-up to have ischemia
and kidney atrophy. 7 of the 21 cases showed renal atrophy in three months postoperation, and the other 14 cases
showed different amount of ischemia in the affected kidney.
4. 27 cases showed hydronephrosis and dilation of ureter with
normal renal function.
5. 9 cases were found to have some minimal abnormalities, 2
with dislocation of kidney, 2 with renal caculus and calc
deposition, 5 with outline of kidney undistinguished by
adhesion.
6. 2 cases underwent renal arterial reconstrution intraoperately because of severe injury of the artery and ischemia
of the kiney. One showed normal blood supply to the kidney and the other with renal atrophy in the following-up.
Conclusions:
1. Surgical complications of kidney and urinary tract are
common.
2. The continual improvement of manipulation of surgery is
important.
3. Imaging indication helps to tailor the surgical strategy for
neuroblastoma.
O-150 Our Experience with Neuroblastoma in
Children - Outcomes Based on Risk Stratification
S. Mishra1 , S. Jain2 , G. Kapoor3
SIOP ABSTRACTS
1 Rajiv
Gandhi Cancer Institute and Research Centre, Pediatric Surgical
Oncology, Delhi, India; 2 Rajiv Gandhi Cancer Institute and Research
Centre, Pediatric Hematology Oncology, Delhi, India; 3 Rajiv Gandhi
Cancer Institute and Research Centre, Pediatric Hematology and Oncology,
Delhi, India
Background/Objectives: With few exceptions, the outcome
of Neuroblastoma (NB) is dismal, especially in developing
countries. The aim of this study was to analyze the overall
survival (OS) and disease free survival (DFS) in Low, Intermediate and High risk groups of NB managed in our Institute
in the last 7 years.
Design/Methods: Retrospective analysis of hospital records
of patients with NB was done from January 2009 to Dec 2016.
In 57 patients with a median age of 3 yrs and M:F ratio of
1.19, primary sites were adrenal (n=39), paraspinal (n=5),
retroperitoneal (n=3), mediastinal (n=3), olfactory (n=2),
cervical (n=1) and unknown (n=4). Twenty-four came only
for opinion and and 7 were lost to follow up after the 1st admission (including 3 patients who came only for surgery or radiation). Remaining 26 were further studied.
Results: INRG risk stratification showed Low risk (n=11),
Intermediate risk (n=3) and High risk (n=12). IDRF was
present in 7 patients. Two neonates with Stage IVS succumbed
early. The remaining 12 Low and Intermediate risk patients
did well with a combination of chemotherapy and surgery or
close observation alone. Surgery was done in 21/26 patients.
Spontaneous regression was seen in 3/11 low risk patients. Of
the high risk group 9/13 underwent autologous stem cell transplant and differentiating therapy of which 4 are alive and well.
Anti GD-2 therapy was not available. The 2-yr-DFS in Low
intermediate and high risk group patients was 80%, 100% and
40% respectively. The 4-yr-DFS dropped to 20% in the high
risk group as 3 patients did not have long term follow up.
Conclusions: Despite tremendous challenges in resource
challenged nations, treatment of NB is feasible in high volume Pediatric Oncology centres with facilities for autologous
stem cell transplant. The results are comparable to that published in literature.
O-151
People
Future Fertility: Giving Hope to Young
C. Elbourne1 , R. Parry2 , J. Davies3 , S. Lane4 , K. Lakhoo1
1 The
Children's Hospital- The John Rafcliffe- Oxford, Department of
Paediatric Surgery, Oxford, United Kingdom; 2 The Children's HospitalThe John Radcliffe- Oxford, Department of Paediatric Surgery, Oxford,
United Kingdom; 3 The Children's Hospital- The John Rafcliffe- Oxford,
Oxford Tissue Bank, Oxford, United Kingdom; 4 The Children's HospitalThe John Rafcliffe- Oxford, Department of Paediatric Oncology, Oxford,
United Kingdom
Background/Objectives: Ten young people under the age of
twenty-five are diagnosed with cancer every day. Eight will be
S83 of S518
cured but one will become infertile as a result of their treatment. Cryopreservation of gonadal tissue to preserve fertility
and endogenous hormone production has been extremely successful and is available to increasing numbers of children. We
aim to share our experience of this ground-breaking service.
Design/Methods: Initially developed to provide women and
girls with cancer the ability to preserve ovarian tissue
while undergoing intensive treatment, the service has rapidly
expanded incorporating testicular cryopreservation for prepubertal boys and inclusion of children with non-malignant
haematological conditions undergoing curative bone marrow
transplantation.
Referrals are received from across England and Wales and
assessed by the specialist multidisciplinary team. Children
and families receive pre-operative counselling from a specialist paediatric consultant and surgical team. Where possible
the retrieval of gonadal tissue, via testicular biopsy or laparoscopic unilateral oophorectomy, is performed concomitantly
with other required procedures. Tissue is received directly
from theatre and processed by the onsite tissue bank team.
For most children, this is a day case procedure.
Results: Since its beginning in 2013, 84 children have undergone gonadal tissue retrieval for cryopreservation. Testicular
biopsy has been performed for 15 pre-pubertal boys. Unilateral laparoscopic oophorectomy has been performed for 69
girls ages 1-17. Of these, 28 have undergone concurrent procedures including central venous line insertion, lymph node
biopsy and bone marrow aspiration. 53 were girls with cancer
and 16 had non-malignant haematological disease including
8 girls with sickle cell anaemia and 4 with thalassaemia.
The service has grown tenfold between 2013-2016, and continues to expand.
Conclusions: Laparoscopic oophorectomy and testicular
biopsy facilitating gonadal tissue cryopreservation is a safe
and effective service providing hope for children and their
families undergoing treatment for cancer and non-malignant
haematological disease.
O-152 Laparoscopic Ovarian Cortical Strip
Harvesting for Cryopreservation
D. Baker1 , C. Clark1 , F. Munro1 , P. Hammond1 , H. Wallace2 , R.
Anderson3
1 Royal
Hospital for Sick Children, Paediatric Surgery, Edinburgh, United
Kingdom; 2 Royal Hospital for Sick Children, Paediatric Oncology,
Edinburgh, United Kingdom; 3 Royal Infirmary of Edinburgh, Reproductive
Medicine, Edinburgh, United Kingdom
Background/Objectives: Advances in the treatment of childhood cancers show ever improving survival rates. The treatment of childhood malignancy can however lead to premature
gonadal failure. We present our centre's experience of using
S84 of S518
cortical strip harvesting for ovarian tissue cryopreservation
while retaining the remainder of the ovary in situ.
Design/Methods: In this paper we describe the surgical technique and perioperative care regimen. We detail the demographic data for 24 cases over a ten year period and review
complications. We discuss outcomes, and the method of cryopreservation used for the ovarian tissue.
Results: Thirty patients were identified between 2006 and
2016 who have undergone laparoscopic ovarian cortical strip
harvesting, of which follow-up data was available for 24.
Median age at operation was 13, range 4-16. There was no
significant bleeding, adhesional obstruction, or injury to other
organs reported. No cases were converted to open procedures
or returned to theatre. Early postoperative pain has been found
to be a feature, thought to be secondary to gonadal trauma.
Five patients have since died as a result of their underlying
diagnosis. Three have menstruation documented at follow-up.
To date, two patients are known to have fallen pregnant naturally since their surgery, and one of these pregnancies progressed to childbirth.
Conclusions: Laparoscopic ovary-sparing ovarian cortical
strip harvesting is a safe procedure, although it should only be
performed as part of an integrated service with fertility and
laboratory specialists with suitable accreditation and oversight. It offers the possibility of conceiving naturally or via
reimplantation to patients who are at risk of early infertility
as a result of their treatment.
SE SSION 2 : R E NA L T U MO U R S &
LU NG M E TA STA S I S
O-153 Surgery of Bilateral Renal Tumors in
Children Involving the Renal Hilus
S.W. Warmann1 , A. Schmidt1 , M. Ebinger2 , S. Juergen3 , J. Fuchs1
1 University
Children's Hospital, Pediatric Surgery and Pediatric Urology,
Tuebingen, Germany; 2 University Children's Hospital, Pediatric Oncology,
Tuebingen, Germany; 3 University Hospital, Diagnostic and Interventional
Radiology, Tuebingen, Germany
Background/Objectives: Bilateral nephron-sparing surgery
(NSS) is the surgical approach of choice in bilateral renal
tumors in children. However, centrally located tumors with
involvement of the renal hilus represent a surgical challenge.
Design/Methods: We evaluated all children with bilateral
renal tumors involving he renal hilus operated on at our center,
which serves as surgical reference center for pediatric renal
tumors.
Results: Fifteen children were evaluated (8 girls, 7 boys)
with a median age of 32 months (13-67). All children had
undergone neoadjuvant chemotherapy. Median operating time
was 359 minutes (90-383). We performed bilateral NSS in
SIOP ABSTRACTS
10 cases, unilateral NSS in 3 children with single kidneys
after contralateral tumor nephrectomy elsewhere, and unilateral NSS with contralateral tumor nephrectomy in 2 children.
The reasons for the two nephrectomies were loss of function
after NSS prior to referral in one case and cava thrombosis
plus extrarenal disease in the other case. In all but one of the
patients undergoing bilateral surgery we performed a single
stage approach. Median vascular exclusion time in patients
with hilus involvement was 19 minutes (5-45). 2 children
required redo-surgery for urinary leakage. Histology revealed
intermediate risk in 8 patients, high risk in 4 patients and
nephroblastomatosis in 3 patients. One child with high risk
nephroblastoma (blastemal type with diffuse anaplasia, cava
thrombus and extra-renal disease) had a combined pulmonal
and abdominal relapse and died 16 months after surgery.
All other patients are alive without evidence of disease and
with their organs functioning after a median follow-up of 25
months (0-118).
Conclusions: Children with bilateral renal tumors should be
treated and especially undergo surgery in centers with special
expertise in this field. Under this condition, surgery of central bilateral renal tumors can be executed with a satisfactory
surgical, functional, and oncological outcome.
O-154 Feasibility of Complete Resection of
Residual Lung Nodules After Chemotherapy in
Patients with Stage IV Favorable Histology Wilms
Tumor
P. Ehrlich1 , E. Smith2 , G. Khanna3 , K. Gow4 , T. Hamilton5 , S.E.N.
Servaes6 , D. Barnhart7 , R. Glick8 , R. Dasgupta9 , E. Mullen10 , J.
Geller11 , C. Fernandez12 , J. Kalapurakal13 , E. Gratias14 , J. Dome15 ,
D. Dix16
1 University of Michigan, Surgery, Ann Arbor, USA; 2 University of
Michigan, radiology, Ann Arbor, USA; 3 Washington University at St Louis,
Radiology, St Lous, USA; 4 University of Washington, Surgery, Seattle, USA;
5 Harvard University, Surgery, Boston, USA; 6 Childrens Hospital of
Philadelphia, Radiology, Philadelphia, USA; 7 Primary Childrens Hopsital,
Surgery, Salt Lake City, USA; 8 Cohen Childrens Hopsital, Surgery, Long
island, USA; 9 Cincinnati Childrens Hospital, Surgery, Cincinnati, USA;
10 Dana Farber, Oncology, Boston, USA; 11 Cincinnati Childrens Hospital,
Oncology, Cincinnati, USA; 12 IWK Childrens Hospital, Oncology, Halifax,
Canada; 13 Northwestern, Radiation Oncology, Chicago, USA; 14 Childrens
Oncology Group, Renal Tumors, Philadelpahia, USA; 15 Childrens National
Medical Center, Onoclogy, Washington DC, USA; 16 University of British
Columbia, Oncology, Vancouver, Canada
Background/Objectives: Children's Oncology Group (COG)
study AREN0533 showed that patients whose pulmonary
lesions had a complete response (CR) by 6 weeks with
vincristine, dactinomycin, and doxorubicin can avoid pulmonary XRT and have outstanding overall survival. Patients
who did not achieve CR received pulmonary XRT, but
it is possible that some of these patients had benign
lesions, necrotic Wilms tumor, or well-differentiated Wilms
SIOP ABSTRACTS
tumor that may not require XRT. The purpose of this
exploratory study was to examine the feasibility and
extent of surgical resection for PR/SD patients enrolled on
AREN0533.
Design/Methods: Patients enrolled on COG AREN0533 with
stage IV WT due to pulmonary metastasis, and had either
PR/SD with less than 10 lesions after 6 weeks of chemotherapy were eligible. The initial and 6 week chest CT were
reviewed by surgeons and radiologists to evaluate number,
location and resectability of residual lesions. For this study
resection was considered “feasible” if lesions were peripheral,
required only a wedge resection and could be performed thorascopically. Resections that would require a total lobectomy
were not considered feasible.
Results: 302 patients enrolled and at 6-weeks, 189 had either
PR/SD. Of these 93(49%) had less than 10 lesions (14 SD
and 79 PR). 83 of 93 patients has 1-3 residual lesions. In
23/93(28%) surgery was considered not feasible. In 67/93
(72%) thorascopic surgery was deemed feasible(35% of total,
67/189). Extent of surgery included a single wedge resection
in 20 patients; between 2-3 wedge sections in a single lobe
in 5 patients; between 2-3 wedge resections in different lobes
in a single lung in 24 patients. 18 would require 2-5 wedge
resections in both lungs
Conclusions: Thorascopic resection of pulmonary noldues
was considered “feasible” in 35% of PD/SD after 6 weeks of
cheotherapy. Selected PR/SD patient's maybe good candidates
for surgery and could avoid XRT.
O-155 Cross-Sectional and Longitudinal Study of
Renal Function after Nephron-Sparing Surgery
Versus Nephrectomy for Unilateral Renal Tumor in
Children
D. Cozzi1 , S. Ceccanti1 , S. frediani1 , I. Falconi1 , A. Cervellone1 , F.
Cozzi1
1 Sapienza
University of Rome, Pediatric Surgery Unit, Rome, Italy
Background/Objectives: Pre-operative renal dysfunction in
children with unilateral renal tumor (URT) may be a surrogate
marker of low nephrons number endowment. Therefore, we
included baseline renal function among the matching criteria
used to compare the renal function outcome after nephronsparing surgery (NSS) versus nephrectomy in more balanced
pair-matched groups of children with URT.
Design/Methods: We reviewed our prospectively maintained
database of children with URT treated at our institution
between 1992 and 2016. Thirteen patients who underwent
NSS were matched with thirteen patients who underwent
nephrectomy. Propensity scores included age at surgery,stage,
age at follow-up, sex, histologic type, pre-operative estimated
glomerular filtration rate (eGFR), and number of preoperative
S85 of S518
patients with renal dysfunction (eGFR<90/ml/min/1.73m2 ).
The renal function outcomes were evaluated by crosssectional and longitudinal study of eGFR.
Results: Before surgery 5 patients in each group presented
with renal dysfunction. At 20-year follow-up, cross-sectional
study showed a renal function advantage of NSS over
nephrectomy (eGFR 117±18.4 vs. 99.5 ±22.1;p=0.03). The
longitudinal study of eGFR showed a stable renal function
after nephrectomy (p=0.64) and a significant increase after
NSS (p=0.004). At last follow-up, 6 patients after nephrectomy and none after NSS, presented with a renal dysfunction
(p=0.01).
Conclusions: Children with URT treated with NSS, in comparison with pair-matched children treated with nephrectomy,
may present after surgery a better recovery of renal function
reaching at long-term follow-up values within the range of two
kidneys renal function. At a similar follow-up, 46% of children with URT treated with nephrectomy may present with
renal dysfunction.
O-156
How do we Biopsy Renal Tumours?
K. Elmalik1 , E. Gavens2 , S. Marven2 , R. Fisher2 , J. Walker2 , A.
Raghavan3 , D. Hughes3 , L. Smith1 , S. Nour1 , F. Dickinson4 , A.
Rickett4 , B. Davies5 , D. Colliver5 , M. Peeraully5 , L. Morris5 , R.
Stewart5
1 East
Midlands Children's and Young Persons’ Integrated Cancer Service,
Paediatric Surgery, Leicester, United Kingdom; 2 Sheffield Children's
Hospital, Paediatric Surgery, Sheffield, United Kingdom; 3 Sheffield
Children's Hospital, Paediatric Radiology, Sheffield, United Kingdom;
4 East Midlands Children's and Young Persons’ Integrated Cancer Service,
Paediatric Radiology, Leicester, United Kingdom; 5 East Midlands
Children's and Young Persons’ Integrated Cancer Service, Paediatric
Surgery, Nottingham, United Kingdom
Background/Objectives: The management of Wilms tumour
is unique in the UK. The SIOP protocol is followed however currently a biopsy is performed pre-chemotherapy. The
UKW3 team have investigated the potential influence of the
biopsy on local recurrence. The aim of this study was to examine the technique of the biopsy.
Design/Methods: This was a three centre retrospective data
analysis between 2001-2016 using medical records and
Histopathology reports from three centres. Study limitations
were due to variability in documentation within the three sites
over a long period of time.
Results: Hundred and forty cases of renal tumours were identified, 76 were females and 64 were males; average age was
3y 4m (5m – 15y4m). The diagnosis was Wilms Tumour in
95%, others; CCSK, Cystic Nephroma and Renal Cell Carcinoma. Stage I 34%, stage2 13%, stage 3 24%, stage 4 22% and
stage 5 7%. Risk stratification showed 11% were high risk,
82% intermediate and 7% low risk. The approach to biopsy
was open in 7% and percutaneous in 93%. In nine percuta-
SIOP ABSTRACTS
S86 of S518
neous cases a Co-axial sheath was used. The needle gauge
range was 14 to 18G. The radiologist performed the biopsy
in 44% of cases while the surgeon did in 56%. Multiple cores
were taken between 2-11 samples. Ultrasound guidance was
utilised in the majority to guide the biopsy. Only one patient
developed bleeding from a biopsy however none underwent
an emergency nephrectomy.
Conclusions: This is the first study that looked into the technique of biopsy in renal tumours. The results showed that the
technique is safe whether it is performed by a radiologist or a
surgeon. Surgeons and radiologists need to improve their documentation of the fine details when performing percutaneous
biopsies.
O-157 Inter-Ethnic Differences in Wilms Tumors
- A Clinical, Pathological and Molecular Profile of a
Multiracial Cohort
B.N. Loke1 , K.D. Tawng2 , C.H. Kuick3 , M.K. Wong4 , S. Jain3 ,
Y.H. Zou5 , V. Ganesan5 , D.W.Q. Lian3 , S.W. Sim6 , Y.T. Lee6 ,
F.K.C. Chin7 , M.Y. Chan2 , A.M. Tan2 , S.Y. Soh2 , K.T.E. Chang3 ,
A.H.P. Loh6
1 National
University of Singapore, Faculty of Science, Singapore,
Singapore; 2 KK Women's and Children's Hospital, Department of
Paediatric Subspecialties Haematology Oncology Service, Singapore,
Singapore; 3 KK Women's and Children's Hospital, Department of
Pathology and Laboratory Medicine, Singapore, Singapore; 4 KK Women's
and Children's Hospital, VIVA-KKH Paediatric Solid Tumour Research
Laboratory, Singapore, Singapore; 5 National University of Singapore, Yong
Loo Lin School of Medicine, Singapore, Singapore; 6 KK Women's and
Children's Hospital, Department of Paediatric Surgery, Singapore,
Singapore; 7 National Cancer Centre Singapore, Division of Radiation
Oncology, Singapore, Singapore
Background/Objectives: Wilms tumor demonstrates significant epidemiological, histological and outcome differences
between ethnic groups, yet the clinicopathological and molecular profile is poorly studied in Asians. Also, the incidence of
biological risk factors in Asian populations are not known. We
aimed to characterize these features in Wilms tumor patients
from a multiracial cohort.
Design/Methods: Clinical charts and histological slides from
patients with malignant renal tumors seen at our institution
from January 1997 to December 2016 were reviewed. PCRbased genotyping was used to identify loss of heterozygosity
at 1p36 and 16q22. Clinicopathological and molecular characteristics, and survival outcomes of Asian and non-Asian
patients were compared.
Results: Sixty-seven of 80 malignant renal tumors were
Wilms tumors; 53 (79.1%) were Asian and 14 (20.9%) were
non-Asians. Mean age at diagnosis was 4.1 years (s.d.: 3.4
years). There were more girls among non-Asians than Asians
(female:male=1.8 and 1.0, respectively). Unfavorable histology occurred more frequently in non-Asians than Asians
(25.0% and 4.2%, respectively, P=0.02). More non-Asians
had focal or diffuse anaplasia (8.3% and 6.7%) compared to
Asians (2.2% and 2.2%, P=0.059), yet nephrogenic rests were
encountered only in Asian patients (7 perilobar, 6 intralobar).
More non-Asians presented with advanced disease (National
Wilms Tumor Study (NWTS) stage III, 6 (54.5%), stage IV,
3 (27.3%)) compared to Asians (stage III, 13 (27.1%), stage
IV, 5 (10.4%)), but lymph node metastases rates were similar (non-Asian 20.0%, Asian 19.1%). No Asian patients had
bilateral tumors; only one non-Asian patient had stage V disease. Following treatment on NWTS regimens, event-free and
overall survival did not differ between non-Asian and Asian
patients (P=0.660 and 0.782, respectively, Log-rank test).
Conclusions: Asian patients had more equal gender ratio,
less unfavorable histology and anaplasia, and less advanced
disease at presentation. The biological bases for these differences, and the potential implications on treatment recommendations for Asian patients warrants further study.
O-158 Combination Technique Image Guided
Localisation Prior to Thoracoscopy Facilitates
Accurate Identification and Biopsy of Suspiscious
Pulmonary Lesions
M. Collin1 , S. Murthy Chennapragada2 , D. McDowell1,3 , J.
Karpelowsky4,5
1 The
Children's Hospital at Westmead, Paediatric Surgery, Westmead,
Australia; 2 The Children's Hospital at Westmead, Radiology, Westmead,
Australia; 3 University of Sydney, Sydney Medical School, Sydney, Australia;
4 The Children's Hospital at Westmead, Paediatric Oncology and Thoracic
Surgery, Westmead, Australia; 5 University of Sydney, Children's Cancer
Research Unit, Sydney, Australia
Background/Objectives: Image guided localization of pulmonary lesions suspected for metastases or infection prior to
thoracoscopic biopsy has aided identification during the minimally invasive approach. Techniques used to facilitate identification of the lesions at thoracoscopy have included methylene blue tattoo or hookwire localisation under CT guidance.
We describe our surgical results using the techniques alone or
in combination to improve the intra operative localisation of
the lesions at thoracoscopy.
Design/Methods: This retrospective audit included all cases
of CT guided localisation and surgical excision of pulmonary
lesions identified from our institution's surgical and radiology
databases from 2006-2016. We reviewed the method of CT
localisation (single hookwire or methylene blue versus both),
the intraoperative findings including success of the technique,
ability to identify the lesion and histopathological findings.
Results: Eighteen children (14 male and 4 female, age range
4-17 years) underwent CT guided localization prior to surgical
excision of pulmonary lesions. Eleven out of 18 cases involved
the use of both hookwire and methylene blue, 6/18 cases
used methylene blue only and 1/18 case used hook wire only.
SIOP ABSTRACTS
S87 of S518
Histologically, there were 5 metastatic nodules, 1 fungal infection, the remaining 11 being non-specific/infective changes
or lymph nodes. Thoracoscopic resection of the suspicious
lesion was possible in all except one case where methylene
blue only was used and spilt throughout the thorax. In this
case a previously unidentified pleural based lesion was biopsied which was diagnostic for infection. In two cases where
both techniques were used, one of the techniques had failed
(one hookwire and one methylene blue) however the lesions
were successfully biopsied due to localization from the other
technique.
ized. The median number of nodules per patient was 2 [1-52].
Median size was 3 mm [1-13]. Nodules were round in 77% of
cases and calcified in 17%. At pre-operative assessment, nodules were still detectable in 30/46 (65%) patients with nodules
at diagnosis and appeared in one patient with no nodules at
diagnosis. Among these 30 patients, 22 (73%) were operated
on. The 5-year overall and event-free survival (OS/EFS) of
patients with at least one nodule at diagnosis versus no nodule
were respectively 70%(95%CI:50%-84%)/55%(CI95%:35%71%) and 89%(95%CI:70%-96%)/79% (95%CI:61%-89%)
(p=0.04 for OS and p=0.15 for EFS).
Conclusions: Preoperative image guided localisation of pulmonary lesions facilitates minimally invasive thoracoscopic
identification for biopsy of these lesions. We recommend the
use of both hookwire and tattoo to improve the chances of
localising a lesion accurately for biopsy.
Conclusions: The CT-scan detection of lung nodules at diagnosis of osteosarcoma regardless of their evolution and management seems to negatively impact OS.
(PBC-SESSION): THE ROBERT
ARCECI BEST OF I P S O
O-159 Prognostic Impact of Pulmonary Nodules
Diagnosed at Initial Presentation in Patients with
Osteosarcoma
S. Irtan1 , L. Brugières2 , H. Pacquement3 , M.D. Tabone4 , S.
Piperno-Neuman5 , N. Gaspar2 , M. Jimenez6 , M. Larroquet1 , S.
Sarnacki7 , J. Donadieu4 , C. Cellier8
1 Armand-Trousseau
Hospital- APHP, Pediatric Surgery, Paris, France;
2 Gustave Roussy Institute, Pediatric Oncology, Villejuif, France; 3 Curie
Institute, Pediatric Oncology, Paris, France; 4 Armand-Trousseau HospitalAPHP, Pediatric Oncology, Paris, France; 5 Curie Institute, Oncology,
Paris, France; 6 Unicancer, Pediatric Oncology, Paris, France; 7 Necker
Enfants Malades - APHP, Pediatric Surgery, Paris, France; 8 Curie Institute,
Pediatric Radiology, Paris, France
Background/Objectives: Patients with metastatic osteosarcoma have a poor outcome but the surgical removal of all
lung metastases is thought to improve survival. The dramatic
increase of CT-scan quality allows detecting endless smaller
nodules whose exact nature remains difficult to assess. We
aimed to determine if the presence of at least one nodule on
CT-scan at diagnosis has an impact on survival and to describe
the evolution and management of lung nodules during the
course of treatment.
Design/Methods: The analysis was performed on patients
from three centres included in OS2006 trial and treated with
high-dose methotrexate based chemotherapy from 2007 to
2013. Chest CT-scans performed at diagnosis, before and after
lung surgery, at the end of treatment and at relapse in case of
recurrence were centrally reviewed.
Results: Among 80 patients diagnosed at a median age of
13.5 years [3-27], 8 patients (10%) had been classified at
diagnosis as metastatic, 46 (57%) as localized and doubtful
in 26 cases (32%). At central review, nodules were found at
diagnosis in 46 (57%) patients: in all patients classified as
metastatic or doubtful and in 12 patients considered local-
O-160 Outcome of Patients Suffering from
Rhabdomyosarcoma of the Female Genital Tract A Report from the Cooperative Weichteilsarkom
Studiengruppe Trials CWS-81, -86, -91, and -2002P
G. Seitz1 , M. Matle2 , M. Sparber-Sauer3 , J. Fuchs4 , T. Klingebiel5 ,
E. Koscielniak3
1 Center
for Pediatric and Adolescent Medicine, Department of Pediatric
Surgery, Marburg, Germany; 2 Center for Pediatric and Adolescent
Medicine, Department of General Pediatrics and Neonatology, Marburg,
Germany; 3 Klinikum Stuttgart - Olgahospital- Zentrum für Kinder– Jugendund Frauenmedizin, Pediatrics 5 Oncology- Hematology- Immunology,
Stuttgart, Germany; 4 University Children´s Hospital, Department of
Pediatric Surgery and Urology, Tuebingen, Germany; 5 University Hospital,
Department of Pediatric Hematology and Oncology, Frankfurt/Main,
Germany
Background/Objectives: Rhabdomyosarcoma (RMS) of the
female genital tract is rare and vaginal tumors seem to have
a more favorable prognosis. Local control may consist of
surgery and/or radiotherapy, but might be associated with
severe side effects in young children. The aim of the study was
to evaluate treatment and outcome of patients treated within
four Cooperative Soft Tissue Sarcoma (CWS) trials.
Design/Methods: Fifty-four patients suffering from localized
RMS of the female genital tract (vagina/uterus) were enrolled
and analyzed. All patients were treated according to the CWS
study protocols.
Results: The 5-year overall survival rate was 84.6% and the
5-year event free suvival (EFS) 71.5%. Median age was 2.5
years and the median follow-up 7.85 years. 53 patients had
embryonal and one patients alveolar histology. Forty patients
were ≤10 years (EFS: 71.4%) and fourteen >10 years (EFS:
71.4%). Fourty tumors were located at the vagina (EFS:
68.9%) and 14 at the uterus (EFS: 78.6%). Tumors ≤5cm
SIOP ABSTRACTS
S88 of S518
had a better EFS (n = 26; 84.3%) than those >5cm (n = 28;
59.3%). Positive lymph nodes at diagnosis were detected in
3 patients (EFS: 33.3%). Primary resection was carried out in
26 patients (EFS: 68%) and secondary resection in 33 patients
(EFS: 65.3%). Completeness of resection did not influence the
outcome. Radiotherapy was used in 20 patients (EFS: 42.1%).
Only 3 patients were treated with solely chemotherapy.
Conclusions: The outcome of patients suffering from RMS
of the female genital tract is comparable to other localizations
in the urogenital tract. Almost all patients had local control
and tumors located at the uterus seem to have a trend towards
a better EFS than those located in the vagina. Tumor size,
but not patient´s age, is a positive predictive factor for outcome. The extent of surgical resection had no Impact on the
outcome.
O-161 Pelvic Peritonectomy Prevents Recurrence
of Desmoplastic Small Round Cell Tumor After
CRS and HIPEC
A. Hayes-Jordan1 , B. Coakley1 , L. Xiao2 , C. Herzog3 , P.
Anderson4 , W. Huh3
1 MD
Anderson Cancer Center, Surgery, Houston Texas, USA; 2 MD
Anderson Cancer Center, Biostatistics, Houston Texas, USA; 3 MD
Anderson Cancer Center, Pediatrics, Houston Texas, USA; 4 The Cleveland
Clinic, Pediatric Hematology Oncolgy and Blood and Marrow
Transplantation, Cleveland- OH, USA
Background/Objectives: Desmoplastic small round cell
tumor (DSRCT) is a rare form of sarcoma primarily affecting adolescents. Patients frequently present with hundreds of
peritoneal tumor implants. Historically, only 30% of patients
reach 3-year overall survival. Inability to obtain a complete
abdominal resection impacts long-term survival in DSRCT.
We use a combination of systemic chemotherapy, cytoreductive surgery with cisplatin-based hyperthermic intraperitoneal
chemotherapy (CRS-HIPEC) and adjuvant radiotherapy. As
almost 100% of patients have pelvic tumors at diagnosis,
we hypothesized that a pelvic peritonectomy, after neoadjuvant chemotherapy, was essential for control of the ‘primary’
tumor.
Design/Methods: We reviewed 81 patients who underwent
complete CRS-HIPEC with cisplatin for DSRCT from 20062016. Since pelvic peritonectomy was routinely performed
after March 2013, we compared patients who received pelvic
peritonectomy to those who did not, regardless of macroscopically visible disease in the pelvis. All patients received neoadjuvant and adjuvant chemotherapy. Most received adjuvant
radiotherapy.
Results: Patients ranged in age from 4 to 41 years and were
followed postoperatively up to 7.7 years. Before pelvic peritonectomy was added to our standard operative approach, 39%
of patients (18/46) developed a local recurrence. Of these
recurrences, 33% (6/18) were located in the pelvis alone without distant disease. The local recurrence rate decreased to 6%
(2/35) after making this change. Among 59 patients with at
least 36 months follow-up, the median recurrence-free survival was 11.8 months and median overall survival was 36.1
months. Median postoperative survival (31.1 months vs. 18.1
months, p=0.04) was significantly longer in patients who had
a CR0/CR1 CRS-HIPEC than for patients who had a CR2
CRS-HIPEC.
Conclusions: Complete cytoreduction, including routine
pelvic peritonectomy, substantially reduces local recurrence
rates of DSRCT. With this technique, a 94% local control
rate was achieved in DSRCT patients who underwent CRSHIPEC.
O-162 Outcome of Localized Liver-Bile Ducts
Rhabdomyosarcoma According to Local Therapy. A
Report from the European Soft Tissue Sarcoma
Group (EPSSG) RMS 2005 Study
F. Guerin1 , G. Cecchetto2 , T.N. Rogers3 , S. Terwisscha Van
Scheltinga4 , G. Guillen Burrieza5 , V. Minard-Colin6 , H.
Mandeville7 , A. Kelsey8 , G.L. De Salvo9 , G. Bisogno10 , H.
Martelli1
1 Bicetre
hospital APHP, paediatric surgery, Le Kremlin Bicetre, France;
Hospital of Padua, paediatric Surgery, Padova, Italy; 3 Royal
hospital for Sick Children, Paediatric surgery, Bristol, United Kingdom;
4 Prinses Máxima Centrum voor Kinderoncologie, Paediatric Surgery,
Utrecht, The Netherlands; 5 Hospital Universitari Vall d'Hebron, Paediatric
Surgery, Barcelona, Spain; 6 Gustave Roussy Cancer Campus, Paediatric
Oncology, Villejuif, France; 7 The Royal Marsden NHS Foundation Trust,
Clinical Oncology, Sutton, United Kingdom; 8 Royal Manchester Children's
hopsital, Pathology, Manchester, United Kingdom; 9 Istituto Oncologico
Veneto IOV-IRCCS, UOS Sperimentazioni Cliniche- Biostatistica e Nucleo
Ricerca Clinica, Padova, Italy; 10 University Hospital of Padua, Paediatric
Oncology, Padova, Italy
2 University
Background/Objectives: To evaluate the impact of local
treatment therapy on outcome in patients with liver-bile ducts
rhabdomyosarcoma (BD-RMS)
Design/Methods: We analyzed the data of 28 patients (2 liver,
26 bile ducts) included in the RMS 2005 protocol until 2013.
Delayed surgery and/or External Beam Radiation Therapy
(EBRT) were performed after at least 4 courses of chemotherapy.
Results: All but one patient had embryonal RMS, 13 had a
tumour > 5cm, 5 were N1. Median age at diagnosis was 3
years (1-8 years).
– Six patients (21%) had primary surgery (1 IRS I, 4 IRS II,
1 IRS III): ) consisting of bile duct excision (BDE), 1 with
Whipple procedure. Four of them also received EBRT. All
are in first complete remission (CR1) except one (IRS II,
EBRT+, local relapse, death)
SIOP ABSTRACTS
– Five patients (18%) received EBRT alone (one local
relapse, death).
– Seventeen patients (61%) underwent secondary surgery (7
with additional EBRT): 7 BDE including 2 with Whipple procedure, 7 BDE + partial hepatectomy, and 3 partial
hepatectomies. Four R1 patients underwent EBRT without
recurrence. Among 3 R0 patients who received EBRT, one
had a metastatic relapse and died. Ten R0 patients did not
receive EBRT: 3 relapsed locally, 2 died and 1 is in CR2.
S89 of S518
cases received chemotherapy without a tumor biopsy. In the
19 cases with preoperative chemotherapy, 4 died of tumor progression before surgery, while the remaining 15 cases underwent tumor resection including 4 who received a liver transplantation. Postoperative chemotherapy was performed in all
30 cases, including 2 of high dose chemotherapy. However,
11 of these 30 cases showed recurrence and 6 cases died.
In summary, local relapse occurred in 2 among 15 patients
with EBRT and 3 among 12 without EBRT.
Conclusions: Spontaneous tumor rupture is an unfavorable
prognostic factor for pediatric liver tumors. Adequate surgical or interventional treatments to control tumor bleeding and
more aggressive chemotherapy might be necessary to improve
the outcomes of these patients.
At a median follow-up of 5 years (16 months-10 years) 23
patients are alive, 22 in CR1. Five patients died (4 local, 1
metastatic relapse). 5-years OS was 85% (CI:67-94%) and 5years EFS was 75.6% (CI:55.3-88.6%).
R A R E T U M O R S (+ 1 E D U CAT I O N )
Conclusions: Local relapse in BD-RMS is often fatal. This
analysis did not show any difference in outcome between
surgery alone and EBRT+/- surgery. However possible longterm sequelae of EBRT on hepatic pedicle could be balanced
with the safety of BDE + Roux en Y loop.
O-163 Surgical and Interventional Treatments
for Ruptured Hepatic Tumors in Japanese Study
Group Experiences
E. Hiyama1 , T. Hishiki2 , K. Hoshino2 , A. Yokoi2 , Y. Takama2 , T.
Kazama2 , S. Honda2 , T. Taguchi2 , S. Kurihara1 , M. Kawashima1 ,
Y. Ueda1
1 Hiroshima
2 Japan
University Hospital, Peditric Surgery, Hiroshima, Japan;
Children's Cancer Group, Liver tumor committee, Tokyo, Japan
Background/Objectives: We aimed to evaluate interventional and surgical treatments of spontaneous tumor rupture
in hepatic tumors in the JPLT (Japanese study group for Pediatric Liver Tumors) -2 study (1999-2012).
Design/Methods: Of the 404 patients with hepatic malignancies who were enrolled in the JPLT-2 study, 32 showed spontaneous tumor rupture at diagnosis. Age at diagnosis, sex,
pathology of liver disease, PRETEXT classification, and clinical presentation were assessed. Embolization was performed
in a selective fashion when possible. Treatments, complications, and survival were examined.
Results: There were 7 PRETEXT I, 9 II, 10 III, and 6 IV,
including 5 metastatic tumors. The age range at diagnosis was
2-184 months, with 20 males and 12 females. Histological
examination revealed 27 hepatoblastomas, 4 hepatocellular
carcinomas, and 1 sarcoma. Transarterial embolization was
performed in 27 cases, whereas 4 of them showed uncontrollable bleeding, with 2 of these cases dying of massive bleeding. In the remaining 30 cases, 11 PRETEXT I and II cases
underwent primary resection of the tumors, 11 cases had a
tumor biopsy followed by preoperative chemotherapy, and 8
O-164 Systematic Review and Meta-Analysis of
Appendiceal Carcinoid Tumours in Children
I. Njere1 , L. Linnea1 , D. Thurairasa1 , M. Bisharat1 , I. Jefffrey2 , D.
Rex1 , Z. Mukhtar1 , E. Nicholls1 , B. Okoye1 , C. Sinha1
1 St
George's University of London, Paediatric Surgery, London, United
Kingdom; 2 St George's University of London, Pathology, London, United
Kingdom
Background/Objectives: To determine if more invasive procedures are necessary following incidental finding of an
appendiceal carcinoid tumour after appendicectomy
Design/Methods: A search of Medline, Embase, Cinahl and
Cochrane database of systematic reviews were undertaken of
the English language literature. The mesh terms used were
Carcinoid or neuroendocrine, tumour or tumor, appendix or
appendicectomy or appendectomy, child or paediatric or paediatric. Of 369 articles found 37 met the inclusion criteria. Our
hospital records and pathology database identified 11patients
with confirmed histological diagnosis of appendicular carcinoids from January 1996 to December 2016.
Results: A total of 958 cases were identified from the literature and our own experience. There were 566 females and
343 males giving us a ratio of 1.65:1. The frequency was 1 in
333.8 appendicectomies or 0.3% of appendicectomies. There
was a twenty eight-fold increase in risk of having a positive
lymph node if tumour size was >2cm compared with the risk
of having a positive lymph node if tumour size was ≤2cm.
Of 189 patients that met the criteria for Right hemicolectomy
(RHC) following appendicectomy, with a median follow-up of
3.4years (range 0-51years) no recurrence was noted in neither
the 69 that had a secondary procedure nor the 120patients that
were just observed. No mortality from carcinoid was noted
in the 2 groups. No survival advantage was therefore conferred by another procedure. Mean follow-up was 58.6months
(4.8yrs) with a range of 0-396months (33yrs).
SIOP ABSTRACTS
S90 of S518
Conclusions: Appendicectomy alone is adequate treatment
for an appendicular carcinoid in children, irrespective of size,
position, lymph node or mesenteric involvement unless there
are positive margins. Post-appendicectomy investigations not
helpful and long follow-up unnecessary
O-165 Controversies in Surgical Management of
Melanoma in Pediatric Age
M. Ilari1 , G. Torino1 , A. Zangari2 , F. Nino1 , G. Cobellis1 , A.
Martino1
1 "G.
Salesi" Children's Hospital, Pediatric Surgery, Ancona, Italy; 2 San
Camillo - Forlanini General Hospital, Pediatric Surgery, Roma, Italy
Background/Objectives: Malignant melanoma (MM) in
children is rare with an incidence of 0.7/million/year. The risk
of melanoma development in large congenital nevi is widely
accepted. Melanoma occurrence from intermediate congenital nevi has been reported. The purpose of this study is to discuss surgical indications of nevi and diagnosis and treatment
of melanoma.
Design/Methods: From 2003 to 2016 were retrospectively
reviewed 145 children (aged 1 month to 14 years) underwent to surgical excision of 156 nevi. Indications for excision
included clinical appearance, site of difficult monitoring or
of exposure to frequent trauma. After diagnosis of MM, the
patient was underwent to sentinel lymph-node biopsy (SLNB)
for melanoma thickness of ≥ 1 mm associated to excision of
tumor site (with 2 cm margins) and primary closure or skin
graft.
Results: In all cases, first surgical excision included 2 mm
margins of normal skin around the lesion. MM was diagnosed in 5 patients. One infant was underwent to partial excision of large congenital nevus but at 23 months follow-up he
was also submitted to excisional biopsy of an inguinal nodal
mass resulting in metastatic melanoma and he died for cerebral metastasis. The other 4 patients were underwent to scar
excision with 2 cm margins and SLNB for MM diagnosis.
In 3 patients, the SLBN was positive and in 2 of them was
performed an inguino-iliac-obturatory lymph-node dissection
showed micromestases, on the contrary, in the third patient the
parents refused further surgical proposed treatment but she
remains disease free at 8 months follow-up. The remaining
three patients are disease free at 16, 13 and 10 years respectively.
Conclusions: MM in children is less rare than is commonly
believed. The behaviour of this disease is different from that
in adulthood. Clinical trials are needed to define the biological
findings and the most suitable surgical treatment for MM in
children.
O-166 Outcome After Surgery for Solid
Pseudopapillary Pancreatic Tumors in Children:
Report from Trep Project – Italian Rare Tumors
Study Group
A. Crocoli1 , C. Grimaldi1 , M.D. De Pasquale2 , G. Cecchetto3 , C.
Virgone3 , S. Cesaro4 , G. Bisogno5 , V. Cecinati6 , A. Narciso1 , D.
Alberti7 , A. Ferrari8 , P. Dall'Igna3 , M. Spada1 , A. Inserra1
1 Bambino
Gesù Children's Hospital - IRCCS, Surgery, Rome, Italy;
Gesù Children's Hospital - IRCCS, Oncohematology, Rome,
Italy; 3 University of Padova, Pediatric Surgery, Padova, Italy; 4 Policlinico
G.B. Rossi, Hematology, Verona, Italy; 5 University of Padova, Pediatric
Hematology and Oncology, Padova, Italy; 6 Ospedale Civile, Pediatric
Hematology and Oncology, Pescara, Italy; 7 Spedali Civili, Pediatric
Surgery, Brescia, Italy; 8 Istituto Nazionale Tumori, Pediatric Oncology,
Milan, Italy
2 Bambino
Background/Objectives: Solid pseudopapillary pancreatic
tumors (SPPT) are an extremely rare entity in pediatric
patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow up in
children undergone pancreatic resection are scant.
Design/Methods: Retrospective review of Italian pediatric
rare tumor registry (TREP) was performed. Short (<30 days)
and long term complications of different surgical resections,
as well as long term follow up were evaluated.
Results: from January 1st 2000 to February 28th 2017, 40
patients (M:F=8:32) were enrolled. Median age at diagnosis was 13,5 years (range 7-18). Median delay of diagnosis
was 1 month (range 0-7). Fourteen children had an occasional diagnosis, whereas 19 complained of abdominal pain
and 7 were referred for recurrent vomiting. Tumors arose
from head of pancreas (n=12) or from body/tail (n=28).
Resection was complete in 38 patients (duodenocephalopancreasectomy n=11, spleen preserving distal resection n =24,
distal resections with splenectomy n=3); 2 cases of microscopic spillage were recorded. At follow up (median 81
months, range 0-188), local recurrence of disease occurred
in one patient with intraoperative spillage. All patients are
alive. Three pancreatic fistulas occurred in the body/tail
group (conservative management), whereas 3 complications
occurred in head group (one ileal ischemia undergone to
endovascular treatment, one Wirsung duct stenosis undergone to surgical revision and one chilous fistula managed
conservatively).
Conclusions: Surgery proves as the therapeutic option for
these tumors, hence complete resection is mandatory. Extensive resections, including duodenocephalopancreasectomy,
are safe when performed in specialized centres. Long term
follow up must be centered on oncologic radicality and residual pancreatic function.
SIOP ABSTRACTS
O-167 Duodenum-Preserving Pancreatic Head
Resection (Modified Whipple's Procedure) for
Tumors Localized to the Pancreatic Head in
Children
J. Wang1 , X. Chen1 , M. Li1 , J. Cai1 , M. He1 , J. Mao1 , Q. Shu1
1 Children's
Hospital - Zhejiang University School of Medicine, Department
of Surgical Oncology, Hangzhou, China
Background/Objectives: Pancreatic tumor is a rare neoplasm in children. Whipple's procedure is considered as a
standard treatment for tumors localized to the pancreatic head.
However, this radical procedure is still controversial in pediatric population, since most pancreatic tumors in children are
benign or low-grade malignant. Herein, we present 11 cases
duodenum-preserving pancreatic head resection (DPPHR) for
tumors localized to the pancreatic head in children.
Design/Methods: Retrospective single institution study was
performed, 11 cases with tumors localized to the pancreatic
head in our center from Jan. 2015 to Dec. 2016 were included.
Tumor types were pancreatoblastoma (n=4, 1 male and 3
female, aged from 3m to 7y2m) and solid-pseudopapillary
tumor (SPT, n=7, 2 male and 5 female, aged from 8y2m
to 13y4m). All cases underwent DPPHR procedure. Patients
with pancreatoblastoma and 3 cases with SPT received postoperative chemotherapy and other 4 cases with SPT received
close follow-up without chemotherapy.
Results: DPPHR was performed successfully and duodenum
was kept intact in all cases. Eight cases underwent pancreaticojejunostomy only since common bile duct was not injured
during pancreatic head resection. Two cases underwent
pancreaticojejunostomy plus cholangiojejunostomy. Other 2
cases received tumor resection only. Pancreatic pseudocyst
was observed in 1 case (tumor resection only group) and
there was no other early postoperative complication. Followup time from 3m to 27m, recurrence was observed in 1 case
with pancreatoblastoma 6m after chemotherapy. Recurrent
tumor localized to pancreatic body not duodenum wall was
identified during the second operation.
Conclusions: Duodenum-preserving pancreatic head resection combined with appropriate chemotherapy is safe and
effective for tumors localized to the pancreatic head in children.
S91 of S518
Background/Objectives: To present our experience in the
diagnosis and treatment of pediatric thyroid cancer at a Cancer Center in Bogota, Colombia.
Design/Methods: We reviewed 48 cases referred to our institution from 2008-2016 with pediatric thyroid cancer. Thirtyeight had complete information on their charts for analysis.
We analyzed the demographic characteristics, the symptom of
presentation, diagnosis, treatment, recurrence, mortality, and
delay between diagnosis and treatment.
Results: Patients were between 8-19 years old. Mean age
at diagnosis was 12 years of age. Eighty-two percent were
female. Two patients had a positive family history for MEN2 Syndrome. 74% presented with a thyroid nodule, and 13%
with cervical node. Fine needle aspiration biopsy was used for
diagnosis in 71%. All patients underwent total thyroidectomy,
papillary thyroid cancer was the most frequent histologic finding (87%), followed by medullary thyroid cancer (5%), clear
cell and follicular carcinoma (3% each). Eighty-six percent
of patients had positive nodes and underwent cervical lymphadenectomy: 27% central compartment, and 73% central
and modified radical lymphadenectomy. There was a complication rate of 13%, 26% recurrence, 29% metastasis, and
5% mortality in this series. Mean time between diagnosis and
thyroidectomy was 4 months (range: 0-38), and mean time to
iodine ablative therapy was 5 months (range: 0-36).
Conclusions: Pediatric thyroid cancer is more frequent in
adolescent females. It presents with a nodule or cervical
node, and the most frequent histology is papillary carcinoma.
Patients usually need some type of lymphadenectomy in addition to total thyroidectomy because of nodal disease. Mortality remains low even though many patients experienced a
delay in surgical treatment and iodine ablative therapy due to
healthcare issues.
O-169 Cytoreductive Surgery and Hyperthermic
Intraperitoneal Perfusion with Chemotherapy in
Children with Peritoneal Tumor Spreading: A
French Nationwide Study Over 14 Years
A. Scalabre1 , P. Philippe-Chomette2 , G. Passot3 , D. Orbach4 , D.
Elias5 , N. Corradini6 , B. Laurence6 , S. Msika7 , M.D. Leclair8 , S.
Joseph8 , C. Brigand9 , F. Becmeur10 , C. Soler11 , D. Pezet12 , J.
Gagniere12 , O. Glehen3 , S. Sarnacki13
1 University
O-168 Diagnosis and Treatment of Pediatric
Thyroid Cancer – Experience in 38 Cases at a
Fourth-Level Institution
J.P. Luengas1 , C. Correa1 , O. Gil1 , A. Holguín1 , G. Veintemilla1
1 Instituto
Nacional de Cancerología, Cirugía Pediátrica, bogota, Colombia
Hospital of Saint-Etienne- Faculty of Medicine Jacques
Lisfranc- PRES Lyon 42023- Jean Monnet University, Pediatric surgery,
Saint-Etienne, France; 2 University Paris 7 Denis Diderot- Hôpital Robert
Debré- Assistance Publique - Hôpitaux de Paris, Pediatric surgery, Paris,
France; 3 CHU Lyon Sud- Hospices civils de Lyon- University of LyonFrance. EMR 37-38- Lyon 1 University, Surgical Oncology, Lyon, France;
4 Institut Curie, Pediatric- Adolescent and Young Adult Oncology, Paris,
France; 5 Gustave Roussy Cancer Center, Oncologic Surgery, Villejuif,
France; 6 Gustave Roussy Cancer Center, Oncology for Child and
Adolescents, Villejuif, France; 7 University Paris 7 Denis Diderot- Hôpital
Louis Mourier- Assistance Publique - Hôpitaux de Paris, Digestive surgery,
SIOP ABSTRACTS
S92 of S518
Colombes, France; 8 Children University Hospital, Pediatric surgery,
Nantes, France; 9 University Hospital, Digestive surgery, Strasbourg,
France; 10 University Hospital, Pediatric surgery, Strasbourg, France;
11 Hôpital l'Archet- University Hospital, Hematology-Oncology, Nice,
France; 12 Université Clermont Auvergne- INSERM- CHU Clermont
Ferrand, Digestive surgery, Clermont Ferrand, France; 13 University Paris
Descartes- Hôpital Necker Enfants-Malades- Assistance Publique Hôpitaux de Paris, Pediatric surgery, Paris, France
Background/Objectives: The use of Minimally Invasive
Surgery (MIS) has been been greatly expanded in pediatric
surgery. However its application in pediatric cancer still is
a matter of debate. Our purpose is to describe our experience using Minimally Invasive Surgery (MIS) techniques
in tertiary center with specific oncological pediatric surgery
unit.
Background/Objectives: Efficacy and role of cytoreductive surgery and hyperthermic peritoneal perfusion with
chemotherapy (HIPEC) remain unknown in pediatric tumors.
Design/Methods: A retrospective analysis of all patients
undergoing MIS in a pediatric oncology surgery unit at a single institution from a developing country between July 2014
and February 2017. MIS procedures were considered made
by laparoscopy with diagnostic, staging or therapeutic intent.
Demographic features, primary diagnosis, surgical procedure, time length, complications and conversion rate were
reviewed.
Design/Methods: This retrospective multicentric national
study analyzed all pediatric patients with peritoneal tumor
spreading treated by cytoreductive surgery with HIPEC as
part of a multimodal therapy in France from 2001 to 2015.
Results: Twenty-two patients (9 males and 13 females) were
selected. The median age was 14.8 years (4.2-17.6). Seven
had peritoneal mesotheliomas, 7 desmoplastic small round
cells tumors (DSRCT) and 8 other histologic types. Twenty
(91%) patients received prior conventional chemotherapy
before HIPEC. A complete macroscopic resection (CC-0)
was achieved in 16 cases (73 %). Incomplete resections were
classified as CC-1 in 4 cases (18%) and CC-2 in 2 cases
(9%). Fourteen (64%) patients had complications within 30
days from HIPEC, requiring an urgent laparotomy in 8 (36%)
cases. Thirteen patients (59 %) received adjuvant chemotherapy and 4 (18%) received total abdominal radiotherapy after
surgery. Fifteen patients (68%) had a relapse after a median
time of 9.6 months (1.4-86.4) after the procedure and 9 (41%)
eventually died after a median time of 5.3 months (0.1-36.1)
from relapse. Six patients (27%) were alive with progressive disease at last-news. Seven patients (32%) were alive
and in complete remission after a median follow-up of 25.0
months. The mean overall survival (OS) and disease free survival (DFS) were 57.5 months (CI95% [38.59-76.32]) and
30.9 months (CI95% [14.96-46.77]). Patients with a peritoneal mesothelioma had a significantly better OS (p=0.015)
and DFS (p=0.028) than other histologic type
Conclusions: In this French national series, outcomes of
HIPEC are encouraging essentially for the treatment of peritoneal mesothelioma in children. International randomized
trials evaluating the outcomes of cytoreductive surgery and
HIPEC for the treatment of peritoneal tumor spreading in children are mandatory.
O-170 Minimally Invasive Surgery in Pediatric
Surgical Oncology: A Developing Country
Experience
R.C. Ribeiro1 , V. Kremer1 , W.E. Oliveira Júnior1
1 Barretos
Childrens Cancer Hospital, Pediatric Surgery Department,
Barretos, Brazil
Results: Forty-two children, ranging from 3 to 256 months
of age, underwent 45 MIS procedures during this period.
Laparoscopy was performed for tumor resection in 23 cases
(51,1%), diagnostic purposes in 9 cases (20%), and for staging in 3 cases (6,6%). Ten additional laparoscopic procedures
(22,2%) were performed for complications of the malignancy
or its treatment. Median surgical time length was 73 minutes,
ranging from 20 to 420 minutes, with a proctocolectomy as
the longest procedure. In all cases safety principles of oncological surgery were respected. There was only one conversion to open surgery related to a bleeding during a resection
of a mesenteric cyst. Complications were observed only in the
proctocolectomy patients, presenting anastomotic fistulae in
one patient and an episode of bowel obstruction in another.
No trocar site recurrences were observed.
Conclusions: The application of MIS techniques to pediatric cancer patients is a safe and effective diagnostic, staging
and treating modality. MIS techniques are safe, reproducible
and fulfill the objectives of quality of cancer surgery. Proper
equipment remains as a limiting factor, along with the challenge in maintain a learning curve with a wide diversity of
procedures.
L I V E R T U M O R S , GC T A N D R M S (+ 1
E D U CAT I O N )
O-171 Multidisciplinary Management of
Hepatoblastoma: 8 Year Experience
A. Elgendy1,2 , S. Fadel3,4 , I. Zaky5 , A. Younis1
1 Children's
Cancer Hospital 57357 - Egypt, Surgical Oncology
Department, Cairo, Egypt; 2 Tanta University, Surgical Oncology Unit,
Tanta, Egypt; 3 Children's Cancer Hospital 57357 - Egypt, Pediatric
Oncology Department, Cairo, Egypt; 4 National Cancer Institute- Cairo
University, Pediatric Oncology Department, Cairo, Egypt; 5 Children's
Cancer Hospital 57357 - Egypt, Radiology Department, Cairo, Egypt
SIOP ABSTRACTS
Background/Objectives: To evaluate the outcome of patients
with hepatoblastoma treated by surgical resection at our hospital in 8 years.
Design/Methods: Prospective study from January 2008
to December 2015. Evaluation was done by pretreatment
extent staging system (PRETEXT), tumor biopsy and serum
alpha fetoprotein. Overall survival (OS), event free survival
(EFS) and univariate prognostic factors were estimated using
kaplan-meier and log rank test. Recurrence or death was considered as event.
Results: The study included 87 patients (52 males, 35
females). Median age at diagnosis was 1.05 years (0.5 –
12.86). There were 3 (3.4%), 62 (71.3%) and 22 (25.3%) PRETEXT I, II and III respectively. Sixty four patients (73.56%)
were standard risk (SR) and 23 (26.44%) high risk (HR). Thirteen patients were metastatic at diagnosis (11 lung, 2 bone).
Upfront resection was done in 5 patients (5.75%) whereas,
the other 82 (94.25%) underwent surgery after neoadjuvant
chemotherapy according to their risk stratification. Fifty two
patients (59.77%) underwent hemi-hepatectomy (33 right, 19
left), 26 (29.88%) segmentectomy, 5 (5.75%) mesohepatectomy and 4 (4.6%) trisegmentectomy. Follow up till the end of
June 2016 with a median of 23.5 months (6.46 – 100) revealed
that 21 patients (24.1%) had events, among them 12 local
recurrence, 7 distant relapse (6 lung, 1 brain) and 2 patients
died postoperatively. The 5 years OS was 80.4% [85.3% for
SR; 66.6% for HR (P= 0.037)], [82.2% for non-metastatic;
45.5% for metastatic (P=0.018)].The 5 years EFS was 68.7%
[77.8% for SR; 48.7% for HR (P=0.024)], [73.3% for nonmetastatic; 46.2% for metastatic (P=0.029)].
S93 of S518
metastasis of neuroblastoma - 1 case and hemangioma of the
liver - 1 case.
Results: Hemihepatectomy was performed in 6 patients, 5
patients had a diagnosis of hepatoblastoma, in 1 child nodular hyperplasia. The average duration of operations was 90
minutes, the average blood loss was 120ml. No conversions.
Staying in the intensive care and reanimation room was 3
days.Segmentation was performed in 14 patients, in 9 patients
hepatoblastoma was detected, hyperplasia - 3 cases, neuroblastoma - 1 case of hemangioma in 1 case. The average duration of operations was 60 minutes, the average blood loss was
0-50 ml. No conversions. Staying in the intensive care unit
and intensive care was 2 days. There were no immediate and
remote postoperative complications. Among 15 patients with
malignant liver diseases, there was no progression of the disease during the entire follow-up period. Median follow-up
was 60 months.
Conclusions: In the case of malignant pathology, strict selection of patients is required according to the indications, as
well as compliance with all principles of "open" surgery
and, first of all, radical intervention. Laparoscopic operations
allow minimizing postoperative complications, shortening the
course of the postoperative period, which in turn makes it
possible to start a special antitumor treatment in the shortest
possible time and positively influence the long-term results of
therapy
O-173 Current Surgical Intervention for
Pediatric Giant Mediastinal Germ Cell Tumors
Conclusions: Surgical resection combined with systemic
chemotherapy is fundamental for improved outcome with 5
years OS and EFS 80.4% and 68.7% respectively. SIOPEL
risk stratification and distant metastasis were independently
impacted on the survival rates.
S. Fumino1 , K. Sakai1 , M. Higashi1 , S. Aoi1 , T. Furukawa1 , M.
Yamagishi2 , M. Inoue3 , T. Iehara4 , H. Hosoi4 , T. Tajiri1
O-172 Laparoscopic Liver Resections in Children
with Liver Tumors
Background/Objectives: Giant mediastinal germ cell tumors
(MGCTs) in children are rare tumor and often form large mass
at diagnosis. Especially, malignant MGCTs invade surrounding vital tissues, then, they require a well-planned advanced
surgical approach. We retrospectively reviewed our surgical
strategy for giant MGCT.
P. Kerimov1 , A. Kazancev1 , M. Rubanskaya1 , D. Rybakova1
1 Russian
Cancer Research Center. NN Blokhina, Surgical separation of
tumors of thoracoabdominal localization, Moscow, Russia
1 Kyoto
Prefectural University of Medicine, Pediatric Surgery, Kyoto, Japan;
Prefectural University of Medicine, Pediatric Cardiovascular
Surgery, Kyoto, Japan; 3 Kyoto Prefectural University of Medicine, Thoracic
Surgery, Kyoto, Japan; 4 Kyoto Prefectural University of Medicine,
Pediatrics, Kyoto, Japan
2 Kyoto
Background/Objectives: Laparoscopic liver resections for
tumor liver pathology in children have been used relatively
recently. In the literature, there are very few reports of laparoscopic liver resections in children with tumor organ pathology.
Design/Methods: Five children with a median age of 5 years
(range 1-15) with giant MGCT were treated in our institute
from 2012 to 2016. The medical charts were retrospectively
reviewed.
Design/Methods: In our clinic from 2007 to 2016, 20 patients
aged 3 months to 16 years underwent radical laparoscopic
resections of the liver. Boys - 14, girls - 6, the average age
of patients was 4 years. The following pathologies are diagnosed: hepatoblastoma - 14 cases, liver hyperplasia - 4 cases,
Results: The initial diagnosis was made by tumor markers and image inspection in all cases. Benign teratomas (2
girls) were treated with upfront surgery, and malignant MGCT
(3 boys) showed elevated alpha-fetoprotein and underwent
radical tumorectomy after neo-adjuvant chemotherapy. After
SIOP ABSTRACTS
S94 of S518
detailed 3D-CT, radical tumor excision was performed supported by a skilled pediatric cardiovascular surgeon. The
basic approach was as follows: under cardiopulmonary support (CPS) (or with CPS on standby), via median sternotomy,
the pericardium and phrenic nerve were resected en bloc with
the tumor, followed by diaphragmatic plication. Open biopsy
was performed via lateral thoracotomy in 1 patient with malignancy, who showed dense adhesion and fistula formation in
the lung at radical resection; lobectomy via hemi-clamshell
incision was required. Although major postoperative complications including pericardial effusion, chylothorax requiring
thoracoscopic repair, hoarseness, and pyothoraxchylothorax
were noted, no deaths or severe sequelae occurred in this
series.
Conclusions: MGCTs could be initially diagnosed based on
tumor markers and imaging findings. Therefore, open biopsy
should be avoided because of severe adhesion at surgery. Preoperative 3D-CT and CPS can ensure safety during advanced
surgery. Well-functioned surgical team including not only
pediatric surgeons but also pediatric cardiovascular surgeons
and thoracic surgeons is required for successful treatment.
O-174 Incidence, Treatment and Outcome of
Recurrent (REC) Malignant Germ Cell Tumors
(MGCT): A Single Institution Experience
S. Agarwala1 , S. Bakhshi2 , A. Dhua1 , M. Sirnivas1 , S. Thulkar3 , M.
Jana4 , K. Devasenathipathy4 , A.K. Bisoi5 , V. Bhatnagar1
1 All
India Institute of Medical Sciences, Pediatric Surgery, Delhi, India;
All India Institute of Medical Sciences, Medical Oncology,
Delhi, India; 3 BRAIRCH- All India Institute of Medical Sciences,
Radiology, Delhi, India; 4 All India Institute of Medical Sciences,
Radiodiagnosis, Delhi, India; 5 CN Center- All India Institute of Medical
Sciences, Cardiovascular and Thoracic surgery, Delhi, India
2 BRAIRCH-
53.3%; Sacrococcygeal:41.7% and ovarian:7.9%). The 5-year
OS and RFS for the 152 patients was 0.9(95CI 0.83-0.94)
and 0.61(95CI 0.52-0.69). Among the 49 REC-MGCT,
42(85.7%) were alive and 7(14.3%) had died giving a 5-year
OS of 0.75(95CI 0.51-0.89). However, of these 42 survivors
only 21(50%) were DFS, while the remaining 21 had progressive disease at last follow-up and chose to discontinue
treatment. The 5-yr OS was 0.67 for extragonadal and 0.82
for gonadal recurrences (p=0.25). Of the 18 recurrences
after primary treatment by us, 14 were alive (5-yr OS 0.49)
but only 3 were DFS. Among the 31 REC-MGCT referred
after surgery elsewhere, 28 were alive (5-yr OS 0.89) and 18
achieved DFS.
Conclusions: The incidence of REC-MGCT was 32% and
it was similar for gonadal and extra-gonadal tumors (32.5%
vs 31.9%). Though the 5-year OS for REC-MGCT was 0.75,
only 50% achieved DFS. The OS was better (0.89 vs 0.49)
for patients who were operated elsewhere and came to us
with recurrence (chemo naïve patients) than our own patients
(heavily pre-treated).
O-175 Methadone Potentiates the Cytostatic
Effect of Doxorubicin in Rhabdomyosarcoma and
Rhabdoid Tumors
E. Schmid1 , A.S. Raible1 , M.J. Stagno1 , R. Handgretinger2 , S.W.
Warmann1 , J. Fuchs1
1 University
Hospital, Department of Pediatric Surgery and Pediatric
Urology, Tuebingen, Germany; 2 University Hospital, Department of
Pediatric Oncology and Haematology, Tuebingen, Germany
Design/Methods: Prospectively maintained data of patients
of MGCT managed in the pediatric solid tumor clinic from
June 1994 through December 2016 was analyzed to evaluate the incidence of recurrence. Outcome was evaluated in
terms of 5-year overall survival (OS) and disease free survival
(DFS).
Background/Objectives: Rhabdoid tumors (RTs) and Rhabdomyosarcoma (RMS) are aggressive pediatric malignancies. Both entities show an intrinsic refractoriness to standard
chemotherapy in advanced tumor stages, which is associated
with poor prognosis. Alternative therapeutic approaches and
optimization of already established treatment protocols are
urgently needed in these conditions. The �-opioid receptor
(OPRM1) agonist D,L-Methadone is frequently used for analgesia in oncological patients. Recently it has been proposed
that D,L-Methadone exert a role in influencing tumor cell
growth and could be a promising candidate for optimization
of already established treatments. So far there are no related
data in pediatric solid tumors.
Results: Of the 152 MGCT cases (83 gonadal; 69 extragonadal)treated in this period, there were 49(32.2%) recurrences. 113 of 152(74.3%) were primarily treated by us
and of these 18(15.9%) recurred. Thirty-nine(25.7%) were
referred to us after resection and of these 31(79.5%)were with
recurrence. The incidence of recurrence was similar among
gonadal(27/83-32.5%) and extra-gonadal tumors(22/6931.9%). The incidence of recurrence was maximum for
testicular and least among the ovarian tumorts(Testicular:
Design/Methods: Effects of combined D,L-Methadone and
doxorubicin treatment on two rhabdomyosarcoma and two
rhabdoid tumor cell lines were measured using the following
outcome data: cell growth inhibition (MTT-assay), doxorubicin uptake and efflux, apoptosis and reactive oxygen species
(ROS) production (flow cytometry), gene expression studies
(real-time PCR), cell migration (wound healing assay) and
apoptosis and expression of the OPRM1 receptor (Western
Blot).
Background/Objectives: To evaluate the incidence and the
outcome of treatment of recurrent (REC) malignant germ cell
tumors (MGCT).
SIOP ABSTRACTS
Results: Exposure of doxorubicin significantly increased the
OPRM1 expression, whereas D,L-Methadone increased doxorubicin uptake and decreased doxorubicin efflux. Moreover,
combined treatment with D,L-Methadone and doxorubicin
resulted in a suppressed tumor cell growth and enhanced
apoptosis in all cell lines, which was mediated by increased
generation of ROS and through down-regulation of apoptosis proteins. Furthermore treatment with D,L-Methadone and
doxorubicin resulted in a significant decrease of migration in
comparison to D,L-Methadone or doxorubicin alone.
Conclusions: In summary, this new and innovative therapeutic approach displayed a strong anti-tumor effect in rhabdomyosarcoma and rhabdoid tumor cell lines. The combination therapy of doxorubicin and D,L-Methadone merits further investigation as an auspicious anticancer drug in RTs and
RMS, especially when conventional treatment regimens show
limited effects in the clinical setting.
S95 of S518
examinees sat for this first iteration, 2/3 obtained a passing
score.
Conclusions: Where there is overlapping of competencies
between two or more specialties, constructing a Clinical
Model of Practice involving the stakeholders can avoid potential conflict. This model allowed us to clarify boundaries and
develop the competencies and facilitated blueprinting. The
performance of examinees was as expected. The competencybased profile and the contents of the specifications could be
discussed within the IPSO community to assemble a proposal
for a global curriculum in this subspeciality.
Acknowledgment: this work had the support of the FAIMER
Institute.
T R E AT M E N T A N D CA R E - N U R S I NG
O-176 Development of a National
Competency-Based Board Certification in Pediatric
Surgical Oncology, the Coming-of-Age of a
Subspeciality. Is There Room for a Global
Curriculum?
O-177 Key Worker Role in End-of-Life Care:
‘I'D Call it Knitting….Making Sure That The Five
or Six Elements That We Needed, They Were
Knitted Together… Coordinated’
P. Lezama-del Valle1
1 University
1 Hospital
Infantil De Mexico Federico Gomez, SURGERY / SURGICAL
ONCOLOGY SERVICE, Mexico City, Mexico
Background/Objectives: The surgical treatment of complex
pediatric oncology cases is often beyond the scope of expertise of general Pediatric Surgeons. To overcome this situation, formal training in Pediatric Surgical Oncology (PSO)
has been established in several comprehensive cancer centers
across various countries, but formal Assessment for Credentialing and Certification has not been established before. The
goal of this paper is to present the process of developing the
Competency-based Board Certifying Exam.
Design/Methods: A Model of Clinical Practice in PSO was
defined, stratifying which patients could be under the care of
General Pediatric Surgeons and which ones should be referred
to PSO specialists. The competencies for PSO fellows and
specialists were identified and integrated in a profile, and a
Certifying Process was planned, with the Mexican Board of
Oncology and the National Committee for Specialty Boards.
Results: A team of examiners was assembled, and Item banking was done in sufficient amount to have a 150 MCQ test,
and clinical vignettes were designed for the oral exam. The
blueprinting for both components of the examination was
completed and pilot tested. The actual examination took place
in a two-day session in Mexico City, Mexico, in February
2017. Psychometric analysis of the MCQ items was conducted and the pass-fail standard was established. Three
S. Aldiss1 , A. Martins2 , F. Gibson1,3
of Surrey, School of Health Sciences- Faculty of Health and
Medical Sciences, Guildford, United Kingdom; 2 University College London
Hospitals NHS Foundation Trust, Cancer Clinical Trials Unit, London,
United Kingdom; 3 Great Ormond Street Hospital for Children NHS
Foundation Trust, Centre for Outcomes and Experience Research in
Children's Health- Illness and Disability, London, United Kingdom
Background/Objectives: The delivery of end of life care
requires a broad range of health and other care services, this
may include hospitals, hospices, primary care and community
professionals, ambulance services, dedicated palliative care
teams, and other support providers. Essential to this delivery
are good communication, care coordination, and effective networking: the specialist nurse key worker role has been identified to provide this service. The aim was to evaluate the role
of the key worker in end of life care of children and young
people with cancer from the perspective of parents and key
workers.
Design/Methods: In depth semi-structured interviews with
eight parents and fourteen key workers. Interview transcripts
were analysed using framework analysis.
Results: Four main themes were identified: coordination of
care; continuity of care; positive relationships and communication. Key workers provided clinical, emotional, educational and practical support to families, through the coordination of care, their clinical experience and expertise and their
relationships with families and other professionals. Having
a key worker facilitated professionals and parents to get to
know one another and become emotionally close. Positive
SIOP ABSTRACTS
S96 of S518
relationships with key workers were built on trust and open
and honest communication, through which parents were provided with individualised support and reassurance. This support and reassurance in conjunction with key workers’ coordination of resources enabled parents and children to have the
choice of where to receive their care. Support in the palliative phase has its own challenges: lack of out of hours palliative care available in the community, establishing complex
palliative care packages in the home and providing effective
bereavement support for families. Some key workers offered
a 24 hour on call service for these families.
Conclusions: Having a key worker facilitated individualised
and coordinated care and support. The positive key workerparent relationship is central to the support given to and
received by parents.
Results: The group-based trajectory modeling found two distinct trajectory clusters of distress: low distress group (n=24)
and persistent distress group (n=19). The logistic regression
showed that parent negative emotions at T3 can predict a significantly higher distress level (Odds Ratio=1.2, p=0.046).
The Mann-Whitney test showed that the persistent distress
group had a lower procedural anxiety at T4 (p=0.004) and at
T5 (p=0.005), but more pain/hurt at T5 (p=0.023) and more
worries at T4 (p=0.023) and at T5 (p=0.042).
Conclusions: Targeted interventions toward parents may help
improve QOL for children with the persistent distress following painful procedures.
O-179 Does Parent Distress = Child Distress in
Pediatric Cancer? A Review of the Literature
D.M. Bakula1 , C.M. Sharkey1 , M.N. Perez1 , K.L. Gamwell1 , H.C.
Espeleta2 , J.M. Chaney1 , L.L. Mullins1
O-178 Trajectories of Procedure-Related Distress
in Children with Cancer: Risk Factors and Impact
of Persistent Distress on Long-Term Quality of Life
1
2,3
2,3
J. Bai , F.W.K. Harper , L. Penner
1 Emory
University, NHW School of Nursing, Atlanta, USA; 2 Wayne State
University, School of Medicine, Detroit, USA; 3 Wayne State University,
Karmanos Cancer Institute, Detroit, USA
Background/Objectives: Children with cancer undergo distressing treatment-related procedures such as port starts. Traumatic experiences with these procedures can result in negative healthcare outcomes in children with cancer. Limited data
exist on the trajectories of distress over time and the impact
of distress trajectories on children's quality of life (QOL) in
cancer. This study aimed to characterize the longitudinal trajectories of distress in children with cancer and identify the
risk factors of persistent distress and the relationships between
distress trajectories and children's QOL.
Design/Methods: Forty-three children with cancer were
selected from a parent study (R01CA138981). These children
underwent 2-3 continuous port start procedures. Child distress levels during these procedures were assessed by multiple raters using the Revised Wong-Baker Faces Scale (T1,
T2 and T3). The assessed risk factors included: demographic
and clinical variables at baseline (T0) and parent dispositional
attributes (Empathic concern, depression, negative and positive emotions) at T0-T3. Parents reported children's QOL
using PedsQLTM Cancer Module at 3-month and 9-month
after the last procedure (T4 and T5). The group-based trajectory modeling was used to identify the child distress clusters;
the logistic regression analyzed the risk factors of the distress
trajectory clusters; the Mann-Whitney U test was conducted
to examine the associations between the distress trajectory
groups and QOL.
1 Oklahoma
State University, Psychology, Stillwater, USA; 2 Oklahoma State
Univeristy, Psychology, Stillwater, USA
Background/Objectives: The burden and stress of pediatric
cancer leaves both parents and children vulnerable to psychological distress (e.g., depression, anxiety, posttraumatic
stress). Extant research suggests that a relationship exists
between parental distress and child distress, such that parents
who are more distressed tend to have children who are more
distressed. Although Drotar (1997) reviewed this relationship,
the studies reviewed may no longer be considered contemporary. The aim of this project is to provide a current and comprehensive review of literature on this important relationship.
Design/Methods: A review of published pediatric psychooncology literature was conducted via PsychInfo and
PubMed. Articles were chosen for review if they examined
both parent and child distress, were available in English, and
were peer-reviewed.
Results: Forty-one articles were identified as meeting inclusion criteria, of which 26 articles reported a significant positive relationship between parent distress and child distress, 5
articles reported that no relationship existed between parent
and child distress, and 10 articles did not report an assessment of the relationship between parent and child distress.
Articles that supported the existence of a relationship had
sample sizes ranging from N=22-N=309, utilized both crosssectional (n=22) and longitudinal (n=4) designs, and reported
modest correlational coefficients (r=.10-.60).
Conclusions: Available research indicates that there is indeed
a relationship between parent psychological distress and child
psychological distress. Although it is unclear whether the
relationship is directional or transactional in nature, findings
are consistent with transactional stress and coping models
of adjustment to chronic health conditions. Although meta-
SIOP ABSTRACTS
analyses of parent-targeted interventions have not shown consistent reduction of subsequent child distress (e.g., Pai et al.,
2006), this review suggests that parent-targeted interventions
may be capable of reducing child distress. However, given that
not all studies reported analyses on this relationship, findings
may be incomplete. Further research is needed to assess the
mechanisms through which this relationship exists.
S97 of S518
O-181 Children's Participation in Decisions,
Discussions, and Actions in a Pediatric Oncology
Setting in New Delhi, India: A Focused
Ethnography
J. Behan1 , A. Tsimicalis1 , F. Carnevale1 , S. Bakhshi2 , B.
Bhattacharjee2 , R.S. Arora3
1 McGill
O-180 High Levels of Intensity of Moral Distress
among Healthcare Professionals– A National Study
in Pediatric Oncology
C. Bartholdson1
1 Karolinska
Institutet, Women and Children´s Health, Stockholm, Sweden
Background/Objectives: Caring for children with cancer
involves complex decisions about life and death. Moral distress occurs when one has an idea of what is ethically correct
but cannot act accordingly, as well as when one does not know
what is ethically correct but has to make a decision. Studies
of moral distress in pediatrics are rare. The overall aim was to
describe healthcare professional's experiences of moral distress in pediatric oncology in Sweden.
Design/Methods: Data collection was performed by using
a translated and culturally adapted paediatric version of the
Moral Distress Scale-Revised (MDS-R).The instrument contains statements about difficult ethical situations. Healthcare professionals from all pediatric cancer centers (n=6)
in Sweden completed the questionnaire by rating both level
of disturbance and frequency related to each statement.
Total moral distress score was calculated by summing the
composite scores (i.e. level of disturbance x frequency).
Descriptive analysis of data was conducted using Package for
Social Sciences (SPSS).
Results: In total 279 participants answered the questionnaire
(response rate > 80%). Nurses and nurse-assistants reported
similar level of disturbance (intensity) whereas physicians
reported slightly lower scores; the mean value for all professional groups was notably high. Furthermore nurses stated
higher frequencies of distressing events compared to physicians and nurse-assistants; the mean value for all professional
groups was at the lower end of the scale. Nurses also reported
higher level of total moral distress scores compared to other
professions.
Conclusions: Ethically distressful situations disturbs healthcare professionals a lot in pediatric cancer care in Sweden,
however the situations does not occur very often. Nurses
seem to experience the situations more distressful than the
others. By understanding the experiences related to moral
distress, ethical support can be tailored to assist healthcare
professionals.
University, Ingram School of Nursing, Montreal, Canada; 2 Dr. B.
R. A. Institute Rotary Cancer Hospital- All India Institute of Medical
Sciences, Department of Medical Oncology, New Delhi, India; 3 Max Super
Speciality Hospital, Paediatric Oncology, New Delhi, India
Background/Objectives: A participatory approach was
adopted to better understand children's actual and desired participation in decisions, discussions, and actions in a pediatric oncology setting in New Delhi, India. Nested within an
emerging field of childhood ethics, this study was guided by a
moral experience framework, which seeks to understand how
children's values or beliefs are being realized, or not, in their
everyday lives.
Design/Methods: A focused ethnography was conducted in
3 pediatric oncology settings including private, public, and
not-for-profit hospitals. Over a 3-month period, key informant interviews were conducted, followed by a series of
participant observations and semi-structured interviews with
children with cancer, and retrieval of key documents. Data
were consolidated between sources, open-coding was conducted within/between sources, emerging codes categorized,
and themes comparatively analysed.
Results: 7 key informants were consulted to share their
understanding of the moral experience of children with
cancer. Key text analysis informed the contextual descriptions of the settings. Semi-structured interviews were conducted with 22 children, 11 of which were observed during their cancer care. Participants, with varying cancer diagnoses, ranged in age from 3 to 17 years-old. A conceptualization of participation was developed based on how the
children actually or desire to navigate their worlds within
the pediatric oncology setting. Children verbally and nonnegativerbally expressed their preferences for participation
and elicited various dimensions to decision-making, discussions, and actions. Children expressed varying views with
regards to decision-making concerning their health, cancer
treatment, assent, nutrition, and housing. Children's participation varied in discussions and involved asking questions, listening, body language/facial expressions, and speaking. Children's actions included developing an understanding of their
illness, expressing likes/dislikes and desires, addressing problems, recollecting their experiences, receiving treatment, and
engaging in teaching and play.
Conclusions: Children actively participate in matters affecting them. An advanced understanding of their values and
beliefs may enhance their clinical encounters.
SIOP ABSTRACTS
S98 of S518
O-182 Intravenous Chemotherapy at Home:
standard care?! Intravenous Chemotherapy at
Home for Children with Cancer. A Pilot Study
A. Beukhof1 , N. Kok1 , M. van de Wetering1
1 Emma
Children's Hospital/Academic Medical Center, Pediatric Oncology,
Amsterdam, The Netherlands
Background/Objectives: The treatment of a child with
leukemia currently takes place in the hospital, which means
that the child has to come to the hospital daily or weekly for
treatment for a period of at least 2 years. In January 2017, a
pilotstudy was started in these children to receive intravenous
chemotherapy at home, with the aim to give the chemotherapy safe and efficient at home and improve the quality of life
for children and families.
Design/Methods: Through a partnership between the Department of Pediatric Oncology at the Emma Children's Hospital
in Amsterdam, ‘Kinderthuiszorg’ (Children's home care organization ) and ‘Mediq Tefa’ (specialist in medical devices) it's
possible to give intravenous chemotherapy at home.
We performed an explorative comparative study, using questionnaires about the social impact of the treatment and a shortened validated Quality-Of-Life-list. As a baseline the questionnaires were taken before the start of the pilot, and will be
repeated after 6 weeks and at the end of the pilot (at 3 months).
This pilot consisted of 30 parents and 10 children (>12 years)
and took place from January 2017-april 2017
Results: The baseline results showed that 100% of the
children and 86.6% of the parents are enthusiastic when
chemotherapy is given at home. When they will get treatment
at home 90% of the children and 83.3% of the parents expected
to plan their life better, only 30% of parents expected to take
time off work and 83.3% expected that the child will not miss
school. The results of the pilot will be presented at the SIOP
2017.
Conclusions: Because of specialized nurse practitioners in
pediatric oncology both in the hospital and at home the possibility is created to administer the chemotherapy for these
children at home and we hope this will be standard of care in
the future!
O-183 Home Care Services for Sick Children:
Health Care Professionals’ Conceptions of
Challenges and Facilitators
C. Castor1 , I. Hallström1 , H. Hansson2 , K. Landgren1
1 Lund
University, Department of Health Sciences, Lund, Sweden;
2 Copenhagen University Hospital Rigshospitalet, Paediatrics and
Adolescent Medicine, Copenhagen, Denmark
Background/Objectives: Families often prefer home care to
hospital care and the number of home care services for children is increasing. The aim of this study was to explore healthcare professionals’ conceptions of caring for sick children in
home care services.
Design/Methods: An inductive qualitative design was used.
Seven focus group interviews with 36 healthcare professionals
from multidisciplinary home care services were performed.
Data was analysed stepwise using a phenomenographic analysis.
Results: Three description categories emerged “A challenging opportunity”, “A child perspective”, “Re-organise in
accordance with new prerequisites”. Providing home care
for children was a challenging but rewarding task for healthcare professionals used to care for adults conceived to
evoke both professional and personal challenges such as feelings of inadequacy and fear, and professional growth such
as increased competence and satisfaction. Conceptions of
whether the home or the hospital was the best place for care
differed. Adapting to the child's care was conceived as important. Cooperation with paediatric departments and a wellfunctioning teamwork were important organisational aspects.
Conclusions: A sufficient number of referred children and
enabling healthcare professionals to be part of the reorganising and implementation processes might facilitate the
home care services for sick children. Enough time and good
teamwork must be emphasised. Early referrals, continuous
cooperation with paediatric clinics complemented with individualised support when a child is referred were prerequisites that make up for the low number of paediatric patients
and facilitate confidence and competence. The study was
funded by the Swedish Childhood Cancer Foundation and
The Swedish Research Council for Health, Working Life and
Welfare.
O-184 How do Children with Cancer Experience
the Needle Insertion Into Venous Access Port ?
S.E. Egeland1 , H. Lie C2 , E. Ruud1
1 Oslo
University Hospital- 0027 Oslo- Norway., Department of Paediatric
Haematology and Oncology- Unit of Paediatric and Adolescent Medicine.,
Oppegård, Norway; 2 University of Oslo, Oslo University Hospital- 0027
Oslo- Norway., Oslo, Norway
Background/Objectives: Many children with cancer fear
painful needle-related procedures. VAP is commonly used
during cancer treatment, yet little is known about how children experience VAP needle insertion procedures.
Aim: The aims were to 1) explore levels of distress before and
pain after the VAP- needle insertion among young patients,
and 2) to explore how patients’ self-report of distress and pain
correlate with the proxy-reports by parents and nurses.
SIOP ABSTRACTS
Design/Methods: The sample included 43 patients, aged116 years with cancer, treated at two Norwegian hospitals and
who had VAP for 2-6 months. The patient (if old enough),
parent and nurse performing the procedure completed a questionnaire before and after the procedure. The questionnaire
consisted of three developmentally-appropriate 10-point distress and pain scales (higher scores indicate greater distress/pain). Data were analysed using descriptive statistics and
non-parametric correlations.
Results: For the young children (1-5 years), the median distress score was 8 (range 0-9) and pain score was 4 (range 010). Median distress and pain scores for the school-age children (6-12 years) were 3 (range 0-9) and 1 (range 0-10), and
for the adolescents (age 13-16) were 0 (range 0-6) and 1 (range
0-5) respectively. Ten children (23%) reported high distress
and/or pain scores (7-10). The distress level did not correlate with the pain level for the patient's ratings (rho=0.19,
p=0.286) or nurses ratings (rho=0.33, p=0.062), but did for
the parent ratings (rho=0.42, p=0.015). Patients’ ratings of
distress and pain correlated with the proxy ratings of parents (rho=0.83, p<0.001 and rho=0.92, p<0.001) and nurses
(rho=0.89, p<0.001 and rho=0.88, p<0.001).
Conclusions: Reported distress and pain associated with VAP
needle-inserting procedures were greater among the youngest
children compared to the older children. However, clinicians
should be aware of the great individual differences and offer
a CVK that does not involve needle- insertion to highly distressed children.
S99 of S518
instruments measured the children's anxiety and emotional
behavior as secondary outcomes.
Results: The preparation parts were delivered as intended
without any additional staff and without dropouts in the intervention group and therefore found feasible and acceptable.
Three children planned for general anesthesia in the intervention group completed their treatments including 73 fractions
awake. Children receiving general anesthesia, regardless of
group, showed significantly higher negative emotional behavior. No statistic significances were found concerning the number of children receiving general anesthesia or anxiety.
Conclusions: Avoiding general anesthesia for children with
cancer going through radiotherapy gives benefits in terms of
fewer risks and restrictions in life for the child, fewer disturbances in daily life for the family and lower costs for health
care. Giving children individualized preparation may decrease
the need for general anesthesia during radiotherapy treatment.
Acknowledgements: We would like to express our gratitude
to the participating children and to the Swedish Childhood
Cancer Foundation for funding.
O-186 Effects of Age-Appropriate Preparations
for Children with Cancer Undergoing
Radiotherapy on Parents’ and Family Functioning,
Parents’ Anxiety and Hospital Costs
J. Gardling1 , M. Edwinson Månsson1 , E. Törnqvist1 , I. Hallström1
1 Faculty
O-185 Age-Appropriate Preparations for
Children with Cancer Undergoing Radiothearpy A Feasibility Study
J. Gardling1 , E. Törnqvist1 , M. Edwinson Månsson1 , I. Hallström1
1 Faculty
of Medicine- Lund university, Department of Health Sciences,
Lund, Sweden
of Medicine- Lund university, Department of Health Sciences,
Lund, Sweden
Background/Objectives: The aim was to explore if ageappropriate information and preparation procedures for children with cancer undergoing radiotherapy 1) decrease the
impact on parents’ and family functioning, parents’ anxiety
and 2) reduce hospital costs compared to traditional care.
Background/Objectives: Due to the need for complete
immobility during radiotherapy children often require daily
general anesthesia for several weeks. The aim of this study
was to test age-appropriate information and preparation procedures for children with cancer undergoing radiotherapy for
feasibility and effectiveness in terms of the need for general
anesthesia and anxiety.
Design/Methods: The study was a part of a quasiexperimental controlled clinical trial consisting of a control
group including 31 parents to 16 children receiving traditional
care and an intervention group including 32 parents to 17 children receiving age-appropriate preparation including seven
parts. Validated instruments measured the parents’ and family
functioning and parents´ anxiety. Hospital costs were calculated.
Design/Methods: In a quasi-experimental controlled clinical
trial, 17 children aged 3 to 18 years receiving age-appropriate
preparation including seven parts were compared with 16
children in a control group receiving traditional care. Feasibility in terms of recruitment, compliance and acceptability
was assessed. Effectiveness was assessed by the primary outcomes: number of children who underwent treatment without general anesthesia and their respective fractions. Validated
Results: Parents in the intervention group showed statistic
significantly better communication throughout their child's
radiotherapy. At their child´s last fraction, parental social
functioning showed to have improved with a statistical significance. Parents of children receiving general anesthesia,
regardless of group, showed statistically significant higher
levels of anxiety. Hospital costs were lower in the intervention group.
SIOP ABSTRACTS
S100 of S518
Conclusions: If only few children are able to go through RT
without GA it imply for the individual child fewer risks and
restrictions. For the parents´ and family, the benefits are in
terms of less impact on their functioning and less anxiety. For
the hospital, it means lower costs and increased availability
of anesthesia personnel, enabling to prioritize other areas of
care.
Acknowledgements: We would like to express our gratitude
to the participating parents and to the Swedish Childhood
Cancer Foundation for funding.
O-187 Preparing Children for Blood Tests: Using
Arts-Based Techniques in Creative Research and
App Development
F. Gibson1 , N. Oldrieve2 , J. Bayliss3 , S. Hall4 , V. Jones5 , I.
Manning4 , L. Shipway6 , K. Oulton7
1 Great
Ormond Street Hospital for Children NHS Foundation Trust and
University of Surrey, Centre for Outcomes and Experience Research in
children's Health- Illness and Disability Orchid and School of health
Sciences, London, United Kingdom; 2 St Georges Hospital, Community
Children's Nurse in Children's Services, London, United Kingdom; 3 Great
Ormond Street Hospital for Children NHS Foundation Trust, The Louis
Dundas Centre Oncology Outreach and Palliative Care, London, United
Kingdom; 4 Great Ormond Street Hospital for Children NHS Foundation
Trust, GOSH Arts, London, United Kingdom; 5 Freelance Consultant, N/A,
Melbourne, Australia; 6 Great Ormond Street Hospital for Children NHS
Foundation Trust, Charles West Division, London, United Kingdom; 7 Great
Ormond Street Hospital for Children NHS Foundation Trust, Centre for
Outcomes and Experience Research in Children's Health- Illness and
Disability ORCHID, London, United Kingdom
Background/Objectives: Blood tests can be distressing for
children and prove detrimental to their psychological wellbeing with some developing needle phobia, or anticipatory/procedural distress. Preparation for blood taking at the
onset of illness is therefore invaluable in minimising such distress.
Design/Methods: Our aim was to develop a ‘tool’ to help prepare children for blood tests. This was a two-phased study.
A user-experience design, using creative arts/art making was
utilized. In Phase 1, through a range of activities, children
looked at the importance of blood within the body, and why
we need to take blood. Participants made some blood of their
own using some unconventional ingredients. They invented
comical ‘blood’ characters and made life-size maps of their
own bodies. The ‘BLOOD QUEST’ game was subsequently
developed. In Phase 2 we assessed its usefulness and effectiveness with a small group of children (and parents) with haematological disorders who were in/attending hospital. From this
foundation work the ‘app’ prototype emerged.
Results: Phase 1: 7 hospitalised children aged 4-12 participated in a range of creative activities, drawing on their own
experience to help design what the ‘BLOOD QUEST’ game
looked like. Phase 2: 15 children played the game prior to hav-
ing blood taken and completed a questionnaire about its usefulness and effectiveness. Most children who tested the game
found it fun and informative. Half reported that playing the
game made them feel better about having their blood taken
and half felt the same. The game was more suited to children
aged 4-7.
Conclusions: The collaboration between children and an
illustrator enabled ‘idea elaboration’ allowing children to have
genuine influence in research and in shaping the prototype
game into the ‘app’. This presentation will focus on the creative steps that resulted in the Blood Quest ‘app’, available for
the ipad and now free to download from the Apple App Store.
O-188 Multilingual Encounters in Paediatric
Cancer Care – Risking Patient Safety by Insufficient
use of Interpreters
J. Granhagen Jungner1 , E. Tiselius2 , K. Blomgren1 , P. Pergert1
1 Karolinska
Institutet, Women's and children's health, Stockholm, Sweden;
University- Institute for Interpreting and Translation Studies,
Department of Swedish Language and Multilingualism, Stockholm, Sweden
2 Stockholm
Background/Objectives: Overcoming language barriers in
multilingual paediatric cancer care will improve the care situation and reduce costs, but knowledge is needed about how
communication is performed and facilitated in situations with
language barriers as well as how these situations can be
improved. The purpose of this study was to investigate communication over language barriers between healthcare professionals (HCP) in paediatric cancer care and patients/families
with limited proficiency in the country's official language.
Design/Methods: We combine communication and interpreting sciences with medical and nursing sciences in an interdisciplinary project to increase knowledge about the complexity
of communication over language barriers. A national multisite cross-sectional survey has been performed using the Language Barriers and Communication Questionnaire (LBCQ).
HCP (physicians, registered nurses, and nurse assistants) at
all paediatric cancer centres (n=6) in Sweden were invited
to participate and statistical analyses were performed using
SPSS.
Results: A total of 281 questionnaires have been collected
(response rate > 80%). A majority of the respondents reported
that the use of interpreters to a high degree increase patient
safety (87%) and patient/parent participation in care (83%).
Despite this, 50% of the respondents reported that they never
or seldom use interpreters to take arrival status or medical history, and 48% report that they never or seldom use interpreters
when they educate the patients and families.
Conclusions: By identifying weaknesses in communication
between HCP and patients/families with limited proficiency
in the official language, we identified areas in this communi-
SIOP ABSTRACTS
cation which needed to be strengthened. Results showed that
HCP were aware that the use of interpreters increases patient
safety and participation in paediatric cancer care. However,
there is an insufficient use of interpreters, for example when
taking arrival status and medical history or educating patients
and the families, representing a risk to patient safety.
O-189 Symptom Trajectories in Children
Receiving Treatment for Leukemia: A Latent Class
Growth Analysis with Multitrajectory Modeling
M.C. Hooke1 , M.J. Hockenberry2 , C. Rodgers2 , O. Taylor3 , K.M.
Koerner4 , I. Moore4 , M.E. Scheurer3 , P. Mitby5 , W. Pan2
1 University
of Minnesota, School of Nursing, Minneapolis, USA; 2 Duke
University, School of Nursing, Durham- NC, USA; 3 Baylor College of
Medicine, Hematology/Oncology, Houston- TX, USA; 4 University of
Arizona, School of Nursing, Tucson- AZ, USA; 5 Children's Minnesota,
Cancer and Blood Disorders Program, Minneapolis- MN, USA
Background/Objectives: Cancer treatment symptoms play a
major role in determining the health of children with cancer.
Symptom toxicity often results in complications, treatment
delays, and therapy dose reductions that can compromise
leukemia therapy and jeopardize chances for long-term survival. Critical to understanding symptom experiences during
treatment is the need for exploration of “why” inter-individual
symptom differences occur; this will determine who may be
most susceptible to symptom toxicities. The objective of this
study was to examine specific symptom trajectories during the
first 18 months of childhood leukemia treatment.
Design/Methods: A repeated-measures research design was
used to evaluate treatment-related symptom associations
experienced by patients, ages 3 to 18 years, receiving treatment for a new diagnosis of acute lymphoblastic leukemia
at four sites. Symptom trajectories were explored over four
time periods: initiation of post-induction therapy, 4, 8 and
12 months into post-induction therapy. Self-report symptom
measures included fatigue, sleep disturbances, pain, nausea,
and depression. Parents of children ages 3 to 6 completed
proxy measurements. Latent class growth analysis was used
to classify patients into distinctive groups with similar symptom trajectories based on response patterns on the self-report
measures over time.
Results: Among 236 participants, 48% were ages 3 to 6
years, 33% were 7 to 12 years, and 19% were 13 to 18 years.
Sex was evenly distributed; 46% were Hispanic. Three latent
classes of symptom trajectories were identified and classified
into mild, moderate, and severe symptom trajectories. The
only demographic characteristic with a significant relationship to membership in the latent class symptom trajectories
was race/ethnicity. Other demographic characteristics including leukemia risk levels showed no significant relationships.
S101 of S518
Conclusions: This study is unique in that groups of patients
with similar symptoms were identified rather than groups of
symptoms. Further research using latent class growth analysis
is needed.
Funding: National Institutes of Health RO1 CA 1693398
O-190 Three-Phase Intervention Study of the
Need for Systematic Prevention and Treatment of
Constipation in Children and Adolescents with
Cancer
M.D. Jeppesen1 , N. Panduro1 , H. Haslund2
1 Aalborg
University Hospital, Department of pediatric oncology, Aalborg,
Denmark; 2 Aalborg University Hospital, Clinical nursing research unit,
Aalborg, Denmark
Background/Objectives: Children and adolescents with cancer often suffer from constipation due to chemotherapy and
treatment with opioids. Constipation may cause pain, anal fissures, septicemia and delays in therapy. Studies also show that
constipation contributes to poor quality of life. Because of the
many specialized tasks requiring the attention of nurses and
doctors, management of constipation may be neglected. Furthermore, nausea and pain may make oral intake of laxatives
difficult.
Design/Methods: The aim of the study is to reduce severe
complications caused by constipation in children and
adolecents with cancer. The study is a three-phase intervention study. In the first phase the problem is explored
through audit of 15 patient records, parent reported “stool
diaries” using the Bristol Scale, focus group interviews
with pediatric oncology doctors and nurses, and interviews
with parents and patients. In the second phase a practice
guideline will be developed based on the results of phase
one, and in the third phase the interventional guideline is
implemented.
Results: In phase one data from parents showed that it was difficult to accommodate extensive oral information at the time
of diagnosis, and that it is difficult to ensure sufficient intake of
laxatives. The diary has helped clarify stool patterns and has
stressed the importance of using a common assesment tool.
Data from health care professionals demonstrates the importance of systematic observation, documentation and care of
constipation.
Conclusions: Phase one has shown that systematic management of constipation is needed and that the use of an assesment tool by both parents and health care professionals may
support this. In phase two the guideline will be developed,
integrating the continuous use of Bristol scale to maintain
focus on constipation care. In addition, we will write an information pamphlet for parents and promote the use of a stool
diary.
SIOP ABSTRACTS
S102 of S518
O-191 Why all the Questions? Parent
descriptions of the Role of Question-Asking in Their
Learning: A Report from the Children's Oncology
Group
K. Kelly1 , J. Withycombe2 , K. Stegenga3 , C. Rodgers4
1 Children's
National Health System, Nursing Research and Quality
Outcomes, Washington DC, USA; 2 Emory University, Nell Hodgson
Woodruff School of Nursing, Atlanta GA, USA; 3 Children's Mercy Hospital,
Division of Hematology- Oncology and Bone Marrow Transplant, Kansas
City MO, USA; 4 Duke University, School of Nursing, Durham NC, USA
Background/Objectives: Question-asking is used by
researchers to evaluate parent understanding of their child's
cancer and by clinicians to assess parents’ response to
education. During qualitative research to describe parent
perceptions of new diagnosis education (Rogers et.al., 2016),
we noted a preponderance of interview data related to parent
and clinician question-asking. Because question-asking
was not related to our original study aim, we returned
to our data to complete this secondary analysis of parent
descriptions of questioning after diagnosis of their child's
cancer.
Design/Methods: Using secondary qualitative analysis we
reviewed the dataset (n=20 parents) to assure adequate fit
between our research question and the data and then conducted a retrospective interpretation. Data were first independently coded by two members of the study team. After
this, all coding decisions were discussed during weekly
investigator calls with consensus agreement reached by all
investigators.
Results: Question-asking was not a straightforward process.
A negative response to, “Do you have any questions?” was not
always an accurate assessment of parent understanding. Parents sometimes reported being too confused or overwhelmed
to ask. Parent questioning indicated unmet information needs
or that parents were learning, e.g. parents who asked many
questions were verifying their understanding with clinicians.
Parents quickly learned from whom or where they could get
their questions answered, which included written or online
educational materials. Parents also expressed questions that
they asked of themselves which included worries about their
child's diagnosis and treatment or their ability to care for their
child while balancing other life events.
Conclusions: Understanding and responding to the reasons
behind parent question-asking could facilitate parent learning
and coping. Given the nuances ascribed to question-asking in
parents, research is needed to also understand question-asking
in children and adolescents with cancer.
Funding: Children's Oncology Group-National Cancer Institute/National Clinical Trials Network Group Operations Center Grant (U10CA180886: PI-Adamson); Alex's Lemonade
Stand Foundation.
O-192 Oncology Rounds Checklist Enhances
Safety by Promoting Closed Loop Communication
E. Lambrinos1 , L. Morrissey1 , A. Federico1
1 Boston
Children's Hospital, Oncology, Boston- MA, USA
Background/Objectives:
Communication
breakdown
between clinicians is a leading cause of medical errors.
Dr. Atul Gawande describes that the implementation of
checklists improves team communication and ultimately
decrease patient complications[i]. At our institution, oncology rounds offer dedicated time when the multidisciplinary
team and family gather to set daily goals. Interruptions are
common, creating risk for lost or misinterpreted information.
In response, a daily rounds checklist was designed to promote
closed loop communication at the conclusion of rounds.
[i] Gawande, A. (2010). Checklist Manifesto, The (HB). Penguin Books India.
Design/Methods: In 2013, a paper-based checklist was
piloted, providing a tool to prompt the oncology team to summarize and confirm the patient plan before leaving the bedside. The checklist is read aloud and takes 20-30 seconds to
complete, summarizing patient information including treatment plan, upcoming diagnostic tests/procedures, antimicrobials, fever plan, nutrition, lines/tubes, labs, and discharge
planning. Once the feasibility of a rounds checklist was established, a web-based checklist was created which interfaces
with the patient medical record, offering the capability to
store patient information and access medication lists, labs, and
other current information.
Results: A rounds checklist prompts the team to pause and
recap the plan for the day, promoting clear communication and
ensuring that responsibilities are clearly delineated. Clinicians
report that potential errors are identified, discharge planning
is initiated earlier, and unnecessary or redundant labs, tests
and medications are intercepted.
Conclusions: Checklists are cost effective tools that improve
patient outcomes and decrease untoward complications. At
our institution, a daily rounds checklist has been found to
improve the efficiency of rounds while promoting a climate
of safety and family centered care. Future directions include
the development of quality reports to determine the checklist's
impact on safety, patient and staff satisfaction, clear delineation of roles and responsibilities, and cost savings.
O-193 Caregiver - Burden and Coping Strategies
in a Low Resource Country: A Quantitative and
Exploratory Study Conducted in an Indian
Pediatric Oncology Unit
A. Mahajan1 , M. BODHANWALA2 , B. AGARWAL3 , Y.K.
AMDEKAR2
SIOP ABSTRACTS
1 B.J.Wadia
Hospital for Children, Paediatric Hemato-Oncology
department., Mumbai, India; 2 B J Wadia Hospital For Children,
Administration, Mumbai, India; 3 B J Wadia Hospital For Children,
Pediatric Hematology Oncology, Mumbai, India
Background/Objectives: Caregivers often experience difficulty in helping children with cancer to cope with the emotional impact of the illness because of their own psychological
distress. In a low resource country, the child and family often
stagger from hospital to hospital and city to city seeking care,
thus creating emotional and financial hardships. We assessed
the level of burden and coping among caregivers of children
diagnosed with cancer in one Mumbai hospital.
Design/Methods: A quantitative and exploratory study (by
questionnaire) was conducted in 2015-2016, with 100 caregivers, to measure their physical, psychological, social, occupational, spiritual and economic burden and coping strategies.
Level of burden and coping strategies were co-related with
selected demographic variables. Data was analysed and measured using t- test and coefficient of correlation techniques.
Results: Ninety-five per cent of caregivers were parents;
(mothers 60% fathers 35%) and others 5%. A high level of burden among caregivers was observed mainly in parents. Mothers’ emotional strain due to the child's illness and their ability
to manage it and family cohesion were predictive of distress,
both concurrently and prospectively. The greater use of self
-directed coping strategies was related to higher levels of distress, for the fathers, and high levels of burden due to financial
and employment problems were related to number hospital
admissions for the child were significant.
Conclusions: Findings shows that long-term cancer treatment attributes to an increase in caregiver burden and the
impact of stress on parental quality of life. Unfortunately,
caregiver adopted coping strategies can be fleeting due to fears
of relapse and the uncertainty about their child's disease condition. Health care providers can identify gaps in the provision of a holistic clinical and psycho-social care to overcome
caregiver burden and support caregivers to adopt appropriate
coping strategies.
O-194 Evaluation of Parent-Child Conversations
Surrounding Li Fraumeni Syndrome Genetic
Testing
M. Belinda1 , J. Valdez2 , J. Gattuso1 , S. Ogg1 , B. Walker1 , J. Bosi1 ,
K. Nichols2
1 St.
Jude Children's Research Hospital, Division of Nursing Research,
Memphis, USA; 2 St. Jude Children's Research Hospital, Division of Cancer
Predisposition, Memphis, USA
Background/Objectives: Advances in genetic technologies
have revealed a growing number of heritable disorders associated with an increased risk to develop cancer during child-
S103 of S518
hood. Dialogues about cancer genetic testing and the implications of genetic risk status on children rest primarily with
parents. It is vital to understand if, when and how parents
and children communicate about genetic testing for heritable
cancer.
The study objective is to determine whether and how parents
communicate with their children about genetic testing for LiFraumeni syndrome (LFS), a rare and highly penetrant cancer
predisposing condition.
Design/Methods: Semi-structured interviews examined parents’ decisions regarding the pursuit of LFS testing for their
children and the communications surrounding test results.
Transcripts were evaluated using a grounded theory approach
to determine parents decision to initiate a conversation with
their children and their self-efficacy for holding this conversation.
Results: This study evaluated interviews from 14 parents
whose children tested positive for LFS. All 14 parents emphasized the importance of involving their child(ren) in conversations about undergoing LFS genetic testing and disclosure of the test results. Many parents self-identified as being
from a “cancer family”. Based on negative past experiences
consisting of exclusion from conversations regarding cancer,
these parents stated that they would approach communications about cancer with their children in a more open and
inclusive manner. Nevertheless, evaluation of the interviews
showed that only 9 of 14 parents (64%) actually disclosed the
LFS test result to their child(ren).
Conclusions: While parents express a desire for open conversations with their child(ren) regarding LFS genetic testing, such discussions do not always occur. Communication
is essential to enable understanding of genetic risk status and
compliance with treatment, prevention and surveillance measures. Development of educational materials and other interventions to facilitate age-appropriate parent-child conversations about genetic testing and genetic risk status for cancer is
needed.
O-195 Oncology Nurse Case Managers:
Improving Care for Children in Sub-Saharan
Africa
N. Mariam1
1 Uganda
Cancer Institute, Nursing, kampala, Uganda
Background/Objectives: Treatment adherence plays a critical role in cancer management and leads to better clinical
outcomes. Treatment adherence is a significant issue at the
Uganda Cancer Institute (UCI), with many patients abandoning treatment before it is complete. The primary reasons for
this, we believe, are poor communication, lack of social and
financial supports. The role of nurse case manager (CM) was
SIOP ABSTRACTS
S104 of S518
developed to improve patient outcomes by addressing these
issues.
Objectives:
1. Describe the role of nurse case managers in improving treatment adherence and clinical outcomes for patients treated at
the Uganda Cancer Institute.
Design/Methods: Barriers to treatment adherence were identified and the role of CM was developed to address these
issues. based on personal experience as a CM on the pediatric
ward for 4 years at the UCI.
Results: UCI is the only cancer treatment center in Uganda,
treating over 30,000 patients annually from Uganda and surrounding countries. Treatment begins 2 to 4 weeks after diagnosis due to the complex health care navigation processes and
limited resources of families. Before CM, these ongoing challenges frequently led to treatment abandonment. Now, the CM
is the first contact for patients when they arrive at UCI and
are given our contact information so they can contact us. We
assess the family's social and financial resources, explain the
diagnosis, treatment plan including the number of hospital
visits and treatment duration. We closely monitor the patients’
progress and facilitate communication between the patient,
family, and clinicians. We follow-up between hospital visits,
provide counseling, and direct nursing. Most importantly, we
advocate for our patients by relaying patient concerns to clinicians, mobilizing funds when possible, and connecting families with community resources.
Conclusions: Oncology treatments are increasingly
complex, and present unique challenges for oncology
nurses in resource limited countries like Uganda. Nurse
case managers will play an important role in improving
outcomes.
O-196 Survey Reveals Barriers to the Delivery of
Quality Pediatric Oncology Nursing Care in Lowand Mid-Income Countries (L&MIC)
L. Morrissey1 , M. Lurvey1 , C. Sullivan2 , S. Day3 , L. Abramowitz4 ,
J. Challinor5 , R. Hollis6 , G. Afungchwi7 , P. Rehana8
1 Boston
Children's Hospital, Hematology/Oncology Nursing, Boston, USA;
2 St. Jude Research Hospital, Internationa Outreach Program, Memphis,
USA; 3 St. Jude Research Hospital, International Outreach Program,
Memphis, USA; 4 University of California at San Francisco UCSF Hospital,
Nursing, San Francisco, USA; 5 Unaffiliated, Unaffiliated, Amsterdam,
Netherlands Antilles; 6 Leeds Teaching Hospitl NHS Trust, Nursing, London,
United Kingdom; 7 Banso Baptist Hospital, Oncology Nursing, Banso,
Cameroon; 8 Indus Childrens CAncer Hospital, Oncology Nursing, Karachi,
Pakistan
Background/Objectives: In 2014, the SIOP PODC Nursing
Workgroup published baseline standards describing elements
of nursing care essential to promote optimal patient outcomes.
The SIOP Baseline Standards Taskforce developed a validated
survey to measure the degree to which nursing standards are
being met in paediatric oncology programs worldwide, and to
compare responses from low, mid and high income countries
(HIC) to identify trends by income level.
Design/Methods: A validated survey addressing the six
baseline standards was electronically distributed to a
convenience sample of 208 pediatric oncology nurses
from 64 countries. The survey was translated into four
languages and administered in REDCap.TM Responses
were compared based on World Bank defined income
levels.
Results: A 50% response rate from 104 nurses from 56 countries was achieved. Results revealed that nurse staffing levels
on oncology wards and intensive care units in L&MIC are significantly lower than HIC (p < .0001). Nurses in LIC nurses
caring for oncology patients are rotated more frequently (65%
vs. 97%, p = .002) and are less likely to receive formal orientation programs. Significant differences exist in the inclusion of
nurses in multidisciplinary meetings (p < .0001). Resources
for safe care such as infusion pumps and personal protective
equipment are often insufficient in L&MIC. Evidence based
policies are available in 64.5% of reporting LIC, compared to
96.7% in HIC (p = .003).
Conclusions: Results from the SIOP PODC Baseline Standards survey indicate that significant gaps exist in staffing levels, education, resources and institutional support for L&MIC
pediatric oncology nurses. Survey results will be used to advocate for increased nursing support in L&MIC pediatric cancer units. Further research will determine if adherence to the
baseline standards for pediatric oncology nurses is linked to
favorable patient outcomes.
O-197 Pediatric Oncology Nurses’ Experiences
with Prognosis-Related Communication
A. Newman1
1 Medical
College of Wisconsin, Pediatric Oncology, Milwaukee, USA
Background/Objectives: Providers in pediatric oncology are
faced with the challenge of communicating the devastating
news of a cancer diagnosis and prognosis. While the initial
conversation regarding prognosis is generally considered the
responsibility of the physician, patients and family members
will subsequently turn to nurses for clarification of the information presented. If nurses are excluded from initial conversations, they may feel as though they are “working in the
dark,” trying to answer questions while not contradicting what
the physician said. Little has been reported regarding pediatric oncology nurses’ experiences with such communication.
The purpose of this research was to examine nurses’ experiences with prognosis-related communication (PRC) and the
SIOP ABSTRACTS
associations with interprofessional collaboration, quality of
care, and nurse moral distress.
Design/Methods: A mixed-methods approach utilizing an
online survey incorporating validated measures of PRC, interprofessional collaboration, quality of care, and moral distress accompanied by focus groups was used to meet study
objectives.
Results: Findings demonstrated that nurses strongly agreed
that prognostic disclosure is critical for decision making, but
are challenged in determining their role. Nurses who had
more years of experience, more training in PRC, worked
outpatient or inpatient/outpatient, and indicated higher levels of collaboration reported more positive experiences with
PRC. A significant correlation was identified between experiences with PRC and collaboration, and both were significantly associated with measures of quality of care and moral
distress.
Conclusions: Nurses should work to be active participants
in PRC. When nurses sense that prognostic discussions have
not occurred or if clarity is needed, nurses should feel confident in approaching physician colleagues to ensure parent understanding and satisfaction around communication.
Future research and education should aim to develop interprofessional training to enhance communication and collaboration among nurses and physicians to ensure the highest quality of communication and care to patients and
families.
S105 of S518
removal due to non-infectious complications (accidental dislodgment or catheter obstruction) and the number of patients
with CVC per day, multiplied by 100.
Results: Hundred-fourteen CVC were inserted into 110 children during the 6-month period. From 110 catheters removed,
thirteen were due to non-infectious reasons, nine related to
accidental dislodgment, four to obstruction. Average catheter
life was 12.8 days, with a total of 911 catheter days. Regarding
CVC events, the pediatric ward had an average of 143 CVC
insertions per month, and an incidence of CVC removal of
0.85 per 100 catheter-days. At Bone Marrow Transplant Unit
had an average of 59 CVC patients per month, and removal
incidence of 1.07 per 100 catheter days. The Pediatric Intensive Care Unit had an average of 118 CVC patients per month,
what represented 60% of it occupation, and removal incidence
of 0.11 per 100 catheter days. Overall hospital CVC removal
incidence was 0.41 per 100 catheter days.
Conclusions: Non-infectious CVC removal can be used as an
indicator of nursing care at pediatric oncology hospitals and
give an assertiveness related of improvements, to decrease this
rate improving children nursing care.
O-199 Telephone Triage: Standardized Practice
in Paediatric Oncology
L. Ollett1 , K. O'Driscoll1 , S. Forrest1 , J. Palmer1
1 Great
O-198 Accidental Dislodgment and Obstruction
of Central Venous Catheters as a Nursing Care
Indicator at an Brazilian Pediatric Oncology
Hospital
R.C. Ribeiro1 , A. Ribeiro1 , L. Lima1 , F.F. Gonçalves2 , V. Kremer2 ,
W.E. Oliveira Júnior2
1 Barretos
Childrens Cancer Hospital, Quality Department, Barretos,
Brazil; 2 Barretos Childrens Cancer Hospital, Pediatric Surgery
Department, Barretos, Brazil
Background/Objectives: Use of Central Venous Catheters
(CVC) is essential in children when treating malignant diseases. The maintenance of catheter reflects the quality of nursing care. Catheter obstruction or accidental dislodgement due
to traction are non-infectious complications and can be considered as a quality indicator in an oncologic pediatric hospital
setting. Our purpose was analyze those complications related
to CVC removal in a hospitalized pediatric oncology patients
from a developing country hospital.
Design/Methods: A prospective analysis using the reporting
system (SAS Interact ®) from a pediatric oncology hospital
at a developing country database between February 2016 to
August 2016. We analyzed demographic features, rate of CVC
North Childrens Hospital, Paediatric Oncology, Newcastle, United
Kingdom
Background/Objectives: Paediatric Oncology nurses are
often the first point of contact for overwhelmed parents.
Patients are often assessed over the telephone with regards
to acute oncology emergencies and advice/symptom management. Nurses are expected to make clinical decisions regarding patient care without visually assessing the patient or using
a systematic uniformed approach. The Great North Children hospital, a principal treatment centre (PTC) has adopted
the use of the United Kingdom Oncology Nursing Society
(UKONS) Telephone Triage Kit. An audit as to the effectiveness of the tool was conducted.
Design/Methods: The UKONS telephone triage kit provides
a pathway for a nurse assessment over the telephone. The
nurse will use a traffic light toxicity grading system to initiate emergency treatment or advice. In addition, patients who
score an amber toxicity are required a 24 hour call back to
promote early intervention and patient safety. A retrospective
peer review of telephone triage calls were evaluated including
diagnosis, time of call, duration of call, main complaint, toxicity grading and patient journey over a four month period from
January 2016.Nurses perceptions and challenges of using the
tool in the clinical environment were also explored.
SIOP ABSTRACTS
S106 of S518
Results: 384 calls were received within the four month period,
this having a significant impact on service provision as the
average call lasted ten minutes. Data indicated nursing staff
gave concise advice and symptom management using a valid
tool. Nurses reported using toxicity grading gave them confidence and consistency in the advice offered. Highlighted areas
for improvement included documentation regarding patient
details and establishing contact within 24 hours after the initial telephone call.
Conclusions: The UKONS triage tool is an invaluable
resource within PTC setting. Data collected was discussed
with management to allocate resources appropriately. Further
educational and peer review sessions to highlight the importance of documentation and telephone call back are recommended.
O-200 AYA Involvement in Cancer Treatment
Decision Making: An Ethnographic Study
1
2
3
involvement and appreciated their support in TDM. Friends
and other family members were supportive but not involved
in TDM. Factors influencing TDM included uncertainty about
the treatment, altruism and quality of life.
Conclusions: Findings highlight the range of involvement of
the AYA in TDM. Overall, they felt informed, part of discussions and viewed themselves as sharing in or making treatment decisions. AYA preferences for participation in TDM
may vary over time and by type of decision. Parents play a
particularly important supportive role.
O-201 Intervention to Improve Adherence to the
Use of Personal Protective Equipment for the
Administration of Chemotherapy
L. Segovia1 , L. Rojas1 , P. Francisca1 , A. Torelli1
1 Hospital
Luis Calvo Mackenna, Unidad de Oncologia, Santiago, Chile
4
K. Pyke-Grimm , B. Halpern-Felsher , L. Franck , R. Goldsby , R.
Rehm3
1 Lucile
Packard Children's Hospital, Center for Nursing Excellence,
Stanford, USA; 2 Stanford, Department of Pediatrics, Palo Alto, USA;
3 UCSF, School of Nursing, San Francisco, USA; 4 UCSF, Department of
Pediatrics, San Francisco, USA
Background/Objectives: Survival rates among adolescent
and young adult (AYA) cancer patients have improved minimally over the past decade. AYAs experience treatment nonadherence rates as high as 60% that can lead to relapse and
even death. Open communication, positive family relationships and involvement of AYAs in treatment decisions and
illness management support treatment adherence. However,
there is limited research exploring AYA involvement and
experiences in treatment decision-making (TDM). The purpose of this ongoing study is to explore and describe AYA
experiences with cancer TDM.
Design/Methods: Twelve AYAs on treatment for cancer and
within one year of their diagnosis participated in an interpretive ethnographic study that included interviews and informal participant observation. Participants were asked to reflect
on a major TDM experience (e.g., clinical trial or surgery)
and other decisions since diagnosis. Analysis included field
notes, analytic memos and coding of interview transcripts
using Atlas.ti.
Results: Preliminary findings were drawn from 22 interviews
with 12 AYAs (6 male, 5 female, 1 non-binary) between
15 and 20 years old. AYAs distinguish between major treatment decisions and care preferences. Involvement in decisionmaking varied from having no involvement in the decision, accepting the decision, being involved in discussions
and assuming a shared or primary role in decision-making
and for some, changed over time. AYAs preferred parental
Background/Objectives: Chemotherapy administration is a
high risk procedure for nursing staff because of the potential
teratogenic, carcinogenic, mutagenic damage and other toxic
effects associated with exposure. In the oncology unit of
the Hospital Luis Calvo Mackenna there are protocols of
administration, based on the recommendation of international organisms. The unit has all the necessary personal
protective elements (PPE) for safe administration. Every
nurse who joins the unit receives a comprehensive four-week
orientation program that emphasizes the safe administration
of chemotherapy, content that is reinforced annually in
the continuing education program. Adherence to protocol
compliance is monitored monthly by applying a checklist.
This checklist assesses aspects of safety management for both
the patient and the nursing staff. The item related to staff protection assesses whether the nurses use all the PPE described
in the protocol. Monitoring conducted in August 2016 shows
that 100% of nurses are not using all the PPE defined in the
protocol.
Design/Methods: In September 2016, an educational intervention to 100% of the Oncology Nurses was carried out
focused on chemotherapy safe handling and administration.
In October of the same year the checklist is reapplied.
Results: 83% of the Oncology Nurses do not use all the
PPE according to the Chemotherapy Administration Protocol.
100% of the nurses assesses do not use eye protection and 17%
do not use gloves.
Conclusions: Despite all the information and training that
nurses receive, there is a low adherence to the policy and protocol, which mainly impacts on a potential risk to the health
of nurses. A new intervention is proposed to know the reason
for this low adherence by the nurses.
SIOP ABSTRACTS
O-202 Parental Distress 6 Months After a
Pediatric Cancer Diagnosis in Relation to Family
Psychosocial Risk at Diagnosis
S. Schepers1,2,3 , S.M. Sint Nicolaas4 , H. Maurice-Stam3 , L.
Haverman3 , C.M. Verhaak4 , M.A. Grootenhuis2,3
1 St
Jude Children's Research Hospital, Department of Psychology,
Memphis, USA; 2 Princess Maxima Center for pediatric oncology,
Psychosocial Research and Care Innovation, Utrecht, The Netherlands;
3 Emma Children's Hospital- Academic Medical Center, Psychosocial
Department, Amsterdam, The Netherlands; 4 Amalia Children's HospitalRadboud University Medical Center, Medical Psychology, Nijmegen, The
Netherlands
Background/Objectives: Parents of children with cancer are
at increased risk for experiencing distress and it is important to
identify families that are in need for support at an early stage.
This study aimed to (1) assess fathers’ and mothers’ distress
as measured by the Distress Thermometer for parents (DTP) at 6 months post-diagnosis (T2), and (2) assess if distress
at 6 months post-diagnosis could be predicted from Psychosocial Assessment Tool (PAT) risk profiles at approximately one
month post-diagnosis (T1).
Design/Methods: A sample of 119 mothers and 98 fathers
completed the DT-P at T2. The sample was compared to a
healthy reference group of 671 mothers and 463 fathers. The
DT-P consists of a thermometer score (ranging from 0-10,
>= 4 is clinical distress), and problem domains (total, practical, social, emotional, physical, cognitive, and parenting <2
years and ≥2 years of age). The PAT, a family psychosocial
risk screener, was assessed at T1. Within the pediatric cancer
group, DT-Ps of parents with elevated total PAT-scores (targeted/clinical) were compared to DT-Ps of parents with low
PAT-scores (universal).
Results: Parents of children with cancer more often reported
clinical distress than parents of healthy children on the DTP thermometer score (fathers: 59.2% versus. 32.3%, p<.001,
mothers: 63% versus 42.3%, p<.001) and reported more problems on all DT-P domains (p<.001-.042), except for the parenting domain for children <2 years of age. Furthermore,
parental distress at T2 was predicted from family psychosocial
risk at T1, as parents with elevated total PAT-scores reported
more problems than parents with low PAT-scores on the DTP thermometer score (fathers: p=.026, mothers p=.018) and
on most of the DT-P domains (p<.001-1.00).
Conclusions: The results of this study point towards the
importance of family psychosocial risk screening at diagnosis, and the need for applying tailored interventions, such that
later parental distress can be reduced or prevented.
O-203 The Interventions Core to Pediatric
Oncology Nursing: A National Survey of Clinical
Application in China
S107 of S518
J. Sun1 , N. Shen2 , H. Lu2
1 Shanghai
2 Shanghai
Children's Medical Center, Nursing, Shanghai, China;
Children's Medical Center, Nursing, Shanghai, China
Background/Objectives: In our previous study, we investigated the application frequency of 5 hospitals in 4 regions,
and found that there had differences between the hospital in
North China and the others, but the single hospital can not
fully represent the region. Thus, in this study, we want to
know national clinical application of the core interventions
performed by pediatric oncology nurses and analysis its variance of region.
Design/Methods: An online survey of application frequency
of 82 core interventions, conducted by experts consensus
based on Nursing Interventions Classification (NIC) was send
to all the pediatric oncology nurses from 18 nation wide
selected hospitals in January to February 2016.
Results: 444 clinical nurses completed the questionnaire. The
application rate of 82 core interventions were from 74.1% to
100%. As to domains, there were differences in basic and complex physiology domain (North China vs East, West China,
p<0.05), behavioral and family domain (North China vs East
China, p<0.05), health system domain (North China vs West
China, p<0.05). As to classes, nurses in different region performed different frequently (p<0.05) in elimination, immobility management, nutrition support, self-care promotion, electrolyte and acid-base management, respiratory management,
skin/wound management, thermoregulation, tissue perfusion
management, Patient Education, Psychological Comfort Promotion, lifespan care.
Conclusions: Core interventions of pediatric oncology nursing were frequently performed in practice, showing difference
by the groups of regions, especially North China. When doing
the homogenization training, trainers need to think about the
reasons for the different clinical application by regions as
shown in this study, in order to develop different proportion
of training content.
Found: Shanghai Municipal Education Commission –
Gaoyuan Nursing Grant Support (Hlgy16073qnhb)
O-204 Development of a Pediatric Oncology
Nursing Curriculum in Cambodia
E. Sniderman1 , P. Johnson2 , S. Sath3
1 Ann
& Robert H. Lurie Children's Hospital of Chicago, Division of
Hematology- Oncology- Stem Cell Transplant, Chicago, USA; 2 Children's
Mercy Hospital, Pediatric Oncology, Kansas City, USA; 3 Angkor Hospital
for Children, Pediatrics/Pediatric Oncology, Siem Reap, Cambodia
Background/Objectives: The Angkor Hospital for Children
(AHC) is one of two facilities in Cambodia that offers comprehensive cancer care for children, however treatment is currently limited to retinoblastoma and Wilms tumor, partially
SIOP ABSTRACTS
S108 of S518
due to nursing limitations. AHC's pediatric oncology program is currently expanding. As part of the hospital's fiveyear strategic plan, the development of a nursing curriculum
and ongoing mentoring and training of oncology nurses were
identified as priorities.
Design/Methods: In conjunction with ASCO-Health Volunteers Overseas, volunteer oncology Nurse Practitioners (NPs)
visited AHC over a two year period. A formal assessment
of the current knowledge base, resources, and challenges of
the pediatric oncology nurses was performed using the SIOP
PODC Baseline Standards for Paediatric Oncology Nursing
Care in Low and Middle Income Countries. AHC nurses, educators, and other oncology team members collaborated in the
assessment process.
risk-stratified pathway of LTFU for life (4, 5). A crucial stage
of this pathway occurs in late adolescence as patients move
from child to adult services, a process that should be one of
proactive transition rather than sudden transfer (6).
To meet these recommendations a model of transition was
introduced to children's and TYA principal treatment centre
over a two year period. In 2016 a service evaluation was carried out to assess the acceptance and effectiveness of this
model.
Design/Methods: Using a mixed methods approach a sample
of TYA aged 16-25 years olds attending the TYA LTFU clinics were identified and data collected to measure acceptance
and effectiveness of the mode through:
Results: The formal assessment identified gaps in knowledge,
unsafe chemotherapy administration practices, and misconceptions regarding chemotherapy safety. This informed the
creation of a curriculum adapted to the needs and resources
of the hospital. Seven modules were created to be taught
over 6 months. Content includes an introduction to childhood
cancer/diseases, chemotherapy, supportive care and symptom management, infection control, emergencies, palliative
care and pain management, and psychosocial considerations.
Future modules will focus on late effects and central line care.
Several interactive teaching strategies help create a dynamic
teaching environment. Modules will be taught by the director
of education and pediatric oncologist at AHC as well as by
visiting international nurses/NPs.
• online patient experience survey
Conclusions: Nurses with specialized education and training in pediatric oncology are essential for successful comprehensive cancer care. Formal assessment using internationally
accepted standards of pediatric oncology nursing care, adaptation of education to the limited resource setting, and collaboration with local team members were key steps in ensuring
high quality cancer care will be provided to the children of
Cambodia.
Conclusions: This service evaluation has highlighted key factors in establishing a transition model and identified areas to
ensure transition is truly holistic.
• 1:1 patient telephone interviews
• qualitative and quantitative analysis of clinic consultations
• qualitative and quantitative analysis of patient contact to the
CNS for LTFU outside clinics.
Results: The model of transition though largely accepted was
for some a significant challenge; at times this went beyond the
patient to the family, in particular mothers whose role as carer
was also in transition. The need for time, a multidisciplinary
and multi-method of approach to facilitate patient knowledge
and self confidence in transition was identified as a key factor
in both acceptance and effectiveness of the model.
O-206 Sustainable Model for Nursing Education
in Latin America: 10 Years Later
C. Sullivan1 , L. Segovia Weber2 , P. Viveros Lamas3 , S. Day4 , G.
Rivera1
1 St.
O-205 Evaluation of a Teenage and Young Adult
(TYA) Long Term Follow-Up (LTFU) Service for
Survivors of Cancer in Childhood
L. Soanes1 , E. Potter2
1 University
College London, Children& Young People Services, London,
United Kingdom; 2 The Royal Marsden NHS Foundation Trust, Oak Centre
for Children & Young People, London, United Kingdom
Background/Objectives: Each year 1600 children are diagnosed with cancer in the United Kingdom; the survival rate for
whom is now 80% (1). Survivors are known to be at increased
risk of poorer psychosocial and physical outcomes than their
peers (2). These effects occur soon after treatment or many
years later (3), therefore it is recommended survivors follow a
Jude Children's Research Hospital, Dept. of Global Pediatric Medicine,
Memphis, USA; 2 Luis Calvo Mackenna Hospital, Latin American Center
for Pediatric Oncology Nurisng Education, Santiago, Chile; 3 Luis Calvo
Mackenna Hospital, Latin American Center for Pediatric Oncology Nursing
Education, Santiago, Chile; 4 St. Jude Children's Research
Hospital/University of Tennesse Health Science Center, Dept. of Global
Pediatric Medicine/College of Nursing, Memphis, USA
Background/Objectives: Ten years ago, the Latin American
Center for Pediatric Oncology Nursing Education was created
at Calvo Mackenna Hospital in Santiago, Chile as an initiative
of the International Outreach Program at St Jude Children´s
Research Hospital (SJCRH), to enhance the quality of pediatric oncology nursing care in Latin America through establishing the pediatric oncology nurse educator role.
Design/Methods: The program consists of 4 weeks theoretical/skills training and clinical observation (176 hours) in
SIOP ABSTRACTS
pediatric oncology nursing, supportive care, and education.
Theoretical portions include expositive-participative lectures
in pediatric oncology and education, using adult learning principles. Onsite and ongoing mentoring is provided in development of tailored education programs and quality projects.
Program evaluation consists of pre-/post-tests and successful
demonstration of curriculum development and delivery.
Results: To date, 25 nurse educators from Mexico, Central
America, South America, and the Caribbean completed the
program. A network of Latin American nurse educators developed through ongoing mentoring/collaboration with graduates. Active members represent 13 hospitals in 8 countries
and presently impact over 800 nurses. Additionally, quality
improvement projects for correct patient identification are
ongoing at several sites.
Conclusions: The Latin American Center for Pediatric
Oncology Nursing Education has proven to be a successful and sustainable model to promote excellence in pediatric
oncology nursing education and quality in Latin America
through development of the pediatric oncology nurse educator
role.
O-207 Promoting Standardized
Chemotherapy/Biotherapy Education in Latin
America: An Aphon Initiative
S109 of S518
St. Jude Children's Research Hospital (SJCRH). The Task
Force, Chemotherapy Committee, and Spanish WG modified/expanded the course over the next year, and materials
were professionally translated with support from SJCRH.
Spanish-fluent APHON-certified instructors were identified
to teach the courses.
Results: An inaugural two-cohort pilot was held in Chile (32
nurses, April-May 2016), followed by a second pilot with
Central American nurses and an English instructor course
(Associación Hemato/Oncología Pediátrica de Centro America pre-conference at SJCRH (24/6 nurses, February 2017)).
Additional pilots are scheduled in Argentina (Sociedad Latina
Americana de Oncología Pediátrica (110 nurses, April 2017))
and Mexico (55 nurses, May 2017). All nurses of the Chilean
pilots and 82% of nurses of the AHOPCA pilot passed the
exam. Comparison of results for the four pilots will be
presented.
Conclusions: Since 80% of children and adolescents with
cancer live in LMIC, it is paramount that their nurses
have specialized training in chemotherapy/biotherapy. The
APHON survey documented interest and need for standardized chemotherapy/biotherapy education across Latin America. Pilots have demonstrated course appropriateness for
nurses’ practice. Future plans include developing an instructor community to promote sustainable, standardized Spanish
courses and exploring expansion to other regions.
C. Sullivan1 , K. Belderson2 , L. Segovia Weber3 , P. Viveros
Lamas4 , J. Avila5 , R. Ramos6 , D. Navarro Diaz7 , J. Challinor8
1 St.
Jude Children's Research Hospital, Dept. of Global Pediatric Medicine,
Memphis, USA; 2 Children's Hospital Colorado, Nursing Education,
Denver, USA; 3 Luis Calvo Mackenna Hospital, Latin American Center for
Pediatric Oncology Nurisng Education, Santiago, Chile; 4 Luis Calvo
Mackenn Hospital, Latin American Center for Pediatric Oncology Nursing
Education, Santiago, Chile; 5 Renaissance Doctors Hospital, Compliance,
Edinburg, USA; 6 Stanford Children's Hospital, Hematology/Oncology, Palo
Alto, USA; 7 Hospital Civil de Guadalajara "Dr. Juan I. Menchaca",
Pediatric Oncology/Education, Guadalajara, Mexico; 8 UCSF, Nursing,
Amsterdam, Netherlands Antilles
Background/Objectives: Association of Pediatric Hematology Oncology Nurses (APHON) has received numerous
inquiries from nurses in low- and middle-income countries
(LMIC) interested in the Chemotherapy/Biotherapy certification course. APHON certification is recommended by the
American Academy of Pediatrics and aligns with SIOP PODC
Nursing baseline standards recommendation for formalized
training in chemotherapy preparation and handling globally.
In response to international interest, the International Task
Force set out to evaluate the feasibility of adapting and piloting Spanish courses throughout Latin America.
Design/Methods: A survey of nurses in Latin America verified interest and need for the course in 2015. Recommendations for adaptation were incorporated from two bilingual
Chilean nurse educators, who took the English course at
O-208 Analysis of the Interventions Performed in
Pediatric Hematology-Oncology Unit Based on
Nursing Interventions Classification (NIC-6TH)
J. Sun1 , N. Shen2 , H. Lu2 , M. He3
1 Shanghai
Children's Medical Center, Nursing, Shanghai, China;
Children's Medical Center, Nursing, Shanghai, China;
3 Shanghai Children's Medical Center, Pediatric Hematology-Oncology,
Shanghai, China
2 Shanghai
Background/Objectives: In previous study, we used experts
consensus to identify the core interventions done by pediatric hematology-oncology nurses, but core interventions was
just the interventions which nurses mostly performed in discipline.Therefore, this study was to identify all the interventions
performed by pediatric hematology-oncology nurses through
records in hospital information system (HIS) and analysis its
characteristic.
Design/Methods: The research team selected a 42 beds pediatric hematology-oncology unit, and drawn all the nursing
interventions in nursing record and doctor's order from our
HIS from 1 September 2016 to 30 December 2016, using
Nursing Interventions Classification (NIC) to do the matching
and then counting their frequencies.Then giving each intervention its own time and difficulty code according to NIC
SIOP ABSTRACTS
S110 of S518
Time code refers to the average time needed to perform the
intervention, 1=15 minutes or less; 2=16 to 30 minutes; 3=31
to 45 minutes; 4=46 to 60 minutes; 5=more than 1 hours. Difficulty code refers to the minimal education level necessary to
perform the intervention in most cases, 1=nursing assistant;
2=RN ; 3=RN with post-basic education or certification.
Results: 4044 unique statements (1908 from nursing record,
2136 from doctor's order) were drawn from HIS matching
to 77 interventions (56 from nursing record, 61 from doctor's order, 30 were the same).77 interventions belonged to
6 domains and 20 classes. The average difficulty was 1.88 and
average time was 2.06.
Conclusions: Nurses in pediatric hematology-oncology unit
performed totally 77 interventions. There still had some interventions just needed by nursing assistant but done by nurses,
which should call for nurse managers to think about the suitable stuffing. The result of this study was expected to be useful
in understanding how to improve pediatric hematologyoncology nursing and the standardization of nursing
interventions.
Found Clinical Management Optimization Project
of Shanghai Shen Kang Hospital Development Center(SHDC2014615);Shanghai Municipal Education Commission - Gaoyuan Nursing Grant Support (Hlgy16073qnhb)
O-209 Checking In: The Next Generation of
Pediatric Oncology Distress Screening
L. Wiener1 , S. zadeh bedoya1 , M. Pao2
1 NCI,
Pediatric Oncology Branch, Bethesda, USA; 2 National Institute of
Mental Health, Office of the Director, Bethesda, USA
Background/Objectives: An interdisciplinary group of
experts and stakeholders developed evidence-based standards
for psychosocial care in pediatric cancer. One standard, supported by 149 high quality papers, recommends that youth
with cancer and their family members routinely receive systematic assessments of their psychosocial needs. While valid
and reliable measures are available for parents to report on
their family and child's psychosocial needs, there are limited psychometrically valid self-report measures to assess distress in medically ill children. A multi-phase study guided the
development of a brief electronic distress screen called Checking In.
Design/Methods: Phase I: 281 Patient-Caregiver-Provider
triads, with youth aged 7-21 with cancer and other chronic
illnesses completed the Distress Thermometer (DT) and measures of depression, anxiety, pain, and fatigue. Findings identified items to include in a new version of a pediatric distress
screen. Phase II: 15 cognitive interviews were conducted with
patients in each age group (8-12; 13-17; 18-21). Health care
providers gave input on development of a summary report.
Results: Substantial discrepancy between parent and child
specific distress symptoms on the DT indicated that parent
input alone is not sufficient to identify child distress or to
guide referrals. 15 most frequently endorsed symptoms were
included in Checking In. Cognitive interviews tested the accuracy and quality of the items and identified errors in the
response choices. Differences in wording recommendations
based on age were found. Suggestions for design, format, and
response options were incorporated.
Conclusions: Checking In assesses emotional, physical,
social, practical, and spiritual concerns of pediatric patients
as well as suicidal ideation and adherence. An accompanying
provider document summarizes patient and caregiver report
of the child's distress in real time, to allow providers to triage
services. Testing the reliability, validity, measurement variance, and responsiveness of Checking In and assessment of
concordance of symptom ratings by patients and caregivers
will follow.
E D U CAT I O NA L DAY - FE RT I L I T Y
O-210 Decision Support Tools in Paediatric and
Adolescent Oncofertility for Clinicians and Parents
Y. Jayasinghe1 , M. Kemertzis1 , M. Hand2 , C. Allingham3 , L.
Gillam4 , L. Orme5 , S. Jayasuriya6 , M. Zacharin7 , Y. Heloury8 , M.
McCarthy5 , M. Sullivan5 , M. Peate2
1 Royal
Children's Hospital, Gynaecology, Melbourne, Australia;
of Melbourne, Obstetrics & Gynaecology, Melbourne,
Australia; 3 Notre Dame University, Medicine, Sydney, Australia; 4 Royal
Children's Hospital, Clinical Ethics Service, Melbourne, Australia; 5 Royal
Children's Hospital, Children's Cancer Centre, Melbourne, Australia;
6 Monash University, Medicine, Melbourne, Australia; 7 Royal Children's
Hospital, Endocrinology, Melbourne, Australia; 8 Royal Children's
Hospital, Surgery, Melbourne, Australia
2 University
Background/Objectives: Fertility preservation decisions for
children are difficult and there is a need for decision support
for clinicians and families. Our aim was to develop and evaluate electronic decisional support tools for clinicians and parents of children with cancer at The Royal Children's Hospital,
Melbourne.
Design/Methods: Electronic decision support systems were
developed based on the literature and consultation with stakeholders. The clinician tool outlined clinician roles and responsibilities, linked to educational guidance, and included ’alerts’
for best practice. Clinicians completed a survey on acceptance, and results were compared to a previous survey of 56
clinicians in 2014. The parent decision aid was based on International Patients Decision Aids Standards. Parents’ of children with cancer who had previously made a fertility preservation decision were invited to complete surveys before and
after review of the decision aid.
SIOP ABSTRACTS
Results: Thirty-nine oncofertility clinicians (18% involved in
over 100 fertility consultations) reviewed the clinician decision support system. Compared to 2014, clinician satisfaction with fertility consults increased from 33% to 54%, and
confidence from 40-70% (p<0.005). Most (92%) wanted to
improve their fertility consultation skills, and stated the clinician tool clearly outlined responsibilities, with 88% stating
they would always or often use it. Thirty-four parents consented to the decision aid study, of whom 15 reviewed the
parental tool. They reported it was appealing, ’very clearly’
presented (73%), ’clearly’ or ’very clearly’ explained their
child's fertility choices (87.0%). The tool improved fertility related knowledge by 15% (p=0.04) and 87% of parents reported it would have been ’helpful’, ’very helpful’ or
’extremely helpful’ if available when making a fertility preservation decision.
Conclusions: The clinician tool appeared acceptable to clinicians however further development is required. The parental
decision aid was very acceptable and improved knowledge
in parents. Prospective assessment in a clinical setting is
planned.
O-211 Factors Associated with Fertility-Related
Knowledge in Survivors of Pediatric Cancer
A.C. Ferrante1 , N.M. Caltabellotta1 , L. Nahata1 , C. Gerhardt1 , V.
Lehmann2
1 The
Research Institute at Nationwide Children's Hospital, Center for
Biobehavioral Health, Columbus- OH, USA; 2 St. Jude's Children's
Research Hospital, Department of Psychology, Memphis- TN, USA
Background/Objectives: Infertility is one of the most common late effects of certain cancer treatments. However, there
is limited research on infertility in survivors of pediatric cancer. Thus, we assessed knowledge of cancer-related infertility
risk, perception of personal infertility risk, and knowledge of
current fertility status and examined associations with demographic (i.e. gender, age, income level) and medical factors
(i.e. diagnosis type, neurotoxicity of treatment).
Design/Methods: Ninety-one survivors of pediatric cancer
(M=29.82 years) participated in an online survey assessing
knowledge of cancer-related infertility risk, perception of personal infertility risk, and knowledge of current fertility status.
All participants were ages 20-40, diagnosed between ages 518 with leukemia (n=25), lymphoma (n=22), pediatric brain
tumor (n=26), or other solid tumors (n=18), and at least 5
years post-diagnosis.
Results: Most survivors were aware of their general risk for
cancer-related infertility (n=79, 87%), which varied by type of
diagnosis (p<0.001) and treatment (p=0.032), such that survivors of brain tumors and those who received high-dose neurotoxic treatment were less likely to know. Forty-seven survivors (52%) perceived that they were personally at risk for
S111 of S518
infertility, which was unrelated to examined factors. Almost
half of all survivors (n=44; 48%) did not know their current fertility status, which was more common for younger survivors (p<0.001), survivors of brain tumors (31%; p=0.012),
and those with lower income (p=0.013).
Conclusions: Most adult survivors of pediatric cancer were
aware of the general risk for cancer-related infertility, and
about half perceived themselves at risk or knew their fertility
status. Several demographic and medical factors were related
to knowledge in these domains. Future research should continue to identify strategies to provide reproductive counseling
to survivors of pediatric cancer before and after treatment, and
optimize fertility preservation rates for those at risk.
Acknowledgements: Thank you to The Research Institute at Nationwide Children's Hospital and CTSA Grant
(UL1TR001070) for providing resources.
O-212 Development of Web Based Tailored
Treatment Information to Enable Patient
Participation and Empowerment. A Pilot Study in
Wilms Tumor Patients and Families
J.E. Dijkstra Pinto Leite1 , M.A. Grootenhuis2 , J.G. de
Ridder-Sluiter2 , R.L. Kamman3 , E.M.M. van den Bergh4 , W.C.
Alers5 , I. Sieswerda5 , M.C. Naafs-Wilstra6 , Y. Wiersma7 , S.J.
Uitdehaag4 , M.E. van der Veen5 , M.A. Brouwer- van de Poll4 ,
M.M. van den Heuvel-Eibrink5 , A.M.C. Mavinkurve-Groothuis5
1 Princess
Máxima Center, User Experience Design ICT, Utrecht, The
Netherlands; 2 Princess Máxima Center, Psychosocial Research, Utrecht,
The Netherlands; 3 Princess Máxima Center, ICT, Utrecht, The Netherlands;
4 Princess Máxima Center, Psychosocial Care, Utrecht, The Netherlands;
5 Princess Máxima Center, Paediatric Oncology, Utrecht, The Netherlands;
6 VOKK, CEO, Nieuwegein, The Netherlands; 7 Princess Máxima Center,
Children's advisory council, Utrecht, The Netherlands
Background/Objectives: In the Princess Máxima Center for
pediatric oncology stimulating development is leading in care.
Key principles are reduction of medical traumatic stress, adequate communication and family focus. Treatment of children
with cancer is stressful for the child and the family. They are
often overloaded with information, which is not always tailored to their needs. Their daily life is taken over by hospital visits and missing overview and control can lead to avoidable medical traumatic stress. Our aim is to design a tool that
provides overview and tailored information of the treatment
schedule.
Design/Methods: In the first phase we analyzed the needs of
different families. Personas were created with a focus group
of 6 healthcare professionals to profile different family types.
Contextual inquiry is performed to map activities in different stages of treatment. It will lead to knowledge on how and
when information is shared with the families. In depth interviews will provide insights on preferences children and their
SIOP ABSTRACTS
S112 of S518
families have in obtaining information about their disease and
treatment.
Results: We discussed and grouped 23 families with the focus
group and identified 6 personas; reflecting differences in how
families deal with disease, disease information and how they
interact with health care professionals. The studies in the first
phase lead to guidelines for a tool to communicate the Wilms
Tumor treatment schedule addressing these differences.
Conclusions: The result will be a visual, web-based, tailored
treatment information tool, to increase patient participation
and empowerment. By creating overview of the treatment
program, understandable for children and their parents, we
aim to support them in making decisions and preparing for
procedures. We use personas to profile different families and
address their specific needs. The next step is to design the tool
and investigate whether this tool will lead to reduction of medical traumatic stress.
O-213 Attitudes and Concerns About Parenthood
and Fertiltiy Preservation among Adolescent and
Young Adult Males and Their Parents During
Cancer Survivorship
N. Caltabellotta1 , A. Ferrante1 , C. Gerhardt1 , V. Lehmann2 , S.
Whiteside3 , N. Yeager3 , L. Nahata1
1 Nationwide
Children's Hospital, Center for Biobehavioral Health,
Columbus, USA; 2 St. Jude Children's Research Hospital, Department of
Psychology, Memphis, USA; 3 Nationwide Children's Hospital, Division of
Hematology/Oncology, Columbus, USA
Background/Objectives: One in three males experiences
fertility problems after pediatric cancer treatment yet less
than 25% of pubertal males pursue fertility preservation (FP)
before treatment. Although parents are responsible for making
the majority of health-related decisions (including FP) during
pediatric illness, it is unknown if parents are discussing parenthood and FP with their sons and are aware of their attitudes
and concerns. The aims of this study were to examine attitudes
about parenthood and FP among AYA males and their parents
within the first seven years of cancer survivorship.
Design/Methods: Ninety-one participants (35 AYA males, 31
mothers, 25 fathers) completed questions based on the Health
Belief Model. Participants ranked items on a 5-point Likert
scale for themselves (if an AYA male) or their sons (if a parent). Analyses compared attitudes of male AYA survivors (1525 years, M=18.94) and parents as two distinct groups, and
within 26 mother-son pairs and 20 father-son pairs on items
pertaining to parenthood and benefits/barriers to FP.
Results: Eighty percent of AYA males endorsed wanting a
biological child, and 51% of survivors agreed a future without a child would make them sad. Thirty-one percent of AYA
males thought speaking about FP with their parents would be
embarrassing; a minority reported having conversations with
their mothers (23%) and/or their fathers (17%) about sperm
banking. Although 51% of AYA males were concerned they
could pass on their cancer to their future children; neither
mothers (p=0.003) nor fathers (p=0.002) shared this concern.
Conclusions: Although most male AYA survivors desire biological children after treatment, they report difficulties discussing this with their parents and report barriers to FP of
which their parents may be unaware. Future research needs to
identify factors that contribute to these perceived barriers and
strategies to facilitate conversations about parenthood and FP
between AYA males and their parents.
HAEMATOLOGY - ACUTE
LYMPHOBLAST IC LEUKAEMIA
PD-001 The Cost-Effectiveness of Pegaspargase
for First-Line Treatment of Acute Lymphoblastic
Leukaemia: A Cost-Utility Analysis
S. Basu1 , P. Lin2 , C. Rowntree3 , V. Saha4,5
1 Shire,
Head of Medical Affairs Oncology, Staines upon Thames, United
Kingdom; 2 Shire, Global HEOR Lead- Oncology, Cambridge, USA;
3 University Hospital of Wales, Consultant Haematologist, Cardiff, United
Kingdom; 4 University of Manchester, Paediatric Oncology, Manchester,
United Kingdom; 5 Tata Medical Center, Senior Consultant in Paediatric
Oncology, New Town- Kolkata, India
Background/Objectives: Asparaginase is a key component
in the treatment of patients with acute lymphoblastic leukemia
(ALL). In the UK, patients with newly diagnosed ALL receive
PEG-ASP followed by Erwinia-derived asparaginase (ERWASP) in cases of hypersensitivity. Although native ASP is no
longer used as the first choice of asparaginase therapy, it was
the standard of care before PEG-ASP was available. This analysis evaluates the cost-effectiveness of PEG-ASP in patients
with newly diagnosed ALL compared to native asparaginase
(native-ASP).
Design/Methods: A combined decision tree/health state transition Markov model was developed to compare treatment
sequences starting with PEG-ASP versus native-ASP, followed by ERW-ASP in cases of hypersensitivity. Pediatric,
young adult (≤25 years), and adult (26-65 years) patients were
modelled using UKALL2003 and UKALL14 protocols. Analyses were stratified by high-, intermediate-, and standard-risk
in pediatric patients, between patients aged ≤40 vs. ≥41 years,
and on transplantation eligibility in the adult model. Key
model parameters (survival, risk of hypersensitivity) were
publication-based with clinical input from key experts. In
the base-case analysis, OS and EFS were assumed equivalent
for PEG-ASP, native-ASP, and ERW-ASP, with 1,000IU/m2
dosing (per UKALL protocols) used for PEG-ASP. In
SIOP ABSTRACTS
S113 of S518
scenario analyses, 2,500 IU/m2 of PEG-ASP was examined
(per SmPC), including variations in comparative survival and
hypersensitivity rates. Incremental cost-effectiveness ratios
(ICER; incremental costs/quality-adjusted life years [QALYs]
gained) were produced.
Results: The base-case scenario demonstrated that PEGASP followed by ERW-ASP resulted in reduced costs and
increased QALYs (total cost savings, £4,741; total QALYs
gained, 0.05) versus native-ASP followed by ERW-ASP. Scenario analyses highlighted the robustness of the results. Differences in total QALYs between PEG-ASP and native-ASP
were driven primarily by the difference in hypersensitivity
rates.
Conclusions: This analysis demonstrates that PEG-ASP, as
part of multi-drug chemotherapy, is cost-effective compared
to native-ASP for children, young adults, and adults with
newly diagnosed ALL.
PD-002 Consequences of Decreasing Asparginase
and Dexamethasone Theray to Avoid Excessive
Toxicity in Childhood Acute Lymphoblastic
Leukemia: A Prospective Trial from a
Middle-Income Country
1
1
1
1
1
K. Ghanem , D. El Tabech , C. Al-Aridi , N. Tarek , R. Saab , M.
Abboud1 , H. El-Solh1 , S. Muwakkit1
1 American
University of Beirut, Department of Pediatrics and Adolescent
Medicine, Beirut, Lebanon
Background/Objectives: The best outcome of childhood
acute lymphoblastic leukemia (ALL) is achieved through
an adequate balance between disease control and treatmentrelated toxicities. At the Children's Cancer Center of Lebanon,
we implemented the St Jude Total-XV protocol with minor
modifications to treat patients with ALL 1-18 years old.
Between 2002-2013 (period-I), the protocol resulted in an
excellent 5-year overall (92.3%) and disease-free survival
(88.6%), however, excessive toxicities were observed, including CMV retinitis (3.5%), disseminated varicella (6%) and
CNS thrombosis (6.2%).
Design/Methods: Between 2013-2015 (period-II), and in a
prospective, non-randomized trial, we decreased dexamethasone dosage during continuation and intensification therapy by 25% for low-risk and 33% for intermediate/high risk
patients and stopped monthly dexamethasone pulses at 1.3
years instead of 2 years from initiation of continuation therapy. Asparaginase dose was decreased by 40% in induction
for all patients, and 40% in intensification therapy for low-risk
patients. No prophylactic cranial irradiation was given.
Results: The number of enrolled patients was 156 in period-I
and 61 in period-II. After a median follow-up of 88 months
(range: 24-177 months), the 3-year cumulative incidence of
isolated CNS relapse increased from 1.3% (n=2) (SE 0.01%)
in period-I to 10.2% (n=5) (SE 0.4%) in period-II (Gray
P: 0.003). In period-II, 3/5 patients with CNS relapse were
low-risk, without initial CNS involvement. All five patients
achieved second remission. One patient is currently in third
remission after developing a second isolated CNS relapse. All
CNS relapses occurred after 1.7 years from treatment initiation. The incidence of CMV retinitis, disseminated varicella,
and CNS thrombosis decreased to 0%, 0% and 1.4%, respectively. The 3-year cumulative incidence of death was not statistically different between the two periods (7.7 versus 9.3%,
Gray P: 0.32).
Conclusions: Decreasing dexamethasone and asparaginase
dosages during childhood ALL therapy aiming to avoid
treatment-related toxicities resulted in significant increase in
isolated CNS relapse.
PD-003 Molecular Genetic Profile in BCR-ABL1
Negative Pediatric B-Cell Acute Lymphoblastic
Leukemia Can Further Refine Outcome Prediction
in Addition to That by End-Induction Minimal
Residual Disease
S. Gupta1 , S. Bakhshi2 , A. Chopra1 , R. Kumar1
1 All
India Institute of Medical Sciences AIIMS- New Delhi, Lab Oncology,
New Delhi, India; 2 All India Institute of Medical Sciences AIIMS- New
Delhi, Medical Oncology, New Delhi, India
Background/Objectives: Many patients with B-cell Acute
Lymphoblastic Leukemia (B-ALL) don't respond satisfactorily to the standard therapy. Currently, the poor responders
are subjected to aggressive chemotherapy based on minimal residual disease (MRD) status. Recently, Moorman et
al (2014) proposed molecular genetic criteria for better riskprediction in B-ALL. We undertook this study to assess their
utility in BCR-ABL1 negative pediatric B-ALL, particularly
with respect to the end-induction MRD status.
Design/Methods: The new cases of BCR-ABL1 negative,
pediatric B-ALL, enrolled over 18 months were classified as
standard, intermediate, high risk and treated as per the institutional protocol. The patients with MRD positivity (>0.01%)
by flow cytometry, at the end of induction chemotherapy were
treated as high risk. The genomic DNA was analyzed for copy
number alterations (CNAs) in CDKN2A/B, PAX5, IKZF1, and
other genes using multiplex ligation dependent probe amplification. The genetic-profile was assessed using Moorman criteria. Event free survival (EFS) and overall survival (OS) were
noted.
Results: Seventy-six cases with median age 7 years (2
months-18 years) were finally analyzed. CNAs were detected
in 49 (64.5%) cases. 24 cases were MRD positive, remaining
SIOP ABSTRACTS
S114 of S518
were MRD negative- low (20), intermediate (20), high risk
(12) cases. The genetic profile could identify two subgroups
with significantly different EFS (p=0.045) and OS (p=0.037)
in the MRD negative intermediate risk group. The genetic profile also separated two subgroups with significantly different
EFS (p=0.036) in the MRD positive group, however the OS
was not different (p=0.293). The analysis in other subgroups
did not reveal any significant differences.
Conclusions: The genetic profile identified distinct subgroups
in MRD-negative intermediate-risk and MRD-positive cases
of B-ALL. This indicates that the intermediate-risk patients
can be further segregated for therapy assignment, based on
the genetic-profile. More importantly, the empirical therapy
up-gradation in MRD positive cases may not be appropriate or adequate, particularly in those with poor molecular
genetic-profile.
PD-004 Insert Vincristine and Dexamethasone
During the Maintenance Therapy of Non-High Risk
Pediatric Acute Lymphoblastic Leukemia was
Unnecessary: A Randomized Controlled Trial
Study from Single Center
L.B. Huang1 , L. xue-qun1 , K. Zhi-Yong1 , T. Hui-Zhen1 , Z. Xiao-li1
1 the
first affiliated hospital of SUMS, Pediatrics, Guangzhou, China
Background/Objectives: The benefit of vincristine (VCR)
plus dexamethasone (DXM) during maintenance in ALL
is controversial. A multicenter clinical trial, GD-2008
(NCT00846703), which is based on the ALL IC-BFM 2002
protocol, was designed to evaluate the benefit of VCR and
DXM pulses in the maintenance therapy. Here, we report the
results from our single center.
Design/Methods: 194 children, diagnosed with ALL with
non-high-risk features, were enrolled in our department from
Aug 1, 2008 to Dec 31, 2014. All were treated with the
same protocols based on the ALL IC-BFM 2002 protocol,
which included induction, consolidation, re-induction, and
maintenance therapy. At the beginning of the maintenance
therapy, those patients in complete remission were randomly
assigned to either protocol A or protocol B. In protocol A,
patients were given conventional 6-mercaptopurine (6MP)
and methotrexate (MTX). Patients in protocol B were given
6MP and MTX for 7 weeks, and then substituted by VCR
and DXM for 1 week, and every 8 weeks as a cycle. The primary outcome measure was disease-free survival. The study
is registered at http://www.clinicaltrials.gov with the identifier NCT00846703.
Results: 4 patients (2.1%) died during the therapy before randomization. Of the remaining 190 patients, 177 (93.1%) were
randomly assigned: 93 to protocol A and 84 to protocol B.
With median follow-up of 60 months, 10 children in protocol
A and 17 in protocol B had relapses, and 1 child in the protocol A died of infection during maintenance treatment. The
5-year event-free survival (EFS) were 87.0%±3.7% in protocol A and 78.9% ±4.8% in protocol B, respectively (p=0.126).
The 5-year overall survival (OS) were 94.1%±2.6% in protocol A and 85.4%±4.2% in protocol B, respectively (p=0.04).
Conclusions: There are no benefits that intermit the MM
maintenance therapy with vincristine and dexamethasone in
children with non-high risk ALL who received chemotherapy
based on BFM protocols.
PD-005 Favorable Outcome of TCF3-PBX1
Genetic Translocation in Acute Lymphoblastic
Leukemia in Chinese Children: CCLG2008 Study
C. Li1 , L. Cui2 , Z. Li2 , Y. Chai3 , J. Yu4 , J. Gao5 , X. Zhu6 , R. Jin7 ,
X. Shi8 , L. Zhang9 , Y. Gao10 , R. Zhang2 , H. Zheng2 , S. Hu3 , Y.
Cui4 , C. Zhou5 , Y. Zou6 , M.H.L. NG11 , T. Wang2 , M. Wu2
1 The
Chinese University of Hong Kong, Paediatrics, Hong Kong, Hong
Kong S.A.R.; 2 Beijing Children's Hospital of Capital Medical University,
Hematology Oncology, Beijing, China; 3 Children's Hospital of Soochow
University, Hematology Oncology, Suzhou, China; 4 Children's Hospital of
Chongqing Medical University, Hematology Oncology, Chongqing, China;
5 West China Second University Hospital- Sichuan University, Hematology
Oncology, Chengdu, China; 6 Institute of Hematology & Hospital of Blood
Disease- Chinese Academy of Medical Science & Peking Union Medical
College, Pediatric Hematology, Tianjin, China; 7 Union Hospital- Tongji
Medical College- Huazhong University of Science and Technology,
Pediatrics, Wuhan, China; 8 Capital Institute of Pediatrics, Hematology
Oncology, Beijing, China; 9 Peking University People's Hospital,
Pediatrics-, Beijing, China; 10 Children's Hospital of Fudan University,
Hematology Oncology, Shanghai, China; 11 The Chinese University of Hong
Kong, Anatomical & Cellular Pathology, Hong Kong, Hong Kong S.A.R.
Background/Objectives: TCF3-PBX1 gene fusion happened
in 3-5% of childhood ALL. In a prospective multicenter trial
of Chinese Children Leukemia Group (CCLG) 2008 Study,
patients were treated with standard BFM-based protocol. The
outcome of this genetic subgroup was studied.
Design/Methods: Newly diagnosed ALL patients were
recruited from 10 hospitals in China from 04/2008 to 12/2012,
2231 patients were stratified into 3 risk groups according to
age, WBC, genetic subtypes and 7-day prednisone response.
Two hospitals piloted MRD study by Flow and PCR with
adjustment of treatment according to MRD response. TCFPBX1 group was assigned to intermediate risk (IR) at diagnosis.
Results: There were 121 patients (5.4%) identified to be
TCF3-PBX1 positive by PCR and 41 also had t(1;19) on
karyotyping. Mean age and WBC at diagnosis was 5.9 years
and 42.2 x109 /L, male to female was 68:53. At diagnosis, 3
patients had CNS 3 and 3 with CNS 2 status. Compared with
604 of other IR patients, TCF3-PBX1 group had higher good
7-day prednisone response (91.5% vs 81.5%, p=0.007), less
Day15 M3 (6.8% vs 15%, p=0.013), and better Day33 remission (99% vs 94.9%, p=0.047). Day33 MRD response was
SIOP ABSTRACTS
assessed in 286 IR patients, MRD negativity (<0.01%) was
significantly higher in TCF3-PBX1 group (63.3% (31/49) vs
26.6% (63/237) p<0.001⟩⟩. There were 11 relapses at BM but
without any CNS relapse. Death occurred in 15 patients, 10
due to relapses and 5 due to infection. There was trend of better EFS for TCF3-PBX1 group (87.1% vs 80.4%) but not significant (p=0.099).
Conclusions: The incidence of TCF3-PBX1 in Chinese children was 5.4% and CNS3 was only 2.5%, CNS relapse was not
observed. The early response to treatment was better in TCF3PBX1 subset, and there was also trend of better survival.
Supported by grants from National Natural Science Foundation of China (Nos. 81200392 and 81170504)
PD-006 Functional Mitochondrial Apoptosis
Signaling Indicates Anti-Leukemia Activity of the
BCL-2-Seletive Inhibitor ABT-199 in BCP-ALL
F. Seyfried1 , S. Demir1 , R. Hörl1 , J. Ryan2 , A. Scheffold3 , M.
Villalobos-Ortiz2 , S. Köhrer1 , J. Zinngrebe1 , S. Stilgenbauer3 , A.
Letai2 , K.M. Debatin1 , L.H. Meyer1
1 Ulm
University Medical Center, Pediatrics and Adolescent Medicine, Ulm,
Germany; 2 Dana-Farber Cancer Institute, Medical Oncology, Boston, USA;
3 Ulm University Medical Center, Internal Medicine III, Ulm, Germany
Background/Objectives: In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), deficient cell death pathways are associated with treatment failure. Anti-apoptotic
BCL-2 family proteins regulate apoptosis, thereby serving
as targets for novel, directed therapies. The BCL-2 inhibitor
ABT-199 binds to BCL-2, leading to release of pro-death
BCL-2 family molecules and apoptosis induction. Here, we
assessed the efficacy of ABT-199 in BCP-ALL and investigated factors mediating ABT-199 susceptibility or resistance,
indicative of anti-leukemia activity.
Design/Methods: ABT-199 sensitivities were investigated
in BCP-ALL (cell lines and patient-derived xenografts).
Expression of apoptosis regulators was detected by western blot analysis. MCL-1 deficient leukemias were generated by CRISPR/Cas9. Mitochondrial apoptosis signaling was
assessed by BH3-profiling. ABT-199 anti-leukemia activity
was evaluated in vivo.
Results: The vast majority of BCP-ALL samples showed
sensitivity to ABT-199-induced cell death in the nanomolar
range. Interestingly, expression of the anti- and pro-apoptotic
regulators MCL-1 and BCL-2 were significantly associated
with ABT-199 effectivity and MCL-1 knockout in ABT-199resistant leukemias resulted in ABT-199 sensitization, pointing to MCL-1 as a mediator of ABT-199 resistance. Next, we
characterized the functional interplay of apoptosis regulators
by BH3 profiling. Mitochondrial dependence on BCL-2 was
associated with ABT-199 sensitivity, in contrast to low BCL2-dependence and addiction to other regulators (BCL-XL or
S115 of S518
MCL-1) in ABT-199-resistant samples. Most importantly, in
a preclinical in vivo setting in a xenograft mouse model, prolonged leukemia-free survival upon in vivo ABT-199-therapy
was indicated by high mitochondrial BCL-2-dependence, in
contrast to low BCL-2-dependence in ABT-199 insensitive
leukemias.
Conclusions: Taken together, most of BCP-ALL show ABT199 sensitivity. However, ABT-199 resistance occurs and is
characterized by the level of the target molecule and counterplayers. Importantly, functional assessment of mitochondrial
BCL-2-dependence (BH3-profiles) is indicative of ABT-199
sensitivity and anti-leukemia activity in vivo, providing a
marker for the upfront identification of patients who would
benefit from novel effective ALL-treatment strategies with
BCL-2 inhibitors.
HAEMATOLOGY - MYELOID
LEUKEMIAS, MYELODYSPLASTIC
AND MYELOPROLIFERATIVE
SY N D RO M E S
PD-007 Molecular Findings of Infant Acute
Myeloid Leukemia
F. Gomes Andrade1 , I. Sardou Cezar1 , F. Vicente dos Santos
Bueno1 , G. Dallapicola Brisson1 , E. Pereira Noronha1 , E.
Terra-Granado1 , M.S. Pombo-de-Oliveira1
1 Instituto
Nacional de Câncer, Research Center, Rio de Janeiro, Brazil
Background/Objectives: Initiating somatic mutations
detected in dried neonatal blood spots and in cord blood
samples of affected children with leukemia have been proved
to be acquired prenatally. However, few epidemiological
studies have been carried out exploring infant acute myeloid
leukemia (i-AML) that include infants and children under 24
months of age at the diagnosis. Our aim was to describe the
molecular characterization of i-AML cases and investigate
the contribution of gene mutations in the probability overall
survival (pOS).
Design/Methods: One hundred and seventy-eight non-Down
Syndrome cases with i-AML were assessed throughout a
multicentric network study. Mutations in hotspot regions
of RAS pathway affecting genes (FLT3, NRAS, KRAS,
PTPN11, and c-KIT) were analyzed, as well as fusion
genes [MLL/KMT2A and NUP98 rearrangements (KMT2Ar and NUP98-r, respectively), MYST3-CREBBP, RUNX1RUNX1T1, CBF�-MYH11, and PML-RAR�] associated with
AML. The majority of patients was treated following the
BFM-AML2004, although out of clinical trials.
Results: Eleven cases (6.2%) were congenital leukemia (≤1month-old), 80 (44.9%) were aged between 2-12 months
SIOP ABSTRACTS
S116 of S518
old and 87 (48.9%) cases were aged ≥13 months old.
The mostly morphological differentiation observed in blast
cells was myelomonocytic (28.7%), monocytic (25.8%), and
megakaryocytic (22.5%). All phenotypes presented with low
white blood cell (WBC) count (≤50x109 /L) at diagnosis,
other than acute myelomonocytic leukemia. Frequent molecular abnormalities were KMT2A-r (34.6%), mainly KMT2AMLLT3 and KMT2A-AFF1, followed by NUP98-r (7.4%) and
RUNX1-RUNX1T1 (6.0%). RAS pathway gene mutations were
observed in 30.1% of i-AML, affecting mostly cases aged ≥13
months old and associated with KMT2A-r (29.7%). The cumulative 5-year pOS was 33.8±4.7%, with no statistical differences in survival rates among years or associated with molecular alterations.
Conclusions: Despite presenting fewer genetic abnormalities
than older pediatric AML, disease-related death rate was high
in i-AML. Our data indicate that diagnosis and management
of i-AML raise questions that should be considered for further
action.
was 37.5±2.9% for total AMLs and 59.4±7.2% for APL
(p=0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year
pOS (47.6±4.7%) whereas the Northeast-Midwest regions
presented the poorest pOS (23.7±4.9%). PTPN11 mutations
conferred adverse prognosis, as an independent prognostic
factor.
Conclusions: The identification of genetic subgroups contributes to the molecular epidemiology and biology of AML
worldwide, reflecting the profile of pediatric AML cases
in Brazil. Survival data for the specific c-AML subtype in
Latin countries are found rarely in the literature. Inclusion
of cytogenetic-molecular markers in the characterization of
AML are of great predictive value for OS.
PD-009 Prognostic Impact of Hyperdiploidy in
Pediatric Acute Myeloid Leukemia Patients
S. Salem1 , S. Mahmoud2 , S. Soliman3 , K. Shaaban4 , M. Hammad5 ,
N. Elguindy6 , A. Haddad5
PD-008 Molecular Characterization of Pediatric
Acute Myeloid Leukemia: Results of a Diagnostic
and National Multicentric Study in Brazil
F. Gomes Andrade1 , E. Pereira Noronha1 , F. Vicente dos Santos
Bueno1 , I. Sardou Cezar1 , G. Dallapicola Brisson1 , E.
Terra-Granado1 , M.S. Pombo-de-Oliveira1
1 Instituto
Nacional de Câncer, Research Center, Rio de Janeiro, Brazil
Background/Objectives: The biological characterization of
childhood acute myeloid leukemia (c-AML) is an important
outcome predictor. In Brazil, little is known about the frequency of AML subgroups, although c-AML accounts for
about 18% of leukemias. Aim. To investigate the contribution of type I and II gene mutations in the probability overall
survival (pOS) of c-AML in Brazil.
Design/Methods: Seven hundred and three de novo pediatric
AML cases (2000-2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3,
NRAS, KRAS, PTPN11, and c-KIT genes were analyzed,
as well as fusion genes (RUNX1-RUNX1T1, MLL/KMT2Ar, CBF�-MYH11, and PML-RAR�) associated with AML.
Patients were treated out of the protocol, but the BFMAML2004 was followed since the year 2008. Acute promyelocytic leukemia (APL) was treated differently. AML with
Down syndrome was excluded.
Results: There were significant differences in gene mutations between age ranges (≤2 years-old; >2-10 years old and
≥11 years old) and the nonrandom association between type
I/II mutations. Lower white blood cell count (≤50x109 /L)
was associated with RUNX1-RUNX1T1 whereas higher WBC
with CBF�-MYH11 (p<0.05). The cumulative pOS in 5 years
1 NCI
- Egypt and Children's Cancer Hospital Egypt, Cytogenetics, Cairo,
Egypt; 2 NCI - Egypt and Children's Cancer Hospital Egypt, Pediatric
Oncology, Cairo, Egypt; 3 NCI - Egypt and Children's Cancer Hospital
Egypt, Hematolgy, Cairo, Egypt; 4 NCI - Egypt and Children's Cancer
Hospital Egypt, Immunolgy, Cairo, Egypt; 5 NCI - Egypt and Children's
Cancer Hospital Egypt, Pediatric Oncolgy, Cairo, Egypt; 6 Children Cancer
Hospital Egpyt- 57357, Research, Cairo, Egypt
Background/Objectives: Acute myeloid leukemia (AML)
patients with hyperdiploid or triploid/tetraploid (TT) karyotype represent a relatively poorly understood entity. We aim
to study the characteristics of this group as regards the karyotype, clinical and laboratory features and treatment outcome.
Design/Methods: We retrospectively analyzed data of 447
patients with de novo AML who were treated in Children Cancer Hospital Egypt, 57357 on AML0431 COG adopted protocol, from July 2007 to January 2014. Patients with Down
syndrome and acute promyelocytic leukemia were excluded.
Results: Thirty four patients had ≥49 chromosomes. Seven
cases with core binding factor translocation were excluded
from analysis. Out of the 27 hyperdiploid and TT cases, 9
cases (33%) were AML-M7. Three cases had pure hyperdiploid karyotype. KMT2A gene rearrangement was found in
10 cases (37%), trisomy 8 in 11 cases (40.7%), gain of chromosome 21 in 16 cases (59%), and chromosome 5q abnormalities in 3 cases (11%). None of the patients had monosomy 7,
t(6;9) or 17p/p53 deletion. Two patients died early in induction 1 and were excluded from further analysis. The two year
overall survival was significantly lower (33%) compared to
non-hyperdiploid KMT2A rearrangement, normal karyotype
and core binding factor AML; t(8;21) and inv(16)/t(16;16)
40.6%, 51%, 69.5% and 76%, respectively (P-value=<0.05).
The 2 year disease free survival for the hyperdiploid group
SIOP ABSTRACTS
was 35.5% while for non-hyperdiploid KMT2A rearrangement, normal karyotype, t(8;21) and inv(16) was 61%,
70%, 88%, and 95.5%, respectively (P-value=<0.05). Relapse
occurred in 37.5% of patients with hyperdiploidy compared to
27%, 26%, 11.5% and 3% in non-hyperdiploid KMT2A rearrangement, normal karyotype, t(8;21) and inv(16), respectively. The cumulative incidence of relapse in the hyperdiploid
group is 48.2 with CI (27.7 to 66).
Conclusions: Hyperdiploid and TT karyotype is a rare and
adverse risk abnormality in pediatric AML compared to other
genetic groups.
S117 of S518
Conclusions: ECS is capable of both detecting and monitoring MRD in DS-AML. Interestingly, we detect MRD in 53%
of the paired EOI1 samples, yet DS-AML patients have exceptionally high event-free survival rates (80-100%). This suggests that secondary events in addition to GATA1 mutations
are involved in relapsed DS-AML and are the focus of additional research.
PD-011 Therapy-Related Acute Myeloid
Leukemia/Myelodysplastic Syndrome Following
Treatment for Childhood Cancer: Experience from
a Tertiary Care Centre in North India
PD-010 Detection of Minimal Residual Disease in
Down Syndrome-AML by Error-Corrected
Sequencing: A Children's Oncology Group Study
C. VYAS1 , S. Jain1 , G. Kapoor1
R.S. Tong1 , A.L. Young1 , W.H. Wong1 , J. Hitzler2 , J.N. Berman3 ,
T.E. Druley1
Background/Objectives: Therapy-related acute myeloid
leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating complication of cancer treatment. In view of paucity
of literature from India, we report the incidence, risk factors
t-AML/MDS over a period of 20 years at our institute.
1 Washington
University School of Medicine, Pediatrics, St.Louis- MO,
USA; 2 The Hospital for Sick Children, Hematology/Oncology, Toronto- ON,
Canada; 3 IWK Health Centre, Pediatrics, Halifax- NS, Canada
Background/Objectives: Down Syndrome (DS) neonates
have a 10-20-fold higher incidence of acute myeloid leukemia
(DS-AML), which is characterized by mutations in exons 2 or
3 of GATA1 (Xp11.23) (Alford KA et al. Blood, 2011). Given
the unstable surface immunophenotypes in this leukemia,
there has never been a bona fide method for detecting minimal residual disease (MRD) following chemotherapy. Nextgeneration sequencing for GATA1 mutations would provide
such a platform, however, is limited by a high error-rate
(∼1:100). Error-corrected sequencing (ECS) can circumvent
this error-rate and detect mutations with a limit of detection of
1:10,000 (Young AL et al. Leukemia, 2015). In collaboration
with the Children's Oncology Group (COG), we are applying
ECS in parallel with flow cytometry to improve MRD detection in DS-AML.
Design/Methods: Exons 2 and 3 of GATA1 were amplified
by high-fidelity PCR. The resulting 300bp amplicons were
ligated to an 8bp individual-specific barcode to enable sample multiplexing as well as a random 16bp index to allow
for error-correction. ECS libraries were sequenced on the
Illumina MiSeq and analyzed using published computational
methods (Wong T et al. Nature, 2015).
Results: To date, 51 samples from 30 DS-AML patients
enrolled on the COG AAML1531 study have been analyzed
[diagnosis, n=29; End of Induction 1 (EOI1), n=22]. Nonsynonymous mutations were detected in 83% of diagnosis samples at an average variant allele frequency (VAF) of 0.1145
(range: 0.00101 - 0.88847). MRD was detected in 53% of the
paired EOI1 samples at an average VAF of 0.0016 (range:
0.00003 – 0.01405).
1 Rajiv
Gandhi Cancer Institute & Research centre- New Delhi- India,
Department of Pediatric Haematology-Oncology, Delhi, India
Design/Methods: This is a retrospective analysis of patients
(≤18 years of age) treated in the pediatric hematologyoncology unit at our institute between January 1996 and
December 2015. Amongst these, patients who developed tAML/MDS were identified. Information pertaining to primary malignancy, treatment details along with clinical, hematologic, cytogenetic features and outcome of t-AML/MDS
were obtained.
Results: Amongst 1285 children, 8 patients developed t AML/MDS (6 males and 2 females, median age of 15.5 years)
with a median latency period of 24 months. The incidence
of t-AML/MDS was 0.62% [0.99% (4/402) for solid tumour
and 0.45% (4/883) haematological malignancies respectively,
P= 0.26] with 6390 person-years of follow-up. The primary
malignancy was sarcoma [bone (2), soft tissue (2)], B-nonHodgkin lymphoma (2) and acute lymphoblastic leukemia
(2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8gm/m2 (range,
3-28.3 gm/m2 ), 270 mg/ m2 (range, 180-375 mg/m2 ) and
2.5gm/ m2 (range, 1-4 gm/m2 ) respectively. Two patients
received radiotherapy to the primary site. The dominant FAB
morphology was M4/M5 (7/8) and cytogenetic abnormality
was 11q23 translocation (4/8). Five patients opted for treatment and 4 achieved remission. Three patients died (2 toxic
deaths and 1 relapse). Two patients are alive and disease free.
The median survival was 5.5 months.
Conclusions: We observed a high incidence of t-AML/MDS
in children with sarcoma compared to haematological malignancies. Shorter latency period and presence of 11q23 translocation implicates epipodophyllotoxin to be the probable
SIOP ABSTRACTS
S118 of S518
causative agent. In view of poor outcome of t-MDS/AML,
strategies to identify host risk factors and to practise precision
medicine need to be considered.
PD-013 Second Biopsy of Residual Mass in
Pediatric Mature B-Cell Non-Hodgkin Lymphoma:
Benefit Patients or Not?
M. Cai1
1 Shanghai
HAEMATOLOGY - LYMPHOMAS
PD-012 Outcome of Hodgkin Lymphoma in a
Developing Country: The Children's Hospital
Lahore Pakistan Experience
A. Ahmad1 , N. Uddin1 , F.S. Khan1 , N. Asghar1
1 The
Children's Hospital and the Institute of Child Health Lahore,
Haematology/ oncology, Lahore, Pakistan
Background/Objectives: The Children's Hospital Lahore is a
tertiary government centre with 60 paediatric Oncology beds.
It receives over 1000 new cancer patients per year. The purpose of this study was to analyze treatment and outcome of
children with biopsy proven Hodgkin Lymphoma and discuss
various factors causing poor outcome as compared to developed countries.
Design/Methods: Retrospective review of 315 patients
enrolled between January 2011 - June 2016 was done. Data
regarding age, stage, histopathology, treatment, outcome and
impact of delayed presentation were analyzed. Patients were
treated according to Euronet-PHL-C1 protocol receiving 4-6
courses of OEPA/COPDAC.
Results: Total 315 patients with age ranging from 2 to
15 (80% <10 yrs) were included. M: F Ratio was 5.7:1.
294/315(94%) presented with advanced stage and only
21(6%) had stage II at presentation. The histopathological examination showed Mixed Cellularity in 212/315(67%),
Nodular Sclerosis in 62/315(20%), Lymphocytic Predominance in 8/315(3%) and Lymphocytic Depletion in 6/315(2%)
cases, whereas 27 (8%) reports did not specify the subtype.
Bone marrow/lung was involved in 110/315 (35%) patients.
Total 251/315 (80%) have completed treatment, 22/315 (7%)
left against medical advice (LAMA) and 28/315 (9%) expired
due to sepsis and progressive disease. 5/315 relapsed and
9/315 had progressive disease (4%)
Conclusions: Survival is good 251/315 (80%) for the whole
group (70% in 2014 ISCAYAHL data) Mortality of 11% can
be reduced by early diagnosis and aggressive infection control
measures. In developing countries, late referrals are strongly
associated with metastatic disease. The prognosis can significantly be improved by public awareness to seek early treatment and establishing safe and effective shared care oncology pathways, multidisciplinary team approach. By providing strong social support, intense psychosocial counseling and
efficiently run Day Care Oncology can help increase patients
compliance.
Children's Medical Center- Shanghai Jiao Tong UniversitySchool of Med, Pediatric Hematology & Oncology, ShangHai, China
Background/Objectives: The reliable assessment of residual
masses remains a diagnostic problem in patients with nonHodgkin lymphoma (NHL). The objective of this study was
to assess the impact of second-look biopsy of residual mass
during or after chemotherapy in pediatric mature B-cell NHL.
Design/Methods: Patients with mature B-cell NHL who were
suspicious of residual mass at mid or end of treatment and
subjected to second biopsy were treated and followed at our
medical center between 2001 and 2015. Their clinical characteristics, imagings, pathology, treatment and prognosis were
reviewed retrospectively.
Results: A total of 31 children were included. Twenty-two
with Burkitt lymphoma, 6 with Diffuse large B cell lymphoma
and 3 with B-cell lymphoma, unclassified. Median age at diagnosis was 6.1 years (2.5-14 years). The median time from
diagnosis to second biopsy was 3.15 months (2.3-18 months).
Biopsy confirmed the presence of viable tumor in 8 patients.
The specificity and positive predictive value (PPV) of conventional imaging in detecting residual disease were poor, at 9%
and 28.6%. Three of the histologic positive patients experienced progressive disease or relapse while the others achieved
complete remission (CR) at the completion of therapy and
21 patients achieved long-time CR at a median follow-up of
3.2 years (1 year-7 years). The median progression-free survival (PFS) time was 28 months (5-84 months) and 5-year
PFS rate was 90.0%. 5-year PFS rate of negative-biopsy group
was 100% while that of positive-biopsy group was 62.5%.
(P=0.002<0.05)
Conclusions: Residual mass is not uncommon in children
with mature B-cell NHL. An integrated tactics is important for
the accurate determination of residual disease. Conventional
imaging has low specificity and PPV. Second-look biopsy is
necessary to differentiate viable tumor from necrosis or fibrosis and is solid evidence-based foundation of subsequent treatment. It also can help clinician to avoid overtreatment and to
predict prognosis.
PD-014 AHOPCA LH 2004: Treatment of High
Risk Hodgkin Lymphoma in LMIC: Drug
Availability and Logn Term Outcomes
S. Luna-Fineman1 , M.E. Castellanos2 , M. Metzger3 , F. Baez4 , Y.
Gamboa5 , A. Peña6 , S. Alabi7 , R. Nieves8 , J. Blanco9 , E. Rossi10 , P.
de Alarcon11
SIOP ABSTRACTS
1 Stanford
University, Pediatrics, Palo Alto, USA; 2 Unidad Nacional de
Oncologia Pediatrica, Oncología Pediátrica, Guatemala, Guatemala; 3 St
Jude Childrens Research Hospital, Oncology, Memphis, USA; 4 La Mascota
Hospital, Oncologia Pediatrica, Managua, Nicaragua; 5 Hospital de Niños,
Oncología Pediátrica, San Jose, Costa Rica; 6 Hospital Escuela Materno
Infantil, Oncología Pediátrica, Tegucigalpa, Honduras; 7 Hospital de Niños
Benjamin Bloom, Oncología Pediátrica, San Salvador, El Salvador;
8 Hospital Universitario, Oncología Pediátrica, Santo Domingo, Dominican
Republic; 9 School of Medicine and Surgery- University of Milano-Bicocca,
Center of Biostatistics for Clinical Epidemiology, Milan, Italy; 10 School of
Medicine and Surgery- University of Milano-Bicocca, Biostatistics for
Clinical Epidemiology, Milan, Israel; 11 University of Illinois College of
Medicine and St Jude Midwest Affiliate, Department of Pediatrics, Peoria,
USA
Background/Objectives: High risk Hodgkin lymphoma in
children is curable with chemotherapy and radiation. Multiple
chemotherapeutic drugs are often not available for purchase
by low-middle income countries (LMIC). AHOPCA implemented a modified treatment guideline with the aim to reduce
abandonment while conserving survival.
Design/Methods: 239 patients with high risk Hodgkin lymphoma (IIB, IIIB, IV) were diagnosed from August 2004September 2009 and followed-up to March 2017. Costa Rica
(n=20), El Salvador (n=30), Guatemala (n=87), Honduras
(n=50), Nicaragua (n=39) and Dominican Republic (n=13)
contributed to this report. All patients were staged with
ultrasound or computer tomography. Chemotherapy regimen
was a modified StanfordV, substituting cyclophosphamide
for mechlorethamine. Response evaluation was performed
after 12 weeks of chemotherapy All patients received either
2000cGy for a CR and 2500cGy for PR to involved-field radiation therapy (IFRT).
Results: 192 patients eligible and evaluable were enrolled.
Median follow-up time was 7.6 years; 152 were boys, median
age was 9 years (2.6-17.5 years), 47 were IIB, 88 IIIB and 57
IV; 106 finished therapy. 43 did not get IFRT due to death
(n=7), abandonment (n=28, 14%) or progressive disease
(PD, n=8); 28% (42/149) got IFRT later than 6 weeks after
end of chemotherapy without affecting outcome. Overall, 34
patients had PD, 29 relapsed, 8 died and 28 abandoned. 8-year
abandonment-sensitive EFS and OS for the whole cohort was
47%±3.7 (±SE) and 56%±3.8; 8-year abandonment-sensitive
EFS was 68%±6.9, 53%±5.5 and 23%±5.6 in IIB, IIIB and IV
stages.
Conclusions: Treatment abandonment remains as an important failure (14% vs 12%, p=0.242). As previously described,
substituting cyclophosphamide for mechlorethamine in StanfordV did not bring the expected results. The OS for earlier
stages was better than stage IV. Substitution of drugs in LMIC,
related to availability is dangerous and affects the outcome. A
new regimen with available drugs is now implemented. Advocacy and compliance of drug availability are needed.
S119 of S518
PD-015 Clinico-Epidemiological Profile and
Outcome of Pediatric Anaplastic Large Cell
Lymphoma (ALCL): Single Center Experience
from India
N. Pradhan1 , D. Philip2 , G. Narula1 , M. Prasad1 , G. Chinnaswamy1 ,
T. Vora1 , B. Arora1 , S. Banavali1
1 Tata
Memorial Centre, Pediatric Oncology, Mumbai, India; 2 Tata
Memorial Centre, Medical Oncology, Mumbai, India
Background/Objectives: ALCL is a rare form of NHL in
children. We evaluated the clinical, epidemiological profile
and outcome of pediatric ALCL patients at Tata Memorial
Center, Mumbai, India.
Design/Methods: This is a retrospective study of 10 years
data of ALCL patients, who were registered at our centre from 01/01/2005 to 31/12/2014. All patients who were
treated at our centre received Vinblastin based MCP-842
multi-agent chemotherapy (Regimen-A- Cyclophosphamide,
Doxorubicin, Cytarabine, Vinblastin and Regimen-B- Ifosfamide, Etoposide, Methotrexate, Vinblastin). Intensive phase
consisted of alternating regimens of 8 cycles with 6 intrathecal
Cytarabine and 8 intrathecal Methotrexate, followed by oral 6Mercaptopurine and Methotrexate maintenance therapy (Six
months for stage 1 and 2 disease and one year for stage 3 and
4 disease).
Results: We include 68 patients (<15 years) of ALCL. The
male to female ratio was 3.5:1. Number of patients having Stage1,2,3 and 4 disease at diagnosis were 6(8.8%),
7(10.3%), 39(57.3%) and 16(23.5%) respectively. Forty-three
(63.2%) patients had B-symptoms at presentation. The common sites of disease involvement were lymph nodes (85.3%),
bone (29.4%), bone-marrow (23.5%) and skin (19%). Fiftyfive (80.8%) patients had ALK-positive disease on immunohistochemistry. For outcome analysis details of 4 patients
were not available. Out remaining 64, complete remission
(CR) was achieved in 55(85.9%), 4(6.2%) achieved partial
response (PR) while 5(7.8%) had progressive disease. Six
(9.3%) patients relapsed, of which 3 achieved second remission and are alive in CR at last follow-up. Five (7.8%) patients
died in remission. Thirteen (20.3%) died due to disease, all
had advanced stage (3/4). Three-year EFS and OS were 67.5%
and 72.7% respectively at a median follow-up 40 months (1132).
Conclusions: Pediatric ALCL has reasonable outcome with Vinblastin based multi-agent chemotherapy. Advanced stage disease is associated with
higher risk of mortality, and requires innovative
therapies.
SIOP ABSTRACTS
S120 of S518
PD-016 Impact of Secondary Chromosomal
Abnormalities on Treatment Outcome in Pediatric
Burkitt Leukemia
S. Salem1 , H. Abdelrahman2 , M. Tantawy3 , S. Talaat2 , R. Mohey4
1 NCI
- Egypt and Children's Cancer Hospital Egypt, Clinical Pathology,
Cairo, Egypt; 2 NCI - Egypt and Children's Cancer Hospital Egypt,
Pediatric Oncology, Cairo, Egypt; 3 Children Cancer Hospital Egypt,
Clinical Pathology, Cairo, Egypt; 4 Children Cancer Hospital Egypt,
Research Department, Cairo, Egypt
Background/Objectives: Burkitt leukemia (BL) is
characterized by translocation of the MYC gene to
one of the immunoglobulin genes. The clinical significance of secondary chromosomal abnormalities
associated with this characteristic translocation remains
unknown.
We aim to analyze the impact of secondary chromosomal abnormalities on treatment outcome in pediatric
BL.
Design/Methods: Patients with BL presenting to Children
Cancer Hospital in Egypt-57357 (CCHE) from July 2007
till March 2015, were reviewed for karyotyping and MYC
status by FISH. These results were correlated with survival
analysis.
Results: Eighty-eight patients with BL were diagnosed and
treated according to the FAB/LMB 96 protocol. Majority
were males (78%) and above 10 years of age at presentation (43%). Associated central nervous system involvement was diagnosed in 33% of the patients. Informative
karyotype for 67 patients demonstrated translocation of the
MYC and IGH genes in 85% of patients while translocation
of the IGK and IGL were found in 3% and 12%, respectively. Secondary chromosomal abnormalities were detected
in 60% of patients. Duplication of chromosome 1q was
found in 17 patients, followed by chromosome 14q abnormalities (6 patients), chromosome 6q deletion (4 patients),
and chromosome 13q deletion (3 patients). The five year
OS was 57.5%, while the 5 year EFS was 51.6% of the
whole group. After excluding 24 patients with treatment
related mortality, relapse or tumor progression on chemotherapy was seen in 16 patients. The 3 years relapse free survival in patients with complex karyotype was 47.1%, while
in patients having non-complex karyotype it was 76.8%
(p-value=0.022).
Conclusions: The frequency of secondary chromosomal
abnormalities in our series is in concordance with other publications with duplication 1q being the most common, followed
by deletion 6q, 13q, and 17p. Complex karyotype was significantly associated with higher incidence of relapse and poor
outcome.
HAEMATOLOGY - STEM CELL
TRANSPLANTAT ION
(HAEMATOLOGICA L
DISEASES/TECHNIQUE AND
S UP P O RT IVE CARE)
PD-017 Effect of Activating KIR-Ligand Match
on the Outcome of Pediatric Allogeneic
Hematopoietic Stem Cell Transplantation
Y.B. Choi1 , L. Ji Won2 , Y. Keon Hee2 , K. Eun-Suk3 , S. Ki Woong2 ,
K. Hong Hoe2
1 Chung-Ang
University Hospital, Pediatrics, Seoul, Republic of Korea;
Medical Center, Pediatrics, Seoul, Republic of Korea; 3 Samsung
Medical Center, Laboratory Medicine and Genetics, Seoul, Republic of
Korea
2 Samsung
Background/Objectives: Natural killer (NK) cells are precisely controlled by a network of activating and inhibiting signals through surface receptors. In this study, we evaluated the
impact of KIR genotype on the outcome following allogeneic
HSCT for malignant disease in children.
Design/Methods: The donor's activating KIR and recipient's
KIR ligand (KIR-L match) were considered compatible if
the donor had one or more activating receptors for which
the cognate ligand was present in the recipient. KIR2DS1,
KIR2DS2, KIR2DS4, and KIR3DS1 were deemed activating
KIRs. The donors were classified as KIR haplotype A or B
donors according to their gene content. Haplotype A donors
were defined as individuals only possessing genes of the group
A KIR haplotypes. All individuals possessing having one or
more haplotype B-specific genes were defined as haplotype B
donors.
Results: Fifty-three patients received allogeneic HSCT from
siblings (n = 11), unrelated donors (n = 20), or haploidentical donors (n = 22) between January 2011 and December
2014. The transplants were performed in patients with acute
myeloid leukemia (n = 17), acute lymphoblastic leukemia (n
= 14), neuroblastoma (n = 17), and other solid tumors (n =
5). Twenty-eight donor-recipient pairs had a KIR-L match and
the remaining twenty-five donor-recipient pairs had a KIR-L
mismatch. The 2-year relapse-free survival was 72.3 ± 9.0%
in recipients with a KIR-L match and 42.9 ± 10.1% in recipients with a KIR-L mismatch (P = 0.043). Recipients who
received HSCT from haplotype B donors had no survival benefit compared to those who received HSCT from haplotype A
donors (60.6 ± 9.8% vs. 54.0% ± 10.3%, P = 0.558).
Conclusions: This analysis revealed that allogeneic HSCT
with activating KIR-L match decreased relapse and improved
relapse-free survival. Therefore, for a successful HSCT
SIOP ABSTRACTS
outcome, KIR genotyping should be performed before selection of NK cell alloreactive donors.
SOLID NON B R A I N T U MO U R S NEUROBLASTOMA
PD-018 Spinal Canal Invasion in Peripheral
Neuroblastic Tumors - A Siopen Prospective Study
Registry
S. Ash1 , R. Haupt2 , K. Kraal3 , D. Plantaz4 , A. Wiecrorek5 , D.
Kachanov6 , C. Owens7 , C. Trager8 , K. McHugh9 , C. Gandolfo10 , T.
Trahair11 , B. De Bernardi12 , S. Sorrentino12
1 Schneider
Children's Medical Center of Israel, Pediatric Hematology
Oncology, Rosh Haain, Israel; 2 Istituto G. Gaslini-, Epidemiology and
Biostatistics Unit, Genova, Italy; 3 Princess Maxima Center PMC for
Paediatric Oncology, Pediatric Oncology, Utrecht, The Netherlands;
4 Hôpital Albert Michallon-CHU de Grenoble, Département de Pédiatrie,
Grenoble, France; 5 University Children's Hospital of Krakow, Pediatric
Oncology, Krakow, Poland; 6 Federal Scientific and Clinical Center of
Pediatric Hematology-, Department of Clinical Oncology, Moscow Russian
Federation, Russia; 7 Our Lady Children's Hospital, Pediatric Oncology,
Dublin, Ireland; 8 Astrid Lindgren‘s Children Hospital, Childhood Cancer
Research Unit, Stockholm, Sweden; 9 Great Ormond Street- Hospital for
Children, Radiology Department-, London, United Kingdom; 10 Istituto
Giannina Gaslini, Neuroradiology Unit, Genova, Italy; 11 Sydney Children's
Hospital-Centre for Children's Cancer & Blood Disorders, Paediatric
Haematologist & Oncologist, Sydney, Australia; 12 Istituto Giannina
Gaslini, Department of Haematology-Oncology, Genova, Italy
Background/Objectives: Spinal canal invasion (SCI) occurs
in 10-15% of children with peripheral neuroblastic tumors
(PNTs). These patients have favorable clinical and biologic
features and are cured more often than other patients, but are
especially prone to develop late neurologic, functional and
orthopedic sequelae. The question of their optimal treatment
has not been solved yet. The prospective SIOPEN Study Registry aims to collect data on these patients with the aim 1) to
increase the knowledge on natural history of PNTs presenting
with SCI, 2) to evaluate the combined effects of different risk
factors on their outcome and 3) to ultimately develop common
treatment guidelines.
Design/Methods: This SIOPEN Study intends to collect clinical, biological, therapeutic and follow-up data on symptomatic and asymptomatic patients with PNT and SCI. A minimum of 150 patients are expected. Age adjusted, standardized tools for symptoms grading and functional impacts are
the CTCAE, FLACC, pain scores and ASIA scales.
Results: From June 2014 to February 2017, a total of 57
patients have been registered from 8 countries. Median age
is 17 months, M/F ratio is 0.8. The most common histology
is NB poorly differentiated. Three patients only had MYCN
gene amplification. Twenty-eight patients were symptomatic.
Symptoms included motor deficit in 21, pain in 15 and
S121 of S518
bladder & bowel function in 2. Primary tumour site was
located in the thorax in 18, in the thoraco/abdominal site in
11. The majority (63%) have L2 disease. Patients were treated
according to SIOPEN/institutional protocols. Median followup is 6 months. At 2 months from diagnosis, pain disappear
in all patients presenting this symptom, while motor deficit
persists in 5 of 17 patients available for response.
Conclusions: This is the first cooperative study designed to
collect data to evaluate the combined effects of different risk
factors on neurologic, functional and orthopedic outcome of
PNT's patients presenting with SCI.
PD-019 BRCA1 Hypomethylation Causes
Chemoresistance in High-Risk Neuroblastoma
A. Hakkert1 , M. Ebus1 , J. Koster2 , F. Speleman3 , R. Versteeg2 , H.
Heyn4 , J. Molenaar1
1 Prinsess
Máxima Center, TRST, Utrecht, The Netherlands; 2 Academisch
Medisch Centrum, Oncogenomics, Amsterdam, The Netherlands; 3 Center
for Medical Genetics- Ghent University, Paediatric oncogenomics, Ghent,
Belgium; 4 Bellvitge Institute for Biomedical Research, Cancer Epigenetics
and Biology Program, Barcelona, Spain
Background/Objectives: All induction treatment regimens
for patients with neuroblastoma contain chemotherapeutics
that cause double strand DNA breaks. BRCA1 is a tumor
suppressor gene, and is involved in the repair of these double strand breaks in the DNA. Here we study the effects of
BRCA1 expression on tumor progression and chemoresistance in neuroblastoma.
Design/Methods: We performed an Illumina 450K methylation assay on 67 neuroblastoma tumor samples, and sought for
differentially methylated CpGs between high risk and low risk
tumors. MTT assays were performed to study the effect of target gene methylation on chemoresistance. And shRNA knock
down was utilized to investigate the tumor driving effects of
target gene expression.
Results: BRCA1 was found to be the top hit with 15 significantly differentially methylated CpG between high risk
and low risk neuroblastoma. This is surprising, since BRCA1
is known as a bonafide tumor suppressor gene. In neuroblastoma however, this gene seems to function as a tumor
driver. Hypomethylation of BRCA1 is strongly correlated
with high BRCA1 expression. shRNA knockdown of BRCA1
led to increased DNA damage and cell death in cell lines
with high BRCA1 expression. We hypothesized that BRCA1
hypomethylation, would lead to resistance to chemotherapeutics since the induced double strand breaks would be efficiently repaired. Indeed, cell lines with BRCA1 hypomethylation show resistance against widely used chemotherapeutics.
Conclusions: BRCA1 is hypomethylated in high risk neurblastoma tumors. Knockdown of BRCA1 leads to DNA
damage and cell death in cell lines depending on BRCA1,
SIOP ABSTRACTS
S122 of S518
suggesting that BRCA1 is essential for tumor progression
in BRCA1 hypomethylated tumors. BRCA1 hypomethylation
was shown to cause resistance to chemotherapeutics, indicating that BRCA1 hypomethylation might be involved in therapy resistance of patients with high risk neuroblastoma.
06BG synergistically enhanced the activity of TMZ+IRN
both in vitro and in vivo with clinically achievable dosing.
Further studies evaluating MGMT as a therapeutic target in
recurrent high-risk neuroblastoma are warranted.
PD-020 MGMT Inhibitor O6-Benzylguanine
Enhanced the Activity of Temozolomide +
Irinotecan against in Vitro and in Vivo Models of
Progressive Disease High-Risk Neuroblastoma
PD-021 Exploring the relevance of Primary
Tumour 123I-MIBG Response to Induction
Chemotherapy with Rapid COJEC in Children
with High-Risk Neuroblastoma
A. Hindle1 , M. Makena1 , B. Koneru1 , T. Nguyen1 , W.H. Chen1 ,
C.P. Reynolds1
E. Szychot1 , M. Chopra2 , O. Arthurs2 , N. Sebire3 , P. Humphries2 ,
L. Biassoni last author2 , D. Morgenstern last author4
1 Texas
1 Great
Tech University Health Sciences Center, Cancer Center, Lubbock,
USA
Background/Objectives: Patients with high-risk neuroblastoma (NB) treated with DNA-damaging chemotherapy
often relapse with treatment-refractory disease. Temozolomide (TMZ; DNA-methylating agent) and irinotecan (IRN;
topoisomerase I inhibitor) are well-tolerated and have clinical
activity in relapse/refractory NB. We hypothesized that DNA
repair genes with increased expression in alkylator-resistant
NB models would provide potential therapeutic targets for
enhancing chemotherapy.
Design/Methods: TaqMan Low Density Arrays (TLDA)
were used to analyze mRNA expression of 62 DNA repair
genes in 9 alkylator-resistant and 4 alkylator-sensitive cell
lines. Genes with differential expression were validated in
an expanded NB cell line panel (n=26) by qRT-PCR. In
vitro cytotoxicity was assayed using the digital imaging
microscopy scanning system (DIMSCAN). Double strand
DNA breaks, apoptosis, and DNA fragmentation were
assessed using phospo-histone H2AX, cleaved caspase-3, and
TUNEL, respectively. In vitro testing used the SN38 active
metabolite of IRN. Subcutaneous patient-derived xenografts
(PDXs) in nu/nu mice were treated with TMZ, IRN, and O6benzylguanine (O6BG) via oral gavage, tail vein injection,
and intraperitoneal injection, respectively.
Results:
O6-methylguanine-DNA
methyltransferase
(MGMT) was upregulated in alkylator-resistant relative
to drug-sensitive NB cell lines by TLDA and by qRT-PCR
(p<0.05). MGMT expression positively correlated with
in vitro TMZ+SN38 IC50 (n=14, p<0.05). The MGMT
inhibitor O6BG enhanced TMZ+SN38 in vitro cytotoxicity,
H2AX phosphorylation, caspase-3 cleavage, and apoptosis
by TUNEL. TMZ+IRN+O6BG delayed tumor growth and
increased median survival (p<0.05) relative to TMZ+IRN
in COG-N-564x and COG-N-452x PDXs established at the
time of death from progressive disease.
Conclusions: High MGMT expression is associated with
neuroblastoma multi-drug resistance. The MGMT inhibitor
Ormond Street Hospital for Children NHS Foundation Trust,
Paediatric Oncology and Haematology, London, United Kingdom; 2 Great
Ormond Street Hospital for Children NHS Foundation Trust, Radiology,
London, United Kingdom; 3 Great Ormond Street Hospital for Children
NHS Foundation Trust, Pathology, London, United Kingdom; 4 Hospital for
Sick Children, Paediatric Oncology, Toronto, Canada
Background/Objectives: Assessment of metastatic response
by 123 I-mIBG scintigraphy is important for treatment decisions in management of patients with high-risk neuroblastoma
(HR-NBL). However, the relevance of primary tumour mIBG
response has not been explored. We aimed to compare clinical
and histological (percentage of viable tumour) characteristics
of primary mIBG-avid tumours that became entirely mIBGnon-avid after induction chemotherapy (IC) (responders) with
primary mIBG-avid tumour that remained mIBG-avid (nonresponders).
Design/Methods: Retrospective review of patients with
metastatic HR-NBL (>18 months at diagnosis) treated at
Great Ormond Street Hospital 2005-2016. Patients received
Rapid COJEC (multi-agent IC as per SIOPEN HR-NBL-1).
Patients who did not go on to have surgery after IC alone
were excluded. Post-surgical histopathology specimens were
assessed for percentage of viable tumour. Primary tumour
mIBG response was assessed qualitatively as positive, negative, or intermediate. mIBG uptake was assessed at diagnosis and after IC. Estimates of event-free survival (EFS) using
Kaplan-Meier and comparisons by log-rank test.
Results: Seven of 68 (10.3%) patients had mIBG–negative
tumours at diagnosis and were excluded. 16 of 61 patients
showed complete primary tumour mIBG response, 20 partial
response and 25 no response. There was no statistically significant difference between clinical demographics of responders
and non-responders. Primary tumour mIBG response did not
correlate with extent of metastatic mIBG-avid disease at diagnosis. Mean percentage viable tumour cells was significantly
greater in mIBG-non-responders than responders (44.6% vs
20.6%; p=0.05). 5-year EFS was significantly better in complete responders than non-responders (43±15% vs 7±6%;
p<0.005). 5-year EFS was better in patients whose tumours
SIOP ABSTRACTS
showed <10% viable tumour after IC compared to those with
≥10% viable tissue (77±12% vs 25±10%, p= 0.007).
Conclusions: Primary mIBG response correlates with tumour
necrosis and patient outcome. However, it is not sufficient
alone to be used to confirm complete necrosis and justify a
decision not to resect these tumours.
PD-022 A Key Role for EMT Transcription
Factor SNAI2 in Neuroblastoma Dissemination and
Response to Retinoic Acid Therapy
K. Vrenken1 , J. Middelbeek1 , D. Van Ingen Schenau1 , Y. Derks1 , F.
Van Leeuwen1
1 Radboudumc,
Laboratory of Pediatric Oncology/ Pediatrics, nijmegen, The
Netherlands
S123 of S518
Conclusions: In summary, our results identify SNAI2 as a
key player in regulating neuroblastoma differentiation and
response to RA. Future research will focus on how EMT regulatory networks can be effectively targeted to enhance therapy
response in patients with advanced neuroblastoma.
S O LID NO N BRAIN TUM O URS R E NA L T U M O U R S
PD-023 Neoadjuvant Transcatheter Arterial
Chemoembolization (TACE) and Systemic
Chemotherapy for Treatment of Advanced Wilms
Tumor
Background/Objectives: Despite intensive treatment close
to 50% of patients with high-risk neuroblastoma relapse.
Recurrent disease is characterized by poorly differentiated,
therapy resistant cells. Retinoic Acid (RA)-induced differentiation improves event-free survival, but many patients
fail to respond. Hence, we aim to identify novel therapeutic targets that enhance the sensitivity to RA and promote
neuroblastoma differentiation. The similarities between neural crest development and neuroblastoma progression provide an appealing starting point. During neural crest development the transcriptional program epithelial-mesenchymal
transition (EMT) drives cellular plasticity affecting migration,
self-renewal and pluripotency. We hypothesize that a similar
mechanism maintains neuroblastoma cells in a poorly differentiated state. Therfore, targeting EMT may overcome therapy resistance.
M.J. LI1 , D.X. Tang2 , S. Xu3 , J.H. Wang4 , C. Lai5 , H.F. Tang6 , Q.
Shu4
Design/Methods: By gene expression profiling we investigated the association of EMT transcription factors with neuroblastoma overall survival. Subsequently, we used a variety
of different in vitro methods, including 3D spheroid invasion
assays, to study the effects of CRISPR-CAS9 mediated knockout of the EMT transcription factor SNAI2 on neuroblastoma
differentiation and the response to RA. In addition, immunocompromised mice were used to identify the effect of SNAI2
knockout on in vivo colonization.
Design/Methods: From January 2003 to December 2013,
55 patients (median age 3.3 years; 29 males, 26 females)
with advanced Wilms tumor were treated with preoperative TACE and systemic chemotherapy. Characteristics of
patients were tumor diameter greater than 10 cm, involvement of periaortic lymph nodes, tumor thrombus in inferior
vena cava/right atrium, distal metastasis, or diffuse anaplastic histology (AH). The chemoembolic emulsion for TACE
consisted of pirarubicin, vindesine, cisplatin and iodized oil.
Intravenous chemotherapy with vindesine, ifosfamide and
actinomycin D or etoposide was administered 3 weeks after
TACE. Nephrectomy was performed 2–3 weeks after preoperative therapy. Postoperative radiation therapy and chemotherapy were based on tumor histology and surgical stage.
Results: Expression of EMT transcription factors associate with neuroblastoma disease progression. Moreover, coregulation of genes that are directly controlled by SNAI2 is
highly predictive of disease outcome in two independent neuroblastoma patient cohorts, supporting the idea that increased
SNAI2 activity contributes to neuroblastoma progression.
Consistently, knockout of SNAI2 promotes cellular differentiation, while reducing self renewal capacity, invasion into a
3D matrix and in vivo colonization. In addition, growth of
SNAI2 knockout cells is strongly inhibited by RA treatment
and accompanied by enhanced tumor cell differentiation.
1 Children's
Hospital- Zhejiang University School of Medicine, Division of
Surgical Oncology- Department of Pediatric Surgery, Hangzhou, China;
2 Children's Hospital- Zhejiang University School of Medicine, Division of
Urology- Department of Pediatric Surgery-, Hangzhou, China; 3 Children's
Hospital- Zhejiang University School of Medicine, Division of UrologyDepartment of Pediatric Surgery, Hangzhou, China; 4 Children's HospitalZhejiang University School of Medicine, Division of Surgical OncologyDepartment of Pediatric Surgery, Hangzhou, China; 5 Children's HospitalZhejiang University School of Medicine, Department of Radiology,
Hangzhou, China; 6 Children's Hospital- Zhejiang University School of
Medicine, Department of Pathology, Hangzhou, China
Background/Objectives: The aim of this study was to evaluate the clinical efficacy and safety of neoadjuvant transcatheter arterial chemoembolization (TACE) combined with
systemic chemotherapy for treatment of advanced Wilms
tumor.
Results: No cardiotoxicity, renal and hepatic dysfunction
after neoadjuvant therapy were found. Grade Ⅱ–Ⅲ marrow
suppression developed in 12 (21.8%) patients. In terms of
response evaluation criteria, PR in 34 (61.8%), SD in 19
(34.5%), and PD in 2 (3.6%) patients were observed. Distant
metastasis disappeared in four of six cases. All patients under-
SIOP ABSTRACTS
S124 of S518
went tumor resection after preoperative therapy. Complete
surgical removal of the tumor was achieved in 50 (90.1%)
patients. The 5-year EFS and OS were 92.7% [95% CI: 85.8%–
99.6%] and 94.5% (95% CI: 88.5%–100%) respectively with
a median follow-up of 8.4 years (range, 3.5-14.0 years).
Conclusions: Neoadjuvant TACE combined with systemic
chemotherapy provide a promising choice for treatment of
advanced Wilms tumor.
PD-024 Nephron-Sparing Surgery for Bilateral
Wilms Tumour: Risk Factors for Positive Resection
Margins
A. Mantovani1 , J. Brok2 , L. Calciano3 , C. Duncan2 , T. Choudhury2 ,
W. Mifsud4 , N. Sebire4 , O. Olsen5 , K. McHugh5 , T. Watson5 , S.
Marks6 , R. Shroff6 , M. Gaze2 , A. Cherian1 , I. Mushtaq1 , K.
Pritchard-Jones2 , N. Smeulders1
16 tumorectomies; Histology: 11 regressive, 6 nephrogenic
rest, 5 mixed, 1 anaplasia, 1 blastema, 1 epithelial]). Tumorectomy(Odds Ratio[OR] 7.68, 95%CI 1.48-39.87) and increasing number of lesions/kidney unit(OR 1.68, 1.07-2.64) were
associated with M+. M+ significantly increased the risk
of flank/abdominal radiotherapy(OR 5.29, 1.82-15.32) and
intensified 4-drug chemotherapy(OR 3.45, 1.05-11.3) but did
not significantly increased risk of relapse or death.
Conclusions: Multiple lesions and tumorectomy compared to
partial nephrectomy were associated with M+ in patients with
BWT. M+ increases treatment burden and risk of late effects.
S O LID NO N BRAIN TUM O URS BON E T U M O U R S
1 Great
Ormond Street Hospital, Paediatric Urology, London, United
Kingdom; 2 Great Ormond Street Hospital, Paediatric Oncology, London,
United Kingdom; 3 University of Verona, Epidemiology and Medical
Statistics, Verona, Italy; 4 Great Ormond Street Hospital, Histopathology,
London, United Kingdom; 5 Great Ormond Street Hospital, Radiology,
London, United Kingdom; 6 Great Ormond Street Hospital, Paediatric
Nephrology, London, United Kingdom
Background/Objectives: Nephron-sparing surgery(NSS) for
bilateral Wilms tumour(BWT) is a balance between complete tumour-excision and maximal preservation of renal
parenchyma. This study explores the risk factors for incomplete resection and its oncological impact.
Design/Methods: Retrospective review of patients with BWT
treated at Great Ormond Street Hospital (Aug’01-Dec’16).
Patient demographics, imaging, treatment, surgery, histology
and clinical outcome were recorded. Lesions’ diameter, volume, number, location, distance from vessels, and type of NSS
were assessed by multivariable logistic regression(Stata 14®)
for their association with incomplete resection, and effect on
mortality, relapse and treatment burden.
Results: Fifty-four patients, mean age 31(8-129) months(m)
at surgery, received 72 NSS (excising 108 lesions) and 45
total nephrectomies(TN). All but 2 patients had pre-operative
chemotherapy as per the SIOP-2001 protocol. Follow-up data
were available for 52 patients: At mean of 68m (range 6182m) after surgery, 82% were disease-free, 5(10%) had
disease-recurrences, 4(8%) died from disease-progression.
Renal outcomes at mean 45m(1-190m) post-surgery: 6(12%)
patients were in end-stage-renal-disease after 3 bilateral TN
and 3 completion nephrectomy for 2 recurrences and 1infarction (3 dialysis, 2 renal transplant, 1 died-metastatic progression), 5(10%) patients had hypertension and elevated creatinine, 4(8%) hypertension, 25(48%) elevated creatinine alone
and 18(35%) patients had normal renal parameters. Positive
margins (M+) occurred in 30%(16/35) patients for 35 lesions
(10 TN (22%) and 25 NSS (35%) [9 partial nephrectomies,
PD-025 Mifamurtide and Tam-Like
Macrophages: Anti-Proliferative Effect on
Osteosarcoma Cells
G. Bellini1 , I. Manzo1 , D. Di Pinto2 , E. Pota2 , C. Tortora1 , M. Di
Martino2 , S. Perrotta2 , F. Casale2 , F. Rossi2
1 University
of Campania “Luigi Vanvitelli”, Experimental Medicine,
Naples, Italy; 2 University of Campania “Luigi Vanvitelli”, Woman- Childand General and Specialist Surgery, Naples, Italy
Background/Objectives: The process of osteoblast precursor dedifferentiation causes osteosarcoma, the most common
tumor of the childhood. In contrast to most other tumor types,
TAMs (tumor-associated macrophages), that are M2 polarized macrophages, reduce metastasis and improve survival in
high-grade osteosarcoma patients.
The mifamurtide is an immunomodulatory drug given
together with standard adjuvant chemotherapy in high-grade
osteosarcoma to improve outcome.
The aim of this study was to evaluate the role of mifamurtide
in the macrophage polarization and in the modulation of the
dedifferentiation of osteosarcoma cell line MG63.
Design/Methods: Macrophages, obtained from peripheral
blood mononucleated cells of healthy subjects, and activated or not with mifamurtide [100�M] were collected or cocultured with MG63 cells. By bio-molecular (qPCR) and biochemical (Western blotting, ELISA) analyses, we evaluated
the effects of mifamurtide on: M1 markers INOs, DMT1, IL1� and IL-6; M2 markers CD206, IL-4, IL-10 and iron release;
osteoblast markers RUNX2, OCN, OPG and RANKL; phosphorylation of STAT3.
Results: Mifamurtide-activated macrophages show a significant reduction of both the M1 polarization marker INOS
and the M2 polarization marker CD206, and a significant
increase of both pro-inflammatory (IL-1�, IL-6) and anti-
SIOP ABSTRACTS
S125 of S518
inflammatory (IL-4, IL-10) cytokines. Moreover, they show a
significant increase of the iron transporter DMT1, according
to an increased iron uptake typical of the M1 phenotype, and
a significant increase (more than 7 folds) of the iron release,
according to a M2 polarization.
MG63 cells co-cultured with mifamurtide-activated
macrophages show a significant increase of the osteoblast
markers RUNX2 and OPG and a significant reduction of
RANKL. Moreover, they show a significant reduction of the
proliferation and of the STAT3 activation that several tumors,
instead, constitutively activate.
Conclusions: Collectively, these data suggest that mifamurtide, switching macrophage polarization towards a TAM-like
intermediate M1/M2 phenotype, and reducing STAT3 activation, inhibits the cellular proliferation and induces the tumor
cell dedifferentiation.
PD-026 Impact of Neo-Adjuvant Chemotherapy
Dose Intensity on Outcomes of Children with
Localized Osteosarcoma: Experience of Children's
Cancer Hospital – 57357 Egypt (CCHE)
1
2
3
4
1
M. Zamzam , A. Hassaan , R. Soliman , N. Kamal , S. Ahmed
1 Children's
Cancer Hospital Egypt CCHE/National Cancer Institute- Cairo
University, Pediatric Hematology/Oncology, Cairo, Egypt; 2 Children's
Cancer Hospital Egypt CCHE, Pediatric Hematology/Oncology, Cairo,
Egypt; 3 Children's cancer Hospital - 57357 Egypt, Health Economics and
Outcomes, Cairo, Egypt; 4 Children's Cancer Hospital Egypt CCHE,
Research, Cairo, Egypt
Background/Objectives: Neo-adjuvant chemotherapy for
osteosarcoma is the standard of care, but there is still confusion regarding the optimal dose intensity. This retrospective study aimed to determine the impact of neo-adjuvant
chemotherapy dose intensity on tumor necrosis and the outcomes of children with localized osteosarcoma at CCHE.
Design/Methods: Dose intensity (DI) was determined by calculating the total dose of each drug (Methotrexate, Doxorubicin and Cisplatin) divided by the time duration in weeks.
Relative dose intensity (RDI) was calculated by dividing the
delivered DI by the standard DI as per CCHE Osteosarcoma
protocol. The impact of chemotherapy RDI on histological
response was determined using logistic regression. RDI was
also correlated with the 5-year relapse-free survival (RFS) at a
cut-off point of 75% of the DI using log rank test. Cox regression was done for multi-variate analysis.
Results: One hundred and three patients (< 18 years old)
with localized Osteosarcoma presented to 57357 hospital
from 2009 until 2014 and were followed-up until June 2016.
Seventy-two patients (70%) were poor responders, while
thirty-one patients (30%) showed good response. The histological response was affected by chemotherapy RDI (logistic regression, P = 0.03). Overall survival was 78%, while
RFS was 62.7%. Patients who received the drugs in the
neo-adjuvant phase at RDI above 75% showed improved
5-year RFS which was 80.7%, while those who received
<75% showed RFS of 57.5% (P-value = 0.04). Patients with
good histological response showed RFS of 84.8%, while poor
responders showed RFS of 52.8% (P-value= 0.001). Upon
multivariate analysis, histological response maintained significance (P = 0.007), while RDI lost significance (P = 0.129).
Conclusions: The relative dose intensity is a good predictor
of histologic response, which has a great impact on the relapse
free survival. Therefore, it is recommended to deliver optimal
dose intensity to achieve better outcomes.
PD-027 Long-Term Outcome of
Epiphyseal-Preservation and Biological
Reconstruction Using Tumor-Bone Sterilized with
Liquid Nitrogen for Childhood Osteosarcoma
Around the Knee
H. Tsuchiya1 , A. Takeuchi1 , N. Yamamoto1 , K. Hayashi1 , T.
Higuchi1 , K. Abe1 , Y. Taniguchi1 , H. Aiba1 , Y. Araki1
1 Kanazawa
University Graduate School of Medical Sciences, Orthopaedic
Surgery, Kanazawa, Japan
Background/Objectives: Various methods exist to reconstruct large bone defects after tumor excision such as tumor
prostheses or biological reconstructions using allograft, autograft, or recycled tumor-bearing bone. In 1999, we developed a reconstruction method using tumor-bearing autograft
treated by liquid nitrogen. The purpose of this study was to
evaluate the clinical outcome of this technique for treating
osteosarcoma around the knee in children after epiphyseal
sparing tumor resections.
Design/Methods: We retrospectively reviewed 17 children (7
boys and 10 girls) with osteosarcoma around the knee with
an average age of 12 years (range 6-16). The mean follow-up
period was 49 months (range 19-87). In 11 cases, the lesion
was in the distal femur, while in 6 patients it was in the proximal tibia. Two distinct freezing techniques – resection and
freezing (11 cases) and pedicle freezing (6 cases) – were used
based on the location of the tumor. Complications and oncological outcomes were evaluated and graded using the Musculoskeletal Tumour Society (MSTS) scoring system.
Results: The mean MSTS score was 95% (range 63-100).
Complications that required additional surgery were observed
in 7 (41.2%) patients. The 7 complications consisted of 4
fractures, 2 local recurrences arising from the surrounding
soft tissue, and one superficial infection managed by irrigation and IV antibiotics. Limb shortening (>3 cm) was
observed in 6 patients; 2 of these patients underwent subsequent limb lengthening. One frozen-autograft (5.9%) was
surgically retrieved to manage the soft tissue recurrence.
SIOP ABSTRACTS
S126 of S518
Clinically, 14 patients were able to run normally. Final oncological status was CDF in 13, NED in 3, and DOD in 1.
most patients had disseminated disease. Five patients developed severe treatment related toxicities.
Conclusions: The long-term outcome of epiphysealpreservation surgery using tumor-bone sterilized with liquid
nitrogen for childhood osteosarcoma around the knee was
satisfactory and promising. This procedure proved to be very
beneficial for children with osteosarcoma.
Conclusions: DSRCT is associated with poor outcome. Local
treatment in the form of complete CRS or complete CRS followed by adjuvant RT confers best outcome.
SOLID NON B R A I N T U MO U R S SOFT TISSUE SARCOMAS
PD-029 Mutation of Ras Pathway Should be a
Target of Precision Medicine for
Rhabdomyosarcoma
N. nakagawa1 , K. Kikuchi1 , K. Nakamura1 , T. Tanaka2 , S. Yagyu1 ,
T. Iehara1 , T. Tajiri2 , T. Sakai3 , H. Hosoi1
1 Kyoto
PD-028 Desmoplastic Small Round Cell Tumor
(DSRCT): Outcomes of Curative Intent
Multimodality Treatment
N. Khanna1 , A. Nayak1 , G. Chinnaswamy2 , T. Vora2 , M. Prasad2 , J.
Bajpai2 , A. Shah3 , M. Ramadwar3 , B. Rekhi3 , S. Medhi4 , S. Shah5 ,
S. Qureshi6 , A. Saklani6 , S. Laskar1
1 Tata
memorial hospital, Radiation Oncology, mumbai, India; 2 Tata
Memorial Hospital, Medical Oncology, Mumbai, India; 3 Tata Memorial
Hospital, Pathology, Mumbai, India; 4 Tata Memorial Hospital, Radiology,
Mumbai, India; 5 Tata Memorial Hospital, Nuclear Medicine, Mumbai,
India; 6 Tata Memorial Hospital, Surgical Oncology, Mumbai, India
Background/Objectives: DSRCT is a rare and aggressive
mesenchymal neoplasm. We evaluated the clinic-pathological
profile, treatment response, patterns of failure and prognostic
factors for patients with DSRCT treated at the Tata Memorial
Hospital (TMH).
Design/Methods: Between April 2006 & November 2016, 48
patients with histologically proven DSRCT in the age group
of 6-79 yrs (Median 27 yrs) were treated at TMH. Thirty
eight (79%) were males. Majority (85%) had abdominopelvic disease. Metastatic disease at presentation was seen in
50%. The commonest site being liver (71%). Curative treatment was offered to 24 (50%) patients. Local treatment was
cytoreductive surgery (CRS) alone in 10 patients, CRS followed by adjuvant radiotherapy (RT) in 7 patients and 3
patients received RT alone. One patient underwent hyperthermic intraperitoneal chemotherapy (HIPEC) after CRS. Four
patients progressed on induction chemotherapy and hence, did
not undergo local treatment.
Results: After a median follow-up of 14 months, the progression free survival (PFS) and overall survival (OS) was
29% and 67% respectively. At last follow up, only 7 (29%)
were alive and disease free. On univariate analysis, patients
who were offered local treatment in the form of CRS with or
without RT had improved OS (75% Vs 25%, p<0.05). Superior OS was seen in patients in whom complete cytoreduction
was achieved (90% Vs 50%, p=0.04). At the time of relapse
Prefectural University of Medicine, Pediatrics, Kyoto, Japan; 2 Kyoto
Prefectural University of Medicine, Pediatric Surgery, Kyoto, Japan; 3 Kyoto
Prefectural University of Medicine, Molecular-Targeting Cancer
Prevention, Kyoto, Japan
Background/Objectives: One of the current strategies for
adult malignant tumor is precision medicine based on individual gene mutation. Despite the advances in therapy, the outcome of recurrent or metastatic rhabdomyosarcoma (RMS)
remains poor, and treatment related side effects are still a problem. Embryonal RMS (ERMS) is reported to be a heterogeneous tumor that displays various gene mutations. Investigations of the heterogeneity could contribute to the development of precision medicine for ERMS. CH5126766 is a
potent and selective dual RAF/MEK inhibitor. In this study,
we examined the activity of CH5126766 in RMS tumor cell
lines with/without RAS mutation.
Design/Methods: Human RMS cell lines, RD, CT-TC, RH30,
RH18, RH28, RH3, RH41, RMS-YM, and SCMC-RM2, were
used in this study. RAS pathway mutations in the cell lines
were identified by direct sequencing. Cell survival was evaluated by WST-8 assay. The cell cycle was analyzed by flow
cytometry, and apoptosis was detected using flow cytometry after appropriate staining with Annexin V. ERK phosphorylation and RB de-phosphorylation were analyzed by
immunoblotting.
Results: CH5126766 inhibited growth of cells with RAS
mutations and did not affect the cells that lacked RAS pathway mutations. Cell cycle arrest at the G1 phase was induced
in RMS cell lines with RAS mutations within 24 h of exposure
to pharmacological levels of CH5126766. In the immunoblotting analyses, the drug appeared to suppress ERK phosphorylation in all the cells, but it was found to induce RB dephosphorylation in RAS mutated cells.
Conclusions: CH5126766 is a promising therapeutic option
for molecular targeting of RAS mutated RMS. Our results
suggest that the precision medicine approach targeting individual variability in genes could be an effective therapeutic
strategy for RMS.
SIOP ABSTRACTS
PD-030 Peritoneal Pleuropulmonary Blastoma: A
New Manifestation of DICER1 Syndrome
K.A. Schultz1 , M. Wilhelm1 , G. Williams1 , A. Field2 , J.
Jarzembowski3 , P. Kreiger4 , K. Conard5 , T. Olson6 , A. Bechtel7 , Y.
Messinger1 , L. Dehner8 , D.A. Hill2
1 Children's
Minnesota, Cancer and Blood Disorders, Minneapolis- MN,
USA; 2 Children's National Medical Center, Pathology, Washington DC,
USA; 3 Children's Hospital of Wisconsin, Pathology, Milwaukee- WI, USA;
4 Children's Hospital of Philadelphia, Pathology, Philadelphia- PA, USA;
5 Nemours Children's Health System, Pathology, Jacksonville- FL, USA;
6 Children's Healthcare of Atlanta, Aflac Cancer and Blood Disorders
Center, Atlanta- GA, USA; 7 University of Florida, College of Medicine,
Jacksonville- FL, USA; 8 Washington University, Surgical Pathology, St.
Louis- MO, USA
Background/Objectives: Background: Pleuropulmonary
blastoma (PPB) is the most common primary malignant lung
tumor of infancy and early childhood. Types I and Ir PPB are
purely cystic whereas Types II and III PPB are mixed cystic/solid and entirely solid respectively. Types II and III PPB
are multi-patterned sarcomas often with rhabdomyosarcomatous and cartilaginous differentiation. PPB is linked to underlying germline and tumor specific mutations in DICER1.
Design/Methods: Methods: Cases of primitive sarcoma
resembling PPB but with primary site in the peritoneum were
identified from pathology case files at Washington University Medical Center and Children's National Medical Center. DICER1 sequencing was performed using standard techniques.
Results: A total of five cases of peritoneal PPB were identified. The patients presented at an median age of 13 years. Primary site of origin was fallopian tube in 3 cases. One arose
from the serosal surface of the colon and one from the pelvic
sidewall. One case appeared analogous to Type Ir PPB; the
other 4 were analogous to Type II or III PPB. All had DICER1
mutations identified in germline and/or tumor DNA.
Conclusions: Discussion: Peritoneal PPB represents a
new manifestation of the DICER1 syndrome whose pathologic features may be identical to Types II or III PPB as
a multi-patterned sarcoma with cartilaginous and rhabdomyosarcomatous differentiation. This pattern is also seen
in DICER1-related renal sarcoma and cervical embryonal
rhabdomyosarcoma with cartilaginous features and SertoliLeydig cell tumor with heterologous elements which may
include rhabdomyosarcomatous and cartilaginous components. These newly recognized tumors are distinguished,
however by their unusual origin in the peritoneal cavity. The
differential diagnosis is malignant mixed müllerian tumor
(carcinosarcoma) which is typically seen in women 40 years
of age and older. Tumors arising in the abdomen/pelvis with
heterogeneous rhabdomyosarcomatous and/or cartilaginous
differentiation should prompt consideration of germline and
tumor DICER1 testing.
S127 of S518
PD-031 Prognostic Relevance of Early Radiologic
Response to Induction Chemotherapy in Pediatric
Rhabdomyosarcoma. A Report from the
International Society of Pediatric Oncology
MMT-95 Study
B. Vaarwerk1 , J.H. van der Lee2 , W.B. Breunis1 , D. Orbach3 , J.C.
Chisholm4 , M. Jenney5 , R.R. van Rijn6 , K. McHugh7 , S. Gallego8 ,
H. Glosli9 , C. Devalck10 , M.N. Gaze11 , A. Kelsey12 , C. Bergeron13 ,
M.C.G. Stevens14 , O. Oberlin15 , V. Minard-Colin15 , J.H.M. Merks1
1 Emma
Children's Hospital - Academic Medical Centre, Pediatric
Oncology, Amsterdam, The Netherlands; 2 Emma Children's Hospital Academic Medical Centre, Pediatric Clinical Research Office, Amsterdam,
The Netherlands; 3 Institut Curie, Pediatric adolescent and young adult
department, Paris, France; 4 Royal Marsden Hospital, Children and Young
People's Department, Sutton, United Kingdom; 5 Children's Hospital for
Wales, Department of Pediatric Oncology, Cardiff, United Kingdom;
6 Emma Children's Hospital - Academic Medical Centre, Pediatric
Radiology, Amsterdam, The Netherlands; 7 Great Ormond Street Hospital
for Children, Department of Radiology, London, United Kingdom;
8 University Hospital Vall d'Hebron, Pediatric Oncology, Barcelona, Spain;
9 Oslo University Hospital, Department of Pediatric and Adolescent
Medicine, Oslo, Norway; 10 Hopital Universitaire des enfants, Pediatric
Haematology Oncology Department, Brussels, Belgium; 11 University
College London Hospitals NHS Foundation Trust, Department of Oncology,
London, United Kingdom; 12 Royal Manchester Children's Hospital,
Pathology Department, Manchester, United Kingdom; 13 Centre Léon
Bérard, Department of Pediatric Oncology, Lyon, France; 14 Bristol Royal
Hospital for Children, Department of Pediatric Oncology, Bristol, United
Kingdom; 15 Gustave-Roussy, Department of Pediatric and Adolescent
Oncology, Villejuif, France
Background/Objectives: Early response to induction
chemotherapy is used in current European guidelines to
evaluate efficacy of chemotherapy and subsequently to adapt
treatment in pediatric patients with rhabdomyosarcoma.
However, existing literature on the predictive value of
radiologic response on survival is contradictory. Therefore
we retrospectively analysed the association of early response
with survival from the data of the SIOP-MMT-95 study.
Design/Methods: We studied432 IRS group III (macroscopic residual) patients enrolled in the SIOP-MMT-95 study
with response assessment after 3 courses of chemotherapy
(assessed 2-dimensionally). Patients with progressive disease after 3 courses of chemotherapy were excluded (n=7).
Failure-free survival (FFS) and overall survival (OS), were
assessed between three groups (complete/partial, objective
and no response) with Cox proportional hazards.
Results: After 3 courses of chemotherapy, 85.2% of the
patients had complete/partial response, 8.6% had objective
response, and 6.3% had no response. For all patients 5-year
FFS [95% CI] and OS [95% CI] was 60% [56%-65%] and
74% [70%-78]. Cox proportional hazards regression analysis
revealed no significant difference in FFS and OS rate between
response groups. The adjusted hazard ratios for objective
response and no response were 1.09 [0.63 to 1.88] and 0.81
SIOP ABSTRACTS
S128 of S518
[0.39 to 1.67] for FFS and 0.91 [0.47-1.76] and 1.27 [0.612.64] for OS, respectively.
was a component of cancer related death in 60% vs. 40% in
the No ReRT vs. ReRT group (p= 0.02).
Conclusions: These results provide further evidence that
early radiologic response to chemotherapy is not predictive
for survival in patients with rhabdomyosarcoma. Treatment
adaptations based on early response (except for patients with
progressive disease) should therefore not be incorporated in
future studies.
Conclusions: Salvage RT may reduce the risk of further LR
in patients with favorable disease and relapse characteristics,
although distant failure remains common. Acute toxicities
were minimal while second malignancies and chemotherapy
induced end organ failure were a cause of late mortality.
PD-032 Is There A Role for Radiotherapy in
Pediatric Patients with Locoregionally Recurrent
Rhabdomyosarcoma? Toxicity and Clinical
Outcomes in an Irradiated and Non-Irradiated
Multi-Institutional Cohort
S O LID NO N BRAIN TUM O URS RETINOBLASTOMA
PD-033 Impact of a Multi-Faceted
Retinoblastoma Program Model in a Tertiary
Hospital in the Philippines
D.V. Wakefield1,2 , J.T. Lucas Jr.1 , B. Eaton3 , C.Y. Hsu1 , A. Pappo4 ,
N. Eshiashvili3 , A.M. Davidoff5 , M. Krasin1
A.P. Alcasabas1 , G. Mercado2 , P. Fajardo1 , M. Dolendo3 , C.
Rodriguez-Galindo4 , C. Lam4 , J. Lecciones5 , E. Domingo2
1 St
Jude Children's Research Hospital, Radiation Oncology, Memphis,
USA; 2 University of Tennessee West Cancer Center, Radiation Oncology,
Memphis, USA; 3 Emory University Winshop Cancer Institute, Radiation
Oncology, Atlanta, USA; 4 St Jude Children's Research Hospital, Oncology,
Memphis, USA; 5 St Jude Children's Research Hospital, Surgical Oncology,
Memphis, USA
1 University
Background/Objectives: A paucity of data exist detailing the
role of local therapies (radiotherapy [RT], surgery) following
locoregional recurrence (LR) in pediatric rhabdomyosarcoma
(RMS). We evaluated outcomes and prognostic factors using
a multi-institutional cohort of patients with LR managed with
or without repeat RT (ReRT).
Background/Objectives: Retinoblastoma survival in the
Philippines remains poor due to low detection rates, late referrals and incomplete treatment. Development of a retinoblastoma program involving stage-based treatment protocols, online tumor board meetings, patient navigation, data management and community-based educational campaigns increased
referrals and decreased extra-ocular presentations in a public referral hospital in Mindanao. The same model was later
implemented in three referral centers in Luzon. We review
the program's impact on patient outcomes at Philippine General Hospital where baseline data (2008-2012) showed census
of 22/year, 54% extra-ocular disease, 26% survival and 56%
abandonment rates.
Design/Methods: 23 patients with LR RMS were treated
from 1996 to 2012 were eligible for inclusion. Patient stage,
risk, group, histology, translocation status, primary location,
histology, surgical extent, RT dose and failure pattern were
documented. Overall (OS), local, and distant failure free survival (LFFS, DFFS) were described using the Kaplan-Meier
estimator.
Results: With a median follow-up of 4.6 years from LR,
7 (30%) patients were alive and 5 (22%) had no evidence
of disease. Salvage therapy included ReRT and surgery in
50% and 50% of cases. All patients received chemotherapy
at LR. Median OS and PFS from LR were 19.3 and 16.9
months. Patients with low risk and favorable primary site
had improved PFS and OS. LFFS and DFFS at 3 years following salvage therapy were 54%, and 56% respectively. The
median LFFS and OS in the No ReRT vs. ReRT patients
was 12.4 vs. 19.6 (p=0.1) and 18.8 vs. 26.1 mo (p=0.46).
Patients with favorable site and group 3 disease, LR-only failure, and embryonal histology had improved LFFS with ReRT.
No patients experienced > grade 3 acute toxicity. Late toxicities included second malignancy, and chemotherapy induced
end organ failure in 2 and 2 patients respectively. LR failure
of the Philippines - Philippine General Hospital, Paediatrics,
Manila, Philippines; 2 University of the Philippines - Philippine General
Hospital, Ophthalmology, Manila, Philippines; 3 Southern Philippines
Medical Center, Pediatrics, Davao, Philippines; 4 St. Jude Children's
Research Hospital, Global Pediatric Medicine, Memphis, USA; 5 Philippine
Children's Medical Center, Pediatrics, Manila, Philippines
Design/Methods: Prospective data collection of consecutive
patients diagnosed January 1, 2014 to December 31, 2016.
Study end-point was March 1, 2017.
Results: A total of 96 patients were diagnosed: unilateral 62;
bilateral 32; and trilateral 2. Mean age was 24.6 months (2 –
108). M:F 1.5:1. Majority had extra-ocular disease: International Retinoblastoma Staging System Stage 0: 1 (1%); Stage
I: 38 (40%); Stage II: 2 (2%); Stage III: 31 (32%); Stage IV:
19 (20%); and unknown 5 (5%). Symptom-to-diagnosis lag
time was 12 months (1 - 45). At study end-point, 43% (41)
were alive, 28% (n=27) had died, 16% had refused (4%; n=4)
or abandoned (12%; n=12) treatment; 7% (n=7) transferred
care centers, and 5% (n=5) lost to follow-up. The 1 and 2year overall survival was 69.7% and 55.3%, respectively, with
survival highest for Stage I (100% and 97%, respectively)
SIOP ABSTRACTS
and lower for Stages III (63% and 40%, respectively) and IV
(28% and 26%, respectively). The 1 and 2-year abandonmentsensitive overall survival was slightly lower (60.4% and 46%,
respectively) and followed similar trends by stage as the overall survival.
Conclusions: This multi-faceted retinoblastoma outcome
improvement model demonstrated increases in patient referrals, treatment adherence and survival, and provides data
to support additional replication and extension efforts for a
national protocol for retinoblastoma.
PD-034 Treatment Results In Extra-Ocular
Retinoblastoma with Invasion of the Optic Nerve at
Presentation
B. Chawla1 , F. Hasan1 , R. Agarwal1 , R. Seth2 , S. Pathy3 , S.
Sharma1
1 All
India Institute of Medical Sciences, RP Centre for Ophthalmic
Sciences, New Delhi, India; 2 All India Institute of Medical Sciences,
Paediatric Oncology Division- Department of Paediatrics, New Delhi,
India; 3 All India Institute of Medical Sciences, Department of Radiation
Oncology, New Delhi, India
Background/Objectives: Optic nerve invasion is a significant risk factor for metastasis in retinoblastoma. The purpose of this study was to evaluate the clinical outcome in
retinoblastoma patients who had invasion of the optic nerve
at the time of diagnosis and were treated with a uniform protocol consisting of multi-modal therapy.
Design/Methods: Patients of non-metastatic extra-ocular
retinoblastoma with evidence of optic nerve invasion on
contrast-enhanced MRI scan of the orbits and brain were
studied. Demographic and clinical details were recorded. The
treatment protocol consisted of neo-adjuvant chemotherapy,
enucleation, orbital external beam radiotherapy and adjuvant
chemotherapy. Systemic chemotherapy consisted of intravenous vincristine, etoposide and carboplatin for 12 cycles.
Following neo-adjuvant chemotherapy, the optic nerve status
was re-assessed on MRI scan. Outcome parameters were survival probability and cause of death.
Results: Forty eight children were studied (66.7% unilateral,
60% boys). The median age at presentation was 30 months.
The median follow up was 18.6 months. Of 48 children, 18
(38%) died. The Kaplan Meier survival probability was 79%
and 59% at one year and four years respectively. The most
common cause of death was CNS relapse (83%).
Conclusions: Advanced cases of retinoblastoma with optic
nerve invasion can be managed by a multi-modal treatment
protocol. Although short term results are encouraging, long
term outcomes need further evaluation.
S129 of S518
PD-035 Natural Killer Cell Therapy Against
Retinoblastoma
D.H. Jo1 , J.H. Kim2 , H.O. Jun2 , C.S. Cho2 , E. Bak1 , S. Lee3 , S.R.
Yoon3 , Y.J. Park3 , K.D. Park4 , I. Choi3 , J.H. Kim1
1 Seoul
National University College of Medicine, Department of
Ophthalmology, Seoul, Republic of Korea; 2 Seoul National University
Hospital, Fight against Angiogenesis-Related Blindness FARB LaboratoryClinical Research Institute, Seoul, Republic of Korea; 3 Korea Research
Institute of Bioscience and Biotechnology, Immunotherapy Research Center,
Daejeon, Republic of Korea; 4 Seoul National University College of
Medicine, Department of Pediatrics- Cancer Research Institute, Seoul,
Republic of Korea
Background/Objectives: This study aims to investigate therapeutic potential of natural killer (NK) cell therapy against
retinoblastoma, the most common intraocular malignant
tumor in children. In patients with retinoblastoma, it is
inevitable to perform enucleation, total removal of eyeball,
if conventional treatment options fail. In this context, novel
treatment options are desperately required to treat patients
with retinoblastoma.
Design/Methods: NK92 cells (commercially available cell
line) and cord blood-derived NK cells were prepared for
in vitro cytotoxicity assays and in vivo intracardiac injection. In vitro cytotoxicity was evaluated by coculture of NK
cells and retinoblastoma cells from 3 different retinoblastoma
cell lines (Y79, WERI-Rb1, and SNUOT-Rb1) using calcein
AM assay. For the evaluation of in vivo efficacy, retinoblastoma cells (2 × 104 cells) from 3 different retinoblastoma
cell lines were injected into the vitreous cavity of Balb/c
nude mice (n =12 per group). At 7 or 10 days after intravitreal injection of tumor cells, NK cells (1 or 5 × 106 cells)
were administered via intracardiac route or carboplatin (50
mg/Kg) was administered through intraperitoneal route with
2 more administration on a weekly basis. In vivo cytotoxicity
was evaluated using the visual grading system and histologic
examination.
Results: Both NK cells demonstrated considerable in vitro
cytotoxicity against retinoblastoma cells. In addition, tumors
were formed in a less severe manner in mice treated with
NK cells than in ones treated with carboplatin or phosphatebuffered saline (negative control). It is also remarkable that
mice treated with combination of NK cells and carboplatin demonstrated minimal tumor formation in intraocular space compared to ones treated with only NK cells or
carboplatin.
Conclusions: Taken together, NK cells demonstrated in vitro
and in vivo cytotoxicity against retinoblastoma. We expect
that NK cell therapy might be involved in the treatment of
retinoblastoma.
SIOP ABSTRACTS
S130 of S518
SOLID NON B R A I N T U MO U R S LIVER TUMOURS
PD-036 CD146 Is a Potential Therapeutic Target
in Hepatoblastoma
M. Sonoda1 , K. Umeda2 , S. Nodomi2 , S. Obu2 , S. Saida2 , I. Kato2 ,
H. Hiramatsu2 , E. Ogawa1 , A. Yoshizawa1 , S. Okamoto1 , K.
Morita3 , Y. Kamikubo3 , S. Adachi3 , T. Nakahata4 , H. Okajima1 , S.
Uemoto1 , T. Heike2
1 Kyoto
University Graduate School of Medicine, Pediatric Surgery, Kyoto,
Japan; 2 Kyoto University Graduate School of Medicine, Pediatrics, Kyoto,
Japan; 3 Kyoto University Graduate School of Medicine, Human Health
Science, Kyoto, Japan; 4 Kyoto University, Center for iPS Cell Research and
Application, Kyoto, Japan
Background/Objectives: Hepatoblastoma (HB) is the most
common malignant liver tumor in childhood. Recent progress
in both surgical techniques and in neoadjuvant and adjuvant chemotherapy has markedly improved the prognosis
for patients with HB: however, the survival rate of patients
with metastatic and relapsed disease remains unsatisfactory.
CD146 is an integral membrane glycoprotein that promotes
tumor growth, angiogenesis and metastasis and is regarded
as a promising candidate for immunotherapy against various
CD146-expressing malignancies.
Design/Methods: The expression level of CD146 in two HB
cell lines (HepG2 and Huh6) and clinical samples was examined by flow cytometric and immunohistochemical analyses. The anti-tumor effect of blocking CD146 by rabbit antiCD146 polyclonal antibody or shRNA knockdown of CD146
was then evaluated both in vitro (by WST-8 assay) and in
vivo (by subcutaneous transplantation into immunodeficient
mice).
Results: CD146-positive cells were detected in both HB
cell lines and most of clinical samples. Knockdown of
CD146 significantly inhibited in vitro tumor viability via
induction of apoptosis, and markedly suppressed in vivo
tumor formation in immunodeficient mice. Anti-CD146 polyclonal antibody also showed effective in vivo anti-tumor
activity. Details of underlying mechanism are now under
investigation.
Conclusions: Notable anti-tumor effect of blocking CD146
will facilitate a novel immunotherapy for HB.
PD-037 Impact of the Response to Chemotherapy
on the Clinical Outcome of Hepatoblastoma after
Liver Transplantation: A Single Institute
Experience
K. Umeda1 , H. Okajima2 , K. Kawaguchi3 , S. Nodomi1 , S. Saida1 , I.
Kato1 , H. Hiramatsu1 , E. Ogawa2 , A. Yoshizawa2 , S. Okamoto2 , S.
Uemoto2 , K. Watanabe3 , S. Adachi2
1 Kyoto
University Graduate School of Medicine, Pediatrics, Kyoto, Japan;
University Graduate School of Medicine, Pediatric Surgery, Kyoto,
Japan; 3 Shizuoka Children's Hospital, Hematology and Oncology,
Shizuoka, Japan
2 Kyoto
Background/Objectives: Liver transplantation (LT), which
was performed as a primary surgery (primary LT) or subsequently for recurrent tumor after a primary resection (rescue
LT), has recently contributed to the elevation of cure rates for
patients with unresectable hepatoblastoma (HB). The prognosis of patients with recurrent HB after LT was extremely dismal. However, there are many unresolved problems, including
the risk factors for post-LT relapse and treatment strategy for
post-LT relapse.
Design/Methods: We retrospectively analyzed the clinical
outcome of 24 patients with HB who underwent LT between
1997 and 2015.
Results: The 5-yr OS rate of all patients was 69.6% ± 9.7%.
Both serum AFP level at LT and decline in the serum AFP
level at LT in comparison with that at diagnosis were significantly higher in the remission group than those in the relapse
group. The 5-yr OS rate of patients with a decline of AFP
>95% (81.3% ± 9.8%) at LT was higher than that in patients
with a decline of AFP ≤95% (42.9% ± 18.7%). The 5-yr OS
rate of patients undergoing rescue LT (72.7% ± 13.4%) was
comparable to that of patients undergoing primary LT (69.2%
± 12.8%). In the primary LT group, six of ten patients with
a decline of AFP >95% were alive in remission, whereas
both patients with a decline of AFP ≤95% experienced postLT relapse. In the rescue LT group, all three patients with
any decline of AFP to pre-LT chemotherapy (range, 82.0–
90.8%) were alive in remission, whereas three of six patients
with no response to pre-LT chemotherapy experienced postLT relapse.
Conclusions: Response to chemotherapy might be a reliable
marker for predicting post-LT relapse, even for patients undergoing rescue LT.
S O LID NO N BRAIN TUM O URS GERM CELL TUMOURS
PD-038 Pediatric Testicular Germ Cell Tumors:
The Associazione Italiana Ematologia Oncologia
Pediatrica Study
M. Terenziani1 , M. Conte2 , M.D. De Pasquale3 , F. Barretta4 , D.
Biasoni5 , G. Bisogno6 , R. Boldrini7 , G. Cecchetto8 , P. Collini9 , D.
Di Pinto10 , A. Inserra11 , F. Melchionda12 , F. Siracusa13 , F.
Spreafico1 , P. D'Angelo14
1 Fondazione
IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology,
Milano, Italy; 2 Ospedale Pediatrico G. Gaslini, Pediatric
Onco-Hematology, Genova, Italy; 3 Ospedale Pediatrico Bambino
SIOP ABSTRACTS
Gesù-IRCCS, Pediatric Onco-Hematology, Roma, Italy; 4 Fondazione
IRCCS Istituto Nazionale dei Tumori, Clinical Epidemiology and Trial
Organization, Milano, Italy; 5 Fondazione IRCCS Istituto Nazionale dei
Tumori, Pediatric Surgery, Milano, Italy; 6 University Hospital- Padova,
Pediatric Onco-Hematology, Padova, Italy; 7 Ospedale Pediatrico Bambino
Gesù-IRCCS, Diagnostic Pathology and Laboratory Medicine, Roma, Italy;
8 University Hospital- Padova, Pediatric Surgery, Padova, Italy;
9 Fondazione IRCCS Istituto Nazionale dei Tumori, Diagnostic Pathology
and Laboratory Medicine, Milano, Italy; 10 Seconda Università di Napoli,
Pediatric Oncology, Napoli, Italy; 11 Ospedale Pediatrico Bambino
Gesù-IRCCS, Pediatric Surgery, Roma, Italy; 12 S.Orsola-Malpighi
University Hospital, Pediatric Oncology, Bologna, Italy; 13 Università degli
studi di Palermo, Pediatric Surgery, Palermo, Italy; 14 ARNAS Civico Di
Cristina, Pediatric Oncology, Palermo, Italy
Background/Objectives: We describe the results of a therapeutic approach with a pediatric BEP (bleomycin, etoposide,
cisplatin) from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study on testicular germ cell tumors
(TGCT).
Design/Methods: From March 2004 to December 2016,
males under 18 years were enrolled in the AIEOP study. Treatment, defined as specific chemotherapy regimen and number
of cycles, was allocated by means of risk-group assignment
at diagnosis with consideration for stage. All patients underwent orchiectomy at diagnosis and those with stage I received
no chemotherapy. Patients with stage II and III received three
cycles for total doses of platinum 300 mg/m2 plus etoposide
1200 mg/m2 and bleomycin 45 mg/m2 (BEP). Patients with
stage IV received four cycles for a total doses of platinum 400
mg/m2 plus etoposide 1,600 mg/m2 and blemoycin 60 mg/m2 .
After chemotherapy, retroperitoneal and/or lung residual diseases were removed by surgery.
Results: One hundred and thirteen patients were evaluable
with a median age of 16 year old (range 6 months - 17.10
years) staged as follows: 58 stage I, 9 stage II, 19 stage III
and 27 stage IV. Overall survival (OS) and event-free survival
(EFS) at 5 years for the whole series were 97.8% (CI 96.3% 99.3%) and 75.1% (CI 70.7% - 79.5%), for stage I 100% and
60.6% (CI 53.5% - 67.7%), and for stages II-IV 95.7% (CI
92.7% - 98.5%)and 89.4% (CI 84.9% - 93.9%), respectively.
The median follow up was 42 months.
Conclusions: We confirmed the excellent prognosis of TGCT
in children and adolescents. Reduction of cumulative dose of
etoposide did not seem to compromise survival outcomes for
patients in stages II-IV, but further investigations are needed
to draw conclusions.
SOLID NON B R A I N T U MO U R S RARE TUMOURS
PD-039 Are Very Rare Tumors Correctly
Recognized? A European Survey on
Pleuropulmonary Blastoma
S131 of S518
A. Tagarelli1 , D. Orbach2 , R. Lopez Almaraz3 , A. Pourtsidis4 , E.
Bien5 , G. Osterlundh6 , A. Kolenova7 , M. Cesen8 , C. Devalck9 , E.
Koscielniak10 , J. Rascon11 , N.J. Farinha12 , J. Roganovic13 , S.S.
Teresa14 , Z. Jakab15 , T. Ben Ami16 , D. Kostantinov17 , G. Bisogno1
1 University
of Padua, Department of Pediatric Hematology Oncology,
Padua, Italy; 2 Institut Curie, Département d'oncologie pédiatrique, Paris,
France; 3 Hospital Universitario Cruces, Pediatric Oncology and
Hematology Unit, Bilbao, Spain; 4 P & A. Kyriakou Children's Hospital,
Oncology Department, Athens, Greece; 5 Medical University of Gdansk,
Department of Pediatrics- Hematology & Oncology, Gdansk, Poland;
6 Göteborg University, Department of Pediatrics, Göteborg, Sweden;
7 Comenius University Medical School and University Children's Hospital,
Department of Pediatric Hematology and Oncology, Bratislava, Slovak
Republic; 8 Jožef Stefan Institute, Department of Environmental Sciences,
Ljubljana, Slovenia; 9 Hôpital Universitaire des Enfants Reine Fabiola,
Department of Hemato-Oncology, Brussels, Belgium; 10 Olga Hospital,
Department of Pediatric Oncology, Stuttgart, Germany; 11 Children's
Hospital- Vilnius University, Center of Pediatric Oncology and
Hematology, Vilnius, Lithuania; 12 Centro Hospitalar de São João,
Department of Pediatrics, Porto, Portugal; 13 Clinical Hospital Centre
Rijeka, Department of Pediatrics- Division of Hematology and Oncology,
Rijeka, Croatia; 14 Medical University of Gdansk, Department of Pediatric
Oncology and Oncology, Gdańsk, Poland; 15 Semmelweis University, 2 nd
Department of Pediatrics, Budapest, Hungary; 16 Hadassah Hebrew
University Medical Center, Department of Pediatric Hematology Oncology
and Bone Marrow Transplantation, Jerusalem, Israel; 17 University Hospital
“Queen Johanna”, Children's Oncohaematology Clinic, Sofia, Bulgaria
Background/Objectives: Very rare tumors (VRT) in childhood represent a diagnostic and treatment challenge. In particular, Pleuropulmonary Blastoma (PPB), a rare and potentially aggressive intrathoracic neoplasm, can be confused with
other tumors or malformative lesions. The correct diagnosis is
the first step to establish the right treatment. The aim of the
present study was to assess the ability of diagnosing patients
with PPB for each European country, comparing the number
of the expected PPB cases with the number of registered cases.
Design/Methods: The expected number of PPB was calculated from 2000 to 2014 on the basis of pediatric epidemiological data (www.Eurostat.it) and the reported incidence of
PPB. The number of observed patients with PPB has been
obtained sending a questionnaire to the physicians identified
as the national contact for VRT in 26 European countries.
Results: Twenty countries provided data: overall 121 PPB
cases have been observed, comparing to 109 expected cases.
A low number of patients with PPB has been registered mainly
in eastern countries, in particular: Bulgaria, Slovenia, Croatia,
Bosnia and Lithuania did not observe any case. More patients
than expected were diagnosed in Finland, Sweden, Israel and
especially in France, Poland and Italy where national registries and cooperative groups dedicated to VRT exist. In addition the experience from these countries suggests that the incidence of PPB may be higher than previously reported.
Conclusions: Our study demonstrates that differences in the
number of observed/expected cases of PPB exist across European countries and suggest that this may be related to the presence of national VRT cooperative groups.
SIOP ABSTRACTS
S132 of S518
PD-040 Diagnosis and Treatment of
Pancreatoblastoma in Children: A Retrospective
Study in a Single Pediatric Center
Z. Zhu1
1 Beijing
Children's Hospital Affiliated to Capital Medical University,
Department of Surgical Oncology, Beijing, China
Background/Objectives: Pancreatoblastoma is a very rare
malignant pancreatic tumor in children. A standardize management and therapy is still discussed. To summarize our
experience in the management of pancreatoblastoma in children and adolescents.
Design/Methods: This was a retrospective, observational
study of primary pancreatoblastoma in patients< 18 years of
age who were treated at Beijing children's hospital (BCH)
between 2005 and 2015.
Results: 21 patients with pancreatoblastoma were diagnosed at a median age of 4 years, 7 girls and 14 boys.
The diagnosis of pancreatoblastoma was identified by the
histology examination. The most common syndrome was
abdominal mass(n=11), followed by abdominal pain(N=10),
elevated serum AFP levels were noted in all cases, of
17 patients with disease initially unresectable at presentation, accepted neoadjuvant chemotherapy consisting of CDV,
OPEC, PLADO, IEV, and AVCP. All patients underwent
surgery, including pancreaticoduodenectomy(Whipple's procedure), the Pylorus-preserving pancreaticoduodenectomy
(traverse-Longmire procedure), Spleen-preserving distal pancreatectomy, and Distal pancreatectomy with en bloc splenectomy, Roux-en-Y end to end pancreatojejunostomy. In all,
13 children are disease free with a median follow-up of 53
months (range, 11-156 months).
Conclusions: The pancreatoblastoma in children and adolescents is a curable malignant tumor. Complete resection combined with chemotherapy is associated with long-term survival. For the unresectable tumor at diagnosis, preoperative
chemotherapy (OPEC) were recommended to reduce tumor
volume.
BRAIN TUMOURS
PD-041 Humanized Anti-CD47 Antibody
Combined with an Agonist ANTI-CD40 Antibody is
an Effective Treatment for DIPG Xenografts with
Cranio-Spinal Dissemination
S. Gholamin1 , K. Suzana2 , R. Esparza2 , I. Weissman3 , S. Mitra2 , S.
Cheshier4
1 California
Institute of Technology Caltech, Biology and Biological
Engineering, Pasadena, USA; 2 Stanford, Neurosurgery, Stanford, USA;
3 Stanford,
Institute of Stem Cell Biology and Regenerative Medicine,
Stanford, USA; 4 Stanford, Neurosurgery, Stanoford, USA
Background/Objectives: DIPG is the most common malignant brainstem tumor in children. The resistance of DIPG
to standard treatments along with inoperability of this tumor
because of the anatomical location leave DIPG patients
with dismal prognosis. Multiple studies revealed that DIPG
patients have only a few months of survival after detection
of cranio-spinal metastasis. Our previous work showed that
a humanized anti-CD47 antibody (anti-huCD47 mAb), an
immune-modulatory drug that increases phagocytic activity
of macrophages against cancer cells, has a therapeutic effect
on DIPG xenografts. However, the efficacy of anti-CD47 therapy was inversely correlated with tumor size and presence of
metastasis at the onset of treatment. Therefore, we tested the
synergistic effect of anti-huCD47 mAb combined with antimsCD40 mAb, another immuno-modulatory antibody that
increases the recruitment of macrophages to the tumor site,
on DIPG xenografts with cranio-spinal dissemination.
Design/Methods: Human-derived DIPG cells were infected
with GFP-luciferase expressing virus and injected to the
pons of NOD scid gamma mice. The engraftment was
verified via bioluminescent (BLI) imaging. The mice
with positive signal in forebrain and spine were randomized for treatment with anti-huCD47 mAb alone, antimsCD40 Ab alone, anti-huCD47 mAb coupled with antimsCD40 mAb, and control. The efficacy of treatment
was measured using follow-up BLI imaging and survival
analysis.
Results: Follow-up BLI imaging revealed significant decline
in the flux measures of mice receiving combined treatment
(P< 0.05). BLI signals from the spinal and forebrain strongly
diminished in the mice under combined treatment compared
to the other groups. A significant extension in survival was
seen in this group compared to the other three groups (P <
0.05).
Conclusions: combinatorial treatment with anti-CD47 Ab
and anti-CD40 Ab is effective in the removal of not only DIPG
from a primary site but also a cranio-spinal dissemination of
the disease.
PD-042 Patient Derived Cell Lines to Study
Alternative Lengthening of Telomeres (ALT) in
Pediatric Brain Tumors
H. Ijaz1 , R.L. Dilley2 , M.H. Williams3 , M.P. Koptyra3 , J.L.
Mason3 , A.C. Resnick3 , Y. Zhu3 , B. Zhang3 , A.J. Waanders1 , R.A.
Greenberg2 , P. Raman3 , K.A. Cole1
1 The
Children's Hospital of Philadelphia, Division of Oncology,
Philadelphia, USA; 2 University of Pennsylvania, Perelman School of
Medicine, Philadelphia, USA; 3 The Children's Hospital of Philadelphia,
Center for Data Driven Discovery in Biomedicine, Philadelphia, USA
SIOP ABSTRACTS
Background/Objectives: All cancers acquire a mechanism
of telomere maintenance (TMM) for unlimited replicative
potential. Some cancers, including a subset of pediatric brain
tumors, use the TMM of alternative lengthening of telomeres
(ALT). However, there are few cancer cell lines with ALT,
representing a mixture of histotypes. We aim to generate and
characterize patient derived pediatric brain tumor cell lines
with and without ALT.
Design/Methods: The Children's Brain Tumor Tissue Consortium (CBTTC) database was queried for pediatric and adolescent brain tumor types likely to have ALT, and tumor in
freezing media. Patient derived cell lines were generated as
adherent and suspension lines. Corresponding primary tumor
samples were analyzed for ALT by c-circle assay (CCA) and
genomic analysis for a targeted set of genes.
Results: The CBTTC biorepository had 37 primary highgrade glioma and PNET samples available for processing
into patient derived cell lines, including 2 diagnosis-relapse
pairs. To date, 22/37 are growing well in various stages
of development and validation. Analysis of the cell line's
corresponding primary tumors revealed that 9/35 (25%) are
ALT positive. H3F3A sequencing showed that 3/3 (100%)
of G34R mutant, 2/8 (25%) of K27M mutant and 4/24
(17%) of H3F3A wild-type tumors are ALT positive. As
expected, ALT positive tumors are more likely to occur in
older patients (16 vs 10 years old, p= 0.018) and to be hemispheric (6/9, 67%). WGS was available for 19 tumors, including 4 with ALT. The ALT positive tumors have damaging
mutations in TP53 (4/4), ATRX (2/4), H3F3A (2/4) and IDH1
(1/4).
Conclusions: The CBTTC makes it possible to generate
patient derived cell lines from a well-characterized set of
pediatric primary brain tumors for collaborative science. The
panel is representative of reported characteristics of ALT positive pediatric brain tumors with respect to associated mutations, frequency and location.
S133 of S518
Design/Methods: Retrospective chart review of children
treated with either a BRAF (dabrafenib) or MEK inhibitor
(trametinib). Basic demographic and clinical characteristics
were collected from patient records and the skin findings
assessed in collaborations with a paediatric dermatologist.
Results: Twenty-four children aged 1-16 years (mean 8.4
years) treated with either a BRAF (11) or MEK inhibitor (13)
for BRAF-V600-mutant refractory or relapsed intracranial
malignancy (8), neurofibromatosis type 1 (NF1)-associated
optic glioma and neurofibroma (7), Langerhan cell histiocytosis (LCH) (3), or leptomeningeal melanocytosis/melanoma
(3) were identified. One patient received combination
BRAF/MEK inhibitor therapy. Mean treatment duration was
39 weeks (7-92) for BRAF and 19 weeks (7-37) for MEK
inhibitor therapy.
Six (54%) children treated with dabrafenib developed new
melanocytic naevi (7-36 weeks), 5 of these also developed a
persistent erythema nodsum-like (EN) eruption (onset 1-32
weeks) 2 diffuse alopecia, (onset 29 and 40 weeks) and single
cases keratosis pilaris, an acneiform facial rash.
Six (46%) children on a MEK inhibitor developed paronychia (onset 4-20 weeks), 5 of these also developing hair thinning (onset 4-17 weeks) and generalised xerosis (onset 2-8
weeks). Four patients (30%) developed acneiform eruptions. 1
child required dose reduction of therapy due to cutaneous side
effects. Two patients discontinued treatment and one patient
died because of disease progression.
Conclusions: Cutaneous adverse effects of BRAF an MEK
inhibitor therapy are common and well tolerated in paediatric
patients. Our experience is that prophylactic management is
beneficial.
PD-044 Quality of Life, Growth, and
Hypothalamic Lesions in Childhood-Onset
Craniopharyngioma
H.L. Müller1 , K. Tjaden1 , S. Boekhoff1 , A. Hoffmann1 , M.
Warmuth-Metz2 , M. Eveslage3 , G. Calaminus4
1 Klinikum
PD-043 Cutaneous Toxicities of BRAF and MEK
Inhibitors in Children
T. Loka1 , P. O'Hare1 , C. Mahon2 , D. Hargrave1
1 Great
Ormond Street Hospital, Haematology & Oncology Clinical Trials
Unit, London, United Kingdom; 2 Great Ormond Street Hospital,
Dermatology, London, United Kingdom
Background/Objectives: BRAF and MEK inhibitors are
emerging therapies in childhood malignancy. The cutaneous
side effects are well described in adult patients, but not in children. We undertook to document the spectrum of cutaneous
side effects seen in children treated with these agents at our
tertiary hospital, as well as the onset, duration and severity of
the skin findings.
Oldenburg AöR- Medical Campus University Oldenburg,
Department of Pediatrics and Pediatric Hematology / Oncology,
Oldenburg, Germany; 2 University of Würzburg, Department of
Neuroradiology, Würzburg, Germany; 3 University of Münster, Institute of
Biostatistics and Clinical Research, Münster, Germany; 4 University of
Bonn, Department of Pediatric Oncology and Hematology, Bonn, Germany
Background/Objectives: Quality of life (QoL) after
childhood-onset craniopharyngioma (CP) is frequently
impaired by tumour and/or treatment-related factors such as
endocrine deficits and hypothalamic involvement (HI).
Design/Methods: We prospectively analyzed parental and
self-assessment of CP patient QoL at 3 mo, 1 and 3 yrs after
CP diagnosis related to growth hormone (GH) substitution
and HI. Forty-seven of 194 CP patients recruited 2007-2015
fulfilled the inclusion criteria: 1.) histological CP diagnosis,
SIOP ABSTRACTS
S134 of S518
2.) age at diagnosis 6-18 yrs; 3.) availability of QoL data one
and three yrs after diagnosis. QoL was assessed using the
Pediatric Quality of Life (PEDQOL) questionnaire.
Results: Parents estimated QoL of their children worse than
patients did themselves for the PEDQOL domains emotional
stability, body image, physical function, and social function / friends and family. HI was associated with lower selfassessed QoL 3 mo after diagnosis (body image, p<0.01;
social function/friends, p<0.01). The negative impact of HI
on QoL was greater for parental assessed QoL at all time
points. GH substitution had no relevant effect on short-term
weight and height development. CP patients, GH-treated
at 3 yrs follow-up, presented at baseline (1 yr after diagnosis, before GH substitution) with reduced self-assessed
QoL for the PEDQOL domains autonomy (p<0.05), cognition (p<0.01), physical function (p<0.05), and social function/friends (p<0.01), when compared with GH non-treated
CP patients. QoL stabilized during 1-3 yrs of follow-up in GH
treated patients, whereas non GH-treated patients experienced
decreases in QoL for the PEDQOL domains physical function
and social function/friends.
Conclusions: Parents assess QoL in CP survivors worse than
their children. As HI is a major risk factor for reduced QoL,
treatment strategies in CP should aim at prevention of (further) hypothalamic damage. GH substitution should be considered as an effective option to ameliorate imminent impairments of QoL after CP.
PD-045 Prognostic Factors in Relapsed
Medulloblastomas Treated with a Multimodal
Therapy: A Report of the HIT’2000, HIT-REZ-97
and HIT-REZ-2005 Studies
S. Tippelt1 , J. Buchholz2 , R. Mikasch1 , N. Siegler1 , M.
Warmuth-Metz3 , S. Rutkowski4 , M. Mynarek4 , B.O. Juhnke4 , K.
von Hoff4 , T. Pietsch5 , S. Pfister6 , O. Witt6 , R.D. Kortmann7 , R.
Kwiecien8 , R. Faldum8 , U. Bode9 , G. Fleischhack1
1 University
Hospital Essen, Pediatric Oncology and Hematology, Essen,
Germany; 2 Lukas Hospital Neuss, Children's Hospital, Neuss, Germany;
3 University of Würzburg, Neuroradiology, Würzburg, Germany; 4 University
Medical Center Hamburg-Eppendorf, Pediatric Hematology and Oncology,
Hamburg, Germany; 5 University of Bonn, Institute of Neuropathology,
Bonn, Germany; 6 University of Heidelberg, Pediatric Hematology and
Oncology, Heidelberg, Germany; 7 University of Leipzig, Radiooncology,
Leipzig, Germany; 8 University of Münster, Institute of Biostatistics and
Clinical Research, Münster, Germany; 9 University of Bonn, Pediatric
Hematology and Oncology, Bonn, Germany
Background/Objectives: Despite a multimodal relapse therapy the prognosis of patients with a recurrent medulloblastoma (MB) is poor. The aim of this analysis was to evaluate prognostic factors for progression-free survival (PFS) and
overall survival (OS) of patients with a 1st recurrence of MB
enrolled in the German HIT’2000, HIT-REZ-97 and HITREZ-2005 studies.
Design/Methods: Patients with a recurrent MB between July
1997 and August 2011 were included in this analysis. Data
analyzed at relapse were age, gender, histological subgroup,
metastases stage, relapse therapy, disease state at last follow
up. Kaplan-Meier analysis was used to estimate the PFS/OS
after 1st recurrence. Possible prognostic factors for PFS/OS
were investigated by performing univariate and multivariate
analyses.
Results: This analysis included 229 patients [71 female/158
male, median age at 1st recurrence 11.1 years (0.8–36.1),
median PFS after primary diagnosis 2.0±0.1 years] suffering from a local or metastatic relapse (13.9%/86.1%). At first
recurrence 90.4% of patients received chemotherapy (intravenously 56.3 %, orally 28.8%, intrathecally 45.4%, high-dose
23.6%), 28.4% of patients underwent total to partial tumor
resection, 31.4% of patients received radiotherapy. Median
PFS after 1st recurrence was 1.0±0.1 years (0.1-25.4), the
median OS 1.8±0.2 years (0.1-26.2). The 2-, 5- and 10-yearPFS and -OS rates were 25.9%, 7.8%, 4.4% and 46.6%, 17.7%,
6.7%, respectively. In the multivariate analyses the metastatic
relapse [Hazard ratio (HR) for PFS (1.9); OS (2.1)], the nonapplication of radiotherapy (HR 2.0;1.9), and the application
of only an oral chemotherapy (HR 1.7;1.8) turned out to be
poor prognostic parameters.
Conclusions: Multimodal therapy led to long-term OS in a
few patients with recurrent MB. Local recurrent disease, reresection, re-irradiation and systemic intravenous chemotherapy were associated with a prolonged PFS/OS. Future studies
will identify the prognostic relevance of molecular subgroups
and of new targeted or antiangiogenic therapies, therefore rebiopsy is highly recommended.
Supported by German Children's Cancer Foundation
PD-046 Pseudoprogression After Irradiation in
Pediatric Low Grade Glioma
D.S. Tsang1 , E.S. Murphy2 , J.T. Lucas Jr.1 , P. Lagiou3,4 , T.E.
Merchant1
1 St
Jude Children's Research Hospital, Department of Radiation Oncology,
Memphis, USA; 2 Cleveland Clinic, Department of Radiation Oncology,
Cleveland, USA; 3 Harvard T.H. Chan School of Public Health, Department
of Epidemiology, Boston, USA; 4 School of Medicine- University of Athens
NKUA, Department of Hygeine- Epidemiology and Medical Statistics,
Athens, Greece
Background/Objectives: The goal of this study was to characterize the incidence of pseudoprogression after radiation
therapy (RT) for pediatric low-grade glioma (LGG).
Design/Methods: Patients age ≤21 with intracranial pediatric
LGG (WHO grade I-II) treated with curative-intent RT at a
single institution were included in this retrospective review.
Pseudoprogression was defined for this investigation as an
increase in tumour size ≥10% in ≥2 dimensions between
two MR imaging studies, or serial growth <10% in two
SIOP ABSTRACTS
dimensions over three studies, while accounting for competing risks of true progression or death. Event-free survival
(EFS) was defined as survival without true progression or secondary high-grade glioma.
Results: Sixty-two of 221 patients (28%) developed pseudoprogression, with a 9-year cumulative incidence of 29.0%
(95% CI 23.0-35.2). Median time to pseudoprogression was
6.1 months after RT (interquartile range [IQR] 3.5-14.6, range
0.9-105). Symptomatic pseudoprogression was managed with
subtotal resection, shunt/Ommaya, and corticosteroids in
11 (18%), 7 (11%), and 2 patients (3%), respectively. The
median time to pseudoprogression-related procedure was 3.4
months after RT (IQR 1.8-6.1). The remaining asymptomatic
patients (68%) were observed; 30 (48%) had shrinkage and
11 (18%) stabilized. Median duration of pseudoprogression
was 6.2 months (IQR 3.2-11.7) among asymptomatic patients.
Patients with pilocytic astrocytoma (PA) had increased odds
of developing pseudoprogression relative to other histology
(odds ratio 5.7, 95% CI 2.7-12.0, p < 0.0001). Among patients
with PA (n = 127), the 9-year cumulative incidence of pseudoprogression was 42.9% (95% CI 33.8-51.7) and in this
group, pseudoprogression was associated with improved 10year EFS (84.5% vs. 58.5%, log-rank p = 0.008) and overall
survival (98.0% vs. 91.2%, log-rank p = 0.030).
Conclusions: Pseudoprogression after irradiation is common,
especially in patients with pilocytic astrocytoma, and appears
to be prognostic for survival. Knowledge of the incidence and
temporal course of pseudoprogression may help avoid unnecessary salvage treatment.
T R E AT M E N T A N D CA R E - N E W
DRUGS/EXPER I ME N TA L
THERAPEUTICS
PD-047 Development of a Small Molecule
Inhibitor for SAMHD1 to Improve Outcome for
Patients with Acute Myelogenous Leukaemia and
Relapsed T-Lymphoblastic Malignancies Treated
with Nucleoside Analogues
N. Herold1 , S. Rudd2 , I. Hed Myrberg1 , K. Sanjiv2 , L. Ljungblad1 ,
J. Kutzner3 , D. Grandér4 , P. Kogner1 , G. Rassidakis4 , T. Helleday2 ,
J.I. Henter1 , T. Schaller3
S135 of S518
cytarabine (ara-C) together with anthracyclines constitutes
the backbone of AML-directed therapy. Treatment failure is
frequently caused by resistance to ara-C, more specifically, by
the lack of intracellular accumulation of the triphosphorylated
active metabolite ara-CTP in leukemic blasts.
Nelarabine, a pro-drug of ara-G, has sparked hope to
improve the dismal survival for children with relapsed Tlymphoblastic leukaemia or lymphoma, but remission rates
are only about 30% Just like ara-C effects are mediated by araCTP, nelarabine toxicity relies on its intracellular conversion
to ara-GTP.
We have previously shown that SAMHD1 hydrolyses ara-CTP
and ara-GTP and confers resistance to ara-C both in leukaemia
mouse models. Retrospective analyses of 300 AML patients
suggested a therapy-limiting effect of SAMHD1.
Design/Methods: Using a cell-based phenotypic cell proliferation inhibition assay, we screened approximately 35,000
small molecule compounds to identify lead substances
that synergise with ara-C in wildtype SAMHD1, but not
CRISPR/Cas9 SAMHD1-knockout cells. SAMHD1 inhibition was confirmed using an in vitro activity assay with
recombinant SAMHD1. Target engagement was assessed by
cellular-thermal shift assays (CETSA) and X-ray crystallography.
Results: We identified lower nanomolar small molecule
inhibitors of SAMHD1 that sensitised wildtype SAMHD1
leukemic cells more than 100-fold to ara-C and nelarabine, i.e.
completely abolished SAMHD1-mediated resistance while
leaving SAMHD1-knockout cells unaffected. These results
could be recapitulated in vivo using paediatric AML mouse
models.
Conclusions: We suggest that SAMHD1 might play a dual
role for future leukaemia therapies: 1) a biomarker to guide
dose adjustments with the aim to reduce toxicity for low
expressers. 2) a target for drug candidates amenable for clinical trials based on our pre-clinical SAMHD1 inhibitors to
improve efficacy of ara-C and nelarabine treatments for high
expressers of SAMHD1.
PD-048 Reporting of Clinical Significance in
Pediatric Oncology Randomized Control Trials: A
Systematic Review
1 Karolinska
F. Howard1 , K. Goddard2 , O. Samargandi3 , H. Hasan2
2 Karolinska
1 University
Institutet, Women's and Children's Health, Stockholm, Sweden;
Institutet, MBB, Stockholm, Sweden; 3 Heidelberg University
Hospital, Department for Infectious Diseases, Heidelberg, Germany;
4 Karolinska Institutet, Onk-Pat, Stockholm, Sweden
Background/Objectives: Acute myelogenous leukaemia
(AML) accounts for approximately 5% of all childhood cancers, and despite highly toxic multidrug regimens more than
30% of patients cannot be cured. The deoxycytosine analogue
of British Columbia, School of Nursing, Vancouver, Canada;
Columbia Cancer Agency, Radiation Oncology, Vancouver,
Canada; 3 QEII Health Sciences Centre, Division of Plastic Surgery,
Halifax, Canada
2 British
Background/Objectives: Traditionally, the interpretation of
randomized control trials (RCTs) have relied on statistical
significance as opposed to clinical significance, including
S136 of S518
the use of minimally clinically important difference (MCID),
which raises questions about study design rigor and utility
of results. The degree to which clinical significance has been
applied and reported in RCTs in pediatric cancer has not been
determined.
The objective of this review was to systematically assess the
reporting of clinical significance based on the delta value
reported in the sample size calculation and to identify factors
associated with clinical significance in RCTs in the pediatric
oncology literature.
Design/Methods: This systematic review involved a comprehensive search of MEDLINE, EMBASE and the Cochrane
Childhood Cancer Group Specialized Register through CENTRAL from inception to July 2016. Eligible studies included
RCTs of primary cancer treatments in pediatric patients diagnosed with cancer.
Results: RCTs (101), representing 126 randomized questions were included. The minority (19.8%) of randomized
questions reported conclusions based on clinical significance. Only 6.3% of randomized questions explicitly identified that the delta value in the sample size calculation was
based on the MCID. The statistical significance of the primary outcome was based on a p-value in 77.8% of randomized questions, while over half (63.5%) reported confidence intervals or standard error bars for the point estimate
in question. The median publishing journal impact factor and
planned sample size were larger for randomized questions
that reported clinical significance as opposed to those that did
not.
Conclusions: A minority RCTs in the published pediatric
oncology literature have reported methodological attributes
related to clinical significance and have drawn study conclusions based on clinical significance. The integration
of clinical significance into study design and subsequent
reporting in future pediatric oncology trials will enhance
evidence-based decision making in clinical practice and
policy.
PD-049 Comparing Arsenic Trioxide and Indigo
Naturalis Formula in Pediatric Patients with Acute
Promyeloid Leukemia: An Interim Report of
Muticenter and Randomized Clinical Trial
SCCLG-APL
SIOP ABSTRACTS
Children's Hospital, pediatrics, Shenzhen, China; 8 The Third Affiliated
Hospital of Zhongshan University, pediatrics, Guangzhou, China; 9 The first
people's Hospital of Huizhou, pediatrics, Huizhou, China; 10 Nanfang
Hospital of Southern Medical University, pediatrics, Guangzhou, China;
11 Huizhou Central Hospital, pediatrics, Huizhou, China
Background/Objectives: Indigo naturalis formula (RIF) is
a traditional Chinese medicine with tetraarsenic tetrasulfide, indirubin and tanshinone IIA as major active ingredients. RIF can be taken orally, which reduces hospital days. Event-free survival (EFS) is about 90% in adult
patients with acute promyelocytic leukemia (APL) treated
on protocol containing RIF, all-trans retinoic acid (ATRA)
and chemotherapeutic agents (RIF+ATRA+chemotherapy),
which is comparable to that of patients on arsenic trioxide (ATO)+ATRA+chemotherapy. However, the efficacy and
safety of RIF in pediatric counterpart have not been evaluated,
and it is unclear whether RIF can replace ATO.
Design/Methods: SCCG (South China Children Leukemia
Group)-APL protocol was started in august 2011. Patients
of age 0-16 were enrolled except those having intracranial hemorrhage / central nervous system leukemia with
coma, convulsion or nervous paralysis at diagnosis.
Patients were randomized into ATO or RIF group and
received
“ATO/RIF+ATRA+low-dose
anthracycline”
for induction and consolidation therapy followed by
“ATO/RIF+ATRA+MTX+6MP” for 96 weeks of maintenance therapy. Those with high-risk APL (WBC ≥ 109 /L at
diagnosis) received additional Ara-C in consolidation phase.
Results: Among 84 patients diagnosed, 78 met the enrollment
criteria and were willing to be randomized. Headache and
vomit/nausea were the commonest treatment-related adverse
effects occurring in 18% and 12% of patients in each group
during induction and consolidation therapy respectively. Significant treatment-related infections including sepsis, pneumonia, cellulitis and etc. were observed in 13% and 8% of
patients during induction, and 12% and 8% of patients during
consolidation, in ATO and RIF groups, respectively (P>0.05).
There were two drop-out cases in ATO group, one abounded
treatment and the other deviated from the protocol because of
adverse effect. The 4-year EFSs (median follow-up of 2 years)
of both groups were 100%.
Conclusions: SCCG-APL protocol containing arsenic (either
ATO or RIF), ATRA and low-intensive chemotherapy
obtained a good outcome in childhood APL (including highrisk).
X.Q. Luo1 , L.Z. Cao2 , W.Q. Wan3 , Y.D. Lin4 , J.P. Fang5 , L.H.
Yang6 , C.G. Li7 , H.Q. Chen8 , G.H. Chen9 , X.Q. Feng10 , R.Y. Liu11
1 The
First Affiliated Hospital of Sun Yat-sen University, Pediatrics,
Guangzhou, China; 2 XiangYa Hospital Central South University,
pediatrics, Changsha, China; 3 The Second XiangYa Hospital Central South
University, pediatrics, Changsha, China; 4 Guangdong General Hospital,
pediatrics, Guangzhou, China; 5 The Second Affiliated Hospital of Sun
Yat-Sen University, pediatrics, Guangzhou, China; 6 Zhujiang Hospital of
Southern Medical University, pediatrics, guangzhou, China; 7 Shenzhen
PD-050 Development of GD2 and CD3 Targeted
Bispecific T-Cell Engaging Antibodies for
Neuroblastoma
A. Patel1 , C. Thevanesan1 , J. Anderson1 , M. Pule2 , K. Straathof1
SIOP ABSTRACTS
S137 of S518
1 UCL
Great Ormond Street Institute of Child Health, Developmental
Biology and Cancer Program- Cancer Section, London, United Kingdom;
2 UCL Cancer Institute, Haematology, London, United Kingdom
1 Children's
Background/Objectives: New treatment strategies for highrisk neuroblastoma are needed to improve outcome and
reduce treatment-related late effects. Using bi-specific T-cell
engagers (BiTEs) to redirect the patient's own T-cells to recognize and eliminate neuroblastoma tumour cells proves an
attractive novel treatment option. Indeed, CD19/CD3 BiTE
Blinatumumab has shown great promise in treatment of highrisk leukemia. Here, we describe the selection of the optimal
GD2/CD3 BiTE format for use in treatment of neuroblastoma.
Background/Objectives: Relapse of hematologic malignancies after hematopoietic cell transplantation (HCT) confers
high mortality because of progressive disease and graft-vs.host disease (GVHD). Hence, we hypothesized that tumorassociated antigen-specific lymphocytes (TAA-L) would be
specific, diminish immune escape, and could safely decrease
cancer burden.
Design/Methods: Fourteen BiTE variants were constructed
using single chain variable fragments (scFv) derived from
three different humanized CD3-specific antibodies and two
different humanized GD2-specific antibodies fused with three
different size linkers. First, BiTEs were characterised by measuring thermal stability profiles using differential scanning
fluorimetry, and antigen specificity and binding affinity to
antigen-positive and negative tumour cell lines using flow
cytometry and Scatchard analysis. Then, functional comparisons were performed by determining antigen-specific tumour
cell lysis at a range of BiTE concentrations.
Results: All BiTE formats tested demonstrated specificity for
GD2 and CD3. BiTEs based on the GD2-specific scFv with
the highest binding affinity had the lowest IC50 values i.e.
concentration that achieved half maximal cytolytic activity
of GD2-positive cells. In contrast, differences in CD3 binding affinities for scFv tested did not translate into significant
differences in ability to redirect T-cells to GD2-positive cell
lysis. BiTEs with medium and long linkers mediated T-cell
lysis of GD2-positive cells at lower concentrations than BiTEs
with shorter linkers.
Conclusions: This study demonstrates that binding affinity
of tumour-specific scFv as well as linker length determine
the potency of GD2/CD3 BiTEs. For selected BiTE formats
detailed studies of anti-tumour response including T-cell proliferation and cytokine secretion profile are currently ongoing. This data set will inform the selection of the optimal
GD2/CD3 BiTE format which will be taken forward for development into a novel clinical therapeutic for neuroblastoma.
PD-051 Complete Remissions Post Infusion of
Multiple Tumor Antigen Specific T Cells for the
Treatment of High Risk Leukemia and Lymphoma
Patients After HCT
K. Williams1 , M. Grant1 , M. Ismail1 , F. Hoq1 , M. Martin Manso1 ,
J. Hoover1 , E. Mintz1 , A. Namata1 , E. Williams1 , C. Barese1 , S.
Albihani1 , R. Cruz1 , H. Lang1 , P. Hanley1 , J. Barrett2 , S.
Gottchalk3 , S. McCurdy4 , R. Jones4 , C. Bollard1
National Medical Center, CETI, Washington DC, USA; 2 NIH,
NHLBI, Bethesda, USA; 3 Texas Children's Hospital, BMT, Houston, USA;
4 Johns Hopkins School of Medicine, BMT, Baltimore, USA
Design/Methods: We expanded lymphocytes reactive to
TAA: WT1, PRAME, Survivin, which are over-expressed and
immunogenic in hematologic malignancies. On a prospective study: NCT002203902, eligible patients received TAA-L
infusions at sequential dose levels: 0.5 to 4.0e7/m2 per dose.
Results: Twenty-five donor-derived TAA-L products were
generated and lacked alloreactivity in vitro. TAA-L products contained T cells were predominantly effector memory,
with >30% expressing the activation markers, and <15% of
T-cells expressing exhaustion markers (PD1, TIM3, LAG3).
Specificity of TAA-L showed greatest response to PRAME
by ELIspot. Ten HCT recipients (aged 9-70 years) with
relapsed Hodgkins disease (n=2), B-ALL (n=3), or AML
(n=5) received 1-3 doses of TAA-L. All patients had relapsed
2-12 months after HCT (9 allo, 1 auto). Post infusion, there
were no adverse events attributed to TAA-L and no GVHD.
One patient withdrew prior to study completion due to progressive disease in the setting of steroids for sepsis. Responses
of evaluable patients (n=9) were: PD (n=2), PR (n=3),
CR (n=4). Of the CR patients: 3 had AML (1 received
adjunct vidaza after TAA-L); 1 patient had Ph+-ALL and
achieved bcr-abl negativity post TAA-L for the first time
post-HSCT without additional therapy. Immunosequencing
of T-cell receptors detected multiple TCRs derived from the
infused TAA-L product 4-5 weeks after infusion.
Conclusions: This unique immunotherapeutic has been well
tolerated without causing GVHD or life-threatening cytokine
release syndrome. Despite aggressive and multiply relapsed
disease, 7/9 evaluable patients have demonstrated evidence of
disease control after TAA-L, with 44% complete response,
suggesting that TAA-L may have efficacy in relapsed highrisk hematological malignancies after HCT.
PD-052 Mechanisms of Efficacy of the
PAN-FGFR Inhibitor AZD4547 in Pediatric Solid
Tumor Models
P. Zage1 , S. Hakim1 , D. Subramonian1 , J. Lesperance1
1 University
of California - San Diego - Moores Cancer Center, Pediatrics,
San Diego, USA
SIOP ABSTRACTS
S138 of S518
Background/Objectives: Children with aggressive pediatric solid tumors such as neuroblastoma, rhabdomyosaroma,
and Ewing sarcoma have poor outcomes, and new therapies are needed. Aberrant expression and activity of
growth factor receptors, including the Fibroblast Growth
Factor Receptor (FGFR) family, are associated with many
malignancies. Therefore, we hypothesized that inhibition
of FGFR family members using the novel pan-FGFR
inhibitor AZD4547 would be effective against pediatric solid
tumors.
Design/Methods: We evaluated the effects of AZD4547
on the viability of neuroblastoma, rhabdomyosarcoma, and
Ewing sarcoma cells using continuous live cell imaging to
measure cell confluence and caspase activity. We also evaluated the effects of AZD4547 on cell migration and invasion
using scratch wound and matrigel chamber invasion assays
and the effects of AZD4547 on intracellular signaling with
western blotting and QT-PCR.
Results: AZD4547 treatment of pediatric solid tumor cells
resulted in decreased cell confluence, with calculated IC50
values varying from 3.7mM to more than 20mM, and in the
induction of apoptosis. AZD4547 treatment at sublethal concentrations inhibited migration and invasion in vitro in all
tested cell lines compared to untreated cells. AZD4547 treatment also resulted in decreased phosphorylation of Akt and
S6 in all tested cell lines. Sensitive cell lines demonstrated
increased levels of phospho-ERK and complete inhibition
of ERK phosphorylation after treatment, while resistant cell
lines demonstrated minimal inhibition of ERK phosphorylation. Sensitive cell lines further demonstrated increased levels of phospho-STAT3 while resistant cell lines demonstrated
decreased or unchanged levels of phospho-STAT3, suggesting
potential markers for AZD4547 response and mechanisms of
resistance.
Conclusions: AZD4547 is effective against pediatric solid
tumors including neuroblastoma, rhabdomyosarcoma, and
Ewing sarcoma, and sensitivity to AZD4547 appears to be
mediated by effects on the Ras/MAPK and JAK/STAT pathways. AZD4547 therefore represents a potential novel therapeutic agent for pediatric solid tumors, and further preclinical
and clinical studies are warranted.
T R E AT M E N T A N D CA R E SUPPORT IVE CA R E
PD-053 Reducing Infection Related Morbidity
and Mortality by Improving Time to Antibiotic
Administration: A Quality Improvement Project in
a Resource Limited Pediatric Oncology Unit
M.C. dolendo1 , D. Aguilar1 , E. Bacus1 , C. Lam2 , M.E. Concha3
1 Southern
Philippines Medical Center, Pediatrics, Davao City, Philippines;
Jude Children's Research Hospital, Global Pediatric Oncology
Department, Memphis, USA; 3 Southern Philippines Medical Center, Family
Medicine, Davao City, Philippines
2 St
Background/Objectives: Childhood cancer is an important
health concern in the Philippines with an estimated 6,800 new
cases annually. Although survival rates have improved, infection related morbidity and mortality continue to be a threat.
Timely recognition of infection and immediate administration of antibiotics have been shown to improve survival. This
project aims to improve time to antibiotic administration for
children with cancer and concomitant infection at our institution through feedback to the different stakeholders about their
performance.
Design/Methods: A quality improvement cycle was implemented at the Southern Philippines Medical Center Pediatric Oncology Unit in Mindanao. Charts of admitted patients
meeting the inclusion criteria were reviewed in terms of
demographics, clinical profile, timeliness of antibiotic administration and outcomes for a 3-month period as baseline data
on performance. A group feedback was then given after which
repeat data collection was done for three months.
Results: A total of 103 charts were reviewed at the beginning
of the quality improvement cycle and 79 charts were reviewed
after group feedback was given. Antibiotic initiation was
delayed at baseline in 80.27% of cases while this decreased
to 44.08% on repeat measurement (p value < 0.001). There
were 24.72% of patients who died at baseline data collection
while 11.39% died on repeat measurement (p value 0.023).
Length of hospital stay at baseline and repeat measurement
was similar at around 17-18 days.
Conclusions: Group feedback significantly reduced delays in
antibiotic administration. There were also lesser number of
unimproved or expired patients probably due to reduction in
delays. Continuous quality improvement initiatives and need
for multifaceted interventions are necessary to improve and
sustain improvements in improving time to antibiotic administration for children with cancer in order to improve outcomes
and reduce morbidity and mortality.
PD-054 Olanzapine is an Inexpensive and
Efficacious Agent for Breakthrough Chemotherapy
Induced Acute Phase Vomiting Among Children
Receiving Moderate or High Emetogenic
Chemotherapy
G. Kapoor1 , S. Koneru1 , S. Jain1
1 Rajiv
Gandhi Cancer Institute and Research Centre, Pediatric Hematology
& Oncology, Delhi, India
SIOP ABSTRACTS
S139 of S518
Background/Objectives: Chemotherapy induced vomiting
remains one of the most distressing adverse effects of cancer therapy and negatively impacts compliance and nutrition.
Antiemetic data related to Olanzepine, an approved antipsychotic drug is mainly restricted to adult and few retrospective
pediatric studies. Its low cost, easy availability and oral preparation make it ideal for use in resource-restricted settings.
The objectives of this study were to study the efficacy of olanzapine for breakthrough vomiting and assess its safety among
children 2-18 years of age receiving moderate or high emetogenic chemotherapy (MEC, HEC, respectively per POGO
guidelines).
Design/Methods: This observational study was done over
6 months from July-December 2016, after obtaining ethical
approval. Acute breakthrough emesis was defined as vomiting occurring within 24hours of last dose of chemotherapy, despite adequate prophylaxis that included 5-HT3 receptor antagonist, dexamethasone and aprepitant (triple-drug for
HEC). The dose of olanzapine was 0.05-0.1 mg/kg per oral
once a day for 3 consecutive days. Patients on prior antiemetics or antipsychotics or with medical or surgical disorders
likely to contribute to vomiting were excluded. Complete and
partial responses were defined as no or 1-2 emetic episode/s
respectively and use of no other rescue medications. Adverse
events were graded as per CTCAE version 4.03.
Results: This study analyses 42 chemotherapy blocks
among 31 children (median age 9 years, male 21/31)
with various hematological and solid malignancies receiving
MEC(18/42) or HEC(24/42). Complete and partial responses
were observed among 83%(35) and 14%(6) blocks respectively, much better than reports with metoclopramide. No statistical difference in efficacy was observed by age, gender
or emetogenic regimen (p 0.2). Side-effects included somnolence (grade 1-2, 11/42), orthostatic collapse(grade 3, 1/42)
and transaminitis(grade 1, 1/42).
Conclusions: Excellent efficacy and safety of an inexpensive agent like olanzapine make it a suitable option for breakthrough emesis for children in developing countries warranting large controlled prospective studies.
PD-055 Age, Sarcoma and Use of Tunneled Lines
are Independently Associated with Requirement of
Tissue Plaminogen Activator for Episodes of
Central Venous Catheter Dysfunction
1
1
1
1
J. MacLean , T. MacDonald , C. Digout , R. Krista , K. Kulkarni
1
1 IWK
Health Center, Pediatric Hematology Oncology- Department of
Pediatrics, Halifax, Canada
Background/Objectives: Dysfunction (defined as inability to
flush and/or draw blood) is a common complication associated with central venous catheters (CVC). Tissue plasmino-
gen activator (tPA) is often instilled to reverse episodes of
CVC dysfunction. However, data on risk-factors associated
with requirement of tPA are unclear. We hypothesized that
clinic-demographic and CVC related variables are associated
with requirement of use of tPA for episodes of CVC dysfunction in pediatric oncology patients.
Design/Methods: In this population based study, case records
of all pediatric oncology patients from Maritimes, Canada
managed by the Izaac Walton Killam Health Centre from January 2,000 to December 2,015 were reviewed after ethics
approval. Clinico-demographic data and characteristics of
first CVC were pooled from: (i) Pediatric Oncology hospital database, (ii) Electronic medical records, (iii) Pharmacy
database and (iv) Central line database. Patients with ≥1
episodes of CVC dysfunction of their first CVC requiring ≥1
dose of tPA were identified. Analysis was done using SPSS
version 24.
Results: At least 1 CVCs was required in 741 patients.
One or more doses of tPA (mean: 2.04±2.0) were required
by 20.1% (n=149) of the patients for episodes dysfunction
related to first CVC. On univariate analysis, age>10 years
(p=0.015), diagnosis (classified as leukemia, lymphoma, sarcoma, brain tumor and others) (p=0.001), and use of tunneled
lines (p=0.006) were significantly associated with use of tPA
while gender (p=0.098) was not. On multivariate analysis,
age>10 years [p=0.016, OR: 1.6 (95% (confidence interval)
(CI): 1.1-2.3)], diagnosis of sarcoma [p=0.001, OR: 3.2 (95%
CI:2-5.3)] and use of tunneled lines [p=0.002, OR: 2.4 (95%
CI:1.4-4.1)] were independently associated with a requirement for tPA.
Conclusions: The present study identified independent risk
factors ascertained at diagnosis associated for use of tPA for
episodes of dysfunction associated with first CVC. After validation, a predictive risk model ascertained at diagnosis could
be developed to identify high risk patients.
PD-056 Effects of Combined Resistance and
Endurance Training in Pediatric Cancer Patients
during Intensive Treatment Phase: Design and First
Insights into the MUCKI-Study
S. Stössel1 , M.A. Neu1 , A. Wingerter1 , F.T. Baumann2 , P. Zimmer3 ,
C. Paret1 , K. El Malki1 , H. Otto1 , T. Abu Tair4 , N. Henniger1 , W.
Bloch3 , J. Faber1
1 University
Medical Center, Center for Pediatric and Adolescent MedicineDepartment of Pediatric Hematology/Oncology/Hemostaseology, Mainz,
Germany; 2 University Hospital of Cologne, Department I of Internal
Medicine- Center of Integrated Oncology Köln Bonn, Köln, Germany;
3 German Sport University Cologne, Institute of Cardiovascular Research
and Sports Medicine- Department of Molecular and Cellular Sport
Medicine, Köln, Germany; 4 University Medical Center, Center for Pediatric
and Adolescent Medicine- Department of Pediatric Cardiology, Mainz,
Germany
SIOP ABSTRACTS
S140 of S518
Background/Objectives: Due to various disease- and
treatment-related factors, skeletal muscle function in pediatric and adult cancer patients is impaired resulting in
decreased muscular strength. Previous studies in adult cancer
patients have shown that specific exercise interventions can
increase muscular strength which was related to positive
effects on whole-body muscle mass, fatigue and quality
of life. The purpose of the MUCKI study is to determine
whether combined resistance and endurance training can
improve muscle strength in pediatric cancer patients during
intensive cancer treatment phase (ICT).
Design/Methods: Based on a pilot experimental phase, a feasible exercise program was developed. A convenient study
design was established aiming to enroll 40 childhood cancer
patients aged between 4 and 18 years. As part of the randomized, controlled and interventional study design, individuals
within the exercise group (EG) participate in supervised exercise training. Training takes place 3 to 5 times per week over
a period of 6 to 8 weeks during ICT. Individuals of the control
group (CG) obtain usual care. Before and after the intervention muscle strength of upper and lower limbs, aerobic performance, body composition, fatigue and quality of life are
determined.
Results: Recruitment started in November 2015. So far 18
patients have been included. 9 patients were randomized to the
EG from whom 7 have already completed the exercise intervention. Comparing pre- and post-intervention the knee flexor
strength increased in the EG in average by 24.3% whereas it
decreased by 7.6% in the CG (p<0.05). Further preliminary
results regarding benefits from the exercise intervention on the
above mentioned parameters show positive trends. In a post
interventional interview patients reported that they enjoyed
the exercise program and would recommend it to others.
Conclusions: Early results of the MUCKI study support the
feasibility of combined resistance and endurance training and
evaluation of muscular strength during ICT.
PD-057 Polymorphisms in Immune Response
Genes and Risk of Infection during Treatment of
Pediatric Acute Leukemia
E. Zhukovskaya1 , M. Avdonina2 , D. Fesenko3 , T. Lisitsa1 , T.
Nasedkina2 , A. Karelin1
1 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Rehabilitation Centre “Russkoe Pole”, Moscow, Russia;
2 Federal Research Center of Pediatric Hematology - Oncology Immunology, Genetic department, Moscow, Russia; 3 Engelhardt Institute of
Molecular Biology- Russian Academy of Sciences- Moscow, Genetic
department, Moscow, Russia
Background/Objectives: Advances in the treatment of
children with leukemia are mostly determined by the use of
intensive chemotherapy. However, the therapy results in the
suppression of immunity, which is a risk factor for the devel-
opment of serious infectious complications, significantly
worsening the prognosis of the underlying disease. The study
of polymorphism of the genes involved in the regulation of
immune response is a prospective direction.
Design/Methods: DNA was isolated from leukocytes of 109
children with leukemia: 53 children with severe infections
(group 1) and 56 children without complications during treatment (group 2). A microarray was designed to determine 14
SNPs in the following genes: PTPN22, TLR1, TLR2, TLR4,
IL-4, IL-10, IL-12b, IL7R, NOD2, Dectin-1. The genotyping
procedure included polymerase chain reaction (PCR) with fluorescent labelling of DNA target followed by allele-specific
hybridization on microarray and image analysis. Two-sided
Fisher's exact test was used for statistical analysis.
Results: The genotype and allele frequencies between two
groups of patients were compared. It was found that the minor
allele -589T of the IL-4 gene (rs2243250) was less frequent in
patients of the group (1) than in patients of the group (2), thus
conferring a decreased risk of infection (odds ratio OR= 0.46,
p=0,03, 96% CI=0.23-0.92). The allele G of the IL7R gene
(rs1494555) was more frequent in the group (1) regarding to
the group (2) (OR = 2.02, p=0.02, 95% CI = 1.12-3.64). The
combination of allele G (rs1494555) with allele T in the IL7R
gene (rs1494558) strengthened this association: the haplotype
GT was much more frequent in the group (1) than in the group
(2) (OR=4.3, р=0.002, 95% CI= 1.76-10.4).
Conclusions: Thus, polymorphisms rs2243250 in the IL-4
gene, rs1494558 and rs1494555 in the IL7R gene were identified as genetic markers that may influence on risk of developing infectious complications during treatment of pediatric
leukemia.
T R E AT M E N T A N D CA R E PSYCHOSOCIAL (PPO)
PD-058 Emotional Adjustment in Siblings After a
Child's Death From Cancer: The Role of
Extrafamilial Relationships
K. Balistreri1 , M. Hagan1 , M. Barrera2 , T. Foster Akard3 , M.J.
Gilmer3 , B. Compas4 , D. Fairclough5 , T. Young-Saleme6 , C.
Gerhardt1,7 , K. Vannatta1,7
1 Nationwide
Children's Hospital, Center for Biobehavioral Health,
Columbus, USA; 2 The Hospital for Sick Children, Child Health Evaluative
Sciences, Toronto, Canada; 3 Vanderbilt University, Nursing, Nashville,
USA; 4 Vanderbilt University, Department of Psychology and Human
Development, Nashville, USA; 5 University of Colorado Denver, Biostatistics
and Informatics, Denver, USA; 6 Nationwide Children's Hospital,
Department of Psychology, Columbus, USA; 7 The Ohio State University,
Pediatrics, Columbus, USA
Background/Objectives: The death of a child from cancer
is traumatic for families. Severe and prolonged parental grief
SIOP ABSTRACTS
S141 of S518
may undermine family resources to meet the unique needs of
surviving siblings. Therefore, extrafamilial social resources
may assume particular importance. We examined whether
relationships with peers and teachers mitigate risk for depression and internalizing symptoms for bereaved siblings.
single nations. Standards are however established as far as
possible to ensure that trainees acquire relatively uniform
experience and knowledge. This study reported here describes
current perspectives on the delivery and assessment of training in paediatric oncology as described in recent literature.
Design/Methods: Children (N=76, 58% female), aged 818 (Mage=12.47, SD=2.54) were recruited from three
US/Canadian hospitals 3-12 months after their sibling's
death from cancer. Non-bereaved comparison-classmates
(CC) were also recruited (N=73). At school, classmates
rated how much they liked each other, yielding mean Peer
Acceptance scores. At home visits, children completed the
Social Support Scale for Children and Children's Depression Inventory (CDI) and parents completed the Child Behavior Checklist. Regression analyses tested variance in Depression/Internalizing symptoms accounted for by group, extrafamilial relationships, and their interactions.
Design/Methods: The NHS evidence portal was used to
search PubMed, PsychINFO, Embase and CINHAL using
clearly defined search terms. Where possible, these terms
were match to the MESH/encyclopaedia of each database.
Results: Groups did not differ in perceptions of Peer,
Teacher, and Friend support or Peer Acceptance. Peer and
Friend Support were negatively associated with both Depressive/Internalizing Symptoms, and Teacher Support was
negatively associated with Depressive Symptoms, regardless
of group (Bs=-0.84- -0.38, SEs=0.12-0.24, ps<0.05). Peer
Acceptance was negatively associated with parent-reported
Internalizing Symptoms (B=-2.27, SE=1.04, p=0.03). A
significant interaction was found between Group and Peer
Acceptance predicting Depressive Symptoms (B=2.18,
SE=1.03, p=.035) in which bereaved siblings reported elevated CDI scores regardless of Peer Acceptance (p=.83), but
a negative association was found for CC (B=-2.34, SE=0.76,
p=0.002).
Conclusions: Bereaved siblings appear to maintain peer
acceptance and support from peers, teachers, and friends,
and extrafamilial support benefits bereaved siblings and nonbereaved CC. In contrast, self-reported depressive symptoms
were elevated for bereaved siblings whether or not they were
‘well-liked’ by classmates. Future research should seek to
elucidate the directionality of these associations and identify
factors that undermine perceptions as well as availability of
extrafamilial support.
Results: Of 172 results, 38 were included as directly relevant
to the delivery and assessment of paediatric oncology education and training. Countries from all five continents were
represented, but weighted significantly towards higher income
countries. Problems that trainees experience in receiving their
training include lack of time, focus on service provision, and
heterogeneous case exposure relative to other trainees, difficulty gaining experience in centres with other tertiary and
quaternary speciality services, and establishing and maintaining work-life balance. Particular areas where there was an
identified need for greater experience included the presentation of brain tumours, survivorship and late effects, and palliative care. Particular challenges in the assessment of paediatric
oncology trainees include heterogeneous career paths (e.g.
less than full time training, academic research, and maternity leave), a lack of validated patient/family assessment tools,
communication, differences in the structure of training programs and lack of formal qualifications.
Conclusions: The ability of paediatric oncologists to travel
between countries and continents for research and employment is testament to the validity of professional certifications
in the speciality despite a lack of formal assessment. Further
research in the area should focus on common and successful
themes in paediatric oncology programs.
PD-060 The Perceived Impact of Pediatric
Cancer on Parental Couples’ Psychological Status
and Relationship Satisfaction During the
Survivorship Period
W. Burns1,2 , K. Péloquin1 , É. Rondeau2 , S. Drouin2 , L. Bertout2 ,
M. Krajinovic3,4 , C. Laverdière3,4 , D. Sinnett3,4 , S. Sultan1,2,3
PD-059 Training and Education in Paediatric
Oncology – Current Perspectives from the
Literature
C. Barton1
1 Alder
Hey Children's Hospital NHS Foundation Trust, Paediatric
Oncology, Liverpool, United Kingdom
Background/Objectives: Clinical training and education
programmes for trainees and fellows in paediatric oncology
are variable between countries, and between centres within
1 Université
de Montréal, Psychology, Montreal, Canada; 2 Sainte-Justine
University Health Center, Research center, Montréal, Canada; 3 Université
de Montréal, Pediatrics, Montreal, Canada; 4 Sainte-Justine University
Health Center, Hematology-Oncology, Montréal, Canada
Background/Objectives: Follow-up studies suggest that the
psychosocial impact of pediatric cancer on parents often
extends beyond the end of their child's cancer treatments, and
parents can continue to experience both individual and dyadic
(couple-based) effects. In a long-term study of parents of children with acute lymphoblastic leukemia (ALL), we aimed to:
SIOP ABSTRACTS
S142 of S518
1) describe couples’ adjustment (psychological distress, relationship adjustment), 2) describe the perceived impact of cancer on couples’ relationships, and 3) identify to what extent
the perceived impact of cancer on the couple is related to both
parents’ long-term adjustment.
Design/Methods: Participants in this study were childhood
ALL survivors and their parents, who were in ‘intact’ couples (i.e. together during the illness and at recall) (n =100).
Survivors’ medical information was collected from medical
records and parents completed questionnaires (Brief Symptom Inventory-18, abbreviated Dyadic Adjustment Scale, and
Impact of Cancer on the Couple). Mothers and fathers’ scores
were compared (e.g., repeated-measures MANOVAs). Using
the Actor-Partner Interdependence Model (APIM), we examined the degree to which a parent's perceived changes in relationship dynamics were associated with their own adjustment
(actor effects), and their partner's adjustment (partner effects).
Results: Distress was normative in this sample of parents
with frequencies ranging from 2-20%. Generally, mothers
and fathers agreed on their reported relationship satisfaction,
and the perceived nature of relationship changes (positive,
negative, or no change) following the illness. Findings from
dyadic models indicate that while mothers’ adjustment was
self-related (relating to their perceived relationship changes),
fathers’ adjustment was primarily other-related (relating to
their partner's perceptions).
Conclusions: Given our findings, it appears that mothers may
act as a bridge connecting illness experiences of survivors and
fathers. This could explain why mothers’ perceptions of relationship changes influence their partners’ long-term adjustment, but the reverse is not true for fathers.
ined longitudinal associations between baseline variables and
peer nominated friendships in PBTSs approximately one year
later.
Design/Methods: Caregivers of children (n = 32) ages 8-16
(39% low grade glioma, 34% medulloblastoma, 28% other)
completed ratings of child adjustment at baseline (T1) and
PBTSs and classmates completed the Three Best Friends
measure approximately 12 months later (T2). Preliminary
descriptive statistics examined friendship nominations and
reciprocated friendships of PBTSs. Bivariate analyses examined associations between baseline independent (anxious and
depressive symptoms, emotional control, global executive
composite, total social skills, diagnosis, treatment, age, gender) and T2 dependent variables (friendships).
Results: On average, PBTSs were nominated as a best friend
by two classmates (range: 0-7). Of the PBTSs, 25% were not
nominated by any classmates as a best friend. On average,
PBTSs had one reciprocated best friend nomination (range:
0-3). Of the PBTSs, 47% did not have any reciprocated best
friend nominations. Greater depressive symptoms in PBTSs
were associated with fewer peer nominations of friendship (r
= -.41, p < .02) and a no reciprocal friendships (t = 2.30, p <
.03). Fewer social skills were also associated with not having
any reciprocated friendships (t = -2.36, p < .03).
Conclusions: Depressive symptoms and social skills at baseline were associated with friendship in PBTSs a year later,
within the context of a multifaceted model. This information contributes to further our understanding of social competence and could guide psychosocial interventions for these
survivors.
Acknowledgments: Cole Foundation (Montreal), CIHR,
FRQs
PD-061 A Longitudinal Examination of Factors
Associated with Friendships in Pediatric Brain
Tumor Survivors
PD-062 The Impact of School Climate on The
Peer Relationships of Pediatric Brain Tumor
Survivors
M. Hagan1 , K. Balistreri1 , E. Meadows2 , E. Semmel3 , C.
Gerhardt1,4 , M. Barrera5 , A. Patenaude6 , K. Vannatta1,4
1 Nationwide
1 The
Hospital for Sick Children, Psychology, Toronto, Canada; 2 London
Health Sciences Center, Hematology-Oncology, London, Canada; 3 British
Columbia Children's Hospital, Psychology, Vancouver, Canada;
4 University of Colorado Denver, Biostatistics & Informatics, Denver, USA
Children's Hospital, Center for Biobehavioral Health,
Columbus, USA; 2 University of Toledo, Department of Psychology, Toledo,
USA; 3 Georgia State University, Department of Psychology, Atlanta, USA;
4 The Ohio State University, Pediatrics, Columbus, USA; 5 Hospital for Sick
Children, Child Health Evaluative Sciences, Toronto, Canada;
6 Dana-Farber Cancer Institute at Harvard Medical Center, Divsion of
Pediatric Oncology, Boston, USA
Background/Objectives: Pediatric brain tumor survivors
(PBTSs) experience impairments in social competence. Anxious and depressive symptoms, insult related variables (e.g.,
diagnosis, treatment), non-insult related variables (e.g., age,
gender), and social information processing (e.g., executive
functions, social skills, emotional control) may be associated
with social competence in PBTSs. The current study exam-
Background/Objectives: Pediatric brain tumor survivors
(PBTS) are at risk for negative peer interactions, less acceptance, and fewer friends relative to healthy peers. Family influences on social competence have been explored, but relevant features of school climate (e.g., structure, safety, peer
and teacher support) have not. Our aim was to investigate
PBTS, comparison classmate (CC) and teacher perceptions
L. Desjardins1 , U. Bartels1 , D. Cataudella2 , J. Chung3 , D.
Fairclough4 , K. Hancock1 , A. Saleh1 , M. Barrera1
SIOP ABSTRACTS
of schools and explore whether school climate moderates the
peer relationship problems for PBTS.
Design/Methods: PBTS (N=85, 53% male), aged 8-13
(Mage =10.8, SD=1.65) at least 1 year post treatment (40%
radiation, 51% chemotherapy, 78% neurosurgery), were
recruited from three sites in the US and Canada. PBTS,
classmates (87% participation) and teachers completed the
Delaware School Climate Survey and sociometric measures
of peer interactions (Revised Class Play), acceptance, and
friendship. One CC, matched for gender, age, and race, was
identified in each class. Dependent t-tests compared school
climate ratings for PBTS and CC, and correlations examined
agreement of students and teachers.
Results: PBTS did not view school climate more negatively
than CC (0.08 < p’s < 0.83), and they had moderate agreement on student-student relations, student engagement, and
school safety subscales (r= 0.33 to 0.43, p’s < 0.01). Little
agreement was found for teacher and student ratings of school
climate. Further multivariate analyses will test if the difference between student and teacher perceptions of school climate moderate differences in peer interactions, acceptance,
and friendship for PBTS and CC.
Conclusions: Findings suggest that despite the negative peer
experiences of PBTS, they do not perceive their school climate differently from CC. However, there is substantial disagreement between students and teachers, highlighting the
importance of gathering information from students about
school climate, rather than just teachers and administrators.
Integrated perceptions of classmates may provide the most
reliable estimates of school level variables that may mitigate
social risk for PBTS.
PD-063 Prospective Family Influences on
Neurocognitive Functioning in Pediatric Brain
Tumor Survivors
M. Hocking1 , Y. Li1 , L. Quast1 , J. Baran1 , C. Brodsky1 , A. Kazak2 ,
P. Phillips1 , L. Barakat1
1 Children's
Hospital of Philadelphia, Oncology, Philadelphia, USA;
Children's Health System, Nemours Center for Healthcare
Delivery Science, Wilmington- DE, USA
2 Nemours
Background/Objectives: Pediatric brain tumor survivors
(PBTS) are at risk for neurocognitive deficits. A theoretical
model of childhood cancer survivorship suggests associations
between family functioning and survivor neurocognitive outcomes over time. This prospective study tested the hypothesis that better family functioning at the end of tumor-directed
treatment would be associated with positive changes in survivor neurocognitive function 9 and 16 months later.
Design/Methods: Fifty PBTS (ages 6-16) completed brief
neurocognitive assessments within four months of complet-
S143 of S518
ing tumor-directed therapy (T1) and again approximately
nine (T2; n=35) and 16 (T3; n=30) months later. Parents
completed measures of family functioning at T1. Neurocognitive domains assessed included working memory, processing
speed, and long-term auditory memory. Family functioning factors assessed included general family functioning,
condition management difficulty, and perceived caregiver
competence. Mixed-effects models evaluated whether T1
family functioning variables predicted slopes of changes in
survivor neurocognitive function over time.
Results: Models predicting long-term auditory memory were
consistent with hypotheses. Better caregiver competence at
T1, t (1, 54)=2.52, p < .05, and less condition management
difficulty, t (1, 55)=-2.54, p < .05, were associated with faster
improvements in auditory memory over time. Models predicting working memory were in the opposite direction than
hypothesized. Worse caregiver competence at T1, t (1, 48)=2.43, p < .05, and greater condition management difficulty
at T1, t (1, 48)=3.32, p < .01, were associated with faster
improvements in working memory over time. Models predicting processing speed were not significant.
Conclusions: Family functioning variables at the end of
tumor-directed treatment may play a role in the trajectory of
survivor neurocognitive function over time. The nature of the
role and which aspects of family functioning should be considered need further study, particularly with longer follow-up
after the conclusion of tumor-directed treatment. Family functioning is an important factor to monitor over time.
PD-064 Never Truth without Hope, Never Hope
without Truth: Parents'views on the Disclosure of
Prognosis in Paediatric Oncology
A. Jankowska1 , I. Pałgan2 , J. Skalska- Sadowska3 , K. SobieralskaMichalak4 , M. Libura5 , M. Wysocki6
1 Collegium
Medicum Nicolaus Copernicus University, Pediatric Oncology
and Hematology Deparment, Bydgoszcz, Poland; 2 J. Brudziński Voivodship
Paediatric Hospital, Pediatrics- Oncology- Hematology and Rheumatology
Department, Bydgoszcz, Poland; 3 University of Medical Sciences,
Department of Pediatric Oncology- Hematology and Transplantology,
Poznań, Poland; 4 Collegium Medicum Nicolaus Copernicus University,
Department of Rehabilitation, Toruń, Poland; 5 Łazarski University, Institute
for Interdisciplinary Studies, Warszawa, Poland; 6 Collegium Medicum
Nicolaus Copernicus University, Pediatric Oncology and Hematology
Department, Bydgoszcz, Poland
Background/Objectives: Identification of the needs and
preferences for the process of prognostic discussion among
parents in paediatric oncology
Design/Methods: Parents of children treated in three oncological centers in Poland participated in one of six focus group
discussions and completed a survey measuring their preferences for the manner of delivery of prognostic information.To
develop survey items, key themes were abstracted from the
SIOP ABSTRACTS
S144 of S518
published literature. Quantitative data were analyzed using
descriptive statistics. Qualitative data were audiotaped and
analyzed.
Results: 116 (80%) of 144 parents invited onto the study participated.The majority of parents preferred detailed prognostic information, presented in an open and honest manner. Factors found to influence parents hope were physician willingness to answer questions and provide information offer the
most up to date treatment and provide emotional support.
Conversely, factors reported as potentially decreasing hope
included pessimistic attitude, an impersonal context for the
disclosure, the doctor appearing to be nervous or uncomfortable or using euphemisms. Parents preferred positive framing
during the discussion about their child's prognosis. 112 (97%)
of parents wanted their doctor to provide an opportunity to
ask questions, and acknowledge them as an individual when
discussing prognosis.
Conclusions:
1. The majority of parents preferred an individualized realistic approach from the doctor.
2. Preferences may vary according to demographic, psychological and disease variables.
3. Study findings highlight the importance of training healthcare professionals in the content, timing, and potential
biases associated with information delivery.
page questionnaire over a two-week period in Mar-2017. Participation was voluntary. Background information, attendance
status at the educational program and attitudes to further
schooling, future ambition, and time taken/ intent to rejoin
school were assessed.
Results: Five-hundred forms were distributed in the studyperiod, 414 responded, of which 313 had attended the program, while 101 did not. Both groups were evenly-matched
for age (median-8 years), sex-ratio (1.8 vs 1.72), treatment
status (72% and 78% on-treatment), prior school attendance
(84% and 78%), and medium of instruction (English- 37%
and 35%; Hindi, Marathi, Bengali and others- 63% and
65%). More than 80% among those on follow-up joined back
school in both groups. In a question on future career, only
41% of non-attendees responded, as compared to 85% attendees (p<0.05). Career choices were more diverse in attendees than non-attendees (28 and 4 respectively), with Doctor being most popular in both. Attendees had more specific,
specialized, niche-area and exotic career preferences than
non-attendees.
Conclusions: An innovative educational interventional program run in out-patient waiting areas impacted preferences towards future education and career with attendees having more positive, open and diverse attitudes than
non-attendees.
PD-065 A Survey to Assess Impact of an
Innovative Educational Interventional Program on
Attitudes Towards Education in Children Treated
in a Large Tertiary Cancer Center
PD-066 Feasibility of In-Hospital Ambassador
Classmates for Children with Cancer as Facilitators
of Social, Physical, and Educational Rehabilitation
(Respect)
S. Jatia1 , S. Imade1 , J. Gupta1 , U. Pandit1 , M. Prasad2 , G.
Chinnaswamy2 , T. Vora2 , G. Narula2 , S. Banavali2
H.B. Larsen1 , A.S. Helms1 , T. Thorsteinsson1 , M.K.F. Nielsen1 , M.
Faber1 , M.H. Nielsen1 , C. Heilman2 , K.V. Andersen2 , P. Roland3 ,
M. Madsen2 , C. Johansen4 , L. Stisen3 , L.W. Gundersen5 , H. Hasle6 ,
K. Schmiegelow7
1 Tata
Memorial Center, ImPaCCT Foundation- Pediatric Oncology
Division, Mumbai, India; 2 Tata Memorial Center, Pediatric Oncology
Division, Mumbai, India
Background/Objectives: Children undergoing treatment at
our center- a large tertiary cancer hospital in India, come
from all parts of the country with diverse socio-economic
backgrounds, educational status, religious-beliefs, vernacular languages, and deep-set family/community traditions. The
diagnosis of cancer and its aftermath makes education their
lowest priority. Since May-2015, we instituted an innovative educational interventional program run by a professional
teachers group, designed for out-patient clinic waiting areas,
largely through visual, auditory and skill-based means reducing dependence on language and able to cater to wide agegroups. A short survey was conducted to assess its impact on
attitudes to education.
Design/Methods: Children attending out-patient clinics at the
center for treatment or follow-up, were issued a standard one-
1 Rigshospitalet,
Pediatric hematology oncology Bonkolab 5704, København
Ø, Denmark; 2 Rigshospitalet, Pediatric hematology oncology 4072,
København Ø, Denmark; 3 Rigshospitalet, Pediatric hematology oncology
5054, København Ø, Denmark; 4 Danish Cancer Society, Unit of
Survivorship, København Ø, Denmark; 5 Rigshospitalet, HovedOrtoCentretClinic of ergotherapy and physical therapy, København Ø, Denmark;
6 Aarhus University Hospital, Departments of Pediatrics, Aarhus, Denmark;
7 Rigshospitalet, Pediatric hematology oncology- 4072, København Ø,
Denmark
Background/Objectives: Background: Aiming at rehabilitating school-aged children with cancer socially, academically,
physically and diminish their treatment induced isolation
and marginalization, the nationwide psychosocial intervention study RESPECT (Rehabilitation including social and
physical activity and education in children and teenagers
with cancer) have included children since 2013.
Intervention: 1. A 60-minutes educational presentation on
cancer in the child´s school class, 2. Alternating in-hospital
SIOP ABSTRACTS
co-admission (9am-3pm) of two ambassador classmates, 3.
In-hospital physical activity program.
Purpose: To examine the feasibility of the educational
and ambassador intervention components of the ongoing
RESPECT study.
Design/Methods: Methods: Inclusion of the first 30 consecutive children (6-18 years) newly diagnosed with cancer in
the intervention group. Feasibility include: participation rate,
acceptability, timeframe, frequency, duration and safety.
Results: Results Of 31 children 30 consented to participate
(97%). Median time from diagnosis to inclusion was six days.
Within a median of 14 days the educational class presentation
on cancer was conducted, with >90 % teacher's satisfaction
with content, level and duration. A median of seven classmates applied for ambassadorship. Median time for ambassador assignments to all children was nine days. The median
one-way ambassador travel distance was 49 km. None of
the patients or ambassadors discontinued study participation.
None of the ambassadors experienced adverse emotional reactions or needed psychological intervention. The total number
of ambassador co-admissions was 422 and the median number
of co-admissions per child was 13.
Conclusions: Conclusion: It is feasible, acceptable and safe
to involve healthy classmates during intensive treatment of
children with cancer. The intervention components are well
suited for rehabilitation intervention in children with cancer
and their school classes. Challenges are practical organization, travel distance, co-admissions, parental language barriers, in-hospital cultural acceptability and disease burden. The
inclusion of classmates as psychosocial motivational supportive network during in-hospital cancer treatment provides a
novel approach to cancer rehabilitation of school-aged children.
PD-067 Psychosocial Screening for Siblings of
Children with Cancer: Development and Initial
Testing of a New Sibling Screening Module
K. Long1 , E. Pariseau1 , A.C. Muriel2 , A. Chu3 , A. Kazak4,5 , M.
Alderfer4,5
1 Boston
University, Psychological and Brain Sciences, Boston, USA; 2 Dana
Farber Cancer Institute & Harvard Medical School, Pediatric Psychosocial
Oncology, Boston, USA; 3 Boston University, School of Public Health,
Boston, USA; 4 Nemours Children's Health System, Center for Healthcare
Delivery Science, Wilmington, USA; 5 Thomas Jefferson University, Sidney
Kimmel Medical College, Philadelphia, USA
Background/Objectives: The absence of a standardized,
sibling-specific psychosocial screener limits healthcare
providers’ ability to identify and pre-emptively intervene
with siblings who may have clinical levels of distress during
or after a brother's/sister's cancer treatment. English and
Spanish versions of a sibling module for the Psychosocial
S145 of S518
Assessment Tool (PAT), a well-validated screener of family
psychosocial risk, were developed. The project also examined
associations between sibling risk factors and sibling and
family adjustment.
Design/Methods: English- and Spanish-speaking families of
children with cancer (29 parents, 17 siblings) participated in
qualitative interviews to inform item content and provide indepth feedback on the wording and format of iterative versions
of the new PAT Sibling Module. Purposive sampling ensured
variability across sibling age (M(SD)=8.9(4.7) years), sibling
gender (55% female), time since cancer diagnosis (M(SD)=
18.8(19.6) months), and parent primary language (34% Spanish/bilingual). Data collection continued until saturation was
reached and the new screening modules were finalized. In
Phase 2, parents of newly-diagnosed children with cancer
completed the PAT Sibling Module and measures of sibling,
parent, and family functioning. To date, 38 families have completed Phase 2.
Results: Sixteen distinct PAT Sibling Modules were developed based on timing (diagnosis, follow-up), language
(English, Spanish), and sibling age (0-2, 3-4, 5-9, 10+ years).
Higher scores on the PAT Sibling Module (i.e., greater sibling
risk) are associated with poorer sibling psychosocial functioning as assessed by the Strengths and Difficulties Questionnaire Total Problem Scale (r=0.67, p=0.00), Emotion Symptoms Scale (r=0.40, p=0.05), Hyperactivity Scale (r=0.67,
p=0.00), Peer Problems Scale (r=0.51, p=0.01), and Prosocial Scale (r= -0.56, p=0.01), and worse family functioning
on the Family Assessment Device (r=0.63, p=0.00). Associations with parent mental health as assessed by the Brief
Symptom Inventory were not significant.
Conclusions: The new PAT Sibling Modules show promise
as screeners of psychosocial risk among siblings of children
with cancer.
PD-068 Is a Brief Parental Intake form Effective
in Identifying Behavioral Adjustment Problems in
Childhood Cancer Survivors?
A. Michaud1 , C. Cadigan1 , C. Mason2 , C. Recklitis1
1 Dana
Farber Cancer Institute, Perini Family Survivors’ Center, Boston,
USA; 2 Imperial College London, Neuroepidemiology and Ageing, London,
United Kingdom
Background/Objectives: Childhood cancer survivors (CCS)
are at elevated risk for behavioral adjustment problems.
Screening is promoted as a means of identifying these problems, but practical and accurate screening methods for clinical settings are not well established. We developed a five-item
Brief Parental Intake Form (BPIF) and assessed its accuracy
compared to parental report on the Brief Pediatric Symptom
Checklist-17 (BPSC-17).
SIOP ABSTRACTS
S146 of S518
Design/Methods: Parents of 291 CCS (ages 5-17) completed
the BPIF and BPSC-17 at a survivorship visit. The BPIF asks
parents to report on emotional, attention, behavioral, school
and ‘other’ problems on a 4-point likert scale. The BPSC17 includes 3 scales capturing depression/internalizing, attention, and externalizing problems. Based on normative data,
BPSC-17 scores were categorized into no significant elevation, moderate elevation, and significant elevation.
Results: Parents reported 87 (29.9%) survivors had moderate or significant elevation on the BPSC-17. Of those, 83 survivors were identified as having at least some behavioral problems on the BPIF. Using any reported problem v. no problem
as a cut-off on the BPIF showed high sensitivity (95.4%). For
the 204 (70.1%) survivors whose parents did not report behavioral problems on the BPSC-17, 93 did screen in on the BPIF,
showing low specificity (54.4%).
Conclusions: Parental report on the BPIF accurately identified symptomatic cancer survivors with high sensitivity compared to the BPSC-17. The five-item BPIF could lessen the
burden for both patient and staff, while still identifying 95%
of survivors with behavioral problems. Because of low specificity, the BPSC-17 or another more detailed measure should
be used as a second screener for survivors who screened in on
the BPIF. Future studies should compare the BPIF with the
Child Behavior Checklist (CBCL) and other measures, to see
how accurately it identifies behavioral problems more broadly.
PD-069 Assessment of Information Needs and
Intervention Preferences in Parents of Survivors
with Neurocognitive Late Effects
C. Peterson1 , N. Morris1
1 Eastern
Michigan University, Psychology, Ypsilanti, USA
Background/Objectives: With approximately half of childhood cancer survivors (CCS) at risk for neurocognitive
late effects (NCLE)1 , parents report high need for information about learning and behavior, but in varying amounts
and stages2 . Understanding specific survivorship information needs, such as preferences for the amount, timing, type,
and delivery of information needed, will inform intervention.
This study assessed parent information needs and intervention
preferences, associations with psychological functioning, and
perceived utility of Internet-based information interventions.
at diagnosis; 34.7% reported finding information on their own
or “never” receiving information. Parents wanted information immediately after diagnosis and before treatment consent,
and again 1-2 months before concluding treatment. Parents
reported frequent reliance on other sources besides their medical team (e.g., internet, other parents) and need for repeated
information at more frequent intervals in survivorship. Topics included: behavioral and school issues; fertility; longterm follow-up transitions; sibling issues; and communicating about late effects with their team. 93.7% of respondents
would use an online program if available. Regression analyses indicated that greater survivorship information needs were
associated with increased family burden and poorer child cognitive, behavioral, and emotional functioning. Family burden
specific to NCLE significantly predicted information needs (B
= .10, SE = .03, p = .001), beyond demographic and treatment
variables.
Conclusions: Families report high needs for information
throughout survivorship, strongly predicted by the burden a
parent experiences managing late effects. Results indicate targets for interventions for highly burdened parents that would
be feasible, acceptable, and disseminable.
PD-070 Health-Related Quality of Life and
Psychological Distress in Adolescent and Young
Adult Survivors of Childhood Cancer and Their
Association with Treatment, Education and
Demographic Factors
J.F. Halvorsen1 , A.M. Sund2 , L. Zeltzer3 , M. Ådnanes4 , H.
Jensberg5 , T.A. Eikemo6 , B. Lund7 , O. Hjemdal1 , T. Reinfjell8
1 Norwegian
University of Science and Technology NTNU, Department of
Psychology, Trondheim, Norway; 2 Norwegian University of Science and
Technology NTNU, Regional Centre for Child and Youth Mental Health and
Child Welfare. St. Olav's University Hospital, Trondheim, Norway; 3 David
Geffen School of Medicine at UCLA, Department of Pediatrics, Los
Angeles, USA; 4 SINTEF Technology and Society, Dept. of Health Research,
Trondheim, Norway; 5 Norwegian Directorate of Health, Division of Health
Economics and Financing, Trondheim, Norway; 6 Norwegian University of
Science and Technology NTNU, Department of Sociology and Political
Science, Trondheim, Norway; 7 Norwegian University of Science and
Technology NTNU, Department of Laboratory Medicine. St. Olav's
University Hospital, Trondheim, Norway; 8 Norwegian University of Science
and Technology NTNU, Department of Psychology. St. Olav's University
Hospital, Trondheim, Norway
Design/Methods: Ninety-five parents of CCS completed
measures of demographic/treatment information, child behavior and neurocognitive functioning, family burden, knowledge
of NCLE, current and preferred sources of survivorship information, and interest in using Internet-based resources.
Background/Objectives: This study investigated the healthrelated quality of life (HRQOL) and psychological distress
of adolescent and young adult (AYA) survivors of childhood
cancer and the association of these factors with treatment
modalities, education and demographic factors ≥ 5 years postdiagnosis.
Results: Parents reported low information: 30% had never
heard of NCLE, and 70.5% wanted “a lot” more information about NCLE. Only 26% reported receiving information
Design/Methods: Participants included cancer survivors
(n=91) recruited through the Cancer Registry of Norway
(CRN) and healthy controls (n=223) recruited from a stu-
SIOP ABSTRACTS
dent population. All participants completed self-report questionnaires, and the Pediatric Quality of Life Inventory
(PedsQLTM ) 4.0 and Hopkins Symptom Checklist-10 (HSCL10) were used to measure HRQOL and distress, respectively.
Results: Survivors reported the same mean levels of HRQOL
as controls, with the exception of worse physical functioning.
Compared with controls, survivors overall and female survivors in particular had higher odds of reporting psychological distress symptoms over the cut-off, but survivors did not
have higher mean levels of distress. Female survivors reported
poorer physical health than female controls. Survivors reporting distress levels above the cut-off had significantly poorer
HRQOL regarding physical functioning and worse total PedsQL scores than controls scoring above the cut-off. Age (for
HRQOL only), female gender, low educational level and perceived low economic status significantly predicted HRQOL
and distress.
Conclusions: Survivors reported similar mean levels of
HRQOL and distress as controls, except for physical functioning. For cancer survivors, demographic variables predicted
HRQOL and distress. Some groups of survivors require closer
follow-up, and more attention should be paid to factors associated with poor HRQOL and psychological distress in survivors, including female gender, lower education level and
lower income.
Acknowledgements: This study was supported by grants
from the Liaison Committee between the Central Norway
Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU) as well as the Norwegian Cancer Organization.
PD-071 Anxiety Symptoms and Neurocognitive
Functioning in Children with Leukemia and Brain
Tumors: A Comparison of Symptomology across
Multiple Informants
C. Sharkey1 , A. Gioia2 , T. Kennedy2 , G. Dome2 , K. Walsh2 , K.
Hardy2
1 Oklahoma
State University, Psychology, Stillwater, USA; 2 Children's
National Health System, Neurology, Washington- DC, USA
Background/Objectives: Children diagnosed with cancer
may experience both psychological and neurocognitive difficulties, yet few studies have examined the relationship
between these outcomes. However, adjustment difficulties,
including anxiety, can contribute to poor cognitive performance. Thus, the present retrospective study aimed to compare the relationship between anxiety symptoms and neurocognitive functioning in children with leukemia or brain
tumors (BT). Due to the importance of multiple informants,
concordance across raters was also assessed.
S147 of S518
Design/Methods: Ninety-seven children with leukemia
(45.4% Female, Mage =11.61 years), and 121 children with
brain tumor (48.8% Female, Mage =11.21 years) completed
the Youth Self-Report and an age-appropriate Wechsler scale,
as part of a clinical neuropsychological assessment. Parents
(N=208) and teachers (N=157) completed Achenbach rating
scales.
Results: BT survivors had significantly lower processing
speed than leukemia survivors (x2(177) =2.78, p<.01).
Although no differences existed in overall anxiety across
survivorship groups, there were differences in rater agreement between leukemia and BT groups. Specifically, BT survivors’ self-reported anxiety correlated with parent-report
(.001<p<.01). Teacher-report of Anxiety Problems only correlated with parent-report (p<.05). Contrastingly, among
leukemia survivors, parent-, teacher-, and self-report of anxiety were unrelated (p>.05). Among BT survivors, reports
of anxiety were unrelated to cognitive performance (p>.05),
whereas among leukemia survivors, parent- and self-report
of Anxious/Depressed symptoms were positively associated
with working memory and IQ (.01<p<.05), and parent-report
of Anxiety Problems was positively related to IQ (p<.01).
Teacher- and self-report of Anxiety Problems were positively
related to processing speed (p<.01).
Conclusions: The relationship between anxiety symptoms
and cognitive performance, and the concordance between
multiple informants of anxiety symptoms differs between BT
and leukemia groups. Self-report is associated with quantitative cognitive performance within leukemia, although in
an unexpected direction, yet is more concordant with otherreports in BT. Thus, multiple informants are essential and further investigation of this positive relationship between anxiety symptoms and neurocognitive functioning is warranted
among leukemia survivors.
PD-072 A Pilot RCT Targeting Caregivers to
Improve the Health Behaviors of Obese Pediatric
Cancer Survivors
M. Stern1 , J.B. Dr.1 , E.D. MS2 , C.L. Ms3 , G.H. Dr4 , L.E. Dr5 , S.M.
Prof6
1 University
of South Florida, Child and Family Studies, Tampa, USA;
of South Florida, psychology, Tampa, USA; 3 University of
South Florida, School Psychology, Tampa, USA; 4 John Hopkins/All
Children's Hospital, Pediatric Oncology, St Petersburg, USA; 5 University of
Pittsburgh, Psychiatry- Psychology and Pediatrics, Pittsburgh, USA;
6 Virginia Commonwealth University, Psychology, Richmond, USA
2 University
Background/Objectives: Objective: Obesity rates in pediatric cancer survivors (PCS) are alarmingly high (40-50%).
Healthy lifestyle changes may prevent future health complications and improve quality of life in PCS. Few interventions
have addressed the negative impact of cancer therapies on
PCS health behaviors. This NIH funded RCT tests the efficacy
SIOP ABSTRACTS
S148 of S518
of a parent-focused intervention (NOURISH-T) on improving
caregiver and child bmi, dietary intake, and physical activity
than caregivers in our control (EUC).
Design/Methods: Methods: A total of 67 PCS from two
sites were consented and 53 were enrolled (M=9.92yrs of
age, 64.4% ALL or lymphoma diagnosis) at least 6 months
off cancer treatment (M=1.96yrs off treatment), and BMI
of 85th% percentile or greater (M=95.42 BMI percentile).
Families were randomized to either a 6-session intervention,
NOURISH-T, or one Enhanced Usual Care (EUC) session.
Assessments were conducted at baseline, post-6-weeks intervention and 4-month follow-up (FU).
Results: Results In comparison to EUC parents, NOURISHT parents showed significant decreases from pre to post to FU
on BMI, waist-hip ratio and total number of daily calories.
NOURISH-T parents also showed similar positive changes in
their child feeding behaviors and perceptions of child vulnerability. Similar decreases on BMI %ile and waist-hip ratio were
found for PCS, but only from pre to post testing. NOURISHT PCS also showed significant increases in number of daily
steps whereas EUC PCS decreased. Caregivers reported being
very positive about NOURISH-T sessions.
Conclusions: Conclusions Results suggest that an intervention targeting parents can have a longer term effect on caregivers, but only shorter-term impact on the PCS. Implications for intervention strategies are discussed. Whether length
of time off treatment plays a moderating factor on treatment
effects will be considered.
PD-073 Attitudes Towards Clinical Trials among
Adolescents and Young Adults (AYA) with A
History of Cancer: Psychosocial Maturity,
Knowledge and Disease-Related Correlates
als, psychosocial maturity (consideration of future consequences), and attitudes (perceived benefits and barriers)
towards clinical trial participation. Covariates included age,
age at diagnosis, sex, cancer type (liquid, solid or brain)
and treatment status (on/off treatment). Preliminary t-tests,
correlations and ANOVAs were conducted. Multivariable
regressions and mediation/moderation analyses were used for
hypothesis testing.
Results: Ninety-eight AYA (Mean age = 22.86, SD = 4.33;
55% Male, 86% non-Hispanic White) had mean knowledge
score of 80.77% correct (SD=13.84). Most frequent incorrect items included types of trials and voluntariness. Greater
knowledge was significantly associated with more perceived
benefits (b=0.69, p<0.001); this relationship was significantly
moderated by cancer type. Knowledge mediated the relationship between consideration of future consequences and perceived benefits (Z=2.07, p=0.04). Cancer type was the only
identified predictor of perceived barriers; AYA with brain
tumors (Mean=46.42, SD=8.91) perceived significantly more
barriers compared to those with liquid tumors (Mean=40.31,
SD=10.32, p=0.04).
Conclusions: AYA have moderate knowledge of cancer clinical trials with critical areas of misunderstanding. Informed
consent processes should be tailored towards psychosocial
maturity and address perceived benefits and barriers that may
differ by diagnosis. Decision support tools may be effective
resources to improve knowledge, enhance full understanding
of clinical trials and their potential benefits, and increase AYA
engagement in their treatment decisions.
PD-074 IMPACT of Family Density on
Illness-Related Parental Adjustment and Family
Burden in Survivorship
E. Stevens1 , B.M. Velázquez-Martin1 , L. Schwartz1,2 , L.P.
Barakat1,2
P. Weaver1 , C. Peterson1
1 The
1 Eastern
Background/Objectives: Relative to younger cohorts, the
progress in rate of survival has been slower for adolescents
and young adults ages 15-29 (AYA). Barriers to clinical trial
enrollment may include limited knowledge of clinical trials, which may relate to limited engagement in the treatment decision-making process, and difficulty of health care
providers and caregivers to include them in shared decisionmaking. This study sought to explore psychosocial maturity,
knowledge and disease related correlates of attitudes towards
clinical trials.
Background/Objectives: Research has shown marital status
and family size to be commonly endorsed psychosocial risk
factors for families of children newly diagnosed with cancer.1
However, for families of children with a chronic illness,
research suggests that family density is a more objective
indicator of the demands on parental resources as compared
to single-parent status.2 Late effects in childhood cancer
survivors (CCS), particularly neurocognitive late effects
(NCLE), may present ongoing demands that burden parents.3
Negative psychosocial outcomes for families of survivors
may be exacerbated in high density families. The present
study examined associations among illness-related parental
adjustment and family burden, moderated by family density,
in parents of CCS.
Children's Hospital of Philadelphia, Pediatrics - Division of
Oncology, Philadelphia, USA; 2 The University of Pennsylvania, Perelman
School of Medicine, Philadelphia, USA
Design/Methods: AYA completed measures of demographics, cancer diagnosis/treatment, knowledge of clinical tri-
Michigan University, Clinical Psychology, Ypsilanti, USA
SIOP ABSTRACTS
Design/Methods: Ninety-three parents (96% mothers) of
CCS completed measures assessing perceived emotional
resources, parent guilt/worry, and family burden of NCLE, in
addition to demographic and disease-related variables. Density was defined as the household's total child-adult ratio, with
at-risk identified as >2.4 In the current study 26% of families
were dense.
Results: Regression analyses revealed that parents reporting more perceived emotional resources reported significantly
less guilt/worry (B=-0.89, p<.001) and family burden (B=1.68, p=.002). Greater subjective experience of guilt/worry
was associated with greater family burden (B=0.62, p=.005).
Feelings of guilt/worry were associated with greater family burden for parents in higher density families (B=0.49,
p=.037). However, despite family density, parents who perceived themselves as having sufficient emotional resources to
manage the demands associated with their child's illness experienced less family burden. Findings were observed above and
beyond the effects of socioeconomic status.
Conclusions: Results highlight the buffering impact of perceived emotional resources in managing caregiver demands
in CCS families, even within relatively higher density families. Interventions should focus on these high density families,
as parents maybe at greater risk for experiencing feelings of
guilt/worry that result in greater overall family burden.
PD-075 Pediatric Cancer Patients in Malawi
Present to the Hospital with Poor Health-Related
Quality of Life as Measured by the Promis-25
Questionnaire
K. Westmoreland1,2 , A. Amuquandoh3 , T. van der Gronde3 , S.
Itimu3 , A. Salima3 , O. Manthalu3 , P. Ward3 , A. Mpasa4 , S.
Wachepa4 , I. Mtete4 , M. Butia4 , P. Wasswa4,5 , N. El-Mallawany
Kim5 , P. Kazembe6 , B. Reeve7 , S. Gopal8,9,10
1 UNC
Project-Malawi, Pediatric Hematology Oncology, Lilongwe, Malawi;
2 University of North Carolina, Pediatric Hematology Oncology, Chapel
Hill, USA; 3 UNC Project-Malawi, Oncology, Lilongwe, Malawi; 4 Baylor
College of Medicine Children's Foundation Malawi, Oncology, Lilongwe,
Malawi; 5 Texas Children's Hospital, Pediatric Hematology Oncology,
Houston, USA; 6 Baylor College of Medicine Children's Foundation Malawi,
Country Director, Lilongwe, Malawi; 7 University of North Carolina, Health
Policy and Management, Chapel Hill, USA; 8 UNC Project-Malawi, Cancer
Program Director, Lilongwe, Malawi; 9 University of North Carolina,
Oncology and Infectious Disease, Chapel Hill, USA; 10 University of Malawi
School of Medicine, Oncology and Infectious Disease, Lilongwe, Malawi
Background/Objectives: Patient-Reported Outcomes Measurement Information System 25-item (PROMIS-25) pediatric questionnaire was translated into Chichewa and validated
for use in Malawi. This is among the first studies from subSaharan Africa (SSA) to report health-related quality of life
(HRQoL) for pediatric cancer patients.
S149 of S518
Design/Methods: Thirty-two pediatric lymphoma patients
were interviewed at Kamuzu Central Hospital in Lilongwe,
Malawi. The PROMIS-25 questionnaire was administered to
patients within three days of presentation before chemotherapy initiation. Participants reported on six HRQoL domains
(mobility, anxiety, depression, fatigue, peer relationships,
and pain interference) by answering four question items per
domain using a 5-point Likert scale. A single-item pain intensity question was scored 0-10. Each domain was transformed
to a T-score with a mean of 50 and standard deviation of 10
based on the original PROMIS reference sample. Median and
interquartile range (IQR) for T-scores was reported for each
domain. A t-test was used to compare our cohort to published
T-scores of 203 pediatric cancer patients in the United States.
Results: Thirty-two patients completed the baseline questionnaire. The median age was 9 years (IQR 6-12). Children
reported very low levels of mobility (median: 28, IQR: 2337), high anxiety (median: 63, IQR: 55-71), high depressive
symptoms (median: 62, IQR: 59-66), high fatigue (median:
62, IQR: 54-68), average satisfaction with peer relationships
(median: 52, IQR: 44-55), and high pain interference (median:
63, IQR: 55-68). The highest score for pain intensity of 10 was
given by 22/32 (68%) of patients. When compared to a United
States pediatric cancer population, the Malawi cohort had
statistically significant worse HRQoL in mobility, anxiety,
depression, fatigue, and pain interference domains (p<0.05).
Conclusions: Baseline HRQoL for pediatric lymphoma
patients in Malawi is poor for all HRQoL domains except peer
relationships. This emphasizes an urgent need for clinical and
research programs to specifically address HRQoL among children undergoing cancer treatment in SSA.
PD-076 Delirium: A Prospective Study within the
Pediatric Hematology, Oncology, and Bone Marrow
Transplant Population (PHO) at a Single Institution
K. Winsnes1 , E. Shereck1 , M. Recht1 , C. Eriksson2 , K. Johnson3 , R.
Loret De Mola1 , L. Stork1
1 Oregon
Health and Science University, Pediatric Hematology / Oncology,
Portland, USA; 2 Oregon Health and Science University, Pediatric Critical
Care, Portland, USA; 3 Oregon Health and Science University, Pediatric
Psychiatry, Portland, USA
Background/Objectives: Delirium affects 10-30% of
patients in pediatric intensive care units (PICU) and causes
increased length of stay, decreased attention in school, and
post-traumatic stress disorder. The Diagnostic and Statistical
Manual of Mental Disorders (DSM V) defines delirium as a
“disturbance of consciousness […] with reduced ability to
focus, sustain or shift attention” due to an underlying medical
condition. Hypothesizing that delirium is under recognized
in the PHO population, we designed a prospective study
using a validated screening tool to determine the frequency
SIOP ABSTRACTS
S150 of S518
of delirium in hospitalized PHO patients and to identify
associated clinical factors.
Design/Methods: The baseline frequency of delirium diagnosis was determined using a data mining program of electronic
medical records (EMR). PHO and PICU nurses have been
trained to use the Richmond Assessment and Sedation Scale
(RASS) and the Cornell Assessment for Pediatric Delirium.
All PHO patients on the inpatient unit and in the PICU are
screened for delirium once every 12-hour shift and the scores
are entered into the EMR. Additionally, specific variables are
collected on each patient to help identify potential risk factors
for delirium.
Results: The frequency of delirium diagnosis in 2015 was
4.5%: 17/379 unique patients on the PHO unit and/or PICU.
A 3-month pre-study feasibility phase identified 5 unique
patients among 49 (10%) with a positive delirium screen, one
which prompted psychiatric intervention. Two months into the
year-long prospective study, which began Jan 2017, 78 unique
patients among 135 consecutive cases have enrolled; 7 pts
(9%) had a positive delirium screening. Initial analysis will
occur at six months.
Conclusions: Delirium exists in the PHO population, however its frequency is yet to be determined. Routine delirium
screening should improve our recognition and diagnosis of
delirium and, thereby, allow us to promptly intervene or prevent delirium in order to avoid potential long term consequences.
Results: Findings indicated that AYA patients prefer
resources that reduce feelings of loneliness, create a sense
of community or belonging, and provide opportunities to
meet other AYA patients. Among the top barriers to optimal
cancer care, AYAs identified a lack of cancer care providers
specializing in AYA care, a lack of connection to an AYA
patient community, and their own lack of ability to navigate
the health system. Participants also described aspects of
cancer information and supportive care resources that they
believe address AYAs’ concerns.
Conclusions: Information derived from this study will help
developers of cancer information and support resources better
reach their intended audience. From the point of view of AYA
cancer patients, optimal cancer care and utilization of information and support resources requires that cancer support programs foster meaningful connections among AYA patients.
Results also suggest that patient resources should equip AYAs
with practical knowledge and skills necessary to navigate the
health system and advocate for themselves.
T R E AT M E N T A N D CA R E - N U R S I NG
PD-078 Memory AIDS: Assistive Tools for
Pediatric Oncology Nurses in Patient Care Area
from Indus Children Cancer Hospital, Pakistan
S. Anwarali1 , R. Punjwani1 , B. Ahmed1
1 Indus
PD-077 What Do Adolescents and Young Adults
Want from Cancer Resources?
B. Zebrack1 , C. Cheung2
1 University
of Michigan, School of Social Work, Ann Arbor, USA;
of California- Los Angeles, Department of Social Welfare, Los
Angeles, USA
2 University
Background/Objectives: As clinicians are encouraged to
provide personalized and patient-centered care, inclusion of
the patient's voice as a component of evidence generation is
critical. The primary purpose of this study was to assess adolescent and young adult (AYA) cancer patients’ preferences
for cancer information and support resources.
Design/Methods: Utilizing a modified Delphi technique,
AYA cancer patients identified barriers to optimal AYA cancer care, cancer resources that address their needs, and specific characteristics of cancer resources they find helpful. The
Delphi panel consisted of a convenience sample of 21 patients
aged 18-39 years, who were diagnosed with cancer between
ages 15-39 years and were no more than eight years out from
cancer treatment at the time of the study. Survey data were
collected in three consecutive and iterative rounds over the
course of six months in 2015.
Children Cancer Hospital, Nursing Education Service, Karachi,
Pakistan
Background/Objectives: Nurses are the pillar of any health
care organization. They are the front line in providing care
to patients. Many organizations seek to enhance the quality
of patient care by improving nursing knowledge and competency. Pediatric oncology nurses working under pressure or
novice nurses tend to miss small but valuable pieces of information which eventually can result in sentinel events. Thus,
Indus Children Cancer Hospital Nursing Education Service
in Karachi, Pakistan we created an essential memory aid–
cue/flash cards– to help nurses as a reference guide.
Design/Methods: An extensive literature review was conducted using key words ‘flash cards’, ‘memory aids’, ‘nurses’,
‘pediatric oncology’ and ‘patient care’ using Boolean (AND,
OR) words, all suggestive of the effectiveness of flashcards.
Selective flashcards were made and printed for personal usage
to nurses in clinical areas. Project shall be evaluated by qualitative approach by asking nurses how and which flash cards
were beneficial.
Results: Evidence-based nursing literature suggests that
learning tools for nurses and other healthcare professionals are
useful, effective and handy for referral to vital information.
SIOP ABSTRACTS
These memory aids have assisted novice nurses in learning
and refreshing basic concepts and retaining knowledge and
learnt skills. These aids have assisted nurses to perform better
care with decreased number of sentinel events. Nurses benefit
from memory aids for chemotherapy and medication calculation, vital signs, height and weight, basal surface area, pain
assessment and management.
Conclusions: Use of memory aids is an innovative way for
ongoing learning in pediatric oncology clinical areas. The
effectiveness of the flash cards will aid in referring to quick
information required rather than making a mistake. The cards
are used as a reference guide and precept pediatric oncology nurses and interns in clinical areas. The memory aids
are expected to increase level of competency and confidence
among pediatric oncology nurses to provide quality care.
PD-079 Pediatric Nurses Knowledge on
Chemotherapy at Komfo Anokye Teaching Hospital
R. Appiah1
1 Staff
Nurse at Komfo Anokye Teaching Hospital, Ghana
Background: Chemotherapy is one of the effective treatments of most oncological conditions with chemo (anticancer drug)
This study was undertaken to evaluate the knowledge on staff
nurses at pediatric wards at Komfo Anokye Teaching Hospital
on chemotherapy.
Methods: This study was a descriptive study structured questionnaire with both open and close ended questions were used.
Systemic random sampling was used in selecting 100 respondents 40% of the respondent have knowledge on chemotherapy and the remaining 60% said they don't have knowledge
on chemotherapy. Regarding the side effects, 45% have the
knowledge and the remaining 55% said they don't have knowledge on it. For the specific chemo for treating specific types of
oncological conditions 30% were able to give correct answer,
70% of the total respondent were not able to give correct
answers.
Results: At the end of the survey minority of the respondent have adequate knowledge on chemotherapy with a percentage of 40%, 45 % of the total respondents have adequate
knowledge on side effect of chemotherapy and minority of the
respondent have adequate knowledge on specific chemo for
treating specific oncological condition/.
Conclution: It is recommended that workshop and in-dept.
service training session on chemotherapy should be organized
for nursing staffs of pediatric wards at Komfo Anokye Teaching Hospital.
S151 of S518
PD-080 A Systematic Review of the Gut
Microbiome, Treatment-Related Symptoms and
Targeted Interventions in Children with Cancer
J. Bai1 , M. Behera2,3 , D. Bruner1,3
1 Emory
University, Nell Hodgson Woodruff School of Nursing, Atlanta,
USA; 2 Emory University, School of Medicine, Atlanta, USA; 3 Emory
University, Winship Cancer Institute, Atlanta, USA
Background/Objectives: With the development of highthroughput DNA sequencing and bioinformatics technologies, a growing body of literature showed that the gut microbiome (GM) plays a critical role in maintaining children's
health and in preventing and treating children's disease.
Current application of the GM in childhood cancer is still
unknown. This systematic review aimed at understanding the
GM, its applications in gastrointestinal symptoms (GIS) and
psychoneurological symptoms (PNS), and the efficacy of targeted interventions in children treated for cancer.
Design/Methods: PubMed, EMBASE, the Cochrane Library,
and the American Society of Clinical Oncology abstract were
searched. Eligible studies included all study types in which
the target population were children with cancer, the GM was
studied as a primary or secondary outcome, and published in
English. The Mixed Methods Assessment Tool was used to
assess the methodological quality.
Results: Seven studies met our eligibility criteria, including two case-control studies, two cohort studies, and three
randomized controlled trails. Our findings showed that children with cancer showed a significantly lower diversity in
the GM (e.g., Bifidobacteria, Lactobacillus, Clostridium XIVa
and IV) than the healthy controls. The total counts of healthy
GM (e.g., Bacteroides and Bifidobacterium) decreased significantly pre- and post-chemotherapy in children with cancer. Dysbiosis in the GM showed potential associations with
GIS and PNS. Use of the probiotic (Bifidobacterium or Lactobacilli) and prebiotic supplementations (fructooligosaccharides) significantly improved dysbiosis of the GM, but did not
significantly influence the adverse events (e.g., abdominal distention and diarrhea) in children treated for cancer.
Conclusions: Children treated for cancer experienced dysbiosis of the GM, which can be improved by the prebiotic and
probiotic supplementations. More studies are needed to investigate the relationships between the GM and GIS and PNS,
and evaluate the effectiveness of prebiotic and probiotic interventions on dysbiosis of the GM in children with cancer.
PD-081 E-Learning as a Tool for Continuing
Education of Nurses in Hematopoietic Stem Cell
Transplantation
T. Bauters1 , J. De Munter2 , S. Van Lancker1 , T. Kerre2 , G.
Laureys1 , A. Mannaerts1 , L. Steendam1 , C. Dhooge1
SIOP ABSTRACTS
S152 of S518
1 Ghent
University Hospital, Pediatric Hematology- Oncology and Stem Cell
Transplantation, Ghent, Belgium; 2 Ghent University Hospital, Hematology
and Stem Cell Transplantation, Ghent, Belgium
Background/Objectives: The complexity of a Hematopoietic
Stem Cell Transplantation (HSCT) with the common toxicities and side effects, necessitates specific and continuing education and training for nurses and care-givers involved with
HSCT.
The aim of this project was to develop a basic educational framework for nurses, medical students and paramedics
involved in pediatric and adult HSCT recipients.
Design/Methods: An educational course in a format that is
easily accessible online has been created.
Results: The theoretical part consists of different topics: aim
of HSCT, indications, donor/stem cell sources, different types
of HSCT, … each highlighting pediatric and adult issues. This
is followed by a self-evaluation test, which can be used for
accreditation purposes. Upon completion, users will be able
to understand the process of HSCT, have knowledge of different conditioning regimens and will be able to identify the
common side effects or toxicities related to HSCT. In addition,
they will have insight in supportive care concepts and preventive or treatment strategies, making sure that the course meets
local needs.
Conclusions: The e-learning tool allows nurses and caregivers involved in HSCT a more flexible learning, such as the
option to choose the time and place to study, and provides
electronic links to more detailed learning materials. Nurses
who have completed the course will have a basic level of
understanding of the principles of treatment and supportive
care in HSCT patients. In the future, supplementary e-lessons
and an advanced level e-learning tool will be developed.
PD-082 Risk Factors for Non-Adherence to
Treatment of Family Caregivers of Children with
Cancer
M. Cardenas1
1 Instituto
Nacional De Cancerologia, Cundinamarca, Bogota, Colombia
Background/Objectives: BACKGROUND: Two important
factors (complete withdrawal and toxic deaths) associated
with suboptimal service by health care providers, have been
identified to explain the failure of treatments and differences
in mortality among children with cancer in developed countries and the treaties in countries with economic limitations,
one of them is the complete withdrawal of treatment.
OBJECTIVES: Determine the risk factors for non-adherence
to treatment of family caregivers of children with cancer at the
National Cancer Institute.
Design/Methods: Descriptive and transversal study, with
quantitative approach, which participants are family caregivers of children with cancer. Implementation of two instruments, Survey characterization care dyad family caregiver –
a person with a chronic disease of the National University
of Colombia´s group of Chronic Care and the Instrument
that evaluates the Factors that Influence the Adherence to
the Pharmacological and Non-Pharmacological Treatments in
Patients, designed and validated by Nursing.
Results: The risk factors for non-adherence are identified such
as, social and economic factors, related to the provider, the
health system and equipment, related of therapy and / or treatment, related to the patient and related to the disease.
Conclusions: The study pretends to intervene in a timely
manner on the needs of families of children with cancer
and in this way create lines of action in nursing to prevent
non-adherence to treatments.
PD-083 Changes of Nutritional Status and
Associated Factors Among Chinese Pediatric
Allogeneic Hematopoietic Stem Cell
Transplantation Patients
B. Zhang1 , N. Shen2 , M. He1
1 Shanghai
Children's Medical Center, Hematology and Oncology,
Shanghai, China; 2 Shanghai Children's Medical Center, Nursing
Department, Shanghai, China
Background/Objectives: Growing evidences suggested that
hematological and oncological disease, chemo-radiotherapy
during conditioning of allogeneic hematopoietic stem cell
transplantation (allo HSCT) and related complications could
induce metabolic change in nutrition, which not only declined
patients’ physical function but also predisposed them to
nutrition-related chronic illness. However, few studies have
examined the changes of nutrition status and associated factors among Chinese pediatric allo HSCT patients.
Design/Methods: This study was designed as a longitudinal study to determine the changes of nutritional status
in 89 Chinese pediatric patients during pre-transplant and
post-transplant periods (pre-transplant day, day+18, day+30,
day+60, and day+100). Data were collected using a questionnaire survey including demographic information, anthropometric measurements and body composition. A repeated measure ANOVA was used to analyze the change of nutritional
status, and mixed linear model was used to evaluate the associations of potential related factors.
Results: During the first 100 days after HSCT, the anthropometric measurements BMIz (Body Mass Index z), TSF
(triceps skin fold thickness) decreased significantly for the
first 30 days (p<0.05)and then gradually increased (p<0.01).
WC(waist circumference) demonstrated a gradually upward
trend from pre-transplant day to day +100 (p<0.01). The
SIOP ABSTRACTS
%BF(percent of body fat) increased significantly during the
first 60 days after HSCT (p<0.01), with summit in the day
+60. The change of TSF was associated with time, diagnosis,
source of stem cell, HLA matching, and BMIz before transplantation. The change of WC was associated with time, gender, source of stem cell, HLA matching, and BMIz before
transplantation. The change of %BF was associated with time,
gender, HLA matching, and BMIz before transplantation.
Conclusions: Nutritional status of Chinese pediatric allo
HSCT patients changed significantly, and was associated with
time, gender, diagnosis, source of stem cell, HLA matching,
and BMIz before transplantation. The transplantation period
witnessed an accumulation of body fat, and central obesity,
especially in girls.
PD-084 Predictors of the Posttraumatic Growth
in Parents of Children with Leukemia
S. Hong1 , H.R. Park2 , S.H. Choi3
1 Kangwon
National University- College of Health Science, Department of
Nursing, Samcheok-si, Republic of Korea; 2 The Catholic University of
Korea, College of Nursing, Seoul, Republic of Korea; 3 Seoul St. Mary's
Hospital- The Catholic University of Korea, BMT Center, Seoul, Republic of
Korea
Background/Objectives: Even though parenting a child with
leukemia is a tremendous challenge that places struggle on
caregivers, parents of children with leukemia experience positive outcomes. The purpose of this study was to identify predictors of posttraumatic growth in parents of children with
leukemia.
Design/Methods: Participants were 137 parents (117 mothers and 20 fathers) of children with leukemia recruited at C
university hospital in Korea from May to August in 2016.
Participants completed self-report measures of posttraumatic
growth, core belief, deliberate rumination, resilience, distress
disclosure, social support, meaning in life and satisfaction
with life.
Results: All the variables except distress disclosure were positively correlated with posttraumatic growth. Resilience, core
belief and social support were significant predictors related to
posttraumatic growth in parents of children with leukemia and
explained for 54% of the variance in posttraumatic growth.
Conclusions: The results show that there are several factors
affecting posttraumatic growth in parents of children with
leukemia. Therefore, nursing intervention programs including
strengthening resilience, revising core belief as well as utilizing social support system should be provide for this population in order to promote positive psychological change
beyond parental traumatic events related to children with
leukemia.
S153 of S518
PD-085 Development of a Virtual Reality
Distraction Intervention for Youths with Cancer
Undergoing Subcutaneous Port Accesses: A
Usability Testing Study
L. Jibb1 , J. Stinson2 , A. Oussama3 , K. Positano4 , K.A. Birnie5 , V.
Hum2 , N. Juma6 , P. Hroch7
1 The
University of Ottawa, School of Nursing, Ottawa, Canada; 2 The
Hospital for Sick Children, Child Health Evaluative Sciences, Toronto,
Canada; 3 The Hospital for Sick Children, Oncology/ Haematology,
Toronto, Canada; 4 The Hospital for Sick Children, Child Life, Toronto,
Canada; 5 University of Toronto / Hospital for Sick Children, Lawrence S.
Bloomberg Faculty of Nursing- University of Toronto / Child Health
Evaluative Sciences, Toronto, Canada; 6 The Hospital for Sick Children,
Nursing, Toronto, Canada; 7 McMaster University, Michael G. DeGroote
School of Medicine, Hamilton, Canada
Background/Objectives: Subcutaneous port (SCP) accesses
with needles are amongst the most painful and distressing treatment-related experiences for youths with cancer.
In response, we developed a virtual reality (VR) intervention with hardware (i.e., head-mounted display, handheld
controller) and software (underwater program where head
movements allow exploration) to distract youths during SCP
accesses. This study aimed to refine this intervention such that
it was acceptable to youths, did not cause adverse events, and
safely allowed communication between youths and healthcare
providers during VR immersion.
Design/Methods: Two iterative cycles of usability testing
were used. Eleven youths (11±2.95 years; 27% female) with
a variety of cancer diagnoses took part. Testing sessions were
audio-recorded and 1 observer took field notes. Youths used
the intervention during SCP accesses while “thinking aloud”
about their impressions. Youths answered open-ended questions addressing the intervention and adverse events. The
observer discussed the session and developed consensus on
themes related to the study aims, referring to audio-recordings
as necessary.
Results: Youths liked both the VR hardware and software
and reported it was easy to use. No adverse events occurred.
Cycle 1 revealed that full engagement with the VR environment (i.e., head movements) was limited by requirements to
remain still during the procedure. Cycle 2 revealed needs for:
(1) more distracting intervention components (e.g., games and
music) and (2) optional notifications related to the status of
the procedure. Software changes to rectify these issues were
made.
Conclusions: Next steps will include feasibility testing before
examining the intervention's effect on pain and distress during
SCP access in a randomized controlled trial. We expect that
an acceptable and safe VR intervention will decrease pain and
distress and improve the quality of care delivered to young
cancer patients.
SIOP ABSTRACTS
S154 of S518
We would like to thank the patients who participated in the
study. Funding was provided by the SickKids Garron Family
Cancer Centre.
PD-086 Adolescent and Young Adult Cancer
Survivors – Information and Support Regarding
Sexual Concerns
M. Olsson1 , M. Jarfelt1
1 Institute
of Clinical Sciences- University of Gothenburg, Pediatrics,
Göteborg, Sweden
C. Wilson1 , A. Li1 , C. Emmanuele1 , T. Hiller2 , B. O'Neil1 , A.
Chang1
1 The
2 The
Hospital for Sick Children, Oncology/Haematology, Toronto, Canada;
Hospital for Sick Children, Oncology/Haematology, Torono, Canada
Background/Objectives: A group of nurses within a paediatric Haematology/Oncology unit has witnessed a steady
increase in, what they believe, burnout and emotional exhaustion from staff. This phenomenon has been evidenced through
verbal expressions of concern among peers, as well as an
increased staff turnover. Oncology nurses support the physical and emotional journeys of their patients while laughing,
crying and celebrating with them (Rishel, 2015)
Background/Objectives: In qualitative research, adolescent
and young adult cancer patients express concerns on the lack
of information on sexuality during treatment. The purpose of
this study was to explore to what extent adolescent and young
adult cancer survivors found information and support concerning sex.
The ongoing stress of burnout is associated with nurse job dissatisfaction. (Potter et al., 2013). By being able to recognize
signs and symptoms of burnout and compassion fatigue, as
well as providing proper support to staff to incorporate wellness behaviours in their own life will help to increase job satisfaction and resiliency.
Design/Methods: A study specific questionnaire has been
developed. The method used for question development
includes expert validity from professionals and face-to-face
validity from former cancer patients. The questionnaire contains several areas in an adolescent and young adult's life
affected by cancer and this study focused on information and
support regarding sexual issues. The web-based questionnaire
was sent to all adolescent and young adult cancer survivors
treated during 2010 and 2011 in the North, South-east and
West Sweden.
Design/Methods: A Current State/Needs Assessment was
done where nurses anonymously submitted “stressors” experienced on the identified unit. The next steps in this project
are Focus Groups where five Focus Groups will be held with
6-8 Registered Nurses from the Haematology/Oncology Inpatient Unit per session. A separate Focus Group will be held
with RNs who have recently left the unit. Discussions will
be recorded/transcribed and analyzed. A survey will be completed which will be developed based on findings from Focus
Groups. The survey will provide richer data on stressors and
potential interventions that would be helpful in self-care and
building resiliency. Based on the findings of the survey, current research, and benchmarking with similar institutions, a
unit-based program on self-care and building resiliency will
be developed and implemented and evaluated.
Results: Adolescent and young adult cancer survivors
reported that health care professionals did not approach them
on sexual issues during cancer treatment in 65% of the cases.
Among adolescent and young adult cancer survivors 50 %,
expressed not having any questions on sex during treatment.
Of the adolescent and young adult cancer survivors who
wanted information, 30 % were not satisfied with the information. They majority wanted information on sexual issues in
person, from a physician or nurse and from written information, fewer wanted internet information and support. Almost
half of the cancer survivors reported not having sex during
treatment due to risk of infection.
Conclusions: The result of this population-based study
encourage health care professionals caring for adolescent and
young adult cancer patients to raise the question of sexual
activity during treatment. To give an adolescent and young
adult cancer patient general basic information on sexual issues
along with individual recommendations may avoid misunderstandings regarding sexual activity during cancer treatment.
PD-087 Initiating a Quality Improvement Project
on Self-Care and Building Nurses’ Resiliency on a
Haematology/Oncology Unit
Results: The Needs Assessment identified the stressors as:
Lack of Breaks, The Number of New Initiatives and changes
in Chemotherapy Protocols, Communication with the Interprofessional Team, Emotional Stress and Moral Distress leading to Burnout and The Increasing Workload Expectations.
Conclusions: The conclusions that have been discovered this
far are that there are stressors and that program development
is needed.
TREATMENT AND CARE - B IOLOGY
AND PATHOLOGY
PD-088 Cancer Predisposition in Childhood
Cancer -The Duesseldorf Experience in
Comprehensive Clinical Evaluation and Trio Whole
Exome Sequencing of Families
SIOP ABSTRACTS
T. Brozou1 , M. Kuhlen1 , A. Borkhardt1 , J. Fremerey1 , E. Velleuer1 ,
D. Wieczorek2 , M. Gombert1 , C. Walter3 , M. Dugas3
1 Heinrich
Heine University Children’ s Hospital- Dusseldorf, Pediatric
Oncology- Hematology and Clinical Immunology, Dusseldorf, Germany;
2 Heinrich Heine University Hospital- Medical Faculty - Dusseldorf,
Insitutute of Human Genetics, Dusseldorf, Germany; 3 University of
Muenster, Institute of Medical Informatics, Muenster, Germany
Background/Objectives: A considerable percentage of
childhood cancers are due to cancer predisposition syndromes
(CPS). The ratio of CPSs caused by inherited versus de novo
germline mutations is unknown and, thus, recurrence risk in
siblings. In addition, the attitude of affected parents towards
genetic testing of themselves is unclear.
Design/Methods: We initiated an ongoing prospective study
performing whole-exome sequencing (WES) of parentoffspring trios to identify CPS and inheritance patterns in
newly diagnosed cancer children
Results: Between 01/2015 and 12/2016, 81 (85.3%) of 95
families participated, 14 (14.7%) refused to participate. Of 81
children, 5 (6.2%) presented with congenital malignancies, 4
(4.9%) with tumors with a high likelihood of an underlying
CPS. Of 68 family pedigrees, in 3 (4.4%) malignancies were
revealed in family members <18 years, relatives with cancer
<45 years in 6 (8.8%), any cancer history in 26 (38.2%), and
>1 relative with cancer in 14 (20.6%). In 10 (14.7%) families,
one first- or second-degree relative developed breast cancer,
in 4 (5.9%) sarcoma and in 3 (4.4%) each lymphatic malignancies and colon cancer.
To date, 57 trios were analyzed (depth 250-700x, median coverage >95%). A bioinformatic pipeline was established, the
actual gene list comprises about 2,000 genes and is ongoing
updated. Based on data of the St. Judes study group (Zhang
et al., NEJM 2015) variants are classified in three pathogenic
categories.
S155 of S518
1 Hospital
for Sick Children, Pediatric Oncology, Toronto, Canada;
Hospital of Eastern Ontario, Pediatric Oncology, Ottawa,
Canada; 3 McGill University, Human Genetics, Montreal, Canada; 4 McGill
University Health Center, Medical and Human Genetics, Montreal, Canada
2 Children's
Background/Objectives: An estimated 10-29% of children
with cancer have an underlying cancer predisposition syndrome (CPS); many are unrecognized. Identifying cancer susceptibility and appropriately referring to a genetics team is
vital to optimize patient care by incorporating potential preventative measures, adapting therapies, improving surveillance and counselling around family risk. Many challenges
limit the likelihood of a physician identifying CPSs and technological advances in cancer genetics/genomics are rapidly
outpacing the knowledge of most clinicians. To address these
issues, we are developing the MIPOGG, an electronic and
educational application for smart devices that include tumorspecific decisional algorithms designed to help identify those
children with cancer at an increased risk of an underlying
CPS.
Design/Methods: For each pediatric cancer included in the
International Classification of Childhood Cancers and the
WHO classification of CNS tumors (2016 revision), an extensive literature review was undertaken to highlight clinical
and/or molecular characteristics that increase the likelihood
of a genetic predisposition. These characteristics were used
to design simple algorithms following a binary tree structure
with “yes / no” answers. Each algorithm ultimately advises
one of two possible outcomes: ‘Referral Suggested’ or ‘No
Referral Necessary’, linked with an educational module. All
algorithms were critically reviewed by expert panels and validated through a multi-institutional retrospective chart review
to ensure sensitivity and positive predictive value.
So far, 2 children with LFS and 1 child each with Dicer1 syndrome, CMMRD and APC associated polyposis were identified. Experimental analyses of various variants of unknown
significance are in progress.
Results: Seventy-five tumor-specific algorithms will have
been finalized and we will present examples including
Osteosarcoma, Rhabdomyosarcoma and Wilms tumor, highlighting the performance of these algorithms in validation
studies. We also outline the rationale for tumors requiring
direct referral to a genetics service.
Conclusions: Testing of an underlying CPS is of extraordinary interest to affected families. The vast majority opts for
their right to know with particularly interest to recurrence risk
in other offspring. Thus, trio sequencing should become common practice.
Conclusions: The MIPOGG offers a clinically targeted
approach, designed to easily identify patients at risk for a CPS,
without the need for extensive or sophisticated investigations.
As a clinical tool, it has potential to optimize management of
children with cancer, across health care systems globally.
PD-089 Identifying Children at Increased Risk
for a Cancer Predisposition Syndrome: The McGill
Interactive Pediatric Oncogenetic Guidelines
(MIPOGG)
C. Goudie1 , N. Cullinan1 , H. Coltin2 , L. Witkowski3 , A. Villani1 ,
D. Malkin1 , W. Foulkes4
EPIDEMIOLOGY - PATHWAY OF
CA R E
PD-090 Complementary and Alternative Medical
Therapies in Pediatric Oncology Patients: A Single
Center Experience in a Low-Middle Income
Country
SIOP ABSTRACTS
S156 of S518
A. Farrag1 , F. Ali2
1 South
Egypt Cancer Institute- Assiut University, Department of Pediatric
Oncology, Assiut, Egypt; 2 Faculty of medicine- Assiut University,
Department of Pediatrics, Assiut, Egypt
Background/Objectives: Many cultures have reported the
usage of complementary and alternative medical therapies
(CAMT) by cancer patients. Some patients waste time and
money seeking advice for potentially harmful alternative
medicine.
Design/Methods: This study included pediatric oncology
patients under all phases of therapy in South Egypt Cancer
Institute. Personal interview with care givers (under consent)
was done, focusing on their educational level, monthly income
and residence. In addition to type, reason, experience and
when they started CAMT, if used.
Results: This study included 86 patients (54 males and
32 females), mean age was 7.7 (0.66-19) years. Diagnoses
included leukemia (44%) and other tumors (56%). Most
patients were living in rural areas (83%), 29% of mothers
were well educated. CAMT were reported by 52 patients
(60.5%), causing delay in presentation (1-2 weeks) in 6
patients (11.5%). Its purpose was complimentary in 37 cases
(71%) and alternative to medical therapy in 15 cases (29%).
CAMT types were herbal (63%), nutritional (33%), magical
(29%), religious (19%), or massage (15%). Multiple CAMT
were used in 25 patients. Advisers to use CAMT were mostly
the family (62%), other therapists (21%), or other patients
(15%). Reasons to use CAMT were either to treat complications (62%), cancer (21%), initial undiagnosed disease (10%),
or pain (21%), or to increase immunity after chemotherapy (15%), or relaxation (10%). Most patients reported that
CAMT was effective (65%) and is the same as or better
than conventional medical therapy (38%), they started its use
mostly in early phases of diagnosis and treatment (73%). Most
patients denied that any physician asked them about using
CAMT (98%). CAMT usage was more in relatively richer
families (n=31, p=0.023). There was no detected relationship
between the use of CAMT and patient's sex, diagnosis, residence, or maternal educational level.
Conclusions: Full medical history including CAMT is essential in all pediatric oncology patients.
PD-091 Baseline Characteristics and Outcomes
of Children with Cancer in the English-Speaking
Caribbean: A Multi-National Retrospective Cohort
T. Gibson1 , S. Beeput2 , J. Gaspard3 , C. George4 , D. Gibson5 , K.
Glasgow6 , V. Leandre-Broome7 , N. Palmer-Mitchell8 , C. Alexis7 , J.
Bird3 , C. Bodkyn4 , R. Boyle6 , S. McLean2 , M. Reece-Mills8 , C.
SinQuee-Brown5 , U. Allen9 , S. Weitzman10 , V. Blanchette10 , S.
Gupta10
1 The
University of the West Indies, Pathology, Kingston, Jamaica;
Children's Hospital, Oncology, Kingston, Jamaica; 3 Victoria
Hospital, Oncology, Castries, St Lucia; 4 Eric Williams Medical Sciences
Complex, Oncology, Port of Spain, Trinidad & Tobago; 5 Princess Margaret
Hospital, Oncology, Nassau, Bahamas; 6 Milton Cato Memorial Hospital,
Oncology, Kingstown, St Vincent and the Grenadines; 7 Queen Elizabeth
Hospital, Oncology, Bridgetown, Barbados; 8 University Hospital of the
West Indies, Oncology, Kingston, Jamaica; 9 The Hospital for Sick Children,
Infectious Diseases, Toronto, Canada; 10 The Hospital for Sick Children,
Haematology/Oncology, Toronto, Canada
2 Bustamante
Background/Objectives: Children with cancer in the
English-speaking Caribbean (ESC) face unique challenges, including distribution across small populations
at vast distances. ESC childhood cancer outcomes are
unknown.
Design/Methods: Through the SickKids-Caribbean Initiative (SCI), we established a multi-national childhood
cancer outcomes database across seven centres in six
countries (Bahamas, Barbados, Jamaica, St. Lucia, St.
Vincent, and Trinidad and Tobago). Trained data managers
at each site actively entered patient demographics, disease,
treatment, and outcome data. Data collection commenced
in 2013, with retrospective collection to 2011 and subsequent prospective collection; data for 2011-2015 were
analysed.
Results: 367 children were diagnosed between 2011-2015;
median age was 5.7 years (interquartile range 2.9-10.6 years).
124 (33.8%) patients were diagnosed with leukemia, 30
(8.2%) with lymphoma, and 149 (40.6%) with a solid tumour.
A relative paucity of children with brain tumours was seen
(N=48, 13.1%). Two-year event free survival (EFS) for the
entire cohort was 48.5%+/-3.2%, while two-year overall survival (OS) was 55.1%+/-3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumour experienced
better two-year EFS (62.1%+/-6.4% and 66.7%+/-10.1%),
while dismal outcomes were seen in children with acute
myeloid leukemia (AML; 22.7+/-9.6%), rhabdomyosarcoma
(21.0%+/-17.0%) and medulloblastoma (21.4%+/-17.8%). Of
108 deaths with known cause, 58 (53.7%) were attributed
to disease and 50 (46.3%) to treatment complications. Death
within 60 days of diagnosis was relatively common in acute
leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite
this, traditional prognosticators adversely impacted outcome
in ALL, including higher age, higher white blood cell count,
and T-cell lineage.
Conclusions: ESC childhood cancer outcomes are superior to
those in many other low- and middle-income settings but are
still significantly inferior to high-income country outcomes.
Based on these data, SCI interventions improving supportive
care, diagnostics, and modifying leukemia treatment protocols are underway. Continued data collection will allow evaluation of these interventions and ensure maximal outcome
improvements.
SIOP ABSTRACTS
PD-092 Childhood Cancer: Survival in
Argentina. Report from the National Pediatric
Cancer Registry, ROHA NET, 2000-2010
F. Moreno1 , C. Cipolla1 , G. Macias2 , D. Loria1 , G. Abriata3 ,
ROHA Network1
1 Argentinian
Oncopediatric Registry- National Cancer Institute-, Ministry
of Health, Ciudad Autonoma de Buenos Aire, Argentina; 2 National Cancer
Institute, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina;
3 Survellance and Epidemiological Analysis - National Cancer Institute-,
Ministry of Health, Ciudad Autonoma de Buenos Aire, Argentina
Background/Objectives: Information on the epidemiology
of childhood cancer is mandatory for the planning of healthcare policies. The Argentine National Pediatric Cancer Registry (ROHA) is a hospital-based registry with national coverage and has been active since 2000. The aim of the current
study was to analyze the 5-year overall survival (OS) of children diagnosed with cancer in Argentina during 2000-2010
by major pediatric cancer subtypes.
Design/Methods: Newly diagnosed pediatric cancer cases are
registered in the ROHA (estimated coverage is 93% of the
country´s cases). Five-year OS was estimated using KaplanMeier methods.
Results: Between 2000 and 2010, a total of 14,239 new cancer diagnoses in children aged <15 years were reported to
the registry. Five-year OS for all cancers was 57.4% (95%CI:
56.5-58.3). Specific 5-year OS for the most common cancer subtypes was: leukemias 58.7% (95%CI: 57.3-60.1), lymphomas and related neoplasms 73.1% (95%CI: 70.8-75.3),
brain neoplasms 41.1% (95%CI: 39.0-43.2), soft-tissue sarcomas 47.0% (95%CI: 43.3-50.7), neuroblastomas 50.3%
(95%CI: 46.4-54.0), renal tumors 72.5% (95%CI: 68.6-76.0),
and malignant bone tumors 42.2% (95%CI: 38.2-46.1).
Conclusions: The 5-year OS for children diagnosed with cancer in Argentina was 57%. Even though this percentage is
lower than what is reported in high-income countries the distribution of pediatric cancers by subtype were similar. Improving these results remains a challenge for our health-care system.
PD-093 Adolescent and Young Adult (AYA)
Cancer Care in Canada: Highlights from A Report
on System Performance Metrics
P. Rogers1 , C. Rae2 , K. Marr1 , S. Gupta3 , D. Szwajcer4 , C.
Hammond5 , J. Pole6 , M. McBride7 , C. D'cruz7 , C. Digout8 , A.
Flanders9 , A. Srikanthan10 , M. Greenberg3 , Y.S. Rho11 , M.
Palumbo11 , P. Kavan11 , T. Buckland12 , P. Grundy13 , B. Schacter4 ,
R. Barr2
1 BC
Children's Hospital, Pediatrics, Vancouver, Canada; 2 McMaster
University, Pediatrics, Hamilton, Canada; 3 Hospital For Sick Children,
Oncology, Toronto, Canada; 4 Cancercare Manitoba, Oncology, Winnipeg,
Canada; 5 Canadian Hospice Palliative Care Association, Palliative care,
Ottawa, Canada; 6 Pediatric Oncology Group of Ontario, Oncology,
S157 of S518
Toronto, Canada; 7 BC Cancer Agency, Cancer Control Research,
Vancouver, Canada; 8 IWK Health Centre, APPHON, Halifax, Canada;
9 IWK Health Centre, Oncology, Halifax, Canada; 10 BC Cancer Agency,
Oncology, Vancouver, Canada; 11 McGill University, Oncology, Montreal,
Canada; 12 University of Alberta, Business, Edmonton, Canada;
13 University of Alberta, Pediatrics, Edmonton, Canada
Background/Objectives: Health care needs for AYAs with
cancer are different from those in older and younger patients.
Reporting of indicators is essential to evaluate projects and
system changes being undertaken to improve care for this population. The goal of this project was to report on indicators to
assess the current state of AYA cancer care in Canada.
Design/Methods: Measures of health system performance
were selected from consensus-based indicators. Data were
obtained from administrative databases and national surveys.
Areas of focus included: epidemiology, active care, palliation,
psychosocial issues, survivorship and research.
Results: Epidemiology: Over the last 20 years there has been
an 18.2% relative increase in new cancer cases in 15-29
year olds. Five-year relative survival was 86.3%, an absolute increase of 6.2% from the early 1990s. Active care:
Among 20–29 year olds, 26.6% began treatment ≥57 days
after diagnosis for breast cancer; approximately 20% of other
age groups waited a similar period. 54% of AYAs with breast
and colon cancer were treated at teaching hospitals as compared to 47.8% of older adults. Palliation: Most AYA cancer deaths in 2012 occurred in hospital (73%). Psychosocial
issues: Emotional support was rated negatively by both AYA
males (24.1%) and females (26.2%). Survivorship: Cancer survivors and the general population shared similar achievement
rates of post-secondary education; cancer survivors reported
higher unemployment. Research: Average annual investment
in AYA-specific cancer research between 2005 and 2013 was
$1.8 million, 0.4% of total cancer research investments in
Canada. As of June 2016, 128 of therapeutic cancer clinical
trials (32.9%) were for a cancer prevalent among AYAs.
Conclusions: Opportunities for improving care for AYAs
with cancer were identified, as was a gap in research investment. Challenges to reporting on AYA indicators were identified e.g. lack of age-specific data; inability to analyze by type
of cancer and age. The report is available through systemperformance.ca.
PD-094 Hispanic Ethnicity is Associated with
Methotrexate-Related Neurotoxicity in Children
Receiving Acute Lymphoblastic Leukemia
Treatment
O. Taylor1 , A. Brown1 , J. Brackett1 , I. Moore2 , C. Hooke3 , R.
Luna-Gierke1 , M. Hockenberry4 , P. Lupo1 , M. Scheurer1
1 Baylor
College of Medicine, Pediatrics- Hematology-Oncology Section,
Houston, USA; 2 University of Arizona, School of Nursing, Tucson, USA;
S158 of S518
SIOP ABSTRACTS
3 University
Background/Objectives: Exposure to anthracyclines such
as doxorubicin (DOX) during childhood cancer treatment is
unequivocally linked to the development of cardiovascular
disease. Clinical strategies to mitigate long-term cardiac morbidity in childhood cancer survivors include pretreatment with
the iron chelator dexrazoxane (DEX) and the use of liposomal doxorubicin (L-DOX). Both strategies decrease acute cardiac toxicity. However, due to the long latent period between
exposure and development of cardiac disease, the long-term
cardiac outcome of survivors treated using these strategies
is mostly unknown. Thus, their use has not yet been widely
adopted in clinical practice. Here we report the evaluation of
DEX and L-DOX in a clinically relevant murine model of
early anthracycline exposure followed by the monitoring of
cardiac function and survival throughout lifespan into aged
adult mice.
of Minnesota, School of Nursing, Minneapolis, USA; 4 Duke
University, School of Nursing, Durham, USA
Background/Objectives: Methotrexate (MTX) is a critically
important chemotherapeutic agent in acute lymphoblastic
leukemia (ALL) therapy. However, MTX-induced neurotoxicity (NT) can lead to treatment modifications, which may
jeopardize long-term survival in affected patients. The objective of this study is to evaluate demographic and clinical factors associated with incidence of acute MTX NT among pediatric patients with ALL.
Design/Methods: Pediatric ALL patients (n=216) undergoing therapy at three major childhood cancer treatment centers in the United States (Texas Children's Cancer Center;
University of Arizona; Children's Minnesota) between 2012
and 2017 were enrolled on a prospective study of treatmentrelated toxicity. MTX NT was defined as any neurologic event
(e.g., aphasia, seizure) following intrathecal (IT) and/or intravenous (IV) MTX that resulted in modifications in IT and/or
IV MTX therapy. Logistic regression was used to generate
odds ratios (OR) and 95% confidence intervals (CI) for the
impact of demographic and treatment features on MTX NT.
Results: Thirty-four patients (16%) experienced acute MTX
NT. Of the patients who experienced NT, 77% (n=26) were
Hispanic compared to 41% (n=75) of those without MTX NT
(n=182). Median age at diagnosis was significantly higher
(p<0.001) in MTX NT group: 12.4 years vs. 6.3 years, respectively. Hispanics were 4 times (OR=4.60, 95% CI: 1.7611.98, p=0.002) more likely to experience MTX NT than
non-Hispanics after adjusting for sex, age at diagnosis, and
ALL risk stratification. Independent of Hispanic ethnicity,
only ALL risk stratification remained a statistically significant
predictor of MTX NT.
Conclusions: In this large multi-ethnic cohort, we found that
Hispanic ethnicity was strongly associated with increased risk
of MTX NT. This adds to the growing body of evidence indicating that Hispanic patients with ALL encounter significant
disparities in treatment outcomes. Understanding the mechanisms and predictors of these disparities is critical to improving the outcomes and survival for these patients.
LATE EFFECTS
PD-095 Long-Term Cardioprotective Efficacy of
Dexrazoxane and Liposomal Doxorubicin Evaluated
in a Murine Model of Early Doxorubicin Treatment
T. Andrews1 , G. Aune1
1 Greehey
Children's Cancer Research Institute/University of Texas Health
Science, Pediatrics- Division of Hematology-Oncology, San Antonio, USA
Design/Methods: Beginning at 2 weeks of age, C57BL6/J
mice (n = 6 per group, equal numbers of males and females)
were treated with weekly intraperitoneal injections as follows:
saline control, 5 mg/kg DOX, 50 mg/kg DEX:5 mg/kg DOX,
and 5 mg/kg L-DOX. Following completion of therapy, mice
were monitored under normal laboratory conditions. Physical
parameters including body weight, survival, and cardiac function using standard echocardiography were evaluated every
three months up to 22 months of age (aged adult mouse).
Results: Compared to controls, mice treated with DOX exhibited significantly reduced body weight (26% decrease), survival (50% decrease), and cardiac function (12% decrease in
ejection fraction- E.F.) In contrast, mice treated with DEX +
DOX or L-DOX exhibited normal body weight (no decrease),
enhanced survival (100%), and normal cardiac function (normal E.F.) compared to DOX-treated animals.
Conclusions: These studies performed in mice indicate
that both dexrazoxane and L-DOX significantly mitigate
cardiac damage induced by early anthracycline exposure,
throughout the lifespan and into old age. Clinical practice
should incorporate widespread use of these cardioprotective
strategies.
PD-096 Neurocognitive Change Following
Treatment for Pediatric Brain Tumors with Proton
Beam Radiotherapy Versus Surgery Only
L. Kahalley1 , M.D. Ris1 , A. Mahajan2 , M.F. Okcu1 , M.
Chintagumpala1 , W. Whitehead3 , A. Paulino4 , J. Orobio1 , H.
Stancel1 , C. Minard5 , D. Grosshans4
1 Baylor
College of Medicine, Pediatrics, Houston, USA; 2 Mayo Clinic,
Radiation Oncology, Rochester, USA; 3 Baylor College of Medicine,
Neurosurgery, Houston, USA; 4 The University of Texas MD Anderson
Cancer Center, Radiation Oncology, Houston, USA; 5 Baylor College of
Medicine, Dan L. Duncan Institute for Clinical and Translational Research,
Houston, USA
SIOP ABSTRACTS
Background/Objectives: Cranial radiotherapy is associated with neurocognitive toxicity. Proton beam radiotherapy
(PBRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes.
We examined change in neurocognitive scores over time in
pediatric brain tumor patients treated with craniospinal PBRT
(P-CSI), focal PBRT (P-Focal), and Surgery Only (SO).
Design/Methods: Patients received annual neurocognitive
evaluations for up to 5 years. We examined Full Scale IQ
(FSIQ), Working Memory Index (WMI), and Processing
Speed Index (PSI) scores. Separate general linear mixed models examined change in scores over time by treatment group.
Results: Scores were available for 69 patients (16 P-CSI,
21 P-Focal, 32 SO). Groups did not differ on demographic or clinical variables (47.8% male, 37.7% infratentorial tumor, mean age-at-treatment=9.8 years, mean followup interval=2.3 years). Tumor types included: 55.1% glioma,
17.4% medulloblastoma, 7.2% ependymoma, 7.2% germ cell,
5.8% craniopharyngioma, and 7.2% other. Median RT dose
was 54.0 Gy for P-CSI and 50.4 Gy for P-Focal. FSIQ, WMI,
and PSI scores remained stable over time in all treatment
groups (all p>0.05). Means for all three groups were within
normal limits across scores and available time points. Even
though FSIQ did not decline significantly in any group, the
FSIQ slope of the P-CSI group differed significantly from the
slopes of the P-Focal and SO groups (both p=0.03).
Conclusions: Within early survivorship, PBRT was not associated with significant cognitive decline. Outcomes were similar whether patients received PBRT (CSI or focal) or no
radiotherapy. Not only was global IQ within normal limits
for age, but processing speed and working memory (domains
known to be particularly radiosensitive) were also consistent
with age-expectations across groups. CSI emerged as a cognitive risk factor, consistent with photon outcomes research.
While findings are hopeful, replication with a larger sample
and later outcomes is needed and underway.
S159 of S518
possibly underlying the elevated risk for preterm labor in cancer survivors.
Design/Methods: Nationwide cancer and birth registries
were merged to identify 1,831 first deliveries of cancer survivors (diagnosed below 40 years of age) and 5,281 first deliveries of matched female controls between January 1991 and
December 2013. Multiple unconditional logistic regression
models were used to estimate the risk for pregnancy related
conditions adjusting for maternal age, year of delivery, gestational age and smoking.
Results: We found a significantly elevated risk for hospitalization due to threatened preterm labor (OR 1.42, 95% CI
1.03-1.95), fear of childbirth (OR 1.99, 95% CI 1.30-3.05)
and mental disorders and diseases of the nervous system (OR
3.99, 95% CI 2.13-7.48) among survivors compared to controls. An increased risk for overall hospitalization (OR 1.47,
95% CI 1.28-1.68) and hospital stays exceeding 7 days (OR
1.23, 95% CI 1.04-1.46) was also found.
The risk for premature rupture of the membrane, vaginal bleeding, pre-eclampsia or gestational diabetes was not
increased.
The highest risk for hospitalization due to threatened preterm
labor was seen among survivors delivering 0-5 years after cancer treatment and survivors diagnosed as young adults (age
25-39 years).
Conclusions: Cancer survivors have an increased risk for
preterm delivery possibly explained by spontaneous preterm
labor due to premature contractions and cervical shortening.
Health professionals treating these women should be aware
of these risks. In general, however, our results are reassuring
when it comes to pregnancies among cancer survivors.
PD-098 An Exploratory Analysis of Physical
Activity on Modifiable Aging-Related Risk Factors
Among Survivors of Childhood Cancer
N. Sloof1 , E. Hendershot2 , M. Griffin3 , L. Anderson2 , S.
Marjerrison2,4
PD-097 Risk Factors for Preterm Delivery
Among Early Onset Cancer Survivors – A
Register-Based Study
J. Melin1 , S. Heinävaara1 , N. Malila1 , A. Tiitinen2 , M. Gissler3 , L.
Madanat-Harjuoja1
1 Finnish
Cancer Registry, Institute for Statistical and Epidemiological
Cancer Research, Helsinki, Finland; 2 University of Helsinki- Helsinki
University Hospital, Department of Obstetrics and Gynecology, Helsinki,
Finland; 3 National Institute for Health and Welfare, National Institute for
Health and Welfare, Helsinki, Finland
Background/Objectives: Previous studies have shown an
elevated risk for preterm delivery among female cancer survivors. Our aim was to assess pregnancy related conditions
1 McMaster
University, Kinesiology, Hamilton, Canada; 2 McMaster
Children's Hospital, Pediatric Hematology/Oncology, Hamilton, Canada;
3 McMaster University, Health- Aging & Society, Hamilton, Canada;
4 McMaster University, Pediatrics, Hamilton, Canada
Background/Objectives: By age 45, more than 80% of survivors of cancer in childhood (SCC) have serious chronic
health conditions. The literature remains unclear whether
lifestyle factors, including physical activity (PA), are related
to long-term health outcomes. The objective of this study was
to examine the relationship between PA and established late
effects of treatment in adult survivors of childhood cancer.
Design/Methods: A retrospective chart review including all
adult SCC currently enrolled in the McMaster Aftercare pro-
SIOP ABSTRACTS
S160 of S518
gram was performed. Information on diagnosis, treatment, PA
and other lifestyle behaviours, as well as physiologic measures
was abstracted. Predictors of established late effects of cancer
therapy were examined using logistic regression on multivariable models built with known risk factors determined a priori,
and significant predictors from univariate analyses.
Results: Of the 262 patients included, only 42% reported
behaviour that met PA recommendations, and 27% indicated no PA participation. In multivariable analysis, significant independent associations were shown between normal
left ventricular ejection fraction (LVEF) and adequate PA
(P=0.03), as well as female sex (P=0.04), while accounting
for doxorubicin (P=0.21), chest radiation (P=0.08), as well
as other factors. Low bone mineral density (BMD) was associated with no PA (P=0.03) and ideal body mass index (BMI)
(P=0.02). Body fat percentage was associated with cranial
radiation (P<0.01) and female sex (P<0.01). High BMI was
associated with no PA (P=0.01) and normal BMD (P<0.01).
BMI was the only modifiable risk factor associated with any
lipid levels in univariate analysis.
Conclusions: Despite ongoing healthy active living counselling, only 42% of SCC in our clinic meet PA guidelines.
We identified novel independent associations between PA and
LVEF, BMD, and BMI in SCC, shown to be more strongly
associated with these markers of health than many established predictive treatment and lifestyle-related factors. PA is
an important predictor of healthy aging among SCC.
Results: 246 patients with LGG (106 spinal cord, posterior
fossa (PF), and brainstem; 88 optic pathway and midline; and
52 cerebral hemisphere) were included; median age of diagnosis 7.1 (range, 0.1 – 20.7) years, median PSI 2.1 (<1–131.1)
months, and median time to last follow-up 11.6 (0.1-21.4)
years. Cerebral hemisphere had fewest median neurological
impairments (2) compared to other locations (4) at baseline
(p<0.001); and at last follow-up (3) compared to other locations (5) (p=0.004). In all patients, PSI ≥ 3 months had higher
incidence of ataxia and dysmetria (41.6%) (p=0.003). PSI ≥
3 months had overall worse motor weakness in cerebral hemisphere; dysmetria in optic pathway and midline; and dysmetria and ear and vestibular disturbances in spinal cord, PF, and
brainstem (p≤0.05). PSI < 3 months) in spinal cord, PF, and
brainstem had worsening vagal nerve deficit (p=0.026).
Conclusions: Neurological outcomes in pediatric LGG vary
by location and delayed diagnosis minimally affects neurological outcomes.
IPSO POSTER DISCUSSION
PD-100 Bronchial Blockers in Pediatric Thoracic
Surgical Oncology
L. Martynov1 , N. Matinyan1 , V. Gruzdev2 , A. Sotnikov1 , P.
Kerimov3 , A. Kazantsev3
1 Pediatric
PD-099 Neurological Outcomes in Pediatric Low
Grade Glioma by Tumor Site and Timing of
Diagnosis
Z. Sadighi1 , E. Curtis1 , J. Zabrowski2 , C. Billups3 , R. Khan1 , I.
Qaddoumi4
1 St.
Jude Children's Research Hospital, Neurology, Memphis, USA; 2 ,
Neurology, Memphis, USA; 3 St. Jude Children's Research Hospital,
Biostatistics, Memphis, USA; 4 St. Jude Children's Research Hospital,
Oncology, Memphis, USA
Background/Objectives: Characterization of neurological
outcomes by site of tumor and duration of presenting symptoms in patients with pediatric low grade glioma (LGG) has
not been assessed until now.
Design/Methods: An institutional review board-approved
retrospective study was conducted for patients diagnosed with
LGG at St. Jude Children's Research Hospital between 1995
and 2005. Neurological impairments (severity defined by
Common Terminology Criteria for Adverse Events version
4.03) were compared at first and last visit by tumor location
and pre-diagnosis symptom interval (PSI) (≥ 3months or < 3
months) using Kruskal-Wallis test, Wilcoxon rank sum test,
and Fisher's exact test.
Oncology and Hematology Institute- Blokhin Russian
Oncological Research Center, Anesthesiology department, Moscow, Russia;
2 Blokhin Russian Oncological Research Center, Anesthesiology
department, Moscow, Russia; 3 Pediatric Oncology and Hematology
Institute- Blokhin Russian Oncological Research Center, Oncology
department, Moscow, Russia
Background/Objectives: In pediatric oncology lungs are the
most frequent target of metastasis, so diagnostic and therapeutic surgeries are required. To guarantee optimal conditions for
surgery, collapse of operated lung is required, thus one lung
ventilation (OLV) should be performed. Novel devices for
OLV, such as Cohen, EZ-Blocker and Arndt bronchial blockers (BB) allow to achieve OLV avoiding traumatisation of trachea and other complications.
Design/Methods: During September’14 - March’17, 57 surgeries in patients 10-17 years old were performed. OLV was
maintained using BB. BB was introduced through the lumen
of video endotracheal tube and was placed into bronchus
under video control. Installation of Arndt BB was conducted under endoscopic control. In 24 cases (43%) right
main bronchus, in 33 cases (57%) - left main bronchus were
blocked. Time of BB installation, lung collapse score after
installation of thoracoscopic ports, hemodynamic profile during surgery, frequency of postoperative complications such as
sore throat and aphonia were evaluated.
SIOP ABSTRACTS
S161 of S518
Results: Mean time of intubation and BB installation was 187
+/- 42 seconds. In all cases it was possible to achieve satisfactory lung collapse, but in 16 cases aspiration of air through the
channel of BB had to be performed. Collapsing the right lung
presents some difficulties due to the anatomical features as
higher embranchement of right upper lobe bronchus. In this
case use of EZ-Blocker BB is preferable as it is designed to
be securely fixed over carina, making it less likely to displace
during surgery. In surgeries on the left lung Cohen BB is more
preferable.
chemotherapy or photodynamic therapy is a promising agent
in the treatment of RMS. Further in vivo studies are pending.
Conclusions: The use of BB requires expensive high-tech
equipment for video or endoscopic control, and well trained
staff with skills of BB installation and maintaining OLV. BB is
a promising technique to achieve the effective collapse of the
lung with minimal traumatisation, fewer complications postoperatively and rapid rehabilitation of patients after surgery.
Background/Objectives: More than 40% of neuroblastoma
arise from the adrenal gland. Adrenalectomy has been the
treatment of choice. However, the contralateral adrenal gland
is often also at risk leading to the development of postoperative adrenal insufficiency (AI). We reviewed the risk of AI in
our patients who underwent neuroblastoma surgery.
PD-101 Curcumin in Rhabdomyosarcoma:
Influences on Photodynamic and Cytotoxic Effects
in Vitro
C. Sorg1 , E. Schmid1 , J. Fuchs1 , V. Ellerkamp1
1 University
Hospital Tübingen, Pediatric Surgery and Pediatric Urology,
Tübingen, Germany
Background/Objectives: Rhabdomyosarcoma (RMS) is the
most common soft tissue tumor in children. The outcome for
children with advanced tumor disease is still poor. Curcumin,
a naturally occuring phenol, is investigated in complementary
oncology research for its phytochemical and antiproliferative
effects.
Design/Methods: Alveolar (RH30, ZF) and embryonal (RD,
SRH) RMS cell lines were treated with curcumin alone (211�g/ml), combination of curcumin and vincristine (curcumin: 4-7�g/ml; vincristine: 0,0005, 0,00075, 0,004�g/ml)
and combination of curcumin and photodynamic therapy (curcumin: 0,5-1�g/ml; light with 488nm for 5sec.). The human
skeletal muscle cell line SKMC served as control. Cell viability was assessed with MTT assays. The apoptosis rate was
evaluated via FACS analysis. Migration was investigated with
a wound healing assay. Clonogenic survival of RMS cells was
detected by Colony forming assay.
Results: Combination of curcumin and vincristine led to
dose-depending effects on all cell lines: that appears in a
decrease in cell proliferation and migration potential as well
as an increase in apoptosis rate. The combination therapy
with photodynamic therapy resulted in a highly significant
decrease of cell viability in RMS cell lines even with very low
concentrations of curcumin (1�g/ml). The results also show
that curcumin inhibits the cloning efficiency of RMS cells.
Conclusions: In summary, this study provides first evidence that curcumin, especially in combination with standard
PD-102 The Risk of Adrenal Insufficiency in
Neuroblastoma Surgery
C.H. Chui1
1 Surgery
Centre for Children Pte Ltd, Surgical Oncology, Singapore,
Singapore
Design/Methods: Retrospective analysis of 165 patients
with neuroblastoma in the “suprarenal region”, defined as
retroperitoneal zone superior to the renal veins and arteries.
AI was defined as chronic or transient. Patients were categorized based on loco-regional disease distribution: (A) right
adrenal disease only, (B) left adrenal disease only, (C) right
adrenal and left peri-adrenal disease, (D) left adrenal and
right peri-adrenal disease, (E) bilateral adrenal disease, and
(F) non-adrenal paravertebral disease. Demographic data, surgical records and postoperative charts were reviewed.
Results: 18(10.9%) out of 165 patient developed AI, of
which 3 were chronic and 15 were transient. None of unilateral adrenal-diseased patients in Groups A(n=21) and
B(n=28) developed AI. Half(50%) of 8 bilateral adrenaldiseased patients in Group E developed AI. 2(7.4%) of 27
patients in Group F developed AI. When unilateral adrenal
disease was coupled with contralateral peri-adrenal disease,
9(33.3%) of 27 patients in Group C compared to 3(5.6%) of 54
patients in Group D developed AI (p=0.0009) suggesting that
the left adrenal gland was more vulnerable to surgical damage. The right adrenal gland was more likely to be preserved
due to the shorter course of right adrenal vein.
Conclusions: Preserving adrenal function should be considered in neuroblastoma surgery. Due caution should be rendered to left adrenal gland after right adrenalectomy because
of its vulnerable vasculature. Early hydrocortisone replacement should be instituted when AI is suspected.
PD-103 Radiotherapy Omitted in the Treatment
of Positive Surgical Margins after Nephron-Sparing
Surgery for Wilms Tumor
D. Cozzi1 , S. Ceccanti1 , S. frediani1 , I. Falconi1 , A. Boscarelli1 , F.
Cozzi1
1 Sapienza
University of Rome, Pediatric Surgery Unit, Rome, Italy
SIOP ABSTRACTS
S162 of S518
Background/Objectives: Current treatment of microscopic
residual disease with negative lymph nodes after nephronsparing surgery (NSS) for Wilms tumor includes radiotherapy
and multi-drugs chemotherapy. The aim of present study is to
test the hypothesis that some children with positive margins
after NSS may be successfully treated without radiotherapy.
Design/Methods: Between 1992 and 2016, 50 children with
renal tumor underwent surgery at our institution. Eight
patients with unilateral Wilms tumor and 1 with unilateral
renal oncocytoma underwent partial nephrectomy. In addition, 6 children with unilateral Wilms tumor and 1 with
bilateral Wilms tumor underwent one or multiple enucleation. Two children after partial nephrectomy and 2 after enucleation presented positive surgical margins without lymph
nodes involvement and were treated with chemotherapy without radiotherapy.
Results: The child with bilateral Wilms tumor underwent
second-look operation consisting in new enucleations followed by post-operative chemotherapy without radiotherapy.
This patient is alive and well at the age of 7 years. The other
3 children with positive margins treated without radiotherapy
are alive and well at the age of 24,23, and 6 years. All patients
had an eGFR within the range of two-kidney renal function,
no hypertension and albuminuria.
Conclusions: Some children with positive surgical margins
after NSS for Wilms tumor may be successfully treated without radiotherapy. Larger numbers of patients are needed to
determine whether this approach is generally applicable.
PD-104 Lack of Renal Artery Inspection is
Associated with Low Resectability at the Renal
Hilus in Relapsed High-Risk Neuroblastoma
G. Cernaianu1 , T. Simon2 , B. Hero2 , M. Dübbers1
1 University
2 University
Hospital Cologne, Pediatric Surgery, Köln, Germany;
Hospital Cologne, Pediatric Oncology and Hematology, Köln,
Germany
Background/Objectives: The renal hilus is the main lymphatic drainage route of the adrenal medulla. Inspection and
preparation of the renal artery during debulking of tumor tissue at the renal hilus constitutes a surgical challenge in highrisk neuroblastoma. However, the association of renal artery
exposure with resectability of high risk neuroblastoma during
first line resecting abdominal surgery (S1) at the renal hilus is
not clearly defined.
Design/Methods: Fourty patients with relapse or progression
of high-risk neuroblastoma (R-HR-NB) after first line surgery
enrolled in the German neuroblastoma trials between 20002010 were evaluated. We analyzed the frequency of renal
artery exposure and the resectability at the renal hilus by
means of surgical reports for S1.
Results: The tumor involved the renal vessels in 28/40 (70%)
of patients on the right (R) and left (L) side. Inspection of the
artery during operation was documented on the right side in
9/28 (32%), and on the left side in 6/28 (21%) patients. Exposure of the renal artery was associated with a higher resection
rate at the renal hilus as compared to cases without exposure
(R: 8/9 (88%) vs. 3/19 (16%), P=.000; L: 5/6 (83%) vs. 9/22
(41%), P=.006).
Conclusions: The surgical analysis of R-HR-NB revealed a
high frequency of tumors at the renal hilus but a low rate of
renal artery inspection. Renal artery inspection was associated with a higher resection rate of tumors at the renal hilus.
The results of our study emphasize the importance of renal
artery inspection as instrument of surgical quality during first
resection of abdominal high risk neuroblastoma at the renal
hilus. Vice versa inspection of the renal arteries might also be
an indication of an operation technique more likely to achieve
complete tumor resection.
PD-105 The Role of Radiology Versus Clinical
Follow Up for Identification of Solid Tumour
Relapse
M. Collin1 , K. Schultz2 , D. McDowell1,2 , B. Goh1 , J.
Karpelowsky3,4
1 The
Children's Hospital at Westmead, Paediatric Surgery, Westmead,
Australia; 2 University of Sydney, Sydney Medical School, Sydney, Australia;
3 The Children's Hospital at Westmead, Paediatric Oncology and Thoracic
Surgery, Westmead, Australia; 4 University of Sydney, Children's Cancer
Research Unit, Sydney, Australia
Background/Objectives: The clinical and radiological follow up of paediatric solid tumour patients aims to include
early identification of relapse. Standardised three monthly (or
more frequent) imaging is often employed, however surveillance imaging has not been well studied. The risks of the high
cumulative doses of radiation in these protocols include the
potential for secondary malignancies. Our study aims to identify the role imaging plays in establishing relapse in the solid
tumour population.
Design/Methods: This study involves a retrospective audit
of patients who were managed at our hospital in a sixteenyear period (2000-2015) who presented with common solid
tumours (osteosarcoma, rhabdoyosarcomas, Ewing sarcoma,
neuroblastoma, Wilms tumour, non-rhabdomyosarcoma softtissue sarcoma or hepatoblastoma). Data was collected from
the oncology and radiology databases, as well as medical
records.
Results: We identified 528 patients from the oncology
databases, of which 131 failed to meet inclusion criteria of
achieving radiological remission or had incomplete records
throughout the follow up period and were excluded. This left
397 included patients of which 72 patients had relapse. In
SIOP ABSTRACTS
those cases with relapse 35 were identified clinically, PET,
1 with combined CT/MRI) and 19 cases with other imaging
forms (5 with PET alone, 3 with bone scan, 3 with MIBG
alone, 2 with CXR, 3 with MRI alone and 3 with ultrasound).
There were 4 cases of secondary malignancies identified in the
follow up period. The total number of CT scans performed in
the follow up period was 1,953, resulting in a mean number
of CT studies per patient of 4.9 and equating to one episode
of CT identified relapse per 108.5 CT scans.
Conclusions: We conclude that while radiological investigations play a role alongside clinical history and examination in
establishing relapse, further studies are required to minimise
the radiation exposure in these protocols, while maximising
the clinical benefit.
PD-106 The Violations of The Surgical
Guidelines for Wilms Tumour Nephrectomy
J. Godzinski1,2 , G. Audry3 , G. Cecchetto4 , J. Fuchs5 , S. Irtan3 , B.
Okoye6 , M. Powis7 , D. von Schweinitiz8 , S. Warmann5 , K.P. van de
Veen9 , M. Lopez10 , N. Graf11
1 Marciniak
Hospital, Paediatric Surgery, Wroclaw, Poland; 2 Medical
University, Paediatric Traumatology and Emergency Medicine, Wroclaw,
Poland; 3 Hospital Trousseau, Chirurgie Pediatrique, Paris, France;
4 University Hospital of Padua, Pediatric Surgery Unit-Women's and
Children Health Department, Padoua, Italy; 5 University of Tuebingen,
Paediatric Surgery, Tuebingen, Germany; 6 St Georges University Hospital,
Paediatric Surgery, London, United Kingdom; 7 LEEDS TEACHING
HOSPITALS NHS TRUST, Paediatric Surgery, Leeds, United Kingdom;
8 University of Munich, Department of Pediatric Surgery-, Munich,
Germany; 9 Princess Maxima, Paediatric Surgery, Utrecht, The
Netherlands; 10 NKI, NKI, Amsterdam, The Netherlands
11 Saarland
University, Department of Pediatric Oncology and Hematology,
Homburg, Germany
Background/Objectives: Surgery plays important role in the
treatment of nephroblastoma. The major multicentre studies
precisely recommend the guidelines for the surgical treatment.
Aim of the study was to evaluate the rates and types of potentially most important violations and iatrogenic failures of the
SIOP2001 surgical guidelines.
Design/Methods: The retrospective review of 2429 records of
patients aged > 6 months with unilateral nephroblastoma registered in the SIOP2001. The candidate violations/iatrogenic
failures were (1) preoperative open biopsy, (2) intraoperative tumour rupture and (3) sampling less than 6 regional
lymph nodes. Factors 1 and 2 result in staging patient 3, longer
chemotherapy and radiotherapy. Factor 3 (not representative
sampling) may lead to incorrect lower staging and, in consequence, insufficient aggressiveness and duration of the postoperative treatment.
Results: The preoperative open biopsies were performed in
7% of all patients and were the main reason for staging III in
24% of stage III patients. The intra operative tumour ruptures
were reported in 1.45% of patients. Not adequate sampling
S163 of S518
(less than 6 lymph nodes) of the regional lymph nodes was
reported in 88.2 % of patients. In 13.8% lymph nodes were
not sampled at all. This factor was the only reason for staging
3 in 15% of cases, however the underestimation of the rate of
lymph nodes involvement seems probable.
Conclusions: Surgical guidelines are correctly followed in
majority of patients, main problem considers incorrect sampling of the lymph nodes what results in possible downstaging
of patients, less aggressive postoperative treatment and higher
risk of relapse. The iatrogenic upstaging the patients due to
pre-treatment open biopsy and the intraoperative tumour rupture were less frequent, however majority of such events were
possible to avoid.
PD-107 Follow-Up of Benign Ovarian Tumours:
Should We Change UK Practice?
S. Arul1 , K. Best1 , A. Choudhary1 , M. Pachl1 , I. Jester1
1 Birmignham
Children's Hospital NHS Foundation Trust, Dept. of Surgery,
Birmingham, United Kingdom
Background/Objectives: Established UK practice, following
complete resection of unilateral benign ovarian tumour, was
that the risk of developing a metachronous tumour in the contralateral ovary was very low and therefore, did not require follow up. However this was challenged by a 2014 paper which
showed a 23% rate of metachronous tumours in the contralateral ovary.1 We wished to establish exactly what our follow up
arrangements were and whether there had been any cases of
metachronous tumours in our group of patients which could
help to shape future UK guidelines.
Design/Methods: A retrospective study of girls with ovarian teratomas presenting to us between 2006 and 2016 were
identified from the histology database. Clinical data on age
of diagnosis, biochemical tumour markers, histology, followup appointments and radiology were collected from hospital
records and analysed.
Results: 41 girls underwent surgery for an ovarian teratoma
between 2006 and 2016 (median age 11.9 years (range 4.5
- 16.1 yr)). Patients all presented with abdominal pain or
asymptomatic lower abdominal swelling. Four had raised
tumour markers.
Histology revealed 34 mature teratomas, 4 immature teratomas and two were unclassified. Eleven patients had evidence of torsion.
Radiological follow up with ultrasound occurred in 19
patients (median 6 months, range 1 month to 5 years). In this
time there was not a single case of radiological recurrence. In
addition there were no cases in the remaining 22 patients that
presented with clinical signs of a ovarian tumour.
SIOP ABSTRACTS
S164 of S518
Conclusions: In our series there was not a single case of a
metachronous ovarian tumour to suggest a need for a change
in our practice. However, a prospective study of UK patients
would be required to definitively establish the rate of recurrence.
1 Metachronous
benign ovarian tumors are not uncommon
in children Taskinen a, et al, 2014, Journal Paediatric
Surgery:49;43-545
PD-108 Surgical Challenges and Lessons Learnt
in Paediatric Large Cervicofacial Teratomas
K. Khanna1 , V. Khanna2 , N. Sugandhi3 , D. Bagga3 , M. Bajpai4
1 All
India Institute of Medical Sciences, Pediatric Surgery, New Delhi,
India; 2 Lady Hardinge Medical College & Associated Kalawati Saran
Children's Hospital, Paediatric Surgery, New Delhi, India; 3 Safdarjung
Hospital, Paediatric Surgery, Delhi, India; 4 All India Institute of Medical
Sciences, Paediatric Surgery, New Delhi, India
Background/Objectives: The incidence of mature congenital teratomas at all sites is 1 in 4000 live births. Of these, <2%
are cervicofacial. We highlight the challenges involved in the
perioperative and intraoperative management of large cervicofacial teratomas in infants.
Design/Methods: Four infants operated for large cervicofacial teratomas between June 2015 till February 2017 were
included.
Results: Four infants, age ranging from 12 days to 88 days,
presented with huge cervicofacial teratomas. The average
tumor size ranged from 7×8×4cm to 22×18×12cm. Two
neonates presented with epignathus teratomas with cleft
palate and intranasal extension but no intra cranial extension
on CT scan. The other two presented with giant cervicofacial
teratomas with compression and flattening of underlying skull
bone but no intracranial extension. Preoperative �FP levels
were normal for age in all. Two required 15 days of nasogastric (NG) feeds preoperatively. Intubation was a challenge to
the anaesthetist and was aided by fiberoptic bronchoscopy and
naso-tracheal intubation in 2 cases. Average blood loss was
53.5ml and the mean operating time was 92 ± 11minutes. All
underwent complete excision and histopathology confirmed
the diagnosis of mature teratoma in all.
Conclusions: Large congenital cervicofacial teratomas in
infants are usually benign but they may pose a surgical emergency if airway is compromised. Detailed imaging is required
to delineate the extent of lesion and plan surgery. Good preoperative nutritional status guides the timing of surgery. Nasotracheal intubation/ flexometallic endotracheal tubes may be
required. Large tumor size, distortion of the normal anatomy
and increased vascularity pose a surgical risk. Harmonic
scalpel aids excision. Early institution of postoperative NG
feeds and physiotherapy helped in speedy recovery, return of
function and normalization of appearance.
PD-109 Ablation Techniques as Adjuvant
Therapy for Pediatric Malignancies
J. Daley1 , R. Bhuta2 , D. Tessier3 , A. Chawla2 , B. DeNardo2
1 Rhode
Island Hospital, Department of Pediatrics, Providence, USA;
Island Hospital, Division of Pediatric Hematology-Oncology,
Providence, USA; 3 Rhode Island Hospital, Department of Radiology,
Providence, USA
2 Rhode
Background/Objectives: Image-guided ablation techniques,
including thermal and chemical ablation, are commonly used
therapeutic options for the treatment of malignant lesions in
adults. Ablation may be used with curative intent incorporated
into a multimodal treatment regimen or as palliative treatment
for painful lesions. Although well established in adult malignancies, there is little data regarding the use of such techniques in pediatric oncology patients. This study retrospectively analyzes the use of image-guided ablation as adjuvant
therapy for a pediatric oncology population at our institution.
Design/Methods: A retrospective chart review identified 11
pediatric patients with 21 malignant lesions treated with 36
ablations. Clinical information and treatment details regarding each ablation procedure were collected with institutional
review board approval.
Results: The 11 patients treated with ablation at our institution were 2-22 years of age. Five of the patients were diagnosed with osteosarcoma; the 6 additional patients each had
a solid tumor of varying histology. The majority of patients
had diffusely metastatic or relapsed disease. Of 17 ablation
sessions, 13 were performed for palliative purposes, while
4 were performed with curative intent. Microwave, radiofrequency and cryoablation were used to ablate lesions ranging
in size from 1-7 cm. Common sites of ablation included the
lung, liver, and soft tissues. All 36 ablations were reported
with technical success with limited complications including 1
pneumothorax. All symptomatic patients achieved pain relief.
Local progression occurred in 10% of previously treated
lesions and 10 of 11 patients have died of disease.
Conclusions: Ablation can be performed safely and effectively in children with limited toxicity. Ablation may provide effective local disease control in addition to palliation
for appropriately selected pediatric patients and tumor sites.
Differential considerations must be acknowledged between
adults and children. Ablation represents a minimally invasive
treatment approach that should be considered in the treatment
course of children with metastatic solid tumors.
PD-110 Posterior Retroperitoneoscopic
Adrenalectomy for Pediatric Adrenal Tumors
Y.T. Lee1 , C.P.C. Ong1 , P.H. Tang2 , B.L.K. Lim3 , H. Samsudin4 ,
H.P.A. Loh1
SIOP ABSTRACTS
1 KK
Women's and Children's Hospital, Department of Paediatric Surgery,
Singapore, Singapore; 2 KK Women's and Children's Hospital, Department
of Diagnostic & Interventional Imaging, Singapore, Singapore; 3 KK
Women's and Children's Hospital, Department of Orthopaedic Surgery,
Singapore, Singapore; 4 KK Women's and Children's Hospital, Operating
Theatre, Singapore, Singapore
Background/Objectives: Posterior retroperitoneoscoic
adrenalectomy has been reported as an option for adrenal
tumor resection, but is not commonly performed in children
due to the extreme semi-kneeling position advocated to
flatten the lumbar lordosis in order to achieve adequate
retroperitoneal space. As children have smaller lordosis
angles, flattening of the lordosis and creation of optimal
retroperitoneal space may be achieved with less hip flexion.
We used pediatric lumbar lordosis measurements to develop
a modified prone jackknife position, and report our experiences with this setup for posterior retroperitoneoscopic
adrenalectomy for adrenal tumors.
Design/Methods: Lordosis angles were measured on sagittal
computed tomography (CT) and magnetic resonance imaging (MRI) studies of pediatric patients with adrenal tumors
and compared to normal references. The data was used
to develop our modified prone jackknife position. Selected
patients with adrenal tumors underwent posterior retroperitoneoscopic adrenalectomy in this position. Patient demographics, diagnoses, operative time, complications, post-op analgesia requirements, and length of hospitalization were analyzed.
Results: CT and MRI studies were analyzed for 20
patients with adrenal tumors diagnosed in our institution
from 2012-2017; median lordosis angle was 25.85◦ (range:
24.32◦ -37.41◦ ). Four patients underwent retroperitoneoscopic adrenalectomy between June and December 2016. Histological diagnoses were neuroblastoma, adrenal hyperplasia, pheochromocytoma, and adrenal angiomatoid fibrous histiocytoma. Median age was 5.5 years [range: 3–11 years].
Median operating time was 150.5 minutes [range: 111–181
minutes]. No conversions to open surgery were required. One
patient had intra-operative bleeding from the adrenal vein.
Only 1 patient required postoperative opioids for analgesia.
Median length of hospitalization after surgery was 2 days
(range: 2-3 days).
Conclusions: Pediatric patients can achieve flattening of lumbar lordosis with less extreme positioning. Posterior retroperitoneoscopic adrenalectomy in a modified prone jackknife
position is a feasible operation for pediatric patients with
small adrenal tumors, with advantages of short operative time,
minimal requirements for opioid analgesia and short lengths
of hospitalization.
PD-111 Incidence, Treatment, and Outcomes of
Non-Wilms Renal Tumors in Children: A Single
Institution Experience
S165 of S518
S. Qureshi1 , S. Kembhavi2 , M. Ramadwar-3 , G. Chinnaswamy4 , T.
Vora4 , M. Prasad4 , N. Khanna5 , S. Laskar5
1 Tata
Memorial Hospital, Pediatric Surgical Oncology, Mumbai, India;
Memorial Hospital, Radiology, Mumbai, India; 3 Tata Memorial
Hospital, Pathology, Mumbai, India; 4 Tata Memorial Hospital, Medical
Oncology, Mumbai, India; 5 Tata Memorial Hospital, Radiation Oncology,
Mumbai, India
2 Tata
Background/Objectives: Although Wilms tumour is the
most common paediatric renal tumour, the non-Wilms renal
tumour encountered occasionally may pose a diagnostic and
therapeutic challenge. The aim of this study is to determine
the incidence and analyze the treatment and overall outcome
of non-Wilms tumours in children.
Design/Methods: Materials and methods: Of the 264
patients with primary renal tumours treated between January
2004 to December 2016, 229 (87%) with Wilms and 35(13%)
patients with non-Wilms tumour were identified from the
prospectively maintained database. Patients presenting with
recurrent disease were excluded from treatment and outcome
analysis.
Results: The non-Wilms tumour included renal cell carcinoma (n=9), clear cell sarcoma (n=7), Ewing's sarcoma (n=5), malignant rhabdoid tumour (n=3), congenital mesoblastic nephroma (n=3), synovial sarcoma (n=2),
and metanephric adenoma (n=1). All patients underwent
nephroureterectomy either upfront (n= 22) or after preoperative chemotherapy (n= 8). Adjuvant therapy was offered based
on the histology to 16 patients. Disease relapse was seen in
nine patients, of whom eight have died of disease, including
all the three patients with malignant rhabdoid tumour. The
median survival range from seven months to 11 years and
the projected 5 years overall and event-free survival for all
patients is 65.2% and 63% respectively.
Conclusions: Non-Wilms tumour constitutes less than 15%
of all renal tumours. The treatment depends on the specific
histology and the survival range from a few months to several
years. Accurate diagnosis is essential to select and decide the
intensity of the treatment.
PD-112 Multidisciplinary Approach to
Malignant Solid Tumors in Neonates and Infants
Younger Than 1 Year
T. Sharoev1 , N. Ivanova1 , J. Nesterova1 , O. Polushkina1 , A.
Korneeva1 , K. Savlaev1 , D. Nishonov1 , J. Ishutina2 , A. Kotlovsky3 ,
A. Prityko4
1 St
Luka's Clinical Research Centre for Children- Moscow- Russia,
Oncology, Moscow, Russia; 2 St Luka's Clinical Research Centre for
Children- Moscow- Russia, Neonatology, Moscow, Russia; 3 St Luka's
Clinical Research Centre for Children- Moscow- Russia, Pediatric Surgery,
Moscow, Russia; 4 St Luka's Clinical Research Centre for ChildrenMoscow- Russia, Administration, Moscow, Russia
SIOP ABSTRACTS
S166 of S518
Background/Objectives: Despite advances in pediatric
oncology, the management of neonates and infants younger
than 1 year with malignant solid tumors poses a challenge.
Aiming to achieve the optimal outcome for these patients we
apply the multidisciplinary approach to the comprehensive
care. The objective of this review is to demonstrate the usefulness of the multidisciplinary team for this particular group
of patients.
Design/Methods: From 2011 to 2017, all neonates and
infants aged under 1 year, with malignant solid tumors, managed under the care of the multidisciplinary team in our center
were included in the review. The patient data was prospectively collected and then analyzed.
Results: In total there were 108 patients aged between 3 days
and 1 year (mean 6.8 months). Diagnoses were as follows:
neurogenic tumor n=42 (38.3%), brain tumor n=19 (17.5%),
nephroblastoma n=18 (16.6%), retinoblastoma n=8 (7.4%),
soft tissue sarcoma n=7 (6.4%), hepatic tumor n=7 (6.4%),
germ cells tumor n=5 (4.6%), others n=2 (1.8%). In four cases
tumors were detected intranatally on the fetal ultrasound scan.
In all other cases, the time for making the accurate diagnoses took from 3 to 5 days following the patient presentation. According to internationally accepted guidelines and
protocols all patients underwent combined modality therapy
including surgical resection of the tumor and metastases. The
treatment was completed in 71 patients (65.7%). The overall survival rate was 77% at follow up ranging from 1 to 60
months. 34 patients (31.4%) continue receiving chemotherapy.
Conclusions: In our experience the implementation of multidisciplinary team care for neonates and infants younger than 1
year with malignant solid tumors is a very practical approach
to making a timely diagnosis and initiating promptly the
appropriate treatment thus allowing achievement of the high
survival rate. Further study at longer follow up is warranted
to evaluate the overall effectiveness of this approach.
PD-113 Disease Patterns of Malignant Tumors in
Adolescents
S. Bhatnagar1
1 B.J.Wadia
Hospital for Children- Bombay Hospital, Pediatric Surgery,
Mumbai, India
Background/Objectives: According to Indian demographic
profile, pediatric and adolescent population represents 45.7%
of the entire population. While most of pediatric malignancies are much researched, little is known about the malignant
tumors in adolescents. This population poised between children and adults, has been called the “lost tribe.” An attempt
is made here to study the demographics, disease patterns and
overall outcomes vis-à-vis pediatric malignant solid tumors.
Design/Methods: Patients aged 15-19 years with the diagnosis of malignant tumors, registered with two tertiary care hospitals in Mumbai, India from January 2012 to December 2016
were included. Basic demographic information, clinical, diagnostic details, histology grouping, treatment, outcome and
survival were retrospectively studied.
Results: Of 36 patients, 20F, 16M, various types of
tumors were encountered. In young girls (n=20), ovarian
tumors (n=11), Ewing's sarcoma (n=4), ganglioneuroblastoma (n=2), Osteosarcoma (n=2), Papillary pseudotumor of
the pancreas (n=1). Adolescent boys (n=16) showed, Rhabdomyosarcoma (n=6), Ewing's sarcoma/PNET (n= 4), testicular malignant Germ cell tumor (n=3), Osteosarcoma (n=2),
Carcinosarcoma of abdomen (n=1). Pretherapy staging of the
tumors revealed that 22/36 (61%) of the tumors were found to
be stage 4, the metastatic nodules being present in the lungs
(n=10), abdomen (n= 8), bone/bone marrow (n= 8). Upfront
chemotherapy was given to all patients except 4/36. R0 resection of the primary could be achieved in 13/36 patients. Radiotherapy was utilized as adjuvant therapy in 19/36, including
primary and metastatic sites. Metastatectomy was performed
in 12/22 patients post-chemotherapy. Overall survival was
86%, even though all of them were not tumor free.
Conclusions: High incidence of advanced malignancies is
seen in adolescent age in both boys and girls. The tumors
which are encountered in this age group differ in type, biologic behaviour as well as response to therapy. An attempt at
early detection and treatment is of vital importance to prevent
the presentation at advanced age.
HAEMATOLOGY - ACUTE
LYMPHOBLAST IC LEUKAEMIA
P-001 Prevalence of Tuberculosis Infection in
Children with Acute Leukemia
A. Ahad1 , R. Seth1 , S. Kabra1 , S. Vishnu1
1 All
India Institute of Medical Sciences- New Delhi, Pediatrics, New Delhi,
India
Background/Objectives: Children with acute leukemia are
at an increased risk of infections. There are opposing views
regarding tuberculosis as an etiology in these patients. The
aim of our study was to determine the prevalence of tuberculosis infection in children with acute leukemia, to determine the
Mantoux conversion rate during chemotherapy and to determine the disease rate and treatment outcome of tuberculosis.
Design/Methods: It was a prospective cohort study at All
India Institute of Medical Sciences, New Delhi. A Mantoux
test (5.0 tuberculin units) was given prior to chemotherapy to
determine the prevalence of tuberculosis infection. Children
SIOP ABSTRACTS
were monitored for development of tuberculosis disease over
one year by doing a repeat Mantoux test at 6 and 12 months
of follow up while on chemotherapy or when they developed
symptoms of tuberculosis. Risk factors such as BCG vaccination, family history, age, socioeconomic status and malnutrition were assessed.
Results: One hundred twenty-five children (93 acute lymphoblastic leukemia and 32 acute myeloid leukemia) aged one
to fourteen years (average 6.3 years) were studied. Four percent had tuberculosis infection at diagnosis before chemotherapy. Among the Mantoux negative children, 3.3% became
Mantoux positive during chemotherapy. Isoniazid was given
for 6 months to all the infected children and none developed
tuberculosis during follow up. Mantoux positivity was more
in children older than 5 years of age; however, none of the
other risk factors had a statistically significant association
with tuberculosis infection.
Conclusions: Mantoux positivity increases with increasing age and a low prevalence of tuberculosis infection was
attributed to a younger population in the study. None of the
children who received isoniazid developed disease, emphasizing its efficacy for chemoprophylaxis. The antitubercular
effect of chemotherapy like 6-mercaptopurine and antimicrobials like quinolones used in febrile neutropenia may play a
role.
P-002 DNA Index and Triple Trisomy at
Diagnosis, and Pattern of Relapse in Children with
Acute LYMMPHOBLASTIC Leukemia (A.L.L) –
Reporting Results from a Single Institution
S. al-sweedan1 , R. Jaffri1 , A. Alseraihy1 , A. alahmari1 , I.
Ghemlaz1 , K. Siddiqui1
1 King
Faisal Specialist Hospital & Research Center, pediatric
hematology/oncology, Riyadh, Saudi Arabia
Background/Objectives: Relapse rate of 10-20% in children
with A.L.L., is a major hindrance in achieving excellent overall survival rates.To assess the role of Triple trisomy and DNA
Index at diagnosis in timing and pattern of site of relapse.
Design/Methods: Retrospective review of 455 pediatric (≤14
years at diagnosis) A.L.L patients’ medical charts, diagnosed
and treated at our institute from 2005 to 2014.
Results: 108 (28.7%) from 376 patients with available DNA
Index data were hyperdiploid (HDALL, DNA Index>1.16)
while remaining 268 (71.3%) were non-HDALL. 12(22.6%)
patients in HDALL group relapsed at a median of 2.3
years (1.1 month – 8.3 years) from first complete remission (CR-1). 9 (75%) were isolated hematopoietic (BM),
2(16.7%) extramedullary testis, and 1 (8.3%) CNS. For the
non-HDALL group, 41(77.45) relapsed; 24 (58.5%) were
isolated hematopoietic, 2(4.9%) CNS, 1 (2.4%) testis and
S167 of S518
remaining 14(34.1%) were combined Hematopoietic (BM)
with CNS or testis. Relapses in HDALL group frequently
involved isolated hematopoietic site unlike in non-HDALL
group (P-Value: 0.022). Any of Trisomy (+4,+10, +17) or
triple trisomy (+4,+10, +17) did not exhibit significant role
in providing protection from relapse. Relapses in HDALL
group were occurring early (median: 2.4 years) compared to
non-HDALL group, but the trend was not statistically significant (P-Value: 0.572). Five-year overall survival for HDALL
group (0.952±0.024) was not statistically significantly better
in non-HDALL group (0.878±0.031, P-Value: 0.116). Triple
trisomy (+4,+10,+17) or any trisomy (+4,+10,+17) was
significantly associated with HDALL (P-Value<0.001).
Conclusions: Significantly different pattern of relapse sites
exist between the HDALL and Non-HDALL groups but not
the timings of relapse in our cohort of pediatric patients.
P-003 Allergic Reaction to Asparaginase in
Pediatric Acute Lymphoblastic Leukemia (A.L.L.) –
Does It Have Any Prognostic Value?
S. al-sweedan1 , J. RAFAT1 , A. ali1 , A. amal1 , G. ibrahim1 , A.
hawazen1 , K. Siddiqui1
1 King
Faisal Specialist Hospital & Research Center, pediatric
hematology/oncology, Riyadh, Saudi Arabia
Background/Objectives: We conducted this retrospective
study to assess the incidence of allergic reactions to Asparaginase in pediatric A.L.L. patients and to determine if it is of
any prognostic significance.
Design/Methods: Medical charts of pediatric non-infantile
patients diagnosed with A.L.L. registered at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia,
from 2005 to 2014 were reviewed in retrospective fashion and
the outcome data were analyzed in the backdrop of incidence
of allergic reaction to Asparaginase.
Results: Five hundred and four (504) patients were enrolled in
this study. Median age at diagnosis was 4.8 years (Min-Max:
1.0-14.8), with 41.3%(208) girls. Clinical allergic reactions to
Asparaginase identified by continual measurement of activity levels, were observed in 95(18.8%) patients. 69.5%(66) of
these occurred during consolidation phase. 15.8%(15) were
categorized as severe and 42.2%(40) as moderate and mild,
each. It was significantly more common in High Risk group
than Standard Risk (21.9% vs. 10.2%, P-Value: 0.004), and
in CNS-II (29.6%) than in CNS-I and CNS-III (17.4% and
7.1%, P-Value: 0.033). Rate of first relapse was 14.1%(71).
Incidence of first relapse was higher in those who did not
experience any allergic reaction (14.4%,59 vs. 12.6%,12) but,
this protective effect did not achieve statistical significance
(P-Value: 0.745). Among High Risk patients (374), mortality
rate was significantly lower in patients with recorded allergic
SIOP ABSTRACTS
S168 of S518
reaction to Asparaginase (4.9%,4 of 82) than others (15.1%,44
of 292) with P-value of 0.014. However, no significance difference was observed in probability of five year Event Free
Survival (EFS) between the former and the later (0.854±0.039
vs. 0.797±0.021, P-Value: 0.085) for the whole cohort.
Conclusions: Early switch to erwinia type after reaction to
asperginase improve survival and decrease relapse in patients
with ALL
P-004 MicroRNA Expression Profiles in Brazilian
Childhood T-Cell Acute Lymphoblastic Leukemia
(T-ALL)
R.S. Almeida1 , F.S. Araújo2 , L.L. Coutinho3 , E.A. Donadi4 , N.
Lucena-Silva5
1 Centro
de Pesquisas Aggeu Magalhães/FIOCRUZ-PE, Departamento de
Imunologia, Recife, Brazil; 2 Universidade Federal de Pernambuco and
Centro de Pesquisas Aggeu Magalhães/FIOCRUZ-PE, Departamento de
Imunologia, Recife, Brazil; 3 ESALQ/Universidade de São Paulo,
Departamento de Biotecnologia Animal, Piracicaba, Brazil; 4 Faculdade de
Medicina de Ribeirão Preto/Universidade de São Paulo, Divisão de
Imunologia Clínica, Ribeirão Preto, Brazil; 5 Oncologia Pediátrica/Instituto
de Medicina Integral Professor Fernando Figueira and Centro de Pesquisas
Aggeu Magalhães/FIOCRUZ-PE, Departamento de Imunologia, Recife,
Brazil
Background/Objectives: T-cell acute lymphoblastic
leukemia (T-ALL) is a hematologic malignancy that accounts
for 15% of childhood ALL, and can affect distinct maturation
stages of T cell. MicroRNAs (miRNAs) are small non-coding
RNAs with an essential role in gene expression regulation and
normal hematopoiesis. In this study, we aimed to investigate
differential miRNA expression between bone marrow (BM)
mononuclear cells from patients with childhood T-ALL
and blood CD8+ T cell from healthy adult and neonatal
individuals (control group – CG).
Design/Methods: Patients with T-ALL (7 males, 1 female;
median age= 11,5 years) were referred to Instituto de
Medicina Integral Professor Fernando Figueira in Recife,
Northeast Brazil, where BM was collected. CG data
(adult, n=3; neonatal, n=3) were retrieved from Gene
Expression Omnibus (GEO) database (GSM1627014,
GSM1627015, GSM1627016, GSM1627017, GSM1627018
and GSM1627019). Total RNA was extracted with TRizol
and used for library construction (Illumina Small RNA Kit).
MiRNAs were sequenced in HiSeq plataform (Illumina)
and data analyzed by bioinformatics (FastQC – quality
control, Cutadapt – removing adapters, miRDeep2 – miRNA
identification, and edgeR – differential expression (DE))
using miRBase v21 data and hg38 human reference genome.
A False Discovery Rate (FDR) ≤ 0.05 was considered in DE
analysis, and miRNA target prediction was performed by
miRWalk 2.0. DAVID v6.8 tools were applied to functional
annotation (FA) of miRNA targets.
Results: Forty-nine miRNAs DE were identified between the
two groups, with 33 up- and 16 down-regulated in T-ALL.
Fourteen thousand, three hundred and eighty-one gene targets were predicted, and FA revealed 120 enriched Kegg Pathways (corrected P ≤ 0.05), including Metabolic pathways,
Pathways in cancer, PI3K-Akt signaling pathway, Endocytosis, MAPK signaling pathway and others related to immune
system, cancer and cell function.
Conclusions: MiRNAs play a role in biological pathways
related to cancer development and immune system regulation.
Acknowledgements: Supported by FIOCRUZ-PE, CAPESPROCAD2013, FACEPE-APQ-0040-4.00/13, and FACEPEAPQ-1044-4.01/15.
P-005 Demographics and Disease Response
Evaluation in Pediatric High Risk Acute
Lymphoblastic Leukemia (ALL) Patients at a
Tertiary Care Centre
S. Anwar1 , M. Faizan2
1 The
Children's Hospital &ICH, Paediatric Hematology/Oncology, Lahore,
Pakistan; 2 The Children's Hospital &ICH, Paediatric Haematology
Oncology, Lahore, Pakistan
Background / Objectives: Background: Acute Lymphoblastic leukemia (ALL) is commonest malignancy among
children.Different Protocols are being used in different part of
world to treat ALL.
Objective: The main objective of the study is to discuss presentation and outcome of children with acute lymphoblastic
leukemia (ALL).
Design / Methods: STUDY DESIGN: We present a retrospective study, looking at demographics and outcome of children with ALL presented to the hematology and oncology
department of the children's hospital Lahore between January
2009 and December 2009.
MATERIALS AND METHODS: Children with Bone Marrow biopsy proven ALL were included and data regarding age,
gender, risk categorization and outcome were recorded and
analyzed. Children were stratified as high risk who were <2
and >9 years of age, BFM-risk factor 1.2 or above, CNS disease and mediastinal mass on presentation. Lahore Group Protocol for acute lymphoblastic Leukemia LALL01(BFM and
UKALLXI based ) was used for treatment.
Results: A total of 198 patients were included. Seventy percent were males. Majority 141(66.6%) were between 2-8.9
years of age while 44(22.2%) patients were of 9 years and
above. One hundred and sixteen (60%) had high risk disease and only 55(27%) with standard risk. Initial WBC was
>100,000/mm3 in 35 (17.6%), 50,000-100,000/mm3 in 14
(7%) and 47 (23.7%) had 10,000-50,000/mm3. BFM risk factor was 1.2 and above in 66 (33.3%), 14(7%) patients had
SIOP ABSTRACTS
S169 of S518
CNS disease and 5% mediastinal mass on presentation. Seventy eight (40%) patients had completed treatment, 44(22.2%)
left against medical advice and 38(19.1%) died. Twenty nine
(14.6%) had relapse and among them 76% relapsed while on
treatment.
tion, and inability to ambulate (peripheral and motor neuropathy) requiring removal of this agent from standard treatment
plans. Discontinuation of vincristine within the first year of
treatment in our subset of patients resulted in improvement of
symptoms and continued ALL remission.
Conclusions: High risk disease is the most common presentation of ALL in children at our centre with initial High WBC
count, massive organomegaly and male predominance. Abandonment is another major factor affecting the overall survival
rate. However overall survival is almost 50% in our treated
patients.
P-007 Expression of CD10 on Residual Cells in
Children with B-Cell Precursor Acute Leukemia
K. Bukowska-Strakova1 , K. Pawińska-Wąsikowska2 , M. Marta3 , K.
Anna1 , B. Walentyna2 , S. Maciej1
1 Jagiellonian
P-006 Severe Vincristine Toxicity in Acute
Lymphoblastic Leukemia
R. Bhuta1 , B. DeNardo1 , P. Cole2 , K. Matook1 , J. Welch1
1 Rhode
Island Hospital, Pediatric Hematology/Oncology, Providence,
USA; 2 Montefiore Medical Center, Pediatric Hematolgoy/Oncology, New
York City, USA
Background/Objectives: An integral part of standard treatment for patients with acute lymphoblastic leukemia (ALL)
includes the use of vincristine. While significant side effects
from vincristine are rare, severe neurotoxicity can occur and
result in omission of this chemotherapeutic agent from treatment. This study specifically looked at patients with ALL
who had vincristine removed from their therapy plan to assess
severity of side effects and disease response.
Design/Methods: A retrospective chart review identified 4
patients from 2 institutions with ALL and severe polyneuropathy requiring discontinuation of vincristine. Demographic
information and details about individual treatment course in
relation to vincristine administration were collected with institutional review board approval.
Results: The four children were 3 to 12 years old and were
diagnosed with B-cell ALL. They received treatment on or
as per Dana Farber Cancer Institute Protocols 05-001 or 11001. The first patient developed severe visual loss secondary
to optic nerve atrophy, vocal cord dysfunction, and inability to
ambulate due to severe peripheral neuropathy prompting discontinuation of vincristine after 5 doses. The second patient
developed severe constipation and inability to ambulate secondary to peripheral neuropathy, with discontinuation of vincristine after 6 doses; genetic testing revealed Charcot Marie
Tooth type 2D. The 3rd and 4th patients developed inability to
ambulate due to significant motor neuropathy, and vincristine
was discontinued after 11 doses and 21 doses, respectively.
All four children had improvement in their symptoms after
discontinuation of vincristine and are currently 2-36 months
off therapy and remain in remission.
Conclusions: Severe vincristine toxicity can result in vision
loss (optic nerve atrophy), vocal cord dysfunction, constipa-
University Medical College - Polish-American Institute of
Pediatric, Department of Clinical Immunology, Krakow, Poland;
2 Jagiellonian University Medical College - Polish-American Institute of
Pediatric, Department of Oncology and Hematology-, Krakow, Poland;
3 University Children's Hospital of Cracow, Clinical Immunology, Krakow,
Poland
Background/Objectives: The most common childhood
malignancy is acute lymphoblastic leukemia (ALL), particularly B-cell precursor ALL (BCP-ALL). Leukemic cells
remaining in the bone marrow are the major cause of relapse,
therefore state of minimal residual disease monitoring (MRD)
during the induction therapy is consider a strong predicting factor of treatment outcome. Multicolor flow cytometry
(MFC) is commonly used technique for monitoring MRD.
Design/Methods: MRD was assessed by MFC in patients
with BCP-ALL diagnosed between 2007-2016 (200 patients).
Children were treated according to ALL IC-BFM-2002
(between 2007-2012) or according to ALL IC-BFM-2009
(between 2013-2016) in Oncology and Hematology Department, Children's University Hospital in Krakow. The level
of residual leukemic cells and the quality of antigen expression (mean fluorescence intensity - MFI) was assessed on
leukemic cell on diagnosis day, 15th and 33th day of induction
chemotherapy. To achieve expected sensitivity of the method
(10-4 ), at least 300.000 of nucleated cells were collected. The
sample quality was assessed based on percentage of erythroblasts (<2% poor quality, >2% good quality).
Results: The correlation between surface antigen expression
and response to prednisone therapy was found. The CD10
MFI was down-regulated in patients with good prednisone,
yet in patients with poor prednisone, CD10 MFI on leukemic
blasts was not altered, suggesting insensitivity to chemotherapy.
The most frequent antigenic shifts were seen in CD10, CD34
and CD20 expression, whereas CD19, CD45, CD38, CD58
and CD66c were more stable. The percentage of leukemic
cells in BCP-ALL at 15th and 33th day of therapy were negatively correlated with early clinical outcome.
Conclusions: Our study shows that not only the quantitative
MRD results are important, but also qualitative changes of
immunophenotype of residual leukemic cells might give addi-
SIOP ABSTRACTS
S170 of S518
tional clinical information, especially, in poor quality samples, with admixture of peripheral blood.
P-008 Transfusion-Related Iron Overload
(TRIO) in Children with Leukemia/Lymphoma
C. Cacciotti1 , U. Athale1 , S. Millson1
1 McMaster
Children's Hospital, Department of Pediatrics, Hamilton,
Canada
of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). Recently, it was demonstrated that
rMnSOD, a recombinant new isoform of MnSOD, recently
isolated from human liposarcoma cell line, is able to trigger
apoptosis of human T-ALL cells (99%) without toxic effects
on healthy cells. The present study was aimed to verify if rMnSOD is able to induce apoptosis and to stop in G0/G1 stage
of the cell cycle in pediatric patients with B-cell acute lymphoblastic leukaemia (ALL) and if it displays synergic action
with daunorubicin.
Background/Objectives: Children with cancer commonly
receive red blood cell (RBC) transfusions. Transfusionrelated iron overload (TRIO) is a common complication and
a significant iron burden is documented after only 10 RBC
transfusions. Despite heavy transfusions, few studies have
evaluated TRIO in children with cancer and no guidelines for
screening exist.
Design/Methods: Cells were collected from three patients
diagnosed for B-cell ALL at the Pediatric Oncology of University “Luigi Vanvitelli”. Cell viability, apoptosis and cell
cycle of lymphoblasts and SUP-B15 cell line (ATCC) were
analyzed through “ Muse Kit” after rMnSOD treatment. ROS
analysis was detected with NAC. Apoptotic fragmentations of
SUP-B15 were demonstrated by confocal imaging.
Design/Methods: A retrospective chart review, observational
study was performed to evaluate the screening practices for
TRIO in children (<18 years) with leukemia/lymphoma. In
addition to demographic data, ferritin values, and number of
RBC transfusions were extracted.
Results: We observed that low concentrations of rMnSOD
are able to trigger apoptosis of SUP-B15 cell line and B-ALL
cells from pediatric patients. In detail, we observed an apoptosis rate from 30% to 46% in B-ALL pediatric patient cells
and of 45% in SUP-B15 cell line. Instead, cell cycle analysis
showed a cell fraction decrease in G0/G1 phase. Moreover,
the synergic activity of rMnSOD and Daunorubicin induces
apoptosis in 92% of cells, by comparing the treatment with
the single substances, rMnSOD (64,7%) and Daunorubicin
(23,9%). Confocal microscopy analysis revealed internalization of rMnSOD in SUP-B15 cells and evident apoptotic alterations, such as nuclear fragmentations and apoptotic-bodies.
Results: The study cohort included 155 eligible patients, 91
(59%) had standard risk (SR) ALL, 52 (33%) high risk (HR)
ALL, and 12 (8%) AML. The mean age at diagnosis was 6
years (range 5 months- 18 years). Overall 34% of patients
received > 10RBC transfusions; SR-ALL median 6 (range 092), HR-ALL median 12 (range 4-63) and AML median 23
(range 8-56) transfusions. Patients with HR-ALL and AML
were more likely to receive >10 transfusions (58% and 92%
respectively) in comparison to those with SR-ALL (14%). Ferritin levels were measured in 105 patients (68%); and were elevated (>1,000mcg/L) in 22 (14%). Evaluation of iron overload
with Ferriscan was performed in 4 patients (2%).
Conclusions: The iron burden was not routinely evaluated,
despite high number RBC transfusions. Screening for TRIO
should be incorporated into routine practice in children with
leukemia/lymphoma.
P-009 Enhancer Role of rMnSOD in Apoptosis
Triggering by Daunorubicin of Pediatric B-All Cells
F. Casale1 , V. D'Angelo1 , A. Pica2 , A. Iannotta1 , M. Ramaglia1 , L.
Di Massa1 , M.L. Pollio2 , R. Manca2 , M. Di Martino1 , M. Oreste1 ,
A. Mancini3 , A. Borrelli3 , P. Indolfi1
1 Università
della Campania “L.Vanvitelli” SUN, Department of
Women-Children and General and Specialistic Surgery, Naples, Italy;
2 Federico II University Naples, Department of Biology, Naples, Italy;
3 National Cancer Institute “Fondazione Pascale”, Exp. Oncology, Naples,
Italy
Background/Objectives: Leukemic cells produce higher
amounts of ROS than healthy cells and express low levels
Conclusions: In conclusion, rMnSOD exerts toxic activity
only against cancer cells, by enhancing drug effect, thus allowing to utilize lower concentration of standard chemotherapy to
increase the apoptosis level.
P-010 MIR-125 as Biomarkers in Chemo
Resistant Leukemic Cells
F. Casale1 , M. Ramaglia1 , A. Iannotta1 , A. Lombardi2 , C. Ferri2 , H.
Kawasaki2 , M. Caraglia2 , P. Indolfi1 , S. Perrotta1 , F. Rossi1 , D. Di
Pinto1 , E. Pota1 , V. D'Angelo1
1 Università
della Campania “L.Vanvitelli” SUN, Department of WomenChildren and General and Specialized Surgery, Naples, Italy; 2 Università
della Campania “L.Vanvitelli” SUN, Department of BiochemistryBiophysics-and General Pathology, Naples, Italy
Background/Objectives: The microRNAs (MiRNA) are
involved in the differentiation process of various hematopoietic lineages. Their dysregulation has now clearly been linked
to cancer and particularly to leukemia and to drug resistant process MiRNA miR-125b is the ortholog of lin-4 in
Caenorhaditis elegans. As lin-4 is implicated in several developmental processes and miR-125b negatively regulates many
proteins in the p53 pathway, the deregulation of miR-125b
SIOP ABSTRACTS
expression would impair human and mouse hematopoiesis.
Recently, miR-125b and its homolog miR-125a are analyzed
and resulted highly expressed in hematopoietic stem cells.
In these studies, miR-125b was found to regulate stem-cell
pool size and to confer a competitive advantage to engrafting hematopoietic cells. MiRNA 125b can function dually
as both an oncogene and tumor-suppressor gene depending on the cancer type and cellular context. Aim of our
study was to analyze the expression and correlation with biologic profile of these MiRna in patients with ALL B-cell or
T-cell.
Design/Methods: We examined expression levels of miR125b in 57 children (37 of ALL B-cell and 20 of ALL Tcell) diagnosed and treated to the Pediatric Oncology of the
University “Luigi Vanvitelli”, and in two cell lines, SUP-B15
and Jurkat. Mononuclear cells were isolated from bone marrow samples whereas the biologic fluids (serum and spit) were
collected from ALL children. We tested the expression levels
of miR-125b by quantitative RT-PCR at diagnosis and after
complete remission (to 33◦ and 78◦ day).
Results: Preliminary data showed that miR-125b expression in ALL B-cell samples were upregulated (27/37, 73%),
whereas the expression in T-cell samples were downregulated
(18/20 samples, 90%). Interestingly, the 29% (8/27) of overexpressed B-ALL samples resulted high risk.
Conclusions: These data support the hypothesis that aberrant
expression of miR-125b might contribute to leukemogenesis
and the overexpression is important in the biologic profile of
high risk leukemic patients.
P-011 Adverse Events in Children with Acute
Lymphoblastic Leukaemia Treated from 1994-2011.
Single-Centre Retrospective Study in Poland
A. Szłapińska1 , K. Adamczewska2 , K. Molenda2 , P.
Marciniak-Stępak1 , J. Wachowiak1 , K. Derwich1
1 Poznan
University of Medical Sciences, Pediatric Oncology- Hematology
and Transplantology, Poznan, Poland; 2 Poznan University of Medical
Sciences, Pediatric Oncology- Hematology and Transplantology- Students
Paediatric Society, Poznan, Poland
Background/Objectives: The aim of this study was a retrospective analysis of adverse events in children with acute lymphoblastic leukaemia (ALL) treated between 1994-2011 at
Department of Pediatric Oncology, Haematology and Transplantology in Poznan, Poland.
Design/Methods: Between 1994-2001, 103 children with
ALL (48 [46.6%] girls, 55 [53.4%] boys) aged 1-17 (med 5
yrs) were stratified into SRG:69 [67%], HRG:34 [33%] and
treated with the ALL BFM-90 and the New York (NY) protocols, respectively.
S171 of S518
According to ALL IC BFM 2002 criteria 196 pts (90 [46%]
girls, 106 [54%] boys) aged 1-18 (med 5.04 yrs) were classified to SRG-53 (27%), IRG-74 (37%), HRG-69 (35%).
Results: Among children treated with ALL BFM-90 and
NY protocol, CR1 was achieved in SR: 94.2% and HR:
87.9% pts. Treatment failures were due to: therapy complications 2/102(2%) in HR only. Relapses occurred in 13/102
(12.7%) pts: 6/69 (8.7%) in SR (BM-5/6[83.3%], BM-CNS1/6[16.7%]); and 7/33 (21.2%) in HR (BM-5/7 [71.4%]; BMtesticular-1/7 [14.3%]; CNS-1/7 [14.3%]).
Among children treated with ALL IC BFM 2002 CR1
was achieved by 190 (97%) pts. Among adverse events 29
(14.8%) relapses were observed (1.1-79 months from diagnosis; med 29.5 months): 14 (48.3%) in BM (SR:4, IR:4, HR:5),
4(13.7%) in CNS (SR:1, IR:1 HR:2), 1(3.4%): testis (HR),
1(3.4%): mediastinum (HR) and 9(31%) mixed relapses: 6
BM-CNS (SR:1, IR:3, HR:2), 1 CNS-testicular (IR), 1 BMtesticular (IR) and 1 BM-CNS-abdominal (SR). There were
27 (13.8%) deaths due to: early because of sepsis (1; 0,5%);
treatment complications (14; 7,1%; 9 in CR1 [IR:2, HR:7]),
relapse/progression (16; 8.2%; [SR:3, IR:5, HR:8]), car accident (1; 0.5%).
Conclusions: BM relapses were most frequent in children
regardless of the protocol.
Patients treated with ALL IC BFM 2002 suffered from isolated CNS and mixed relapses more often, than those with
ALL BFM-90.
There were no deaths due to treatment complications in SR
group.
P-012 Results of Treatment with Nelarabine in
Relapsed T-Cell Acute Lymphoblastic Leukemia
(T-ALL) in Children - Report of Polish Paediatric
Leukemia/Lymphoma Study Group (PPLLSG)
P. Marciniak-Stepak1 , K. Derwich1 , J. Owoc-Lempach2 , M.
Mielcarek-Siedziuk2 , W. Balwierz3 , M. Krawczuk-Rybak4 , T.
Szczepanski5 , J. Wachowiak1 , E. Gorczynska2
1 Poznan
University of Medical Sciences, Pediatric Oncology- Hematology
and Transplantology, Poznan, Poland; 2 Wroclaw Medical University,
Department of Paediatric Transplantology- Oncology and Haematology,
Wroclaw, Poland; 3 Jagiellonian University- Medical College, Department
of Paediatric Oncology and Haematology, Cracow, Poland; 4 Medical
University of Bialystok, Department of Paediatric Oncology and
Haematology, Bialystok, Poland; 5 Medical University of Silesia,
Department of Paediatrics- Haematology and Oncology, Katowice, Poland
Background/Objectives: Although good prognosis in children with ALL, there is still 20% risk of relapse. Current protocols for relapse treatment are not highly effective in breaking
resistance of T-ALL, therefore there is a need for an alternative therapies. Nelarabine (Ara-G) may cause significant
SIOP ABSTRACTS
S172 of S518
benefit in patients with T-ALL leading to long-term second
remission (CR2).
The aim was a retrospective analysis of results achieved in
relapsed T-ALL patients treated with Ara-G prepared by
PPLLSG.
Design/Methods: Between 2009-2015 in 5 Polish centers
of pediatric oncology in 8 patients (8 boys) with T-ALL,
diagnosed at age 1.7-13.4 years (median 3.8 years), relapse
was treated according to ALL-REZ 2002 (1 patient) or
IntReAll2010-HR (7 patients). Due to resistance and no CR2,
protocol with Ara-G was introduced.
Results: Relapse was seen 6.7-45.6 months (median 15.85
mths) after diagnosis (during first line [6 pts] or after completing treatment [2 pts; 2.7 and 36.9 mths]). There were 4 isolated bone marrow (BM) and 4 mixed relapses (1 BM-lymph
nodes, 1 BM-mediastinum, 1 BM-central nervous system, 1
BM-testis). Due to failure of previous treatment (5 pts: no CR2
after second line treatment; 2 pts: relapse after alloHSCT; 1
pt: multiple relapses) Ara-G was introduced as a single drug (1
pt) or NECTAR (Ara-G/VP-Cy)(7 pts). In 4 pts: 1, 2 pts: 2 and
2 pts: 3 cycles with Ara-G were given. No significant adverse
effects and toxicities were observed. Among 8 pts CR2 was
achieved in 6 pts (75%); in 5 pts alloHSCT was performed,
1 had another relapse. In 2 pts (25%) there was a progression
of ALL. Currently 3/8 pts (37.5%) in CR2 are alive, while 5/8
pts died (62.5%) due to: progression (2), infection (2), toxicity
after alloHSCT (1).
Conclusions: Ara-G is an effective alternative drug in
patients with relapsed T-ALL not combined with significant
toxicities.
P-013 A Cost-Effective, High Sensitivity 10-Color
Single Tube Flow-Cytometry (FC) Based B-Cell
Precursor Acute Lymphoblastic Leukemia
(BCPALL) Minimal Residual Disease (MRD) Assay
Design/Methods: We studied 234 cases of pediatric
(<15 years) BCPALL registered under ICICLE-treatment
protocol (modified BFM-protocol). MRD was monitored
in 284 bone-marrow (BM) samples at post-induction(PI),
post-consolidation (PC) and subsequent follow-up timepoints (SFU) using 10-color single tube FC-MRD assay.
MRD was defined as cluster 20 events with minimum two
immunophenotypic abnormalities.
Results: We studied 234 pediatric (<15 year) BCPALL
cases for high sensitivity FC-MRD monitoring. High number of events were acquired for MRD-assay (median-events,
4561000; range, 1507860-5106540). Of 284 MRD samples,
PI-MRD were 234 (82.3%), PC-MRD were 40 (14%) and
SFU were 10 (6.1%). Of 284 samples, MRD was positive
in 121(42.6%) (median MRD level, 0.028%; range, 0.0002%
to 48.3%). We categorized positive MRD results into samples with MRD <0.001%, 0.001- <0.01%, 0.01- <0.1%, 0.1<1.0%, 1.0- <10% and >10% and they were 13%, 24%, 27.7%,
24%, 9.3% and 1.9% respectively. Furthermore, in 29 samples with MRD-levels ≤0.01% and >1.5 million acquiredevents, the results were compared between time-gated initial 500000-events, and 1000000 events versus all events
acquired. Of them, eighteen samples turned MRD-negative
in initial 500000-events and eleven in initial 1000000-events
(since MRD-events were <20) highlighting the importance of
acquisition of >1.5 million cells to increase the sensitivity of
FC-MRD assay.
Conclusions: We established a cost-effective 10-color single
tube FC-MRD assay with high sensitivity of 1 in 105 and
applicability in >97% MRD samples. Our study showed that
acquisition of events ≤1 million cells can reduce the sensitivity of FC-MRD assay significantly.
P-014 Treating Adolescents with Acute
Lymphoblastic Leukemia in a Resource-Poor
Setting: A Challenging Proposition
D. Dhaliwal1 , G. Chatterjee1 , P. Subramanian1 , S. Kedia1 , P.
Rodrigues1 , M. Sanyal1 , S. Ghogale1 , N. Deshpande1 , Y.
Badrinath1 , A. Kumar1 , G. Narula2 , B. Aurora2 , S. Gujral1 , S.
Banavali2 , P. Tembhare1
N. Dhingra1 , N. Gupta1 , P. Mishra1 , T. Seth1 , S. Tyagi1 , H.P. Pati1 ,
R. Saxena1 , M. Mahapatra1
1 Tata
Background/Objectives: Adolescents with acute lymphoblastic leukemia (ALL) are distinct from their pediatric
counterparts in terms of disease biology and outcomes. The
high success rates of pediatric ALL have thus far eluded this
cohort of patients. We describe our experience of managing
adolescent patients with ALL in a developing nation.
Memorial Hospital, Hematopathology, Mumbai, India; 2 Tata
Memorial Hospital, Pediatric Oncology, Mumbai, India
Background/Objectives: Minimal residual disease (MRD)
is widely used for monitoring treatment-effectiveness, riskstratification and even for treatment modification. Hence,
methodology for MRD assessment needs to be accurate, fast,
sensitive and affordable. Previous studies have shown that
flow-cytometry based MRD (FC-MRD) cannot reach beyond
“1 in 104 ” sensitivity. We are presenting a study of high sensitivity, cost effective 10-color BCPALL-FC-MRD assay.
1 All
India Institute of Medical Sciences, Hematology, New Delhi, India
Design/Methods: Medical records of adolescents (age 11
- 18 years) with ALL treated as per a uniform augmented
BFM protocol between 2011 and 2016 were retrospectively
reviewed.
SIOP ABSTRACTS
Results: Seventy-four patients met the inclusion criteria of
which 64 were evaluable. The median age was 15 years,
male-female ratio was 9.6:1. Forty-four patients (68.75%) had
B-ALL and 20 (31.25%) had T ALL. The median presenting WBC count was 41630/mm3 (range 600-800000/mm3).
20 patients (31.25%) had a presenting WBC count of >1,
00,000/mm3. Adverse cytogenetics were seen in 5 patients
while 3 had favourable cytogenetics, the remainder being normal. Of 61 patients whose baseline CNS status was available,
55 were CNS 1, 3 were CNS 2, 2 were CNS 3 and 4 had a traumatic tap without blasts. Early treatment response, assessed
by day 7 bone marrow, was performed in 55 patients of which
30 (54.5%) were M1, 7 (12.7%) were M2 and 18 (32.7 %) were
M3. Nine patients died during induction and 2 had refractory
disease. Therapy omissions due to infectious or drug-related
complications were observed in 34.38%. Remission rates were
82.8% at end of induction. Relapses were documented in 17
(26.56%) patients (8 CNS, 8 medullary, 1 combined). Kaplanmeier estimates for 2 year event-free survival were 44.74 %
(CI 29.6 to 60.05 %).
Conclusions: Adolescents in this study had poor outcomes.
An Increased prevalence of high-risk features such as male
preponderance, T-cell phenotype, elevated presenting WBC
count and poor therapy responses on day 7 were identified.
P-015 Target for Minimal Residual Disease
Detection in Pediatric Patients with PHI-ALL:
IG/TCR Rearrangements or BCR-ABL1
Transcript?
J.A. Digiorge1 , P. Rubio1 , E. Sajaroff2 , A. Medina1 , E. Baialardo3 ,
J. Rossi2 , M. Guitter1 , M.S. Felice1 , C.N. Alonso1
1 Hospital
de Pediatría Prof. Dr. J.P. Garrahan, Hematology and Oncology,
Ciudad Autónoma de Buenos Aires, Argentina; 2 Hospital de Pediatría Prof.
Dr. J.P. Garrahan, Immunology and Rheumatology, Ciudad Autónoma de
Buenos Aires, Argentina; 3 Hospital de Pediatría Prof. Dr. J.P. Garrahan,
Cytogenetics, Ciudad Autónoma de Buenos Aires, Argentina
Background/Objectives: Minimal residual disease (MRD) is
useful for risk-group stratification in pediatric ALL-protocols.
Detection of patient-specific Immunoglobulin/T-cell-receptor
(Ig/TCR) rearrangements by quantitative-PCR (q-PCR) is a
reliable tool for MRD detection. In Phi-ALL cases, q-RT-PCR
quantification of BCR-ABL1 transcript can be used as additional target.
Aims: 1-To compare MRD results detected by both methodologies. 2-To evaluate the predictive value of both targets as
prognostic factors.
Design/Methods: A total of 212 follow-up samples from 16
Phi-ALL patients were analyzed. MRD for Ig/TCR was performed following standardized EuroMRD recommendations.
BCR-ABL1 minor/major transcripts quantification was performed as described in EAC program.
S173 of S518
Results: BCR-ABL1 was quantified in 201 and Ig/TCR
in 164 samples. One-hundred-fifty-six samples were
available for analysis by both techniques, correlation coefficient: 0.5725(p<0.00001). Concordant results by both
methods were observed in 15(9.6%) positive and 51(32.7%)
negative samples. However, 90(57.7%) samples showed
MRD positivity only by BCR-ABL1, with a median of 0.036;
[r:0.001-77.9]%. Of them, 40(44.4%) were ≥0.1%. No cases
were positive only by Ig/TCR. From the 15 samples positive
by both methods, 2 samples showed >1 log-difference
between BCR-ABL1 and Ig/TCR values, median logdifference: 0.21 [r:-0.59-1.49]. Outcome: Fourteen patients
achieved complete remission (CR). Two patients died in
CR, 3 relapsed and 11 remain in CR (median follow-up:32
months). MRD≥0.1% was observed in 2/3 relapsed patients
by both targets. In the group of 11 CCR patients, MRD≥0.1%
was found in 4 patients by Ig/TCR (4 day-33; 0 week-12)
and 9 by BCR-ABL1 (any time point). MRD-Ig/TCR<0.1%
at week-12 correlated with better outcome (p<0.00001).
Conclusions: No correlation was observed between both
MRD methods, with almost 60% of samples being positive by BCR-ABL1 while negative by Ig/TCR. Regarding the
prognostic value of MRD targets, Ig/TCR<0.1% at week-12
showed a significant correlation with outcome, while both
measurements of Ig/TCR on day-33 and BCR-ABL1 at any
follow-up time were not significantly associated with outcome.
P-016 Reducing Hospital Length of Stay for
Patients Newly Diagnosed with Acute
Lymphoblastic Leukemia
A. DiNofia1 , J. Wilkes2 , T. Flaherty3 , R. English3 , J. Sullivan1 , K.
Oranges1 , E. Dwyer1 , S. Powell1 , S. Rheingold1 , S.P. Hunger1 , A.
Reilly1
1 Children's
Hospital of Philadelphia, Department of Pediatrics- Division of
Oncology, Philadelphia, USA; 2 Seattle Children's Hospital, Department of
Pediatrics- Cancer and Blood Disorders Center, Seattle, USA; 3 Children's
Hospital of Philadelphia, Office of Clinical Quality Improvement,
Philadelphia, USA
Background/Objectives: Most patients with newly diagnosed acute lymphoblastic leukemia (ALL) at the Children's
Hospital of Philadelphia (CHOP) were discharged after day 8
of chemotherapy and many stayed 2-3 weeks into their first
month of therapy, called Induction. The goal of this quality
improvement project was to reduce the length of stay (LOS)
for patients newly diagnosed with ALL to less than 5 days
after the start of chemotherapy.
Design/Methods: Clinicians, nurses, and administrators were
educated on the data regarding the safety of earlier discharge from the hospital and the plan for implementation of an earlier discharge goal at CHOP. Family edu-
SIOP ABSTRACTS
S174 of S518
cation, planned procedures, and chemotherapy side effect
surveillance and management that usually take place in the
inpatient setting were transitioned to the outpatient clinic.
LOS following administration of first chemotherapy was measured. In addition, the average number of emergency department (ED) visits, inpatient and intensive care unit (ICU)
admissions, telephone calls from parents, and sick visits into
oncology clinic within the Induction course were collected to
ensure these metrics did not rise following implementation of
this new practice.
Results: The mean LOS following administration of the first
dose of chemotherapy was reduced by 78.5% from 20 days in
the months prior to the intervention was implemented to 4.3
days 11 months after the intervention was introduced. There
was no change in average number of ED visits, inpatient and
ICU admissions, telephone calls from parents, or sick visits
into oncology clinic during Induction following patients’ initial discharge.
Conclusions: It is feasible and safe to discharge newly diagnosed patients with ALL from the hospital within 5 days of
initiation of treatment.
P-017 Cost-Analysis of Treatment of Childhood
Acute Lymphoblastic Leukemia Based on UKALL
Protocol
M. Ehsani1 , H. Hayati2 , E. Shahgholi1 , A. KebriaeeZadeh2 , S.
Nikfar2 , M. Tashvighi3 , A. Mehrvar3
Aims: a study on the direct and indirect costs of ALL based on
the United Kingdom protocol (UK-ALL), in pediatrics ALL
management in Iran.
Results: The total direct medical cost per patient was 8282 US
dollars. Most of costs were from inpatient beds (3338±1110
USD) and drug expenditures (2157±1035 USD). The direct
non-medical cost incurred by study participants was 1286.4
USD, The total indirect cost of due to productivity loss was
769.9.
Conclusions: Treatment of pediatrics ALL is less costly in
Iran comparing other countries. So, physicians and policy
makers and health care system administrators should devise
an appropriate strategy to reduce the direct medical costs
which have more economic burden special for hospitalization
days and chemotherapy costs based on the findings.
P-018 Cost-Effectiveness of Pediatric-Inspired vs
Hyper-CVAD Protocols for First-Line Treatment of
Adolescent and Young Adult (AYA) Patients with
Philadelphia-Negative Acute Lymphoblastic
Leukemia (ALL)
E. Hooper1 , X. Xingdi Hu2 , P. Lin3
1 Shire,
Medical Director- Oncology, Cambridge, USA; 2 Shire, Analytics
and Statistics Lead- GHEORE, Cambridge, USA; 3 Shire, Global HEOR
Lead- Oncology, Cambridge, USA
This study on the direct and indirect costs of ALL based on
the United Kingdom protocol (UK-ALL), in pediatrics ALL
management in Iran.
Background/Objectives: Various protocols exist for first-line
treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; aged 16-39 years). Evidence suggests pediatric-inspired protocols for ALL that
include asparaginase as part of a multi-therapy chemotherapy regimen are associated with better outcomes than conventional adult regimens, such as Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
dexamethasone).1 Evidence regarding the cost-effectiveness
of pediatric-inspired protocols versus Hyper-CVAD in AYA
patients is limited. The objective of this study was to estimate the cost-effectiveness of a pediatric-inspired protocol
(CALG-10403) versus Hyper-CVAD for first-line treatment
of AYA patients with Philadelphia-negative (Ph-) ALL from
a US payer perspective.
Design/Methods: A retrospective study design was used to
study children with ALL managed with UKALL protocol
in specialized pediatric hospitals from 2010-2015. The data
was collected from patients’ medical records. MsoNormal
style=’tab-stops:252.75pt;border:none; Health systems have
adopted financing to enhance access to care for patients with
cancer. the cost of ALL treatment is a blurred image for hospitals and third party payers. The cost of each component of
the care should be analyzed to differentiate justifiable cost and
to act on waste full practices.
Design/Methods: A 6-state Markov model was developed to
estimate overall survival, treatment-related costs, and qualityadjusted life years (QALYs) over a lifetime horizon. The modeled health states were: no first complete remission, first complete remission, first relapse, second complete remission, second relapse, and death. Model inputs for survival, adverse
events, health utility, and costs were obtained from published
sources. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER; incremental costs/QALY
gained). Deterministic and probabilistic sensitivity analyses
1 Tehran
University of Medical Sciences, Pediatric Hematology and
Oncology, Tehran, Iran; 2 Tehran University of Medical Sciences,
PediatrPharmacoeconomics and Pharmaceutical Administrationic
Hematology and Oncology, Tehran, Iran; 3 MAHAK Charity Hospital,
Pediatric Oncology, Tehran, Iran
Background/Objectives: Health systems have adopted
financing to enhance access to care for patients with cancer.
the cost of ALL treatment is a blurred image for hospitals
and third party payers. The cost of each component of the
care should be analyzed to differentiate justifiable cost and to
act on waste full practices.
SIOP ABSTRACTS
S175 of S518
were performed to evaluate uncertainty around model input
values.
ASP and PEG-ASP, respectively. Safety was consistent with
the product class for both asparaginases.
Results: The base-case analysis suggested that the pediatricinspired protocol resulted in increased QALYs and reduced
costs (QALYs gained, 2.05; cost savings, $41,685) compared with the Hyper-CVAD protocol. Sensitivity analysis
indicated that the probability of receiving stem cell transplantation at second complete remission was the key driver
of cost-effectiveness. At a willingness-to-pay threshold of
$50,000/QALY, the probability of the pediatric-inspired protocol being cost-effective relative to Hyper-CVAD was ∼92%.
Conclusions: The results of this assessment support a favorable efficacy profile for PEG-ASP vs. native ASP in treatment of newly diagnosed pediatric patients with ALL, with
the benefits of less frequent administration. Safety was consistent with the known class profile.
Conclusions: The pediatric-inspired protocol (CALG-10403)
is cost-effective compared to Hyper-CVAD for first-line treatment of AYA patients with Ph- ALL. Cost should not be a barrier to the use of a pediatric-inspired protocol in AYA patients.
Reference: 1. Ram R., et al. Am J Hematol 2012.
P-019 Systematic Literature Review and
Meta-Analysis of Event Free Survival and Overall
Survival Rates for Pegaspargase in Pediatric
Patients with Acute Lymphoblastic Leukemia
E. Hopper1 , A. Wijatyk2 , D. Bollag3
1 Shire,
Medical Director- Oncology, Cambridge, USA; 2 Shire, Global
Clinical Development Lead at Shire, Cambridge, USA; 3 Shire, Global
Franchise Medical Lead Hematologic Tumors, Zählerweg, Switzerland
Background/Objectives: PEGylated L-asparaginase (pegaspargase, PEG-ASP) is a foundational component of combination therapy for acute lymphoblastic leukemia (ALL) that,
when compared to native asparaginase (native-ASP), offers
sustained asparaginase activity with less frequent dosing and
reduced immunogenicity. The objective of this assessment
was to compare the clinical benefit of PEG-ASP vs nativeASP in newly diagnosed pediatric ALL patients with regard
to event free survival (EFS) and overall survival (OS).
Design/Methods: A systematic literature review was undertaken to identify all available evidence for newly diagnosed patients treated in pediatric ALL protocols using
PEG-ASP or native ASP. Randomized and observational
studies were included. Outcomes were EFS and OS.
Safety/immunogenicity was also examined. Asparaginasespecific pooled estimates were calculated by patient risk level.
Results: A total of 39 studies met criteria for abstraction; 13
used PEG-ASP and 27 used native ASP. For standard-risk
patients treated with native ASP, 5-year EFS was 82% (95%
Confidence Interval (CI) 75-88) vs 89% (95% CI 85-93) with
PEG-ASP, and OS was 81% (95% CI 67-96) vs 85% (95% CI
64-100) in favor of PEG-ASP. For high-risk patients, 5-year
EFS was 71% (95% CI 67-76) vs 80% (95% CI 75-86), and OS
was 73% (95% CI 59-86) vs 80% (95% CI 73-87) for native
P-020 MIR-3117 and MIR-3689D2 in MAPK
Signaling Pathway: Implication in Childhood Acute
Lymphoblastic Leukemia Susceptibility
A. Gutierrez-camino1 , I. Martin-guerrero1 , N. Garcia De Andoin2 ,
A. Navajas3 , A. Sastre4 , A. Carbone-baneres5 , M. Garcia-ariza6 , I.
Astigarraga6 , A. Garcia-orad1
1 University
of the Basque Country UPV/EHU, Genetics- Physic
Anthropology and Animal Physiology, Leioa, Spain; 2 University Hospital
Donostia, Pediatrics, Donostia, Spain; 3 BioCruces Health Research
Institute, Pediatrics, Barakaldo, Spain; 4 University Hospital La Paz,
Oncohaematology, Madrid, Spain; 5 University Hospital Miguel Servet,
Pediatrics, Zaragoza, Spain; 6 University Hospital Cruces, Pediatrics,
Barakaldo, Spain
Background/Objectives: Recently, several Genome wide
associations studies (GWAS) have found genetic variants
associated with pediatric acute lymphoblastic leukemia
(ALL) risk. These studies were mainly focused in coding
regions. Nowadays, it is known that more than 40% of significant variants associated with cancer risk are situated in
non-coding regions, where non-coding RNAs are located.
MicroRNAs (miRNAs) are non-coding RNA molecules dysregulated in ALL, suggesting a role in ALL risk. Despite
miRNA SNPs interfere with miRNA levels or function, only
3 studies in ALL susceptibility were done, showing significant results. Therefore, variants in miRNAs could contribute
to childhood B-ALL predisposition. Nowadays, a large number of new miRNAS were annotated. Therefore, the aim of
this study was to determine if any of SNPs in these new miRNAs are involved in B-ALL susceptibility.
Design/Methods: Blood samples of 217 pediatric patients
with B-cell ALL in complete remission and 330 healthy
controls of Spanish origin were analyzed. We selected all
the SNPs described in pre-miRNAs with a MAF>1% (213
SNPs in 206 miRNAs). VeraCode GoldenGate platform was
used. MirWalk, RNAFold web server and Consensus Path
Databases were used to performed bioinformatic analysis.
Results: The SNPs rs12402181 in mir3117 and rs62571442
in mir3689d2 were associated with B-ALL risk possibly
through its effect on MAPK signaling pathway.
Conclusions: Therefore, in this study we found rs12402181 in
mir3117 and rs62571442 in mir3689 associated with B-ALL
risk. These SNPs could be novel markers for B-ALL susceptibility.
SIOP ABSTRACTS
S176 of S518
This project was supported by UPV/EHU (UFI 11/35) and
Basque Government (IT989-16).
P-021 Experience with Clofarabine use in
Refractory/Relapsed Acute Leukemia Pediatric
Patients at the Instituto Nacional De Enfermedades
Neoplasicas (INEN), LIMA - PERU
J.L. Garcia1
1 Institutoi
Nacional de Enfermedades Neoplásicas, Pediatric Oncology,
Lima, Peru
Background/Objectives: To know the usefulness of Clofarabine regimens in refractory/relapsed Leukemia patients at our
setting and find the best scenario for it's use.
Design/Methods: Retrospective review of medical charts of
pediatric patients below 15 years old with refractory/relapsed
acute leukemia between 2009 and 2017, clinical data, laboratory results and bone marrow results with Minimal Residual
Disease (MRD) by flow cytometry study were recorded.
Results: Thirty three courses of Clofarabine regimens were
administrated in 27 patients with refractory/relapsed acute
leukemia, 24 had Acute Lymphoblastic Leukemia (ALL),
Clofarabine, Cyclofosfamide and Etoposide (CCE) combination was used in 22 patients, only one patient was in first
relapse, he achieved complete remission (CR) with negative
MRD, 6 patients were in second relapse, 2 of the evaluable
patients had CR, one with negative MRD, in the other the test
was not done. Four patients were in third relapse, none had
CR. One patient was in fourth relapse, he had CR with positive MRD. Seven patients had refractory disease, only one
had CR but with positive MRD. Of the 19 relapsed patients,
CR was achieved in 29.4% of them, only one with negative
MRD. CCE regimen was used in 8 patients with MRD positive disease, negative MRD was achieved in 75% of them,
all of these patients went to bone marrow transplant (BMT)
therapy. Severe hematologic toxicity was seen in 87.8% of the
courses given, followed by febrile neutropenia in 72.7% and
hepatic toxicity in 51.5%, there were 3 patients dead during
chemotherapy.
Conclusions: CCE regimen was very useful in MRD positive
disease, achieving a good rate of negativization of disease,
giving the option for BMT therapy.
P-022 Efficacy and Toxicity of Inotuzumab in a
Patient with Relapsed/ Refractory Acute
Lymphoblastic Leukemia
1
1
1
1
G. Giagnuolo , F. Petruzziello , G. Maisto , M.R. D'Amico , M.
Ripaldi1 , G. Loffredo1 , S. Buffardi1 , G. Menna1 , R. Parasole1
1 Santobono-Pausilipon
Hospital, Pediatric Hemato-oncology, Napoli, Italy
Background/Objectives: The outcome of relapsed/
refractory acute lymphoblastic leukemia (ALL) in childhood
is still poor; current chemotherapies’ regimen are associated
with significant toxicities and scanty responses. Recently,
physicians’ attention has been directed toward alternative drugs with different mechanism of action compared
to standard chemotherapy. Inotuzumab ozogamicin is an
anti-CD22 monoclonal antibody conjugated to the toxin,
calecheamicin. The complex Inotuzumab-CD22 receptor is
rapidly internalized with intracellular calicheamicin release.
Calicheamicin binds to the DNA, inducing double-strand
cleavage and apoptosis. Herein we describe the case of a
young girl with hypodiploid ALL relapsed for the second
time after allogeneic bone marrow transplantation (BMT).
Since the patient had an early relapse ( 5 months after BMT)
and was resistant to previous chemotherapy, we opted for
immunotherapy with Inotuzumab as bridge to a second
allogenic BMT.
Design/Methods: The drug was administered in monotherapy
at the dosage of 1.8 mg/mq/course, given weekly for 3 times,
every 29 days. The patient obtained hematological remission
after the first course and minimal residual disease (MRD) negativity after the second; a third course was administered before
haploidentical transplant.
Results: Treatment with inotuzumab was well tolerated; the
patient showed grade IV hematological toxicities after the
first course and grade I-II hepatotoxicities in the subsequent
cycles. During transplant VOD prophylaxis with defibrotide
was administered. During transplant no toxicity was reported;
the engraftment occurred at day +13 and MRD negativity was
documented at day +35. Unfortunately, 5 months after the second transplant, the patient relapsed again.
Conclusions: The good toxicity profile and the efficacy on
MRD suggests a larger using of inotuzumab, possibly in combinations with chemotherapy or other biological drugs before
BMT; this association could allow long-lasting disease-free
survival in patients with relapsed/refractory ALL. Further
study are needed to evaluate the optimal use of Inotuzumab
to improve cure rates in these patients.
P-023 Parvovirus B19 Induced Cytopenias in
Children on Maintenance Phase of Acute
Lymphoblastic Leukemia (ALL) Chemotherapy
Lead to Prolonged Chemotherapy Interruptions
B. Gupta1 , A. kumar1 , N. verma1 , G. pant1 , A. sharma1
1 King
Georges Medical University, Pediatrics, Lucknow, India
Background/Objectives: Chemotherapy interruptions during maintenance phase of ALL may lead to relapses and
hence are avoidable.In the present study role of parvovirus
SIOP ABSTRACTS
B19 infection in causing these chemotherapy interruptions
was evaluated.
Design/Methods: A cohort of 90 children with ALL during
the maintenance phase chemotherapy of ALL were evaluated
for 840 cycles (3 months each,2520 months).IgM,IgG,PCR
were done for Parvovirus B19 infection during episodes of
cytopenias requiring chemotherapy interruption.
Results: Of total 90 patients( 42 new entrants during study
period,48 already in various phases),30(33.3%) patients were
found to be parvovirus B19 Positive by PCR at various phases
of maintenance chemotherapy which was tested on grounds
on clinical suspicion.
Out of 30 parvovirus B19 positive patients 24 (80%) required
multiple blood tranfusions whereas amongst the 60 Parvovirus B19 negative patients only 23(38%) required multiple
tranfusions(p<.0.00).
During maintenance phase chemotherapy,18 patients had
more than 2 episodes of neutropenia and 11 out of 18(61%)
patients were parvovirus B19.
One twenty two cycles of maintenance phase were observed
to be delayed by more than 7 days and parvovirus B19 was
found positive in 85 out of 122(69.6%) cycles(p<0.000).
Conclusions: Parvovirus B19 infection emerges to be an
important cause of cytopenias leading to chemotherapy interruptions in maintenance phase of ALL Chemotherapy. So
Screening of ALL patients by PCR in cases of unexplained
cytopenias is recommended.
S177 of S518
Results: Thirty-one patients (25.8%) out of 120 had evidence
of IFI at baseline or during induction chemotherapy. As per
standard definitions, 16 (51.6%), 12 (38.7%) and 3 (9.6%)
patients had possible, probable and proven fungal infections
respectively. Positive galactomannan antigen was documented
in 12 (38.7%). Aspergillus species was isolated in all 3 proven
cases. The most common site of infection was lungs (83.8%),
followed by sino-rhinal (6.4%), 2 patients (6.4%) had multiorgan involvement while 1(3.2%) had cutaneous aspergillosis. Therapy omissions and interruptions during induction
occurred in 16 cases (51.6%). Induction mortality attributable
to progressive fungal infections was 16.1% (5 cases). Median
duration of follow up of 26 patients who achieved remission
was 9 months (range 1-54 months). Six patients (23%) out of
these had early relapses, of which 5 died.
Conclusions: A high incidence of fungal infections, particularly invasive aspergillosis, was observed. Invasive fungal
infections during induction lead to morbidity and mortality
in patients with ALL and contribute to therapy interruptions,
which would influence long term outcomes.
P-025 Subclavian Vein Access to Long Term
Catheter Placed in the ARM: A New Surgical
Strategy in Pediatric Oncology
R. Vianna1 , J.T.D.S.D. Oliveira1 , S. Coelho1 , M.F. Grabois1 ,
V.D.N. Santos1 , E.C. Lopes1 , C.S.D. Santos1 , R.H. Junior1 ,
A.L.D.M. Guaraldi1 , F.F. Lima1 , C.A.S. Martins1 , F.N. Gutierrez1
1 Instituto
P-024 Impact of Invasive Fungal Infections in
Children and Adolescents with Acute
Lymphoblastic Leukemia in a Resource Poor
Setting
N. Gupta1 , N. Dhingra1 , P. Mishra1 , T. Seth1 , S. Tyagi1 , H.P. Pati1 ,
R. Saxena1 , M. Mahapatra1
1 All
India Institute of Medical Sciences, Hematology, New Delhi, India
Background/Objectives: Infectious morbidity and mortality is a major concern in patients with hematological malignancies. Invasive fungal infections (IFI) during induction
chemotherapy in acute lymphoblastic leukemia (ALL) can
adversely impact outcomes. Experience with fungal infections
in children and adolescents during ALL induction from a tertiary care centre in north India is discussed here.
Design/Methods: Records of 120 patients (age < 18 years),
who underwent ALL induction at our institution between
1/1/2011 and 31/12/2016, were retrospectively reviewed. All
patients were on primary prophylaxis with fluconazole. Incidence and characteristics of IFI were identified. We assessed
therapy delays and interruptions in this group and the impact
of IFI on outcomes.
Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil
Background/Objectives: To evaluate the follow up and complications of long term catheters implanted in pediatric oncology patients with a subclavian vein puncture and an arm
port/tunneled catheter insertion technique
Design/Methods: Since 1994, about 140 long term central
venous catheters/ year were inserted in the pediatric oncology patients, and the arm was the first choice as site of insertion. Dissection of basilica, brachial and axillar veins were the
venous access. Since 2014, puncture of subclavian vein has
been used as the first option to venous access in some cases,
utilizing the reservoir/tunneled catheter positioned in the arm.
A retrospective review of the long-term catheters implanted
in pediatric oncology patients from 2014 to 2017, in children
ranging from 2 months to 16 years old (median 5 years old)
Complications as infections, thrombosis, and rupture were
compared in all techniques.
Results: 447 long term catheters were inserted, 267 totally
implanted and 174 tunneled catheters (in 6 cases weren´t identified), 294 dissection of arm veins, 115 Subclavian punctions,
6 Jugular punctions (in 26 cases weren't identified). Causes
of catheter removal were: infection, thrombosis, obstruction, rupture, exteriorization and others. Infection rates were
SIOP ABSTRACTS
S178 of S518
15% in port catheters: 12,7% dissection technique and 2,2%
(6/267 subclavian puncture) and 24% (42/174) in tunneled
catheters: 19% dissection technique, 4% subclavian puncture and 1,1% Jugular puncture. Trombosis rates were 1 in
port catheters (100% dissection technique) and 2 in tunneled
catheters (100% dissection technique).
brain was performed at the end of treatment in 22 patients and
no leukoencephalopathy was detected. Small (3 mm) bilateral
high signal intensity lesions in the frontal area were detected
in one patient. Low FA doses were not associated with other
severe clinical toxicity, steady state MTX concentration, age
or gender of the patients.
Conclusions: The use of the arm to place the reservoir/tunneled catheter was widely used since 1994, providing
a safe, comfortable and a good quality of life during oncologic
treatment in children. The use of subclavian vein puncture as
venous access to arm reservoir/tunneled catheter insertion has
shown a good choice without major complications with literature comparing results.
Conclusions: Single dose of FA after HDMTX seems to be
sufficient to prevent neurotoxicity in children with ALL who
have received extended alkalinization and prehydration and
have rapid clearance of MTX.
P-026 Single Dose of Folinic Acid Rescue after
High-Dose Methotrexate is not Associated with
Neurotoxicity in Children with Acute
Lymphoblastic Leukemia
A. Harila-Saari1 , J. Banerjee2 , P. Riikonen3 , T. Pokka4 , R.
Niinimaki5
1 Astrid
Lindgren Children's Hospital- Karolinska, Pediatric Oncology,
Stockholm, Sweden; 2 Helsinki University Hospital, Paediatric oncology,
Helsinki, Finland; 3 Kuopio University Hospital, Paediatric oncology,
Kuopio, Finland; 4 Oulu University Hospital, Paediatrics and Adolescents,
Oulu, Finland; 5 Oulu University Hospital and University of Oulu,
PEDEGO Research Unit and Department of paediatrics and adolescents,
Oulu, Finland
Background/Objectives: Folinic acid (FA) is needed after
administration of high-dose methotrexate (HD-MTX) in order
to rescue normal cells from toxicity. Low FA doses have been
associated with increased toxicity, including neurotoxicity,
whereas high doses may be related to decreased antileukemic
effect. NOPHO-ALL2000 protocol used in Finland included
15 mg/m2 FA given every 6 hours from 42 hours after
HDMTX (5 g/m2 ) and continued until serum MTX concentration was < 0.20 �mol/L. Extended alkalinization and prehydration (> 12 hours) was used. Only one or two doses were
given in patients with rapid clearance of MTX. We studied
here the association between low doses of FA after HD-MTX
and severe clinical toxicity, especially neurotoxicy.
Design/Methods: Patient files of 44 children (27 males; mean
age at diagnosis 5.7 years) with standard or intermediate risk
acute lymphoblastic leukaemia (ALL) treated with NOPHOALL2000 protocol in two Finnish centers were reviewed. Data
on HD-MTX clearance, FA dosing and clinical toxicity with
special focus on neurotoxicity were collected and analysed.
Results: Patients had received a total of 351 HD-MTX
courses. After 181 courses (51.6%, CI 46.2–56.9) only one
or two doses of FA were administered. Single dose was given
after 55 courses (15.7%, CI 12.0–19.9). None of the patients
had clinical neurotoxicity. Magnetic resonance imaging of the
P-027 XRCC1 Gene Polymorphism and the Risk
of Childhood Acute Lymphoblastic Leukemia: A
Case Control Study
T. Hassan1 , N. Khalifa1 , A. Baraka2 , M. Abdel Alim2
1 Faculty
of medicine- Zagazig university-Egypt, Pediatrics, Zagazig, Egypt;
of medicine- Zagazig university-Egypt, Clinical Pathology,
Zagazig, Egypt
2 Faculty
Background/Objectives: DNA repair systems have a crucial
role in maintaining genome integrity and stability. Defects in
repair pathways may promote development of cancer, including leukemia. Currently, research activities have focused on
polymorphisms in DNA repair genes as an important component of susceptibility to cancer. Among them, XRCC1 (X-ray
repair cross-complementing groups 1) gene polymorphisms
were reported to induce defective functional capacity of the
DNA Polymerase �, PARP, and ligase III enzyme, resulting
in defective DNA repair. We aimed to assess whether XRCC1
gene polymorphisms contribute to development of childhood
ALL or not, and to evaluate their prognostic significance as
regards to induction of remission and relationship to wellknown pretreatment risk factors.
Design/Methods: A case control study was carried out at clinical pathology and pediatric oncology departments, Zagazig
University, Egypt, during period from March 2016 to February 2017. Ninety subjects were included ;45 children with denovo ALL and 45 age and sex matched healthy children as
a control group.Patients were subjected to complete history
taking, thorough clinical examination and routine laboratory
investigations according to our local standards. Genotyping
of XRCC1 gene polymorphisms was performed for all study
participants using polymerase chain reaction and restriction
fragment length polymorphism (PCR-RFLP).
Results: There was no significant difference between patients
and controls as regards to different XRCC1 genotypes. Apart
from the significant association between Arg 399 Gln and
Gln 399 Gln genotypes and common ALL immunophenotype,
there was no significant difference among XRCC1 genotypes
in relation to any of the demographic,clinical and laboratory
data of patients as well as remission rates.
SIOP ABSTRACTS
Conclusions: There is no relation between XRCC1 gene polymorphism and risk of developing ALL in children. Apart from
the significant association between certain XRCC1 genotypes
and common ALL immunophenotype, XRCC1 gene polymorphism has no prognostic significance in childhood ALL.
Larger studies are still needed to support our findings.
P-028 Differences Between Urban and Rural
Areas of Castilla-Leon in the Incidence and
Survival of Childhood Leukemias (SPAIN)
R. Garrote Molpeceres1 , R. Herraiz Cristobal2 , E. Urbaneja
Rodríguez3 , M.A. Pino Vázquez4 , P. Gutiérrez Meléndez5 , F.J.
Álvarez Guisasola6 , H. González García2
1 Hospital
Clínico Universitario Valladolid, Servicio de Pediatría,
Valladolid, Spain; 2 Hospital Clínico Universitario Valladolid, Sección de
Oncohematología Pediátrica, Valladolid, Spain; 3 Hospital Clínico
Universitario Valladolid, Sección de Inmunología Pediátrica, Valladolid,
Spain; 4 Hospital Clínico Universitario Valladolid, Jefe Servicio de
Cuidados Intensivos Pediátricos, Valladolid, Spain; 5 Dirección General de
Salud Pública Junta de Castilla y León, Servicio de Salud Pública,
Valladolid, Spain; 6 Hospital Clínico Universitario Valladolid, Jefe de
Servicio y Catedrático de Pediatría, Valladolid, Spain
Background/Objectives: To analyze the differences between
urban and rural children population in incidence and survival
of children under 15 years old diagnosed with leukemia in the
region of Castilla-León (Spain) during the period 2003-2014.
Design/Methods: Leukemia cases were extracted from the
registry of childhood tumors of population base of CastillaLeón, with an annual mean of childhood population of
296,776 children under 15 years old. Cases were classified
by age and sex. Leukemia incidence was adjusted by age
to world population (ASRw, 95%CI) and their differences
through standardized rate. For three-year survival analysis, we
included cases with follow-up until 31/12/2013. Survival rates
were calculated by Kaplan-Meier analysis and their comparisons with log-rank test. Rural population was considered to
be one with ≤ 20,000 habitants.
Results: From 155 leukemias diagnosed, we could identify the rural/urban population in 145(93.55%), 79(54.48%)
rural and 66(45.52%) urban. Leukemia incidence was
significantly greater in rural areas [ASRw: 51.08(40.3164.02) vs 33.65(25.93-43.07)], p=0.018. Incidence analysis by age showed greater significantly rural leukemia incidence in 0-4 years old children [ASRw: 59.23(39.96-84.56)
vs 36.18(22.93-54.28)], p<0.0001. Global survival was of
83%(76.1-88), with a mean follow-up of 7.25 years (Quartiles: 3.77-9.5). Urban leukemia survival was significantly
less than rural [76%(64.5-84.2) vs 91%(82.9-95.4)], p=0.005.
There were no survival differences by sex in 0-4 years old children between rural and urban populations. In the 5-9 years old
group, female survival was greater in rural areas (p=0,006)
S179 of S518
and in the 10-14 years old group, survival was greater in males
from rural areas (p=0.018).
Conclusions: We found higher incidence of childhood
leukemia in rural areas due to an increase of incidence in 04 years old children. Survival was greater in rural areas in
children older than 5 years at diagnosis. These differences in
incidence and survival could help to investigate epigenetic or
environmental factors of childhood leukemia.
P-029 IDH1 and KRAS Mutations are Involved
in Acute Lymphoblastic Leukemia in Maffucci
Syndrome
S. Hirabayashi1 , M. Seki2 , D. Hasegawa1 , M. Kato3 , N. Hyakuna4 ,
T. Shuo5 , S. Kimura2 , K. Yoshida6 , K. Kataoka6 , Y. Fujii6 , Y.
Shiraishi7 , K. Chiba7 , H. Tanaka7 , N. Kiyokawa8 , S. Miyano7 , S.
Ogawa6 , J. Takita2 , A. Manabe1
1 St.
Luke's International Hospital, Department of Pediatrics, Tokyo, Japan;
of Tokyo, Department of Pediatrics, Tokyo, Japan; 3 National
Center for Child Health and Development, Children's Cancer Center,
Tokyo, Japan; 4 Hospital of University of the Ryukyu, Center of Bone
Marrow Transplantation, Okinawa, Japan; 5 St. Luke's International
University, Institute for Medical Innovation, Tokyo, Japan; 6 Graduate
School of Medicine- Kyoto University, Department of Pathology and Tumor
Biology, Kyoto, Japan; 7 Institute of Medical Science- University of Tokyo,
Laboratory of DNA Information Analysis- Human Genome Center, Tokyo,
Japan; 8 National Center for Child Health and Development, Department of
Pediatric Hematology and Oncology Research, Tokyo, Japan
2 University
Background/Objectives: Somatic mosaic mutations of the
genes encoding isocitrate dehydrogenase 1 and 2 (IDH1,
IDH2) cause Maffucci syndrome, rare nonhereditary disorders in which patients develop multiple enchondromas combined with hemangiomas. Although malignant transformation
of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia,
are serious complications, reports of acute lymphoblastic
leukemia (ALL) as a secondary neoplasm are limited.
Design/Methods: In this study, we present a 15-year-old
girl with Maffucci syndrome who developed B-cell precursor (BCP)-ALL as a secondary neoplasm. IDH1 and IDH2
mutations in leukemic cells at relapse and hemanigoma were
screened by Sanger sequencing. Additionally, whole exome
sequencing and SNP array were done in leukemic cells at
relapse.
Results: The girl was diagnosed Maffucci syndrome because
of shortness of right arm and hemangioma at infant. At the
age of 12 years, she had fever, anemia and severe pain on her
systemic body. Bone marrow examination revealed necrotic
bone marrow and chondromatosis. She had severe anemia 6
months later, and was diagnosed with B-precursor ALL. She
received chemotherapy, however, she relapsed at the age of 15
years 4 months after cessation of maintenance therapy. Mutational analysis of IDH1 revealed p.R132C in leukemic cells
at relapse. A somatic mutation in IDH1 c.394C>T (encod-
SIOP ABSTRACTS
S180 of S518
ing p.R132C) was detected in her hemangioma and leukemic
cells, and the KRAS mutation c.38G>A (encoding p.G13D)
and deletion of IKZF1 were detected in her leukemic cells.
cephradine. All Pseudomonas spp. showed 100% sensivity to
imipenem, amikacin, ciprofloxacin & colistin and resistantance to ceftazidime,
Conclusions: Patients with Maffucci syndrome might be at
risk of BCP-ALL associated with secondary genetic events
that affect lymphocyte differentiation. Our observations suggest that secondary mutations may account for the development of ALL in patients with Maffucci syndrome. Prospective
registration of any patient suspected of genetic predisposition
is mandatory to identify the mechanism of leukemogenesis
and variation of penetrance of ALL.
Conclusions: The species of Klebsiella were the predominant causative bacterial agent followed by Escherichia
coli, Acinetobacter spp, pseudomonas spp. and enterobacter
spp.’They showed resistance to commonly prescribed antibiotics ceftazidime, gentamicin, ceftriaxone & ciprofloxacin
and sensitive to imipenem, colistin-sulphate & piperacillintazobactam.
P-030 Isolation of Pathogenic Bacteria and Their
Antibiotic Sensitivity Profiles in Hospitalized
Febrile Neutropenic Children with Acute
Lymphoblastic Leukaemia
1
1
C.Y. Jamal , M.B. Yeamin
1 Bangabandhu
Sheikh Mujib Medical University, Paediatric Haematology
and Oncology, Dhaka, Bangladesh
Background/Objectives: Acute lymphoblastic leukemia
(ALL) is the commonest malignancies in childhood. Common
obstacle in the treatment of ALL is febrile neutropenia and
its complications. To identify bacteria causing infection, their
isolation rate and antibacterial sensitivity pattern in hospitalized febrile neutropenic children with ALL in different cycle
of chemotherapy.
Design/Methods: This cross sectional study conducted in
2014 - 2015 in the department of paediatric haematology/
oncology, BSMMU, Dhaka BANGLADESH. Sixty febrile
neutropenic episodes from 52 diagnosed cases of ALL aged 0
to18 years were included. Complete blood count, blood culture, urine microscopy and culture, serum alanine aminotransferase, serum creatinine were done in every patient. X-ray
chest, stool microscopy and culture, pus, wound, throat and
aural swab for culture & sensitivity were done in selective
patient.
Results: Bacterial infection was confirmed by culture in 15
(25%) episodes from 60 febrile neutropenic episodes. Fifteen (25%) organisms were isolated from the study subjects
from sample of blood (60%), pus (13.3%), aural swab (13.3%),
wound swab (6.7%) and throat swab (6.7%) respectively. All
isolates were gram negative. The organism isolated were
Klebsiella spp 5 (33.31%), E. coli 4 (26.7%), Acinetobacter
3 (20%), Pseudomonas 2 (13.3%) and only one (6.7%) Enterobacter species. All the isolates of the Klebsiella spp., E.coli
and Acinetobacter spp. were resistant to amoxicillin. All isolated E.coli were resistant to cotrimoxazole, ceftazidime, ceftriaxone, cefotaxime and ciprofloxacin, Acinetobacter spp.
Isolated were100% sensitive to imipenem, colistin sulphate
& piperacillin-tazobactam and resistant to cotrimoxazole and
P-031 Bone Disease in Childhood Acute
Lymphoblastic Leukemia
K. Katsibardi1 , K. Roka1 , G. Avgerinou1 , N. Tourkantoni1 , M.
Filippidou1 , H. Tsipou1 , N. Krallis2 , A. Kattamis1
1 Aghia
Sophia Children's Hospital, Pediatric Hematology Oncology,
Athens, Greece; 2 Aghia Sophia Children's Hospital, Orthopaedic Unit,
Athens, Greece
Background/Objectives: Bone abnormalities, such as low
bone mineral density, osteoporosis and non-traumatic bone
fractures, frequently occur in children under chemotherapy
for acute lymphoblastic leukemia (ALL). Their pathogenesis seems to be multifactorial, due to chemotherapeutic agents
and the leukemic process.
Design/Methods: Children diagnosed with ALL were evaluated in regards to the occurrence of bone abnormalities within
a 4-year period (January 2013- December 2016). Severe
bone abnormalities were defined as: significant bone pain
associated with activity restrictions, and significant loss of
bone mineral resulting in objective osteoporosis or/and nontraumatic bone fractures.
Results: During this period, 70 children were diagnosed with
ALL (N=35, 50% girls), of median age 4.42 years (range:
1.02- 16.91 years). Among them twelve (17%) experienced
bone abnormalities.
Bone pain with activity restriction and gait disturbances was
observed in eight patients, half at diagnosis and during maintenance. Four patients experienced bone fractures (two at
diagnosis, one during reinduction and one during maintenance). Osteoporosis was documented in two patients, at
maintenance. Four patients (3 girls / 1 boy, of six, ten, thirteen
and fifteen years old) developed aseptic necrosis of femoral
head with severe limping. Most patients were treated conservatively. Arthroplasty was performed in 1/4 patients after
maintenance completion. Four children received Zoledronic
acid, with median number of 6 doses, for 13.2 months (median
duration). Symptoms improved slowly and had resolved by
the end of treatment. Bone mineral density measured at the
dual energy x-ray absorptiometry (DEXA) return to ageappropriate levels by a median period of seven months.
SIOP ABSTRACTS
Conclusions: We documented a high incidence of bone disease in children with ALL. Bisphosphonate therapy with
Zoledronic acid seems to decrease skeletal pain and increase
bone density. Early recognition of patients at risk and timely
application of adequate preventive and therapeutic measures
are essential to prevent this debilitating complication in ALL
patients.
P-032 Prevalence and Clinical Correlation of
TPMT, ITPA and NUDT15 Gene Polymorphisms in
Children with Acute Lymphoblastic Leukaemia in
North India
S. Khera1 , A. Trehan1 , P. Bhatia1 , M. Singh2 , D. Bansal1 , N.
Varma3
1 PGIMER,
Pediatrics, Chandigarh, India; 2 PGIMER, Lab Hematology,
Chandigarh, India; 3 PGIMER, Hematology, Chandigarh, India
Background/Objectives: Toxicity of 6-Mercaptopurine (6MP) is related to single nucleotide polymorphism (SNP)
in genes coding for metabolizing enzymes; with thiopurine S-methyltransferase (TPMT) analysis being recommended prior to maintenance therapy in Acute Lymphoblastic
Leukemia (ALL). However, inosine triphosphate pyrophosphatase (ITPA) and nucleoside diphophate–X-type motif 15
(NUDT15) SNP's appear more important in the Asian population.
Design/Methods: In this prospective Mendelian randomisation study consecutive patients with ALL ( Jan 2016 to Jun
2016), entering maintenance phase were evaluated for TPMT,
ITPA and NUDT15 by PCR RFLP. Haematological and hepatic toxicities were monitored for 9 months.The two groups
with and without SNP's mutation (Mut+ and Mut-) were compared.
Results: Sixty three patients of ALL [5.3 years (4.61- 6.06)]
underwent molecular analysis. Fifty eight were followed for
9 months. Eighteen (28.6%) patients had SNP mutations.
ITPA, NUDT, TPMT*3C mutations: 11(17.5%),6(9.5%) and
2(3.1%).One patient had TPMT3*C and ITPA. All mutations except 1 ITPA were heterozygous. Mean cumulative
dose of 6MP was lower 10927 mg/m2 in Mut+ compared to
12533 mg/m2 in Mut- group (P=0.009). Neutropenic events
were greater in Mut+ (P=0.03), Weeks of full dose of 6
MP were lower in Mut + (21 versus 30; P=0.0009). Risk
of Neutropenia>2 weeks was pronounced (OR=4.41; 95%CI
1.21-16; P=0.024) and the weeks off chemotherapy were
greater in Mut + group (5 versus 2.8; P=0.019). The ITPA
and NUDT SNP subgroups had similar cumulative 6MP doses
and chemotherapy interruptions. There was no difference in
average cumulative dose of Methotrexate in 2 groups. Malnourishment did not correlate with doses. No significant hepatotoxicity was noted.
S181 of S518
Conclusions: Polymorphisms in 6MP metabolizing enzymes
are notably related to ethnic ancestry. TPMT (3.1%) SNP's do
not appear to have a significant role in our population. ITPA
(17.5%) and NUDT (9.5%) polymorphisms appear to be the
important SNP's in the north Indian population for optimizing
chemotherapy doses.
P-033 Dual Inhibition of Beta-Catenin and RAS
by Targeting AXIN-RGS Domain (KYA1797K*) in
Acute Leukemia
M.K. Kim1 , M.R. Lee1 , J. Lim1 , S.M. Hahn1 , J.W. Han1 , C.J. Lyu1
1 Yonsei
Cancer Center- Yonsei University Health System, Department of
Pediatrics, SEOUL, Republic of Korea
Background/Objectives: Signaling pathways in acute
leukemia are aberrantly activated to cause leukemogenesis
and relapse after treatment. Upregulation of WNT/betacatenin pathway is common and hyperactive RAS is strongly
associated with treatment resistance in leukemia. Small
molecule therapy opened a new window for cancer treatment
but targeting one subject may have limitations. KYA1797K
binds directly to RGS domain of axin and enhances the betacatenin destruction complex which activates GSK3beta and
results in degradation of beta-catenin and RAS. In the current
study, the effects of KYA1797K on acute leukemia were
studied in leukemic cell mono-culture and in co-culturing
with human BM-derived MSC (hBMSC).
Design/Methods: Leukemic cells (MOLT-4, Jurka, KG1, THP-1) were cultured in RPMI1640 media under various concentration (0.2-10 microM) of KYA1797K and with
Erlotinib (1 microM) for comparison. Cell proliferation assay
on KYA1797K was done and Immunoblotting for betacatenin, GSK3beta, Pan-RAS was checked and compared
between monoculture and co-culture with hBMSC. Downstream targets of WNT pathway (c-Myc, CD44, LEF1, Met,
TCF1/TCF7) were studied by Immunoblotting in monoculture.
Results: Suppression of leukemic cells by KYA1797K was
evident starting from the concentration of 5 microM. Betacatenin was downregulated in all cell lines by KYA1797K.
Pan-RAS was downregulated in MOLT-4 and THP-1. All
the downstream targets evaluated were downregulated by
KYA1797K in MOLT-4 monoculture which was evident at
the concentration of 5microM. Co-culture of MOLT-4 with
hBMSC showed similar pattern with monoculture for betacatenin and Pan-RAS. Pan-RAS of hBMSC was not affected.
Conclusions: This preclinical study suggest that KYA1797K
may be an option for patients with acute leukemia especially
who experience relapse. KYA1797K effectively destabilized
beta-catenin and RAS in acute leukemia. Difference in effective concentration may mean the need of further study in each
SIOP ABSTRACTS
S182 of S518
leukemia cell line. The effect of KYA1797K on leukemiaMSC crosstalk needs further research.
* KYA1797K (Nat Chem Biol 2016, 12:593) kindly provided
by Kang-Yell Choi.
P-035 Demographics and Outcome of
Philadelphia Chromosome Positive ALL in
Pediatric Population in a Resource Constraint
Setting – A Single Centre Experience
A. Kumar1 , G. Pant1 , N. Verma1 , B. Gupta1 , A. Sharma1
P-034 In Vivo Effect of Interferon-Gamma
Primed Mesenchymal Stem Cells on the Growth of
Acute Lymphoblastic Leukemia Cells
H.H. Koo1 , Y.T. Lim2 , Y.J. Park1 , H.J. Park1 , M.W. Lee1 , D.S.
Kim1 , K.W. Sung1 , K.H. Yoo1
1 Samsung
Medical Center, Pediatrics, Seoul, Republic of Korea; 2 Pusan
National University College of Medicine, Pediatrics, Busan, Republic of
Korea
Background/Objectives: Although many studies have been
tried to clarify cellular interactions between human mesenchymal stem cells (MSCs) and cancer cells in vitro models,
the role of MSCs in the growth of tumor cells in vivo is still not
fully understood. In this study, we examined the effect of naive
MSCs or interferon (IFN)-�-primed MSCs on the growth
of acute lymphoblastic leukemia (ALL) cells in an in vivo
model.
Design/Methods: We established four distinct stable cell
lines expressing firefly luciferase (fLuci) gene by infection of
lentivirus in Jurkat, CCRF-CEM, Sup-T1 and CCRF-HSB2
ALL cells. We measured luciferase activity using an IVIS
optical imaging technique to determine the effects of MSCs
on leukemic mass formation.
Results: 105 ALL/fLuci cells together with 106 MSCs were
inoculated into NOD/SCID mice by intraperitoneal (IP) injection.Much higher luciferase activity was observed when
ALL/fLuci cells were co-injected with MSCs as compared to
that when ALL/fLuci cells were inoculated alone. In addition,
we co-inoculated 105 ALL/fLuci cells with different numbers
of MSCs (1:1, 1:5 or 1:10 ratio) into mice. Although the bioluminescent intensity gradually increased in all groups, the mice
that were co-injected with 106 MSCs showed higher bioluminescent intensity than those co-injected with lower number
of MSC, indicating the possibility that MSCs play an important role in stimulating a leukemic proliferation. To determine the effects of IFN-� priming on the growth of leukemic
cells by MSCs, ALL/fLuci cells together with IFN-�-primed
MSCs were inoculated into NOD/SCID mice via IP injection. Lower luciferase activity was observed when ALL/fLuci
cells were co-injected with IFN-�-primed MSCs as compared
to that when ALL/fLuci cells were co-inoculated with naive
MSCs.
Conclusions: Our results suggest that IFN-� priming may
activate MSC's potential anti-cancer effects. Further studies
are needed to elucidate the precise roles of IFN-�-primed
MSCs on the microenvironment of leukemia cells.
1 King
George Medical University, Pediatric Oncology, Lucknow, India
Background/Objectives: Children with Philadelphia chromosome positive (Ph+) Acute Lymphoblastic Leukemia
(ALL) are considered to have a poor prognosis with high
risk features. This study was conducted to evaluate the frequency, demographics and outcome of induction chemotherapy in such patients in a resource constraint setting.
Design/Methods: Among children with ALL registered from
January 2014 to June 2016, in whom flowcytometry and
translocations could be done, the demographic data of Ph+
patients were compared with Ph- patients. The outcome of
Ph+ patients was compared with Ph- B and T cell ALL on
similar high risk treatment protocols). Ph+ patients additionally received imatinib mesylate as soon as diagnosis was confirmed. Statistical analysis was done by Fischer exact test and
outcome by Kaplan Meyer curves for survival analysis.
Results: Of 207 patients with ALL, 15(7.28%) were Ph+.
No difference was demonstrated between age and sex in Ph+
and Ph- ALL (median age 6 years in both and males -73.3%
and 74% respectively). Median TLC at presentation was significantly higher in Ph+ as compared to Phnegative patients
(2,16,000/mm3 vs 21,000/ mm3 respectively, p<0.0001). A
significantly higher proportion of Ph+ patients 4/15 (26.6%)
had CNS leukemia as compared to 1/131 (0.76%) Phnegative patients (p = <0.0004). Though induction deaths were
higher 6/15 (40%) in Ph+ patients as compared with Ph- high
risk patients 10/63(15.8%) this did not reach statistical significance (p = 0.069, OR=3.533 (1.028 to 12.25). Post induction
D35 bone-marrow showed remission in 73.3% Ph+ as compared to 100% of Ph- high risk patients.
Conclusions: Children with Ph+ ALL (7.28%), had significantly higher TLC and CNS disease at presentation as compared to Ph- ALL patients. Induction deaths and failure to
reach remission after induction was higher in Ph+ ALL as
compared to Ph- high risk ALL, despite similar treatment protocol and addition of Imatinib mesylate.
P-036 CD44 Expression in T Cell Acute
Lymphoblastic Leukemia and ITS Association with
RAS and NOTCH1 Pathways
L.V.C. Marques1 , E. P. Noronha1 , F. G. Andrade1 , E. T. G. Pina1 ,
M. S. Pombo-de-Oliveira1
1 INCA,
PHOP Programa de Hematologia Oncologia Pediatrica, Rio de
Janeiro, Brazil
SIOP ABSTRACTS
Background/Objectives: CD44 is an adhesion glycoprotein widely expressend in hematopoietic cells. In murine Tcell acute lymphoblastic leukemia (T-ALL) models, CD44
expression was associated with organ infiltration and influencing survival. CD44 was also identified as a direct NOTCH1
transcriptional target, as well as a target of the RAS pathway,
which promotes its alternative splicing, throughout a positive feedback loop. We have investigated whether the cellular expression of CD44 in different maturational subtypes of
pediatric T-ALL could predict RAS and NOTCH1 mutations.
Design/Methods: We tested a series of 140 patients with
childhood leukemia, being 110 T-ALL and 30 Acute myeloid
leukemia (AML) with less than 18 years of age; evaluated for
the immunophenotypic profile by multiparameter flow cytometry and used Sanger sequencing to detect mutation in codons
12 and 13 of N/KRAS, 9 and 10 of FBXW7 and 26, 27 and 34
of NOTCH1. CD44 expression was evaluated by median fluorescence intensity (MFI) in leukemic blast cells of patients
and 75th percentile MFI value was used as a cutoff between
high or low CD44 expression T-ALL.
Results: There was no association between high expression of CD44 and organomegaly in T-ALL; and between
the expression of CD44 among T-ALL subtypes. AML
cases have a higher expression of CD44 (MFI:18890[101944720]) than T-ALL (MFI:1211[68-8325]) (p<0.0001).
There was no significant difference in CD44 expression
between NOTCH1/FBXW7mut cases (MFI:2689[194-19150])
and NOTCH1/FBXW7 Wild Type (WT) (MFI:2773[15612750]); and between N/KRASmut cases (MFI:1715[3658325]) and N/KRASWT (MFI:1179[68-5544]) in T-ALL,
whereas in AML, N/KRASmut cases had a lower CD44
expression (MFI:10979[7650-18810]) than N/KRASWT cases
(MFI:21720[1019-44720]) (p=0.032).
Conclusions: CD44 cellular status was not relevant for TALL tumoral profile and its expression was not associated
with T-ALL subtype. CD44 is under expressed in T-ALL
when compared with AML. N/KRAS and NOTCH1/FBXW7
mutations do not seem be associated with different expression
of CD44 in pediatric T-ALL and AML.
P-037 Dyslipidemia and Glucose Metabolism at
Time of Diagnosis in Children with Acute
Lymphoblastic Leukemia
P. Mogensen1
1 University
hospital of Copenhagen, Dept. of Metabolism and Diabetes &
Dept. Pediatric Oncology Research, Copehagen Ø, Denmark
Background / Objectives: Background: Survivors of childhood acute lymphoblastic leukemia (ALL) have a threefold risk of developing type 2 diabetes, probably caused by
intensive chemotherapy including corticosteroids. However,
S183 of S518
it is unknown if the ALL per se contributes to early dysmetabolic manifestations. This study undertook to determine
the glycemic and lipid profiles at time of ALL diagnosis
before the onset of ALL therapy.
Design / Methods: Material and methods: All patients
(Median age 4 years (range 1-17 years) 70 males) were diagnosed with ALL at University Hospital Rigshospitalet, Denmark since 2008.
122 fasting blood samples were collected at time of diagnosis
before onset of therapy. Lipid analyses were performed retrospectively on blood samples collected since 2008. HbA1c,
fasting plasma glucose and fasting plasma insulin were measured prospectively in a subgroup (N=24). Insulin resistance
was calculated by the HOMA-IR based on fasting glucose and
insulin.
Results: Preliminary Results: Preliminary data at baseline showed median (25th -75th quartiles) values of BMI 16.3
kg/m2 (15.4-18.0), cholesterol 3.2 mmol/L (2.0-5.1), HDL
0.42 mmol/L (0.08-1.43), LDL 1.7 mmol/L (0.4-3.3), triglycerides 2.8 mmol/L (0.6-6.7) and a triglyceride/HDL-ratio at
6.8. Median fasting glucose and insulin were 4.9pmol/L (4.45.3) and 24 mmol/L (9-46) and HbA1c are 6.8 mmol/L (6.57.4). Insulin resistance (HOMA-IR) was 0.84 (0.20-1.55).
Conclusions: ALL seems to influence metabolic parameters
including the lipid profile before start of anti-leukaemic therapy. Currently, correlation analysis is ongoing in order to
understand the mechanisms behind these findings.
P-038 Survival Analysis of Pediatric Patients with
Acute Leukemia and Down Syndrome at the
Instituto Nacional De Enfermedades Neoplasicas
(LIMA-PERU)
J.E. Montoya Vasquez1
1 Institutoi
Nacional de Enfermedades Neoplásicas, Paediatric Oncology,
Lima, Peru
Background/Objectives: Children with Down syndrome
(DS) have an increased risk of developing acute leukemia than
children without this syndrome. Usually, this type of patients
develop more chemotherapy-related toxicity, severe infectious
and toxic deaths. The aim of the study is to examine the overall
survival (OS) and the disease-free survival (DFS) at 5 years of
children with DS and acute lymphoblastic leukemia (ALL).
Design/Methods: From January 2000 to December 2016, 45
infants and children younger than 14 years with DS who
was diagnosed and treated as ALL at the Instituto Nacional
de enfermedades Neoplásicas (INEN) were retrospectively
reviewed. Medical charts were evaluated for socio- demographical, clinical characteristics and treatment outcomes.
All descriptive data, OS and DFS was analyzed using Stata
SIOP ABSTRACTS
S184 of S518
14.0 statistical software. We estimated survival rates with the
Kaplan-Meier method and analyzed the results with log-rank
test and Cox proportional hazard model.
Conclusions: Over the three decades, there has been progressive increase in the number of cases referred for malignancies
in children.
Results: With a median follow up time of 50.4 months (range,
1-192), 5-year OS and DFS were 38.4% (Standard error, SE
9.4%) and 27.2 (SE 7.8%), respectively. In univariate analysis,
younger age (<3 years) and risk group were significantly associated with lower OS and DFS rates. The multivariate analysis showed that younger age was an independent predicting
factor for both OS (HR=12.0, p=0.003) and DFS (HR=7.8,
p=0.004). High-risk group patients had worse outcome in
terms of DFS (HR=2.5, p=0.007)
The proportion of infants to childhood and adolescents malignancies remained same in last 3 decades.
Conclusions: In this study, younger age and high-risk ALL
children with DS had poor treatment outcomes. Efforts are
needed to improve survival in these patients.
P-039
Epidemiology of Cancers in Infancy
S. Mudaliar1 , A. Swami1 , B. Agarwal1
1B
J Wadia Hospital, Pediatric Hemato-Oncology, Mumbai, India
Background/Objectives: Incidence and histological distribution of malignancies in Infants are much different than older
children.
This study was done to establish the incidence and types of
malignancies in infants referred in tertiary care centre and to
report changes observed over the last three decades.
Design/Methods: Data retrieved from referral records maintained in Oncology Department (for 1985-2015) was analysed
and compared to assess incidences and types of malignancies
presenting in infants.
Results: During the period, a total of 2,307 children were
referred. Of them 285 (12%) were infants including 28 (1.2%)
Neonates. The sample had 175 male and 110 female (1.5:1).
Neuroblastoma, Sacrococcygeal Teratoma, Hepatoblastoma,
Wilm tumor and leukaemia were 5 major referrals. In span of
10 years, the representation was –
1. Percentage of Infant: 61/553 (11%) in first, 108/806 (13.3%)
in second and 116 /955 (12.1%) in the third decade.
2. Major cases: Sacrococygeal tumours (18%), Neuroblastoma (18%) and Leukaemias (25%) respectively were commonest referrals in the three decades.
3. Ratio of solid to leukaemias was 3:1, 2.6:1 and 1.2:1 respectively in the three decades.
Other cases referred were hemangioendothelioma, fibrosarcoma, hamartoma, infantile myofibromatosis, mesoblastic
nephroma, retinoblastoma, medulloblastoma and ATRT. Very
rare malignancies in infants like CML and pancreatoblastoma,
1 case each were diagnosed during 1996-2005; adrenocortical
cancer and ovarian granulose cell tumor during 2006-2015.
Embryonal tumors like neuroblastoma, nephroblastoma,
retinoblastoma, hepatoblastoma were more prevalent in
infancy. Their early onset and predominantly embryonal
nature suggest pre-natal origin and possibilities of genetic factors. In last two decades, incidence of leukaemias showed
increase in infancy as compared to solid tumours (may be due
to increased awareness/early referral).
P-040 Clinico-Epidemiological Profile and
Outcome Predicted by Minimal Residual Disease
(MRD) in Children with Mixed Phenotype Acute
Leukemia (MPAL)
H.H. Myint1 , S. Tandon1 , G. Narula1 , M. Prasad1 , P. Subramanian2 ,
P. Tembhare2 , S. Gujral2 , B. Arora1 , S.D. Banavali1
1 Tata
Memorial Hospital- Tata Memorial Centre, Pediatric Oncology,
Mumbai, India; 2 Tata Memorial Centre, Pathology, Mumbai, India
Background/Objectives: Mixed Phenotype Acute Leukemia
(MPAL) accounts for 3–5% of acute leukemia of all
age groups and has poor prognosis with currently available treatment modalities. Our study evaluated the clinicoepidemiological profile and outcome of this rare subset of
Pediatric leukemia.
Design/Methods: Records of the children with acute
leukemia from Jan-2010 to Dec-2016 were reviewed by 2008
WHO criteria for MPAL. Patients were treated uniformly
by modified MCP-841 protocol, which included high-dose
cytarabine 24gm/m2 in below 3-years age, 16gm/m2 and cranial radiation for 3 or more-years age. Data collected was subjected to descriptive analysis tools.
Results: Among 3,830 children with acute leukemia,
26(0.68%) had MPAL. Median age at diagnosis was 9
years (range:2-14) with M:F ratio 2.3:1. Median WBC was
13.4×109 /L (range:1.5-364.4). LDH was elevated in 22 cases
(median 433U/L, range:173-4880), while 23% had bulky
disease. B/Myeloid was the commonest in 14(53%) cases,
followed by T/Myeloid 9(35%) and B/T lymphoid 3(12%).
Abnormal cytogenetics was detected in some B/Myeloid
cases (2-AML/ETO, 1-BCR/ABL, 1-MLL rearrangement, 1Monosomy 7 and 1-hypodiploidy). Nineteen patients were
evaluated for outcome, as 5 were treated elsewhere, 1
refused treatment and 1 opted for oral palliative chemotherapy. Seventeen underwent post-induction bone marrow of
which 14(82%) achieved morphological remission. Fourteen
patients had post-induction MRD status available, 5 were
negative, and of the remaining, another 5 became negative
SIOP ABSTRACTS
post-consolidation. Remarkably, 80% of 10 MRD-negative
cases were in sustained remission at last follow-up. None
underwent bone marrow transplant. Projected three-year overall survival was 45% and progression free survival was 40%
with median follow-up of 22 months (range:4-49).
Conclusions: MPAL represented less than 1% of childhood
acute leukemia with B/Myeloid being the commonest. Outcome remains poor without transplant for relapse/refractory
disease. ALL-type chemotherapy incorporating high-dose
cytarabine block was effective in achieving MRD-negativity
defined response rate of 71% in evaluated patients, which correlated with better outcome.
S185 of S518
FN patients to avoid life threatening complications. Strategies
by WHO for prevention of mosquito bite needs to be implemented to reduce morbidity associated with DF in children
with FN in endemic areas
P-042 Detection of Minimal Residual Disease in
Children with Acute Lymphoblastic Leukemia
Treated According to the ALL IC-BFM-2002 and
ALL IC-BFM 2009 Protocols
K. Pawińska-Wąsikowska1 , K. Bukowska-Strakova2 , M. Surman2 ,
W. Balwierz1
1 Institute
P-041 A Rare Demon: Dengue Fever in Febrile
Neutropenia of Pediatric Malignancy
M. Naseer1 , P. Ankit1 , K. Purva1 , C. Shraddha1 , V. Krishnan1 , M.
Sangeeta1 , S. Archana1 , D. Mukesh1 , S. Nitin1 , A. Bharat1
1 Bai
Jerbai Wadia Hospital for Children, Department of Pediatric
Hemato-Oncology, Mumbai, India
Background/Objectives: Febrile neutropenia (FN) is a pediatric oncological emergency where most common organisms are bacteria and fungus, very rarely a virus. In tropical country like India particularly in rainy season lethal
dengue virus can be a common organism complicating FN.
As management of Dengue Fever (DF) with FN is different from conventional management, early diagnosis is warranted. Clinical profile and outcome of patients with FN
with DF in pediatric malignancies at a tertiary care center is
analyzed.
Design/Methods: All cases of FN in children with leukemia
admitted in a tertiary care center between August 2016 till
December 2016 were analyzed. Diagnosis DF or Severe DF
with FN was based on WHO guidelines. Clinical profile and
outcome of patients analyzed.
Results: Of 80 patients with FN in unit, 23 had DF or
Severe DF. Fever was present in all with febrile seizure in
one patient. Typical rash was present in 21%, with third
space fluid accumulation in 8% of patients. Average duration of hospital stay was 3.5 days more as compared to other
FN patients. Two patients required PICU stay for ionotrope
support. All recovered with no mortality. Thrombocytopenia was present in 14 patients with a mean platelet count
of 56,000. Abnormal liver function was seen 21%. Dengue
NS1 Ag was positive in all with a mean duration of diagnosis of 2.6 days. Dengue IgM ELISA was positive in 30% of
patients.
Conclusions: Early diagnosis of DF in FN is important as
treatment focuses more on fluid resuscitation and monitoring
rather than on antibiotics. It reduces the mean duration of hospital stay. Hence, high index of suspicion of DF is required in
of Pediatrics Jagiellonian University Medical College,
Department of Oncology and Hematology, KRAKOW, Poland; 2 Institute of
Pediatrics Jagiellonian University Medical College, Department of Clinical
Immunology and Transplantology, KRAKOW, Poland
Background/Objectives: Monitoring of minimal residual
disease (MRD) during the induction treatment is currently
recognized the most important prognostic factor in acute lymphoblastic leukemia (ALL). Achievement of MRD below
0.1% on day 15 of induction assessed by multicolor flow
cytometry (MFC) is an powerful predictor of survival in ALL
patients. Assessment of MRD in other time points can be also
crucial, however identification of low amounts residual cells is
usually disturbed by excessive regeneration of bone marrow,
or by its hypoplasia.
The main goal of the study was to verify usefulness of monoclonal antibodies’ panel applied in ALL IC-BFM studies, by
4- and 6 and 10-color flow cytometry to define aberrant phenotypic profiles in ALL blasts.
Design/Methods: In this prospective study, we used 4-color
flow cytometry since 2007 to 2009 and 6 –color since
2010 to 2015, and 10-color flow cytometry since 2016 to
detect MRD. Two hundred forty one children with ALL (200
common/preB-ALL, 9 proB-ALL, 32 T-ALL; 140 boys, 101
girls) treated according to ALL IC-BFM protocols 2002 and
2009: 137 and 104 patients, respectively, were enrolled in this
study. Analysis of MRD was performed at day 0 and day 15
and 33 induction of chemotherapy, before consolidation (day
78), as well at the end of therapy. Sensitivity of detection at
all time points was at least 1/10 000 cells.
Results: In patients with common/preB-ALL (CD20/CD10/
CD34/CD19) and (CD58/CD34/CD45/CD10/CD19/CD20)
were most suitable for assessment of leukemic blasts, suggesting that these are the most efficient for MRD detection. Two
weeks after ending maintenance chemotherapy is the optimal
time for reliable assessment of MRD.
Conclusions: Our results shows that even limited panel of
antibodies used in the study allows defining leukemic phenotypes and monitoring levels of MRD at set time points despite
of changes in expression of antigens during the treatment.
SIOP ABSTRACTS
S186 of S518
P-043 Role of Endocannabinoid/Endovanilloid
System in T-CELL LLA
C.D. Quispe1 , E. Baialardo2 , M. Guitter1 , J. Rossi3 , C. Alonso1 , E.
Alfaro1 , C. Sanchez La Rosa1 , N. Millan1 , P. Zubizzareta1 , M.
Felice1
F. Punzo1 , C. Tortora2 , E. Pota1 , I. Manzo2 , V. D’ Angelo1 , E.
Boccieri1 , M. Oreste1 , F. Casale1 , F. Rossi1
1 Hospital
1 Università
degli Studi della Campania “Luigi Vanvitelli”, Department of
Woman- Child and General and Specialist Surgery, Napoli, Italy;
2 Università degli Studi della Campania “Luigi Vanvitelli”, Department of
Experimental Medicine- Division of Pharmacology, Napoli, Italy
Background/Objectives:
The
Endocannabinoid/Endovanilloid (EC/EV) system has been proposed
as possible target to treat several malignancies, including
lymphoblastic diseases. The EC/EV system is composed
of two G-Protein Coupled Receptors (CB1 and CB2), the
Transient Potential Vanilloid 1 (TRPV1) channel, their
endogenous and exogenous ligands and enzymes. CB1 is
expressed mainly in central nervous system while CB2
predominantly on immune and peripheral cells.
We investigated the role of the EC/EV system in T-Cell Acute
Lymphoblastic Leukemia (T-Cell ALL).
Design/Methods: We cultured primary lymphoblasts from 7
children with T-Cell ALL and Jurkatt cell line, and treated
them with a selective CB2 agonist (JWH-133) and a TRPV1
agonist (RTX). We measured the Apoptosis before and after
treatment with JWH-133 (100nM, 1uM, 5uM) and RTX
(2,5uM and 5uM), at 6, 12 and 24 hours, performing a citofluorimetric Annexin V Assay and we evaluated the expression
level of 2 target genes (Caspase 3 and p53) by Real-Time PCR
and Western Blotting.
Results: We observed a dose-response effect after JWH-133
treatment, while stimulating the Vanilloid receptors caused a
non-dose dependent increase in apoptosis. The effect is more
striking at 6 hours after treatment and it decreases with time.
Moreover Caspase-3 and p53 mRNA and protein levels where
increased 12 hours after exposure to JWH-133 at the concentration of 100nM, both in primary lymphoblast cell cultures
as in Jurkatt cell line.
Conclusions: In conclusion we observed a pro-apoptotic
effect induced by EC/EV compounds, by up-regulating 2 target genes (Caspase-3 and p53) both in primary lymphoblasts
obtained from patients with T-Cell ALL and in Jurkatt cell
line. Our results show that both CB2 stimulation and TRPV1
activation, can increase the Apoptosis in vitro, indicating that
a new therapeutic approach to T-cell ALL might be possible
by modulating the Endocannabinoid/Endovanilloid system.
P-044 Monosomy/Total Loss of Chromosome 7 in
Pediatric Acute Leukemia: Report from a Single
Institution in Argentina
de Pediatría Prof. Dr. Juan P. Garrahan, Hematology and
Oncology, Buenos Aires, Argentina; 2 Hospital de Pediatría Prof. Dr. Juan
P. Garrahan, Genetic, Buenos Aires, Argentina; 3 Hospital de Pediatría
Prof. Dr. Juan P. Garrahan, Immunology and Rheumatology, Buenos Aires,
Argentina
Background/Objectives: Chromosome-7 abnormalities are
frequent acute myeloid leukemia (AML) and myelodysplasia.
However, they are not usually detected in acute lymphoblastic
leukemia (ALL). Monosomy/total loss-chrosome-7 has been
associated with adverse outcome in AML and its prognostic
significance in ALL is not clearly defined.
1-To analyze clinical/biological characteristics and outcome
of patients with monosomy/loss-chromosome-7. 2-To compare prognostic value in AML and ALL.
Design/Methods: From January-1990 to January-2017, 447
AML and 1531 ALL patients were admitted. Monosomy/losschromosome-7 was detected in 21 (4.5%) AML and 26 (1.7%)
ALL patients. We evaluated clinical/biological features and
outcome. The pEFS was estimated by Kaplan-Meier and compared with log-rank-test.
Results: No differences were observed in age and WBC
count when comparing AML vs. ALL. Monosomy/losschromosome-7 as unique abnormality was detected in 11
AML and 3 ALL cases. We divided ALL with losschromosome-7 in 2 groups: <45 (n=15) or >45 chromosomes
(n=11). Complete remission (CR) was achieved in 14/21
(66%) AML cases, 3 died early and 4 presented null response.
Of the 14 who achieved CR, 8 relapsed, 3 died in CR and 3
remain in CR. Regarding ALL, 23 (88%) achieved CR, 2 died
early and 1 patient presented null response. Of the 23 patients
who achieved CR, 3 relapsed, 2 died in CR and 18 remain in
CR. The pEFS for AML with monosomy/loss-chromosome7 was 12(10)% vs. 50(3)% for AML without this abnormality (p=0.0113). For ALL cases with loss-chromosome7, pEFS(SE) was 61(11)% and 70(1)% for ALL without this
abnormality (p=0.3925). The pEFS(SE) for ALL patients
with monosomy-7 alone was 33(27)%. If we compare cases
<45 chromosomes vs. >45 chromosomes pEFS(SE) was
38(15)% and 100% respectively (p=0.0067).
Conclusions: Monosomy/loss-chromosome-7 conferred significant inferior outcome to AML patients. In ALL,
monosomy-7 did not influence survival probabilities. However, ALL patients with monosomy-7 and non-hypodiploid
achieved a significant better survival rates than hypodiploid
plus loss-chromosome-7 cases.
P-045 Cytomegalovirus Retinitis in Children with
Acute Lymphoblastic Leukemia During
Maintenance Phase Chemotherapy
SIOP ABSTRACTS
A.A. Rahman1 , F. Begum2 , M. Begum1 , C.S.H. Kibria1 , A. Islam1 ,
C.Y. Jamal1 , S. Fateha Noor3
1 Bangabandhu
Sheikh Mujib Medical University, Pediatric Hematology and
Oncology, Dhaka, Bangladesh; 2 National Institute of Cancer Research and
Hospital, Paediatric Oncology, Dhaka, Bangladesh; 3 Bangabandhu Sheikh
Mujib Medical University, department of dermatology, Dhaka, Bangladesh
Background/Objectives: Viral infections are an under recognized problem in children on standard chemotherapy
for acute lymphoblastic leukemia (ALL). Cytomegalovirus
(CMV) is an important cause of morbidity and mortality
in immunocompromised individuals. But data regarding the
incidence and manifestations of CMV disease in pediatric
ALL patients are scanty. Cytomegalovirus retinitis (CMVR)
is rarely reported in children with ALL who did not receive
hematopoietic stem cell transplantations (HSCT) and quite
rare during maintenance phase therapy. Herein, we report
cases of bilateral cytomegalovirus retinitis in children with
ALL during maintenance phase therapy; highlighting the
importance of eye examination and care in patients diagnosed
with acute lymphoblastic leukemia.
Design/Methods: During the period from January to December’ 2016, we found three cases of CMV retinitis in children
with ALL at our department who were referred to ophthalmologist for reduced vision. CMVR was diagnosed by the presence of characteristic lesion on fundoscopy in immunocompromised state as confirmed by ophthalmologist and positive
CMV DNA in blood sample.
Results: We identified total three male children of CMVR
during one year period with age range 3.8 to 6 yr. The underlying causes of immunocompromise were chemotherapy for
leukemia ; identified as having CMVR during maintenance
phase therapy. All the three children were neutropenic for a
period of days to months before ; were getting treatment for
febrile neutropenia. Cytomegalovirus retinitis was bilateral
in all three children. Discontinuation of immunosuppressive
medications and administration of anticytomegalovirus drugs
led to regression of active retinitis . later 2/3 children died
within 1 to 5 months of being diagnosed with cytomegalovirus
retinitis. The remaining one child is alive, with improvement
of vision.
Conclusions: The present cases suggests that pediatric
patients with ALL in the maintenance phase may be immunosuppressed and immediate ophthalmologic examination and
CMV testing is warranted in cases with disturbances of visual
acuity.
P-046 Acute Lymphoblastic Leukaemia; Are We
Missing Early Diagnosis In Children?
J. Ranasinghe1 , W. Rathnayaka2 , I. Dharshika1 , S. Liyanarachchi1 ,
L. Samaranayaka1 , K. Premachandra1
S187 of S518
1 Lady
Ridgeway Hospital for Children, General Paediatrics, Colombo 08,
Sri Lanka; 2 National Cancer Institute, Pediatric Clinical Oncology,
Maharagama, Sri Lanka
Background/Objectives: Acute lymphoblastic leukemia
(ALL) is the most common childhood malignancy accounting
for one-fourths of all childhood cancers and three-fourths of
all newly diagnosed patients with acute leukemia. The incidence varied from 03 to 04 / 100,000 children with a male
predominance. The objective was to evaluate the presenting
features and time duration to diagnose ALL in children presenting to National Cancer Institute (NCI), Sri Lanka.
Design/Methods: This retrospective cross sectional study
was carried out at Paediatric unit-A of NCI. All patients were
less than 15 years and confirmed with ALL. Data was collected using an interviewer administered questionnaire and
from health records.
Results: A total of 85 children included with 58 (68.2%)
were males. Age ranged from 08 months to 11 years. Majority (n=66,77.6%) were “B”-immunophenotype. CD 10 surface antigen was detected in 31 (36%) and in 33 (38.8%)
none were detected. Others were CD 05(n=01), 13(n=03),
19(n=01), 20(n=02) & 117(n=01). Only 39 patients (47.6%)
were diagnosed within first 14 days. Three patients took 4
months. The longest time taken was 15 months who have had
steroid treatments frequently. The most common symptom
was “intermittent fever” complained by 52 patients (67%).
Other common symptoms were neck lump (n=14,16%),
joint pain (n=11,13%), myalgia (n=7,8%), loss of appetite
(n=05,05.8%), lethargy (n=05,05.8%), respiratory tract infection (n=04,04.7%), rash (n=04,04.7%), acute gastroenteritis, abdominal mass, ecchymosis, limping, investigated for
anaemia, headache, generalized lymphadenopathy and chest
pain etc. Only 13 patients had white cell count <04.0x103 /ml3
and 43%(n=36) had leucocytosis. Only 74.7%(n=56) had
platelet count <150x103 /ml3 and 01.3%(n=2) thrombocytosis and 72%(n=54) had haemoglobin <10g/dl. However these
findings were not statistically significant.
Conclusions: Only 39(47.6%) patients were diagnosed within
the first 14 days. The most common symptom was “intermittent fever” and this was the complaint in 52 (67%) patients.
P-047 Effects of Ubiquitin Ligase HUWE1 on
Metabolic Imbalances in Leukemic Cells
M. Ruckert1 , A. Brouwers-Vos2 , L.G. Tone3 , J.J. Schuringa2 , V.S.
Silveira1
1 University
of São Paulo, Department of Genetics, Ribeirão Preto, Brazil;
Medical Center Groningen, Experimental Hematology,
Groningen, The Netherlands; 3 University of São Paulo, Department of
Pediatrics, Ribeirão Preto, Brazil
2 University
SIOP ABSTRACTS
S188 of S518
Background/Objectives: Acute lymphoid leukemia (ALL)
is the most common childhood malignancy. Philadelphia
chromosome (Ph) is present in 5% of childhood cases.
Ph positive leukemias express the tyrosine kinase BCRABL, that is responsible for constitutive activation of RAS
pathway and mediates leukemic cells proliferation. Even with
high cure rates, a lot of patients develop resistance to treatment and relapse. Previously published data suggests association between hyperactivation of RAS pathway and favorable treatment outcome, pointing to a new research approach.
HUWE1 participates in negative feedback mechanism controlling Shoc2 activity in activation of ERK1/2. Thus, it can be
assumed that loss of HUWE1 would lead to increased activation of ERK1/2 and, therefore, hyperactivation of RAS pathway.
Objectives: To evaluate the impact of HUWE1 knockdown in
leukemic cell lines.
Design/Methods: ALL, chronic myeloid leukemia (CML)
and acute myeloid leukemia (AML) cell lines were transduced
with miR-E lentiviral particles for gene knockdown. Flow
cytometry, qPCR, Western Blot and apoptosis assay were performed.
Results: HUWE1 knockdown cells showed decreased proliferation in Nalm-6, K562 and THP-1, but not HL-60. Nalm6 showed increased apoptosis levels, which correlate with
significant p21 upregulation (P<0.05), however, p-ERK1/2
increase was not seen. K562 showed no changes in apoptosis or p21 expression despite the increase in p-ERK1/2.
Regarding AML cells, THP-1 showed increase in p-ERK1/2
and p21 expression (P<0.05). Besides having no disadvantage in growth, HL-60 showed downregulation of p21 when
p-ERK1/2 was increased, suggesting that hyperactivation of
RAS pathway might have protective effect on them. This
opposite behavior between THP-1 and HL-60 reveals an interesting path involving HUWE1 because these cell lines have
opposite metabolic patterns: THP-1 relies on oxidative phosphorylation while HL-60 are glycolytic cells.
Conclusions: These results suggest that HUWE1 might play a
role in metabolic imbalances in leukemic cells. Further studies
are necessary to investigate this correlation.
Financial Support: FAPESP (Process 2015/12146-5)
P-048 Detection of IKZF1 Deletions by a Very
Simplified and Low-Cost Reverse Transcription
Polymerase Chain Reaction (RT-PCR) Technique
and ITS Impact on Childhood All Prognosis
L.B.P. Moreira1 , R.D.P. Queiróz1 , E. Perna1 , V.K. Suazo1 , L.G.
Tone1 , C.A. Scrideli1
1 Ribeirão
Preto School of Medicine - University of São Paulo, Pediatrics,
Ribeirão Preto, Brazil
Background/Objectives: IKZF1 gene deletion has been
associated with worse prognosis in children with acute lymphoblastic leukemia (ALL). Its detection has been made by
laborious and expensive techniques, making it difficult to
perform at most treatment centers, especially in developing
countries. This study analyzed the presence of deletions of
the IKZF1 gene in children with ALL by a very simplified
and low-cost RT-PCR technique and evaluated its association
with prognosis
Design/Methods: It were analyzed 48 consecutive BM samples obtained from children with ALL (41 pre-B and 7 TALL) treated according to the Brazilian Treatment Protocol,
with a median follow-up of 120 months. The same cDNA used
to the routine translocation studies were amplified by RT-PCR
using only a pair of primers that flanks the exons 1 to 8 of the
IKZF1 gene. The product obtained was electrophoresed in 2%
agarose gel. Association between IKZF1 deletion and eventfree survival (EFS) was assessed by Kaplan Meier curves and
multivariate analysis by Cox Regression Model
Results: Deletion in the IKZF1 gene was observed in 6/41
(14.6%) samples of B-derived ALL and in none of the TALL. Ten years EFS was 70.1 ± 7.3% versus 16.7 ± 15.2
(P = 0.017), for the groups with and without IKZF1 deletion
respectively, with a relative risk of unfavorable event of 3.27
(95% CI: 1.15-9.32) for the presence of the deletion. Multivariate analysis showed that IKZF1 deletion was an independent prognostic factor (P = 0.028) when analyzed in association with age and number of WBC at diagnosis
Conclusions: The present study suggests that the use of a
simplified and low cost IKZF1 deletion analysis technique is
capable of detecting patients at higher risk of relapse and may
be useful in the stratification of patients with B lineage ALL
in future treatment protocols. Larger multicentric studies are
necessary to confirm these Results:
P-049 Angiogenesis in Children with Acute
Lymphoblastic Leukemia Based on Serum VEGF
Concentration Assay
G. Sobol-Milejska1 , A. Mizia-Malarz1 , K. Musioł1
1 Medical
University of Silesia - Upper Silesia Centre for Child's Health,
Department of Oncology-Hematology and Chemotherapy, Katowice, Poland
Background/Objectives: Angiogenesis is a process essential
for growth and development of all human tissues. VEGF has a
key role in angiogenesis stimulation.The purpose of the study
was to assess angiogenesis in children with acute lymphoblastic leukemia (ALL) based on serum VEGF level determined
at diagnosis and at remission (day 33 ), with further subject
subdivision into different risk groups
Design/Methods: Forty children, aged 3-12 y, with newly
diagnosed ALL, treated according to the ALLIC 2002 pro-
SIOP ABSTRACTS
tocol were enrolled in the study. They were classified to
3 groups: SRG-18pts, IRG 12pts HRG 10pts. The control
group-20 healthy children. VEGF serum concentration was
determined at diagnosis and on day 33. of treatment.
Results: At baseline, serum levels of VEGF were determined
in the entire study group and healthy controls. The median
of VEGF serum level of 185.2 pg/mL (22.3-684.4) in study
patients was comparable to the one of controls (144.6 pg/mL;
32.7-237.9). was comparable to the one of controls (144.6
pg/mL; 32.7-237.9).
The median values of serum VEGF at diagnosis were comparable between the SRG and the control groups, and significantly higher in IRG and HRG as compared to the control
group. At remission the median of serum VEGF level was
significantly higher in all study groups, as compared to the
controls.
The median of serum VEGF levels in group SRG was significantly higher at remission. The median values of serum VEGF
on day 33 were higher in groups IRG and HRG without statistical signification.
Conclusions: The significant higher level of serum VEGF in
children with ALL in comparison with healthy control, both at
the diagnosis and in the remission, could suggest the intensification of angiogenesis in the bone marrow, at diagnosis. There
is a tendency for higher serum VEGF level in the groups with
less satisfying prognosis,which suggests the needs of further
studies.
S189 of S518
ical manifestation of thrombosis events was cerebral thrombosis (67%) followed by deep vein thrombosis (33%). The
risk factors of thrombotic event were the administration of
asparaginase (58%) followed by the indwelling of central
line (33%). Older children more than age 10 years were at
higher risk for developing cerebral thrombosis. Management
of thrombotic events was low-molecular-weight heparin at
1 mg/kg/dose twice a day for 1-3 months then switched to
warfarin until the risk factors were resolved. Doppler ultrasound, computed tomography, magnetic resonance imaging
were the methods used in thrombosis detection and follow
up for resolving. Median time for resolving cerebral thrombosis and deep vein thrombosis was 5.6 and 3.2 months,
respectively. Transfusion of fresh frozen plasma before starting asparaginase treatment is currently recommended for preventing recurrent thrombotic events.
Conclusions: The prevalence of thrombosis in childhood
ALL is quite high especially in older children and does interfere with the treatment plan. Thrombosis among childhood
ALL is often observed in patients receiving asparaginase and
central line insertion. Preventive strategies in this group of
patients should be considered.
P-051 Circulating Endothelial Cells and
Metabolic Status in Childhood Cancer Survivors
E. Athanasopoulos1 , G. Martimianaki1 , E. Kampouraki1 , M.
Stratigaki1 , E.A. Markaki1 , N. Katzilakis1 , E. Stiakaki1
1 University
P-050 Thrombosis in Childhood Acute
Lymphoblastic Leukemia
D. Sosothikul1 , N. Yupensuk1 , K. Chiengthong1 , S.
Lauhasurayotin1 , P. Techavichit1 , P. Seksarn1
1 Chulalongkorn
University- King Chulalongkorn Memorial Hospital,
Department of Pediatrics, bangkok, Thailand
Background/Objectives: Thromboembolism is a serious
complication associated with morbidity in childhood acute
lymphoblastic leukemia (ALL). The risk of thrombotic complication in childhood ALL ranges widely from 1-37% worldwide.To study prevalence and risk factor of thrombosis in
childhood ALL.
Design/Methods: A retrospective descriptive study in
patients with thrombosis in children diagnosed as ALL at
King Chulalongkorn Memorial Hospital,Thailand from 2005
to 2016.
Results: The prevalence of thrombosis in 220 cases of childhood ALL was 5.5 %. Twelve patients were diagnosed with
thromboembolism (4 males and 8 females). Age ranged from
4 to 14 years (median 9.7 years). Most thromboembolism
events occurred during the induction phase of chemotherapy (83%). Patients with high risk and very high risk ALL
were likely to develop thromboembolism event (67%). Clin-
of Crete- University Hospital of Heraklion, Pediatric
Hematology-Oncology, Heraklion Crete, Greece
Background/Objectives: Circulating Endothelial Progenitor
Cells (CEPCs) play a significant role in the maintenance of
vascular integrity, balancing the anti-coagulation mechanisms
and regulating the leukocyte trafficking. Additionally, it is
well-established, that patients who underwent chemotherapy
have increased incidence of hypertension and obesity. Nevertheless, numerous studies have shown a negative correlation
between CEPCs and obesity, underlining poor vascular repair.
Objective:The study of CEPCs in childhood survivors of
Acute Lymphoblastic Leukemia (ALL) and solid tumors (ST)
and the investigation of their levels in correlation with patients
Body Mass Index (BMI) and blood pressure (BP).
Design/Methods: Four colour flow cytometry was performed to determine the subpopulations CD34+CD45
negdimCD133+, CD34+CD45negdimVEGFR2+ and CD
34+CD45negdimCD133+VEGFR2+ of CEPCs in
the peripheral blood from children with ALL(n=104),
ST(n=97) and children without malignancies as control
group(n=125).The BMI and BP of the patients were calculated and the percentiles were established specific by the age
and gender.
Results: Patients characteristics.
SIOP ABSTRACTS
S190 of S518
ALL
ST
Time post-treatment
N
N
<1year
20
21
1-3years
28
33
>= 3years
56
43
Normal weight
56
53
Overweight/Obese
48
44
CONTROL
BMI
BP
Normal BP
60
58
High-normal BP/Hypertension
44
39
Mean
SE
Mean
SE
Mean
SE
CD34(+)VG(+)
0.00316
0.00044
0.00575
0.00124
0.003231142
0.00292
CD34(+)CD133(+)VG(+)
0.00290
0.00044
0.00474
0.00096
0.000332029
0.0003
The levels of CEPCs in ALL did not show any significant difference between the time post treatment. In solid tumors the
levels of CEPCs during the 1st year post-treatment are significantly higher than those in the following years. The correlation between BMI and CEPCs in ALL and ST group, showed
statistically significant difference between overweight/Obese
survivors. The study of BP status in ALL and ST have no significant difference.
Conclusions: The levels of CEPCs are increased during the
1st year after treatment of solid tumors, finding that needs further investigation in relation with metabolic factors in childhood cancer survivors.
P-052 Presence of Minimal Residual Disease
Detected by Flow Cytometry is a Predictor of Early
Relapse in Patients with T Cell Acute
Lymphoblastic Leukemia
P. Subramanian1 , P. Tembhare1 , G. Chaterjee1 , S. Goghale1 , Y.
Badrinath1 , N. Patkar1 , G. Narula2 , B. Arora2 , S. Banavali2
1 Tata
2 Tata
Memorial Centre, Hematopathology Laboratory, Mumbai, India;
Memorial Centre, Medical Oncology, Mumbai, India
Background/Objectives: We investigated the value of
assessment of post-induction minimal residual disease
(MRD) in bone marrow by flow cytometry (FC) in childhood T cell Acute Lymphoblastic Leukemia (T-ALL).There
are a few studies on the relevance of Minimal residual disease
(MRD) evaluation in (T-ALL). AIEOP-BFM group showed
that late (Day-78) MRD response determines overall riskof-relapse and event-free-survival (EFS) using RQ-PCR. A
larger study by COG (Brent Wood et al. ASH, 2014) showed
that post-induction (Day-29) FC-MRD was more relevant in
prediction of EFS.
Design/Methods: We studied post-induction (Day-35) MRD
(PI-MRD) in bone marrow samples from 100 children under
the age of 16 years with T-ALL treated using modified
MCP-841 protocol between 2014 & 2016. In T-ALL with
early-T cell-precursor (ETPALL) immunophenotype, patients
received Dexamethasone in place of Prednisolone. MRD was
performed using 10-color FC-MRD assay on Navios flow
cytometer and analysis was performed with Kaluza software
v-1.3 (Beckman Coulter).
Results: Median age of patients was 11.5 years (range 2–15 y;
M:F–4.6). Initial immunophenotype was ETPALL in 12/100
patients. PI-MRD was positive in 58/100 (58%) with median
level of 0.23% (range, 0.002%-6%). PI-MRD positivity was
significantly high in ETPALL as compared to non-ETPALL
(93% vs 53%; p=0.01). Median follow-up of all patients was
13.2 months (3-38 months). Patients were categorised MRD
negative (MRD-N) if PI-MRD was negative and MRD positive (MRD-P) if PI-MRD was positive with any level. Thus,
42% were categorized as MRD-N & 58% as MRD-P. Twenty
patients relapsed & of them six died (2 were ETPALL & 18
non-ETPALL; 3 MRD-N & 17 MRD-P) within 26 months.
Median EFS of MRD-P patients was significantly inferior as
compared to MRD-N (26 months vs. did not reach; & 70.67%
vs. 92.86%; p=0.0017).
Conclusions: We conclude that post-induction FC-MRD positivity is a predictor of early relapse in childhood T-ALL.
P-053 Monocytic Lineage Switch in
B-Cell-Precursor Acute Lymphoblastic Leukemia in
Children – Temporary Escape or Mechanism of
Chemotherapy Resistance?
M. Twardoch1 , A. Sonsala1 , L. Sedek2 , M. Pierzyna2 , J. Bulsa1 , J.
Kulis1 , I. Malinowska3 , J. Trelinska4 , E. Niedzielska5 , K.
Derwich6 , W. Badowska7 , M. Niedzwiecki8 , G. Sobol-Milejska9 ,
SIOP ABSTRACTS
K. Muszynska-Roslan10 , A. Koltan11 , G. Karolczyk12 , M.
Woszczyk13 , T. Ociepa14 , J. Kowalczyk15 , T. Szczepański1
1 Medical
University of Silesia, Department of Pediatric Hematology and
Oncology, Zabrze, Poland; 2 Medical University of Silesia, Department of
Microbiology and Immunology, Zabrze, Poland; 3 Medical University of
Warsaw, Department of Pediatric Hematology and Oncology, Warsaw,
Poland; 4 Medical University- Lodz, Department of Pediatric OncologyHematology and Diabetology, Lodz, Poland; 5 Medical UniversityWroclaw, Department of Bone Marrow Transplantation- Pediatric
Hematology and Oncology, Wroclaw, Poland; 6 University of Medical
Sciences- Poznan, Department of Pediatric Hematology- Oncology and
Transplantology, Poznan, Poland; 7 Regional Specialistic Pediatric
Hospital, -, Olsztyn, Poland; 8 Medical University- Gdansk, Department of
Pediatric Hematology- Oncology and Endocrinology, Gdansk, Poland;
9 Medical University of Silesia, Department of Pediatrics, Katowice, Poland;
10 Medical University- Bialystok, Department of Pediatric Oncology,
Bialystok, Poland; 11 Collegium Medicum in Bydgoszcz, Department of
Pediatric Hematology and Oncology, Bydgoszcz, Poland; 12 Regional
Specialistic Pediatric Hospital, -, Kielce, Poland; 13 Chorzow Center of
Pediatrics and Oncology, -, Chorzow, Poland; 14 Pomeranian Medical
University, Department of Pediatrics- Hematology and Oncology, Szczecin,
Poland; 15 Medical University- Lublin, Department of Pediatric Hematology
and Oncology, Lublin, Poland
Background/Objectives: In a small proportion of childhood
B-cell-precursor acute lymphoblastic leukemia (BCP-ALL),
the leukemic blasts switch their immunophenotype towards
monocytic lineage (swBCP-ALL). The aim of the study was
to determine the frequency and immunophenotypic features
of patients with swBCP-ALL in Poland.
Design/Methods: The study group comprised 940 pediatric
patients with BCP-ALL, aged 0-18 years (median 4.6 years)
treated according to the ALL-IC-BFM 2009 protocol in 14
Polish hemato-oncology centers between 2012 and 2017.
Bone marrow or peripheral blood samples were stained at
diagnosis and during follow up with 7- and 8-color monoclonal antibody panels. Data were analyzed using Infinicyt software (Cytognos SL, Spain) and FACSDiva (BD Bioscience, USA).
Results: The monocytic lineage switch during the induction
treatment was observed in 29/940 (3.1%) BCP-ALL patients
and was usually associated with high expression of CD34
(27/29 cases), weak or partial expression of CD10 (24/29
cases) and expression of CD2 (11/13 cases) at diagnosis.
In all patients with detectable aberrant monocytoid cells during follow up, weak expression of CD19 and CD34 was found.
The expression of CD10 and CD22 in most patients with
swBCP-ALL was decreased in comparison to diagnosis. Furthermore, at least partial expression of CD2, CD14, CD13
and CD33 was detected on residual blasts in most patients
with swBCP-ALL. In addition, in all swBCP-ALL patients
expression of CD2 observed at diagnosis was maintained during treatment.
Finally, the MRD levels at day 15 were significantly higher
in swBCP-ALL patients compared with the remaining BCPALL patients with positive MRD level (MRD>0) (median
MRD level: 10.45%, and 0.68%, respectively; p<0.01).
S191 of S518
Conclusions: In conclusion, swBCP-ALL is a rare subset of
BCP-ALL cases detected mainly during induction treatment.
Significantly higher MRD levels at day 15 suggest slower
response to induction treatment in swBCP-ALL patients. Further investigation and follow up is needed to determine, if the
monocytic lineage switch has significant clinical value.
P-054 Minimal Residual Disease and
ETV6-RUNX1 Predicts Improved Outcomes of
Hypodiploid Acute Lymphoblastic Leukemia
(ALL): A Single Centre Experience of 254 Children
S. Tandon1 , G. Narula1 , M. Prasad1 , B. Arora1 , P. Subramanium2 ,
P. Tembere2 , S. Gujral2 , D. Shetty3 , S. Banavali1
1 Tata
Memorial Centre, paediatric hemato-oncology, Mumbai, India; 2 Tata
Memorial Centre, Haematopathology, Mumbai, India; 3 Tata Memorial
Centre, cytogenetics, Mumbai, India
Background/Objectives: Hypodiploidy constitutes 5 % of
ALL with poorer prognosis on currently available therapy.
Our study evaluated clinico-epidemiological profile, outcomes, cytogenetic, MRD correlation of this subset of paediatric ALL.
Design/Methods: Data of all children with ALL having
hypodiploidy on conventional cytogenetics from Jan2008Nov2016 was retrospectively analyzed from electronic medical records and patient charts. Children were treated on different institutional protocols before and after Feb-2013. Principal differences were use of high-dose cytarabine and cranial
radiation in the earlier era, and routine use of MRD and highdose methotrexate in the latter.
Results: B ALL was diagnosed in 3208 children during the
study period; 254(8%) had hypodiploidy. Median age was
6 years (1-15), M: F 2.5:1. Median leukocyte counts were
15.6x109 /L(0.3-400) and LDH 723U/L(133-20783). Fiftyeight (23%) had bulky disease and 11(4.3%) CNS involvement. NCI-SR and HR were 116(45.6%) and138(54.3%)
respectively. High and low hypodiploidy were seen in
198(78%) and 31(12%) respectively, modal number (MN)45
in 12(4.7%), and near haploid 5(2%). Seventy-two (28.3%)had
normal cytogenetics, ETV6-RUNX1 65(26%), other cytogenetics 37(14.4%.), t(1;19) 26(10.2%), trisomies 26(10.1%),
BCR-ABL 19(7.5%), MLL 9(3.5%). Of 222 patients evaluable
for outcome, 171(77%) achieved remission, 51(23%) did not,
4(7.8%) failed induction. Of 95 children with post-induction
MRD, 19(20%) were positive, 15(79%) of which became negative post -consolidation. At a median follow-up of 32 months
(1-84), projected 7-year OS and EFS were 65.5% and 50%
respectively. CNS status, NCI risk, prednisolone response
were not significant. High and low hypodiploidy had better
outcomes than near haploidy (p<0.01). ETV6-RUNX1 correlated with improved OS and EFS (p<0.01). Post-induction
MRD-negativity translated to significantly improved OS and
SIOP ABSTRACTS
S192 of S518
EFS (p<0.01). Very-early isolated medullary relapse was the
commonest form of treatment failure.
Conclusions: Hypodiploidy remains a high-risk subset
of childhood B-ALL. Post-induction MRD-negativity and
ETV6-RUNX1 had better survival within this subset, while
near haploidy portends poor outcome.
P-055 Immunoglobulin Levels in Children on
Treatment for Acute Lymphoblastic Leukemia
C. Bajwa1 , A. Trehan1 , A. Rawat1 , D. Bansal1
1 Postgraduate
Institute of Medical Education & Research, Pediatrics,
Chandigarh, India
Background/Objectives: Chemotherapy results in depression of humoral immunity. This predisposes patients to severe
infections which may be recurrent and occasionally, life
threatening. This study evaluated immunoglobulin levels in
children with Acute Lymphoblastic Leukemia (ALL).
Design/Methods: Observational prospective study performed from June 2015 – October 2016. Children with
relapsed disease and a known underlying immunodeficient
state were excluded. Immunoglobulin levels (IgG, IgM &
IgA) were analyzed at the following time points in each
patient: (i) At diagnosis, (ii) end of induction and consolidation therapy, (iii) end of the delayed intensification phase of
chemotherapy
Results: Thirty five children, mean age: 5.17± 3.2 years ;
31: B precursor cell ALL ; 4:T cell ALL were evaluated. The
immunoglobulin levels at diagnosis were normal for age with
IgG being on the upper side of normal. IgM and IgG levels decreased after induction and consolidation therapy. IgM
declined to the lower limit of normal for age with 14(40%)
children having low IgM levels. IgG did not fall below normal
for age. Levels did not fall further after intensification therapy.
At no time did IgA levels alter. Forty percent children had 1
episode of FN, 17% had 2 episodes of FN and 7 (20%) had >
3 episodes of FN, whilst 23 children did not have FN. Children with greater episodes of FN did not have lower levels of
immunoglobulins.
Conclusions: Chemotherapy results in an altered immune
profile. IgG and IgM levels both decrease after initiation of
chemotherapy with nearly 40% children having low IgM levels at the end of intensive therapy. A larger patient cohort
would help delineate severity of fall between the ALL risk
groups. Patients need repeat evaluation of their immunoglobulin profile after therapy to look for recovery of immune function. Replacement therapy may deserve recommendation in
patients with recurrent episodes of infections.
P-056 Childhood Leukemia in an ETV6-Related
Thrombocytopenia Family
S. Unal1 , F. Gumruk1 , M. Cetin1 , A. Shimamura2
1 Hacettepe
University Medical School, Division of Pediatric Hematology,
ANKARA, Turkey; 2 Dana-Farber/Boston Children's Cancer and Blood
Disorders Center, Bone Marrow Failure and MDS Program, Boston, Turkey
Background/Objectives: ETV6-related thrombocytopenia is
an autosomal dominant thrombocytopenia that has been
recently identified in a few families and has been reported
to have leukemia predisposition. Normal size, autosomal
dominantly inherited thrombocytopenia has been reported in
patients with RUNX1, ANKRD26 and ETV6.
Design/Methods: A currently 11 year-old boy was referred to
our center with a diagnosis of acute lymphoblastic leukemia
(ALL) at 5 years of age.
Results: Previous history revealed a follow-up period with
a diagnosis of immune thrombocytopenia (ITP) in the preceeding 2 years. During the past medical history prior to ALL
diagnosis, median platelet count was 35x109 /L and did not
receive any specific treatment for ITP. Family history revealed
thrombocytopenia (plt 59 x109 /L, MPV 8.1 fl) in father but
the etiology was not identified. The hemogram at admission for ALL revealed Hgb 8.6 g/dl, WBC 4.4x109 /L, plt 13
x109 /L, MCV 92.6 fl, MPV 9.1 fl. The bone marrow aspiration revealed diffuse leukemic infiltration with L1 type blasts
and immunephenotype was CALLA positive pre-B cell ALL.
Cytogenetics revealed 46, XY karyotype. CNS cytology was
negative and St Jude Total XV protocol for ALL was initiated. After cessation of treatment protocol, he still could not
achieve a normal paltelet count (plt 47 x109 /L). DEB test for
Fanconi anemia was negative. Molecular work-up revealed
ETV6:1358M mutation in both the patient and the father.
Conclusions: ETV6-related thrombocytopenia should be
considered in families with dominant inheritance pattern and
patients should be followed for leukemia development.
P-057 Evaluation of PCR-Based MRD Testing in
Children with Acute Lymphoblastic Leukemia
Treated According to All IC BFM 2009 Protocol:
Slovak Experience
A. Vaská1 , M. Makohusová2 , E. Bubanká3 , I. Oravkinová4 , P.
Švec1 , O. Fábri1 , L. Copáková5 , J. Trnka6,7 , J. Zuna6,7 , E.
Froňková6,7 , A. Kolenová1
1 Comenius University Children´s Hospital, Department of Pediatrics,
Bratislava, Slovak Republic; 2 Comenius University – Medical School and
University Children's Hospital, Department of Pediatric Oncology and
Hematology, Bratislava, Slovak Republic; 3 Children's University Hospital,
Department of Pediatric Oncology and Hematology, Banská Bystrica,
Slovak Republic; 4 University Children´s Hospital Kosice, Department of
Pediatric Hematology and Oncology, Košice, Slovak Republic; 5 National
Cancer Institute, Department of Clinical Oncology, Bratislava, Slovak
Republic; 6 Charles University and University Hospital Motol, Department
of Paediatric Haematology and Oncology- 2nd Faculty of Medicine,
Prague, Czech Republic; 7 Childhood Leukaemia Investigation Prague,
CLIP, Prague, Czech Republic
SIOP ABSTRACTS
Background/Objectives: In the treatment of childhood acute
lymphoblastic leukemia (ALL) the detection of minimal
residual disease (MRD) is a significant determinant of patient
outcome. The aim of the study was to evaluate the impact of
routine PCR-based MRD testing on stratification criteria of
the ALLIC BFM 2009 protocol
Design/Methods: From 2013 to 2016, 89 patients (age-range
1-18 years) were enrolled into ALL IC BFM 2009 protocol. The patients were stratified into a standard (SRG), intermediate (IRG) and high-risk group (HRG) according to age,
WBC, the presence of hypodiploidy, ETV6-RUNX1, BCRABL1 and MLL-AF4 and the prednisone response. Bone marrow response to induction therapy was assessed primarily by
morphology and secondly by flow cytometry on days 15 and
33. PCR-based MRD testing was performed on days 33 and 78
(week 12), before protocol M or first high-risk block, respectively. To the routine PCR-based MRD and survival evaluation 68 patients were included; finally, in 61 patients PCRbased MRD testing was determined.
Results: Based on MRD stratification criteria, 13 patients
were stratified into the HRG (19.1%), 45 patients to IRG
(66.2%) and 10 to SRG (14.7%). Three-year overall survival
and three-year event-free survival rates were 92.5% (N=68; 2
deaths) and 84.6% (N=68; 7 events), respectively. In the study
group with determined PCR-based MRD testing on day 33
(N=61), MRD positivity was statistically significantly associated with T precursor type (P=0.002), bone marrow response
on day 15 (P=0.048) and with event accuracy (P=0.042).
MRD negativity was significantly associated with TEL/AML1
fusion gene (P=0.011). There was no significant association
of PCR-based MRD testing on day 78 with any analyzed factor
Conclusions: Results showed the prognostic value of PCRbased MRD detection for prediction of events in the study
group and also confirmed previous findings treatment impact
on the prognosis for children with ALL during induction.
S193 of S518
unfavorable prognostic sign because of the high resistance to
chemotherapy and the high percentage of relapses.
Design/Methods: We present the first case of a pediatric
patient with Acute Lymphoblastic Leukemia (ALL) at relapse
with a secondary chromosomal t(16; 21) (p11; q22).
Results: A 15 year-old female with ALL L2 type (FAB).
Bone marrow showed 96% lymphoblasts. Leukemic cells
expressed CD34 +, TdT, CD10 +, CD19 +, CD22 +, CD38
+, CD79a + and CD13 +. Cytogenetic study was performed
without showing any alterations. Treatment was given with
St. Jude XIII, with favorable evolution until week 76. At that
moment, the patient presented pancytopenia hemoglobin 7.6
g per dL, 48,000 platelets per mm3, and leucocyte count of
800 per mm3. Bone marrow showed 97% of lymphoblasts.
The immunophenotype presented CD10 +, CD13 +, CD22
+, CD24 +, CD34 +, CD38 +, CD123 +, CD58 +, CD66c
+, CD79a +, Tdt, lambda, CD81 + expression. Cytogenetics
reported t(16; 21) (p11; q22).
It was decided to start treatment with NOPHO 93 and
ATEDOX with complete remission within the first cycle of
chemotherapy. She was presented to the Hematopoietic Stem
Cell Transplantation (HSCT) program.
Conclusions: Only 4 cases have been reported in pediatric
patients with t(16; 21) (p11; q22) and this is the first case
report with this abnormality as a secondary finding. This represents a therapeutic challenge and we propose to treat this
kind of patient as an Acute Myeloblastic Leukemia and salvage therapy with HSCT.
P-059 Posterior Reversible Encephalopathy
Syndrome Treatment Based on Symptoms and
Imaging Findings in Pediatric Patients with Acute
Lymphoblastic Leukemia
M. Velazquez-avina1 , J. Peñaloza-González1
Acknowledgement: MZ SR 2012/7-UKBA-7.
1 Hospital
P-058 Secondary T(16;21)(P11;Q22) In A
Pediatric Patient with Acute Lymphoblastic
Leukemia
Background/Objectives: Posterior reversible encephalopathy syndrome (PRES) is an uncommon side effect of some
chemotherapeutic agents, particularly methotrexate. The clinical presentation depends on the area of brain hypoperfusion.
To date there is no standardized treatment, but a myriad of
drugs and procedures have been proposed.
M. Velazquez-Aviña1 , J. Ponce-Cruz1 , A. Carranza-Castañón1 , E.
García-Jiménez1 , M. Chávez-Zuñiga1 , J. Peñaloza-González1
1 Hospital
Juárez de México, Pediatric Oncology, Mexico City, Mexico
Background/Objectives: The t(16;21) (p11; q22) translocation is a rare chromosomal disorder that occurs mainly in
Acute Myeloid Leukemia, Myelodysplastic Syndromes and
blast crisis of Chronic Myeloid Leukemia. Recently, the karyotype along with this gene has been found in Ewing Sarcoma. It has been observed that in this type of alterations the
TLS / FUS-ERG gene is present. This karyotype represent an
Juárez de México, Pediatric Oncology, Mexico City, Mexico
The purpose of this study is to report our experience in the
treatment of this syndrome in patients with acute lymphoblastic leukemia (ALL).
Design/Methods: We performed a retrospective record
review and included patients with LLA with neurologic focal
symptoms two weeks after methotrexate treatment regardless
route of administration. The study period was from October
2004 to December 2014.
SIOP ABSTRACTS
S194 of S518
The demographic and clinical characteristics are described as
means or proportions according to variable type.
Results: We reviewed 176 charts of eligible patients, of which
eight (4.5%, 4 female, 4 male) presented PRES. The average
age was 11.2 years. Seven patients had high-risk ALL (87.5%)
and 1 (12.5%) standard risk ALL. The onset of symptoms
started at an average of 7.3 days after intravenous (n=6; 75%),
or intrathecal (n=2; 25%) methotrexate. None of the cases had
simultaneous routes of administration.
Patients with localized ischemia (n=3) were treated citicoline (10-20 mg/kg/d) for 5-7 days, with seizures (n=2) were
treated with valproate for 6 months (15 mg/kg/d); and with
areas of brain edema were treated with dexametasone (0.5
mg/kg/d) for 5 days. All patients with brain ischemia without
seizures (n=3) were treated with hyperbaric oxygen therapy.
Five patients had multiple simultaneous therapy according to
clinical and imaging characteristics. Symptoms recovery was
present at 10 days postreatment average. None of the patients
had permanent neurological sequelae.
Conclusions: According to our findings, complete recovery
of PRES can be achieved if therapy is started early based on
symptoms and MRI findings. If no contraindication is present,
multiple simultaneous therapy can be safely prescribed.
P-060 Outcome of All Induction Chemotherapy
in Children Belonging to the Economically Weaker
Sections of a Low-Middle Income Country
N. Verma1 , A. Kumar2 , V. Pooniya2
1 King
George Medical University, Pediatrics, Lucknow, India; 2 King
George's Medical University, Pediatrics, Lucknow, India
Background/Objectives: Most of the children suffering from
Acute Lymphoblastic Leukemia (ALL) from the Economically Weaker Sections (EWS) are unable to reach apex cancer
institutes or corporate hospitals for their treatment. They are
either treated in government medical centers or die in absence
of optimal treatment. There is a dearth of information on the
outcome of induction chemotherapy in this group of children
Design/Methods: Data of all children with ALL belonging to
EWS (Annual income less than USD $1490) treated in a Government Hospital in North India from Jan 2016 to July 2016
was retrospectively reviewed. Children were administered a
risk stratified induction chemotherapy (3 drug induction for
standard risk and 4 drug induction for high risk ALL). Treatment was provided free of cost by support from government
and NGOs.
Results: Out of the total 69 newly diagnosed ALL registered
in Pediatric Oncology clinic at KGMU, from 1st Jan 2016 to
31st July 2016, 57 (83%) belonged to EWS (44 boys, 13 girls).
Eleven children (19%) abandoned treatment during induction.
Of the 46 children who took treatment as per protocol (43 B-
cell, 3 T-cell ALL), 18 had standard-risk disease, while 28 had
high-risk disease. At presentation 54% children were undernourished (33% - moderate; 21% - severe undernutrition),
28% had hypoalbuminemia. Complications during induction
chemotherapy were encountered in 59% (27/46) children,
leading treatment interruptions (of > 2 days) in 46% (21/46)
and death in 30% (14/46) children. Causes of death included
infections (10), Tumor Lysis syndrome (3), and bleeding (1).
70% (32/46) children completed there induction chemotherapy and all of them were in morphological remission.
Conclusions: Outcome of ALL induction in children from
EWS is poor. A significant proportion of these children are
undernourished. Despite the provision of free treatment, abandonment rates are high. The risk of complications and death
is also higher in these children.
P-061 Prevalence and Predictors of Invasive
Fungal Infections in Children with Persistent
Febrile Neutropenia Treated for Acute Leukemia- A
Prospective Study
J. Yadav1 , A. Singh1 , R. Seth1 , I. Xess2 , M. Jana3 , S. Kabra1
1 ALl
India Institute of Medical Sciences, Pediatrics, Delhi, India; 2 ALl
India Institute of Medical Sciences, Microbiology, Delhi, India; 3 ALl India
Institute of Medical Sciences, Radiology, Delhi, India
Background/Objectives: Febrile neutropenia is the most frequent life threatening complication of chemotherapy among
children with cancer. Fungal infections are emerging concern
due to improved survival secondary to better supportive care
and aggressive chemotherapy. The study was planned to ascertain prevalence and predictors of invasive fungal infection following revised EORTC criteria.
Objectives: To ascertain the prevalence of invasive fungal
infections (IFI) during febrile neutropenic episodes in children with acute leukemia, and determine the predictors for
IFI; and to identify the etiological fungal species causing IFI.
Design/Methods: In this observational study children
between 1-12 years of age on chemotherapy for acute
leukemia with febrile neutropenia were enrolled. Diagnosis
of IFI was based on EORTC criteria and was classified as
proven, probable and possible IFI. Prevalence was reported in
mean ± 95% CI form and etiological species were presented
in form of frequency distribution.
Results: 319 episodes involving 187 children of febrile neutropenia were screened and 74 were enrolled. Seventeen
episodes fulfilled EORTC criteria for IFI giving a prevalence of 22.97% (13.99- 34.21). Documented cases were further classified into proven-3(17.6%), probable 11(64.8%) and
possible-3(17.6%). On multivariate analysis, abnormal CXR
and clinical sinusitis were found to be important predictors
of IFI. Most common fungus isolated was Aspergillus sp. followed by Candida sp. Aspergillus and candida species were
SIOP ABSTRACTS
most commonly isolated from sputum and blood respectively.
Most common isolate in oral scrapping was Candida followed by Aspergillus. All the episodes in which we isolated
Aspergillus were positive for galactomannan antigen test. Out
of 74 cases, six (8.1%) were blood culture positive sepsis.
Conclusions: Prevalence of invasive fungal infection in the
study was 23%. Abnormal chest x ray and clinical sinusitis
were found to be important predictors of IFI.
P-062 Acute Lymphoblastic Leukemia Outcome
and Survival in Turkey: Marmara Experience
B. Yilmaz1 , N. Eker1 , O. Dogru1 , G. Tokuc1 , E. Senay1 , B. Berk1
1 Marmara
University Pendik Training and Research Hospital, Pediatric
Hematology and Oncology, Istanbul, Turkey
Background/Objectives: Acute lymphoblastic leukemia
(ALL) is the most common form of cancer in children
accounting for approximately 25% of all pediatric cancers.
The 5-year survival is approximately 85% in developed countries. We examined the our ALL patients 5-year survival rates
and causes of mortality.
Design/Methods: A total of 120 patients with acute lymphoblastic leukemia (one-18 years) diagnosed between 2011
to 2016 were included in the study. The patients with secondary malignancy, age <1year and children with relapsed
disease were excluded. All patients were stratified and treated
according to St-Jude Total XV Study Protocol.
Results: The mean duration of follow-up was 29 months
found. The five-year overall survival was 77% found. Seventeen patients were lost to follow up. Unfortunately, the most
common cause of death was infection-related complications
(82%.[14/17 patients]). We did not see any difference in the
risk of mortality among risk groups (Log Rank p=0.14). But
standard risk better survival than other two risk groups. The
children with Pre-B cell leukemia had better survival compared to other types of cell leukemia although it was statically
significant (Log Rank, p<0.0001) (pre-B 81% vs T-cell:62%
vs Burkitt leukemia 50%)
Conclusions: The infectious complications are still a major
cause of a death in developing countries (etc. Turkey) during the treatment of children with ALL. Our patients died
mainly of infectious diseases and sepsis leading to present difference in the success of leukemia treatment with developed
countries.
P-063 Prognostic Value of Neuropilin-1 /CD304
in Children with B-Lineage Acute Lymphoblastic
Leukemia
M. Zakaria1 , M. Hesham1 , D. El nemer2 , M. Hashem2 , H. Naguib2
1 Faculty
of medicine- Zagazig University-Egypt, Pediatrics, Zagazig, Egypt;
of medicine- Zagazig University-Egypt, clinical pathology,
Zagazig, Egypt
2 Faculty
S195 of S518
Background/Objectives: Neuropilin-1 (NRP-1) is a novel
receptor for vascular endothelial growth factor (VEGF) which
expressed in endothelial and tumor cells and promotes proliferation and chemotaxis of leukemic cells in response to
VEGF. Inhibition of NRP-1 functions may provide a new therapeutic strategy for treatment of ALL. We aimed To study
NRP-1/CD304 expression profile of normal B lineage and
leukemic lymphoblasts, its prognostic value and its role in
Minimal Residual Disease detection.
Design/Methods: A prospective case-control study was conducted on forty newly diagnosed patients with acute Blymphoblastic leukemia (22males and 18 females) with a
mean age of 6.68±4.70 years and forty age and sex matched
subjects as a control group. Expression of NRP-1 (CD304) by
flow cytometry was done at diagnosis and at the end of induction therapy.
Results: Forty five % of the cases were positive for CD304
expression and 55% were negative. There were no statistically significant differences between cases with positive
and–ve expression of CD304 regarding clinical presentation,
morphology, immunophenotyping and CNS infiltration. But
there were statistical significance differences between them
as regards to relapse (77.7% relapsed cases were CD304
positive) and prognosis (55% of cases with positive CD304
expression died). There were positive significant correlation
with CD 304% and age, bone marrow blast cells and LDH
level and –ve significant correlation with WBCs count and
Hb level. There was no significant difference between CD304
positive and negative cases regarding overall Survival rate,
while Disease-free survival at 12 months was 75.4% in CD304
positive cases and 33.3% in negative cases with a high significant difference.
Conclusions: Neuropilin-1(CD304) with a high expression
on bone marrow blasts can be considered as a marker for bad
prognosis in children with B-lineage ALL and could be used
during follow-up and disease monitoring.
Acknowledgment: The authors thank all the participants of
the study for their unstinted cooperation.
P-064 Preliminary Data of Multicenter Project
Concerning Asparaginase Activity – Focus on Silent
Inactivation
B. Zalewska-Szewczyk1 , K. Wyka1 , J. Walenciak1 , A. Dusza2 , O.
Michon3 , A. Mizia-Malarz4 , K. Ospa5 , N. Sekula6 , J.
Urbanska-Rakus7 , W. Mlynarski1
1 Medical
University of Lodz, Department of Pediatrics- OncologyHematology and Diabetology, Lodz, Poland; 2 Medical University of
Warsaw, Department of Pediatrics- Hematology and Oncology-, Warsaw,
Poland; 3 Medical University of Silesia- katowice, Department of PediatricsHematology and Oncology in Zabrze, Zabrze, Poland; 4 Medical University
of Silesia- Katowice, Department of Oncology- Hematology and
Chemotherapy, Katowice, Poland; 5 Mediacal University of Wroclaw,
Deparment of Bone Marrow Transplantation- Pediatric Oncology and
SIOP ABSTRACTS
S196 of S518
Hematology, Wroclaw, Poland; 6 Medical University of Lublin, Department
of Pediatric Hematology- Oncology and Transplantation, Lublin, Poland;
7 Center of pediatric and Oncolgy in Chorzow, Department of Pediatric
Hematology and Oncology, Chorzow, Poland
Background/Objectives: Asparaginase is a crucial agent of
acute lymphoblastic leukemia (ALL). However its use is
limited due to hypersensivity, moreover the generated antiasparaginase antibodies can lead to the inactivation of the
drug without symptoms of allergy. This implies the risk of
ineffective treatment.
The aim of the study is to evaluate the incidence of silent inactivation and allergy to asparaginase in children with newly
diagnosed ALL.
Design/Methods: In June 2016, we started systematic monitoring of asparaginase activity in patients treated in 7 Polish
pediatric centers. The current report summarizes 10 months
of study duration. At present, 113 children, treated according
to ALLIC 2009 protocol were enrolled in the study. In case
of overt allergy/insufficient drug activity, asparaginase preparation was changedfro native E.coli asparaginase to pegylated
E. coli asparaginase, and subsequently Erwinase. Asparaginase activity for native preparations used 2 or 3 times weekly
was determined using ELISA method before each subsequent
dose, and for pegylated asparaginase on 8th and 15th day after
administration.
Results: In total 776 asparaginase measurements were performed. Among 113 children the preparation was changed in
23 patients to pegylated asparaginase and in 8 patients subsequently to Erwinase. In 9 children treated with native E. coli
asparaginase and in 6 children treated with pegylated asparaginase silent inactivation was found. On the basis of previous analyzes, indicating the importance of asparaginase for
the outcome of ALL, it can be stated that implementation of
systematic monitoring of asparaginase activity improved the
effectiveness of treatment in 15 (13%) studied children.
Conclusions: Preliminary data analysis indicate that 13% of
children exhibit insufficient asparaginase activity during treatment according to the ALL IC 2009 protocol, despite the lack
of clinically apparent allergy. Because of the clinical relevance of the study, and the importance to the effectiveness
of therapy, it is advisable to continue the study.
HAEMATOLOGY - MYELOID
LEUKEMIAS, MYELODYSPLASTIC
AND MYELOPROLIFERATIVE
SY N D RO M E S
P-065 Spectrum of Genetic Abnormalities in
Slovak Children with AML During Period
2000-2014
M. Achbergerova1 , J. Puskacova1 , M. Makohusova1 , P. Svec1 , O.
Fabri1 , L. Copakova2 , M. Cermak2 , M. Leitnerova2 , E. Bubanska3 ,
I. Oravkinova4 , Z. Lysa1 , E. Kaiserova1 , A. Kolenova1
1 Children's
University Hospital, Department of Pediatric Hematology and
Oncology, Bratislava, Slovak Republic; 2 National Cancer Institute,
Department of Clinical Oncology, Bratislava, Slovak Republic; 3 Children's
University Hospital, Department of Pediatric Oncology and Hematology,
Banska Bystrica, Slovak Republic; 4 Children's University Hospital,
Department of Pediatric Oncology and Hematology, Kosice, Slovak
Republic
Background/Objectives: Acute myeloid leukemia (AML) is
relatively rare in children. In the Slovak Republic, approximately 2-8 new cases of childhood AML are diagnosed per
year. We sought to describe the incidence of cytogenetic aberrations associated with AML and to evaluate the event-free
and overall survival among children and adolescents with
AML in our population.
Design/Methods: In total, 122 children and adolescents age
0-18 years were diagnosed with AML between 2000 and
2014. These children were treated according to AML BFM
strategy at one of three Slovak centres of pediatric hematology
and oncology. Bone marrow samples were analyzed at a central laboratory using conventional cytogenetics, fluorescence
in-situ hybridization (FISH) and molecular genetic methods.
A retrospective analysis was based on our laboratory and clinical data from Slovak clinical cancer registry of children and
adolescents.
Results: Incidence of selected cytogenetic aberrations was
as follows: t(15,17) was present in 9.02%; t(8,21) in 4.92%;
inv(16) in 4.10%; MLL rearrangement in 7.38%; nine cases
of AML (7.38%) were children with Down syndrome. Fiveyear event-free survival (EFS) and overall survival (OS)
rates in this cohort were 49,0% (N=122; 57 deaths) and
53.2%(N=122; 62 events), respectively. Sixty-six patients
were stratified into the high risk group with OS and EFS
52.95% (32 deaths) and 46.87% (36 events), respectively; in
standard risk group rates 63.2% for OS (N=36; 13 deaths) and
60.58% for EFS (N=36; 14 events) were achieved. Patients
with positive t(15,17) abbrevation achieved better and the
same rates for OS and EFS (73.7%) in contrast to patients
without this genetic change (54.9% and 50.8%).
Conclusions: Based on these results, we have planned a new
strategy with the aim of improving outcomes for these children by centralizing treatment at a single center, optimizing
the timing of stem cell transplant, and implementing additional genetic testing at the AML BFM central laboratory in
Germany.
Acknowledgement: APVV-15-0250.
P-066 Outcome of Pediatric Acute Myeloid
Leukemia in a Developing Country: Is this the
Impact of Invasive Fungal Infection?
SIOP ABSTRACTS
S197 of S518
A. Ahmed1 , A. Kamel1 , E. Kandeel2 , E. Ebeid1
1 National
Cancer Institute, pediatric oncology, Cairo, Egypt;
Cancer Institute, clinical pathology, Cairo, Egypt
1 Institute
2 National
Background/Objectives: Acute myeloid leukemia (AML)
remains a challenging disease in developing countries. To
identify Overall Survival (OS), Disease Free Survival (DFS)
and their correlation with different risk factors, as well as
demonstration of the common causes of mortality.
Design/Methods: A retrospective descriptive study included
103 newly diagnosed AML patients age less than 18 years
receiving treatment at national cancer institute, Cairo University, Egypt in the period from January 2008 till December
2010.Risk factors including age, gender, initial WBC, cytogenetics, CNS status and antifungal prophylaxis were collected.
Results: The 2 years DFS was 27.1%, with a median survival of 10 months, and 2 years OS was 30.4% with a median
survival of 16 months and 95% confidence interval (5.414.8), (11.24-20.76) respectively. Early deaths were seen in
15 patients (14.6%) mainly due to infections. Late deaths
were seen in 48 patients mainly due to progressive disease
and infections. Infection related mortality (IRM) represented
42.9% from all mortality causes, (26.2%) of the patients.
About 74 patients showed picture of possible fungal pneumonia (39 patients during induction chemotherapy, 17 post first
consolidation and 18 post second consolidation). Regarding
antifungal prophylaxis, primary prophylaxis fluconazole was
given in 21 patients (20.4%). Regarding secondary prophylaxis, 45 patients received itraconazole, 24 patients received
voriconazole. Analysis of the data revealed statistically significant correlation between DFS and response to induction
chemotherapy (p value<0.001), presence of chloroma (p value
0.040) and voriconazole prophylaxis (P value<0.001). Correlation with OS was statistically significant with response
to induction chemotherapy (P value0.002), association with
favorable cytogenetic (t (8, 21) and inv 16) (p value 0.039),
with chloroma (p value 0.023) and voriconazole prophylaxis
(p value 0.001).
Conclusions: Infection related mortality is an important
cause of poor survival outcome in our study population. These
results warrant the use of anti-mold primary prophylaxis for
all pediatric patients with AML.
P-067 Polish Experience of the Treatment of
Acute Promyelocytic Leukemia in Children from
2005 to 2016
M. Czogala1 , K. Pawinska-Wasikowska1 , T. Ksiazek2 , A.
Rodziewicz3 , B. Sikorska-Fic4 , J. Skalska-Sadowska5 , R.
Tomaszewska6 , K. Muszynska-Roslan7 , D. Grabowski8 , I.
Karpinska-Derda9 , K. Mycko10 , K. Zielezinska11 , J. Pohorecka12 ,
B. Przybyszewski13 , W. Balwierz1
of Pediatrics Jagiellonian University Medical College,
Department of Pediatric Oncology and Hematology, Kraków, Poland;
2 Institute of Pediatrics Jagiellonian University Medical College,
Department of Medical Genetics, Kraków, Poland; 3 Medical University of
Wroclaw- Poland, Department of Bone Marrow Transplantation- Pediatric
Oncology and Hematology, Wroclaw, Poland; 4 Medical University of
Warsaw, Department of Pediatrics- Hematology and Oncology, Warsaw,
Poland; 5 Medical University of Poznan, Department of Pediatric OncologyHematology and Transplantology, Poznan, Poland; 6 Medical University of
Silesia, Department of Pediatrics Hematology and Oncology, Zabrze,
Poland; 7 Medical University of Bialystok, Department of Pediatric
Oncology, Bialystok, Poland; 8 Medical University of Lublin, Department of
Pediatric Hematology and Oncology, Lublin, Poland; 9 Chorzow Pediatrics
and Oncology Center, Department of Hematology and Oncology, Chorzow,
Poland; 10 Medical University of Lodz, Department of Pediatrics- OncologyHematology and Diabetology, Lodz, Poland; 11 Pomeranian Medical
University, Department of Pediatrics- Hematology and Oncology, Szczecin,
Poland; 12 Province Children's Hospital, Department of Hematology and
Oncology, Kielce, Poland; 13 Province Children's Hospital, Department of
Pediatrics and Hematology and Oncology, Department of Pediatrics and
Hematology and Oncology, Poland
Background/Objectives: Acute promyelocytic leukemia
(APL) characterized by translocation t(15;17) comprises
about 5-10% of childhood acute myeloid leukemia. The aim
of the study was analysis of the treatment outcome of APL in
children in Poland from 2005 to 2016.
Design/Methods: All 36 patients with genetically confirmed
APL treated in Poland in analyzed period were eligible
for the study, 33 of them were treated with AML-BFM2004 Interim (2005-2015 – period I) and 3 with AML-BFM
2012 (2015-2016 – period II). Median observation time was
42 months and 8 months respectively in periods I and II.
All patients in the period I received standard chemotherapy
with all-trans retinoic acid (ATRA), in the period II two
patients were treated with induction chemotherapy, ATRA
and arsenic trioxide (ATO), one patients with ATRA-ATO
without chemotherapy. We analyzed survival rates and the
treatment failures.
Results: Probability of 5-years overall survival (OS), event
free survival (EFS) and relapse free survival (RFS) were
0.822±0.067; 0.828± 0.064 and 0.960±0.036 respectively
for all analyzed patients. Four (11%) early deaths (5-10 days
from diagnosis) caused by severe coagulation disorders were
observed. White blood cell count at diagnosis was significantly higher in children who died early compared to the
other patients (median [range]: 91.6×103 /�l [40-196×103 /�l]
vs 5.6 ×103 /�l [0.45-140 ×103 /�l], p=0.012). One patient
(2.4%) died of severe infection in course of disease progression 1.9 month after diagnosis. Relapse occurred in one
patient (2.4%), 13.5 months after first remission, the patient
died because of disease progression. All events occurred in the
patients from the period I, there were no deaths after the year
2012.
Conclusions: Treatment outcome in analyzed group is similar to the results reported by other study groups. The main
cause of deaths were coagulation disorders at the beginning
SIOP ABSTRACTS
S198 of S518
of disease. Early, accurate diagnosis followed by the specific
treatment enables to reduce number of early deaths.
P-068 Clinical Characteristics and Outcome of
Children with Acute Myeloid Leukemia Below One
Year of AGE: A Single Centre Experience from a
Developing Country
S. Eissa1 , S. Semary1 , M. Hammad1 , K. Shaaban2 , S.I. Salem3 , D.
Yassin4 , M. Jamal5 , D. Albeltagi6 , A. Hadad1
1 Children's
Cancer Hospital-Egypt, Pediatric hematIology/oncology, Cairo,
Egypt; 2 Children's Cancer Hospital-Egypt, Flow Cytometry Lab, Cairo,
Egypt; 3 Children's Cancer Hospital-Egypt, Cytogenetics Lab, Cairo, Egypt;
4 Children's Cancer Hospital-Egypt, Molecular Genetics Lab, Cairo, Egypt;
5 Children's Cancer Hospital-Egypt, Clinical Pharmacy, Cairo, Egypt;
6 Children's Cancer Hospital-Egypt, Clinical Research Department, Cairo,
Egypt
Background/Objectives: Myeloid leukemia occurring in
children below one year of age has distinctive clinical and biological features than that occurring in older children. Hyperleukocytosis, extra-medullary disease and CNS involvement
as well as Mixed Lineage Leukemia gene rearrangements
(MLL-r) at diagnosis are common.
Design/Methods: Retrospective analysis of the clinical and
biological features of infants with AML treated at our cancer
center during the period from July 2007 till December 2015.
Results: A total of 60 patients were diagnosed. Patients with
Down syndrome were excluded. Thirty two males (53%) and
28 females (46.7%), male to female ratio (1:1.2). Mean age
at diagnosis was 5.4, range (1 – 11.9) months, initial Total
Leukocytic Count (TLC) ranged between(1-370) ×109 /L,
mean 71 ×109 /L. Extra-medullary disease was present in
18 (30%) of patients. Nine patients (15%) had CNS disease at presentation. Monocytic differentiation was present in
28 (46.7%) and amegakaryoblastic leukemia M7 in 18(30%)
of patients. MLL gene rearrangements were present in 17
(28.3%) patients, with t (9, 11) being the most frequent; found
in 7(11.7%) patients. Other cytogenetic abnormalities as t(1,
22) and inv (16) were diagnosed less frequently in 6(10%) and
3 (5%) of patients respectively. All patients with t(1,22) had
M7 and all those with inv (16) had M4Eo morphology. Multiple trisomies were identified in 7 (11.7 %) patients. Most
patients experienced significant chemotherapy toxicity and
36 (60%) required ICU admission. Of the whole cohort, 25
(41.7%) patients achieved complete remission after induction,
of them 21 patients (84%) are still alive in first complete remission (CR).
Conclusions: Dealing with infants with myeloid leukemia is a
real challenge especially in countries with limited resources.
Improving supportive care, refinement of the risk stratification to identify those who require more intensive chemotherapy including transplantation is required to improve outcome.
Best survival was for those who entered into CR after induction (84%).
P-069 Mutation of Genes Affecting the RAS
Pathway Associated with PTPN11 in Pediatric
Acute Myeloid Leukemia
F. Gomes Andrade1 , F. Vicente dos Santos Bueno1 , I. Sardou
Cezar1 , G. Dallapicola Brisson1 , E. Pereira Noronha1 , E.
Terra-Granado1 , M.S. Pombo-de-Oliveira1
1 Instituto
Nacional de Câncer, Research Center, Rio de Janeiro, Brazil
Background/Objectives: Deregulation of the RAS signaling
cascade is often caused by somatic mutations in genes encoding proteins which influence the activity of this pathway and
include NRAS, KRAS, FLT3, PTPN11, and c-KIT. Our aim
was to describe a comprehensive mutational screen of key
exons of these genes in a cohort of 439 unselected pediatric
acute myeloid leukemia (p-AML) cases at diagnosis and to
evaluate their prognostic value in the probability of overall
survival (pOS).
Design/Methods: Hotspot regions of NRAS, KRAS, FLT3,
PTPN11, and c-KIT were directly sequenced for the screen
of mutations. Survival analysis was performed in a subset of
patients treated following BFM-AML2004 guidelines, out of
clinical trials.
Results: RAS pathway mutations were found in 35.1% of the
study cohort, mainly represented by FLT3 (16.2%), followed
by NRAS (6.4%), c-KIT (4.3%), KRAS (3.4%), and PTPN11
(2.5%). Mutations were rare among KMT2A rearranged cases
(12.7%) and rarely observed concomitant in more than one
gene (8.8%). Two boys (7 and 13 year old) presented mutation in PTPN11 and NRAS or KRAS, respectively. Both died
less than 1 month after diagnosis. The cumulative 5-year pOS
for p-AML was 36.0±3.8% (excluding acute promyelocytic
leukemia). Patients with skin color considered White presented better outcome than Non-Whites (pOS 43.4±5.9% and
29.5±4.9%, respectively), as well as patients aged >12 years
old (pOS 37.2±5.1%) and those with CBFb-MYH11 (pOS
73.7±11.3%). PTPN11 mutations in exon 3 were found in
overall analysis to be associated with adverse prognosis, and
identified by multivariate analysis as independent prognostic
factor (hazard ratio of 3.6; 95% confidence interval of 1.77.7).
Conclusions: Although there is a need of further action to
improve the overall survival rates of p-AML patients, these
aberrations are likely to guide the stratification and may direct
the development of novel therapeutic targeted therapies.
P-070 Outcome of Acute Myeloblastic Leukemia
in Indian Children in a Newly Established Pediatric
Cancer Center
SIOP ABSTRACTS
K. Viswanathan1 , S. Jayabose1 , A. Annamalai1 , N. Iyer1 , V.
Bharathi1 , K. Rathnam1
1 Meenakshi
Mission Hospital & Research Centre, Pediatric
Hematology-Oncology, Madurai, India
Background/Objectives: There is paucity of data on the outcome of childhood AML in India. The objective of this study
is to analyze the outcome of childhood AML in our pediatric
cancer center established in 2010; and compare the outcomes
with two different treatments.
Design/Methods: We reviewed the data on 78 children consecutively diagnosed from 2010 to 2016, including 5 MDSAML and 5 APL, one DS-AML and one acute megakaryoblastic leukemia; and 12 AML with chloroma. Male: female,
34:44. Median age: 9 years; (range, 0.5 to 21years). First 40
patients seen in 2010 to 2013 (Group I) were treated on a
modified MRC-10 regimen. The next 38 patients (Group II)
received a less intensive regimen (induction with cytarabine
plus daunorubicin; and reduced doses of mitoxantrone in consolidation); but nine received allogeneic stem cell transplantation (SCT), 7 in first remission and two in second remission–6
from matched siblings; 3 haplo-identical parents.
Results: One patient moved to another center; none abandoned treatment. Sixty-three of 77 (81.8%) achieved complete remission (CR). Overall, 40 patients (51.9%) are alive,
including all 9 who received SCT; and 8 of 12 patients with
chloroma. Median follow-up is 24 months (range, 3 - 80).
Estimated 3-yr overall survival (OS): 42.3%. All 12 refractory patients, and 15 of 17 relapsed patients, and 4 of 5 MDSAML patients died of disease. Deaths during induction and in
remission were higher, 7.5% and 21.8% respectively in Group
I; vs 2.7% and 9.7% in Group II, but not statistically significant. Estimated 3-year OS was higher for group II (51% vs
38%), but not statistically significant (p= 0.15).
Conclusions: MRC-10 based regimen results in excessive
treatment-related mortality in Indian children with AML. But
use of less intensive induction and consolidation, with allogeneic stem cell transplant for intermediate and high-risk
patients is likely to improve their survival.
P-071 Clinical Features of Myeloid Sarcoma in
Indian Children with Acute Myeloblastic Leukemia
S. Jayabose1 , N. Iyer1 , K. Viswanathan1 , A. Annamalai1
1 Meenakshi
Mission Hospital & Research Centre, Pediatric
Hematology-Oncology, Madurai, India
Background/Objectives: Myeloid sarcoma (MS) is defined
as extramedullary lesions in acute myeloblastic leukemia
(AML) The reported incidence and prognostic significance
MS has been variable; and there are no data on MS in Indian
children. The objective of our study is to review the clinical
S199 of S518
features of children with MS in a single institution seen over
a period of 7 years.
Design/Methods: We retrospectively reviewed the data on all
cases of AML, including 3 isolated MS seen from 2010 to
2016: clinical and molecular features, details of treatment and
their outcome.
Results: Among 83 consecutively diagnosed cases of AML,
12 patients had MS: three had isolated MS without AML;
excluding those three, 9 of 80 (11%) had AML with MS
(AML-MS); Median age: 8 years (range, 1-20). Male: female,
9:3. Three had disseminated MS, involving two or more
sites–including asymptomatic pelvic and intracranial lesions.
None had leukemic cells in spinal fluid. Seven of 9 patients
with AML-MS had t(8;21). Cytogenetics was not done in
the three cases of isolated MS. Ten patients received treatment as per a modified MRC-10 protocol; one had less intensive treatment—induction with cytarabine pus daunorubicin,
and consolidation with high-dose cytarabine; one infant was
treated according to COG 2971. Eleven patients had 3 to 4
doses intrathecal cytarabine. Five had local radiation: 4 in first
remission; one in second remission. Two had allogeneic stem
cell transplant (SCT); one in second remission. Eight patients
are alive, including all 3 with isolated MS and the two who
had SCT. Median follow-up of surviving patients: 48 months
(range, 9-70).
Conclusions: MS occurs in approximately 11% of Indian children with AML. It is frequently associated with t(8;21); and
may be associated with occult and asymptomatic disseminated lesions. Prognostic significance of AML-MS is unclear;
but isolated MS may have a better prognosis than AML-MS.
P-072 Analysis of Prognostic Factors in Children
with Acute Myeloid Leukemia (M4/M5)
C. kai1
1 Shanghai
Children'S Hospital Affiliated to Shanghai Jiaotong University,
Hematology and Oncology, Shanghai, China
Background/Objectives: To investigate the clinical efficacy
and prognostic factors of M4 /M5 subtypes in children with
acute myeloid leukemia (AML).
Design/Methods: A retrospective analysis of the clinical data
of M4 /M5 subtypes in our hospital from January 2009 to
December 2014 was carried out. The long-term efficacy, prognosis and relapse factors were analyzed.
Results: (1) The clinical data of 46 cases were collected,
among which 38 cases were treated with more than 2 courses,
including male 22 cases, female 16 cases, M4 19 cases and
M5 19 cases. The median age was 5 years.5-year overall
survival rate (OS) and 5-year event-free survival rate (EFS)
were 57.7±9.3% and 47.2 ±8.9%, 5-y EFS of M4 and M5
were 52.4 ±12.7% and 45.4 ±11.9%.(2) Compared with
SIOP ABSTRACTS
S200 of S518
the international risk stratification: 5-y EFS of favorablerisk, intermediate-risk and poor-risk were 77.2 ±12.4%,
49.5±14.9% and 25 ±19.8% (P=0.043). (3) Single factor
analysis showed extramedullary infiltration, d8 assessment
and treatment were prognostic factors (P=0.028, 0.020 and
0.029);Multivariate analysis showed extramedullary infiltration (HR=5.323, 95%CI, 1.620-17.490, P=0.006) and less
than 6 courses (HR= 6.186, 95%CI 1.726-22.176, P=0.005)
were the independent risk factors of affecting survival.
Conclusions: (1) Strengthening treatment and adequate
courses are the keys to improve the overall curative effect in
children with M4 /M5 subtypes.(2) Extramedullary infiltration
was the risk factor for survival and recurrence in M4 /M5 subtypes. (3) We advise the children who have the initial symptoms and molecular biology with poor prognostic factors to
choose hematopoietic stem cell transplantation as early as
possible.
P-073 Control of Childhood Acute Myeloid
Leukaemia with A Dose Reduced Induction
Treatment in Malawi
A. Mpasa1 , S. Wachepa1 , P. wasswa1 , M. Butia1 , I. Kumwenda1 , M.
Chasela1 , P. Ward2
1 Baylor
College Of Medicine Children's Foundation, Paediatric
haematology and oncology, Lilongwe, Malawi; 2 UNC project-Malawi,
oncology, Lilongwe, Malawi
Background/Objectives: Childhood Acute Myeloid
Leukaemia (AML) is challenging to treat, in low income
countries (LICs) like Malawi. Limited supportive care
resources preclude the use of effective treatment protocols,
as used in high income countries. In Malawi, AML is treated
supportively, without chemotherapy. However, inadequate
blood product support and community palliative services
results in poor symptom control, particularly of bleeding. In
order to alleviate symptoms through disease control, we used
a modified chemotherapy protocol for childhood AML. We
hereby share our experience of using this protocol at Kamuzu
Central Hospital.
Design/Methods: Between February and December 2016,
children with AML, without FAB-M3 subtype, were treated
with a modified induction protocol. This comprised of Doxorubicin 20mg/m2 for 4 days and Cytarabine 100mg/m2
twice a day for 10 days. Ciprofloxacin, Itraconazole and Cotrimoxazole were used as infection prophylaxis. The diagnosis
of AML was established by assessment of bone marrow morphology. Data was collected on the demographics, baseline
clinical and hematological features, toxicity, remission status
and survival at the end of induction.
Results: Nine (64%) children, were treated on this induction protocol. Median age was 9 years (range 6-12) and 4
(44%) were male. Baseline median hematological parameters were White cell count: 66 × 106 /L (range 10.7-269);
Platelets 32 × 109 /L (range 6-92); Neutrophils 8.8 × 106 /L
(range 0.54-160) and haemoglobin 5.7g/dl (range 2.0-9.4).
Seven patients (77.7%) suffered from febrile neutropenia. Two
patients (22.2%) suffered from mucositis. Median time to
count recovery was 23.5 days (range 20-44). Median duration of admission was 25 days (range 20-48). Of evaluable patients, post induction overall survival and complete
remission rate were 8/9(88.8%) and 8/8 (100%) respectively.
Median Lansky score at admission and discharge were 80
(range 10-100) and 100 (range 50-100), respectively.
Conclusions: This modified chemotherapy regimen holds
promise as a deliverable, safe and effective regimen for control of AML in LICs.
P-074 Characteristics and Outcome of Children
with Acute Myeloid Leukemia and Down Syndrome
Ineligible for Clinical Studies
K. Nakashima1,2 , D. Hasegawa2,3 , T. Miyamura2,4 , A. Hama2,5 , S.
Iwamoto2,6 , K. Terui2,7 , D. Tomizawa2,8 , S. Adachi2,9 , T. Taga2,10
1 Kyushu
University School of Medicine, Department of Pediatrics, Fukuoka,
Japan; 2 Japan Children's Cancer Group, AML committee, Tokyo, Japan;
3 St. Luke's International Hospital, Department of Pediatrics, Tokyo, Japan;
4 Osaka University School of Medicine, Department of Pediatrics, Osaka,
Japan; 5 Nagoya University Graduate School of Medicine, Department of
Pediatrics, Nagoya, Japan; 6 Mie University School of Medicine,
Department of Pediatrics, Mie, Japan; 7 Hirosaki University Graduate
School of Medicine, Department of Pediatrics, Hirosaki, Japan; 8 National
Center for Child Health and Development, Division of Leukemia and
Lymphoma- Children's Cancer Center, Tokyo, Japan; 9 Kyoto University,
Department of Human Health Sciences, Kyoto, Japan; 10 Shiga University of
Medical Science, Department of Pediatrics, Shiga, Japan
Background/Objectives: High survival rates of 80-90% are
reported on recent clinical trials for children with acute
myeloid leukemia (AML) and Down syndrome (DS: AMLDS) with reduced-dose chemotherapies. However, there are
certain number of children with AML-DS complicated with
congenital heart disease (CHD), gastrointestinal anomaly,
severe infection, and/or other complications, thus are ineligible for clinical trials.
Design/Methods: Because data on outcomes of such children
are scarce, we retrospectively analyzed clinical characteristics
and outcomes of children with AML-DS who were excluded
from the Japanese clinical studies conducted between January 2000 and December 2015: AML99-DS, CCLSG9805DS, JPLSG AML-D05 and AML-D11.
Results: Thirteen children (6 boys and 7 girls) were identified
and were ineligible for the following reasons; CHD (N=8),
pulmonary fibrosis (N=1), hypoxic encephalopathy (N=1),
rapid progression from transient abnormal myelopoiesis
(N=1), complicated with hemophagocytosis (N=1), and age
SIOP ABSTRACTS
excess of 21 years at diagnosis (N=1). Median age at diagnosis was 14 months (range, 5 months to 21.4 years). GATA1
mutation was detected in three out of four screened cases.
Among all, twelve cases were treated with curative intent.
Four cases received low-dose cytarabine-based chemotherapy
(10-30 mg/m2/day): three with severe CHD failed to achieve
remission and died of disease; one with pulmonary fibrosis
successfully achieved remission but eventually died of infectious complications. Eight cases underwent dose-modified
standard chemotherapy for AML-DS: six are alive in remission, whereas two had relapsed (one died of disease and
another are alive with disease). The patient with hypoxic
encephalopathy received best supportive care and died of disease. Finally, six remains in continuous remission, one is alive
with disease, and six died (five of leukemia and one of infection).
Conclusions: Optimal dose intensity of curative chemotherapy for children with AML-DS harboring severe comorbidities should be explored.
P-075 Epigenetic Therapy for Treatment
Pediatric Acute Myeloid Leukemia
V. Nemirovchenko1 , A. Popa1 , G. Mentkevich1
1 Federal
State Budgetary Institution «N.N.Blokhin Russian Cancer
Research Center» under the Russian Academy of Medical Sciences,
Children Hematology, Moskow, Russia
Background/Objectives: The majority of children with acute
myeloid leukemia (AML) respond to initial chemotherapy and
achieve a complete remission, yet only a minority experience long-term survival because a large proportion of patients
eventually relapse with therapy-resistant disease. The combination of epigenetic drugs (DNA hypomethylating agent,
histone deacetylase inhibitor, all-trans retinoic acid) with
chemotherapy may improve the results of treatment children
with AML.
Design/Methods: We report outcomes for 138 children who
underwent chemotherapy for de novo AML between 2002
and 2016. Median age was 5.5±1.1 years. Forty (29.0%)
children were included into AML-2002 protocol, 70 (48.9%)
– AML-2007 protocol, 31 (22.5%) – AML-2007 protocol.
There were Standard, Intermediate and High risk groups. The
vast majority was High risk - 47.8%. he patients got (Induction
therapy, Intensification, Consolidation, Maintenance therapy)
after AML-2002 protocol. Valproic acid (VPA) and all-transretinoic acid (ATRA) were added to the chemo after AML2007 protocol. The patients included into AML-2012 protocol
received chemotherapy with epigenetic drugs (VPA, ATRA,
Decitabine).
Results: The number of the good responses on the 15th day of
the therapy was the same: AML-2002 – 77.5%; AML–2007
S201 of S518
– 80.6%; AML-2012 – 74.2% (p=0.9). We achieved complete
remission in 32 (80.0%) of the patients after Induction AML2002 protocol, 62 (92.5%) – after AML-2007and 30 (100%)
– after AML-2012 (p=0.015). Probability of 5-year disease
free survival was 46.5±8.3% (median follow up 79.6±12.9
month) for protocol AML-2002, 53.5±6.6% (median follow
up 72.8±7.1 month) – AML-2007 and 67.2±11.1% (median
follow up 41,1±4,6 month) – AML-2012 (р=0,035). Overall survival was 47.9±8.2% (median follow up 85.7±12.7
month) for protocol AML-2002, 53.5±6.6% (median follow
up 71.9±6,8 month) – AML-2007 and 69.3±9.2% (median
follow up 40.5±3.9 month) – AML-2012 (р=0.1).
Conclusions: The use of these drugs can be therapeutic used
as part of a combination with other therapeutic modalities.
P-076 Impacts of HUWE1 Knockdown in Human
Hematopoietic Stem Cells with A KRAS (G12V)
Mutation
M. Ruckert1 , A. Brouwers-Vos2 , L.G. Gonzaga3 , J.J. Schuringa2 ,
V.S. Silveira1
1 University
of São Paulo, Department of Genetics, Ribeirão Preto, Brazil;
Medical Center Groningen, Experimental Hematology,
Groningen, The Netherlands; 3 University of São Paulo, Department of
Pediatrics, Ribeirão Preto, Brazil
2 University
Background/Objectives: Acute lymphoid leukemia (ALL)
is the most common childhood malignancy. Philadelphia
chromosome (Ph) is present in 5% of childhood cases. Ph
positive leukemias express the tyrosine kinase BCR-ABL,
that is responsible for constitutive activation of RAS pathway and mediates leukemic cells proliferation. Even with
high cure rates, a lot of patients develop resistance to treatment and relapse. Previously published data suggests association between hyperactivation of RAS pathway and favorable treatment outcome, pointing to a new research approach.
HUWE1 participates in negative feedback mechanism controlling Shoc2 activity in activation of ERK1/2. Thus, it can be
assumed that loss of HUWE1 would lead to increased activation of ERK1/2 and, therefore, hyperactivation of RAS pathway.
Objectives: To evaluate the impacts of HUWE1 knockdown in human hematopoietic stem cells with KRAS
mutation.
Design/Methods: CD34+ cord blood cells were transduced
with miR-E lentiviral particles for gene knockdown. Flow
cytometry, differentiation markers and CFC assays were
performed.
Results: Co-cultures transduced with both KRAS and
shHUWE1 showed reduction in growth when compared
to the ones transduced with shSCR. When compared to
non-transduced cells, all 3 groups presented higher cumu-
SIOP ABSTRACTS
S202 of S518
lative growth. The cobblestone area formation follows
the same pattern shown by cumulative growth. In sorted
co-cultures, after 3 weeks in culture, non-transduced cells
differentiated mainly in granulocytic cells while HUWE1
knockdown shifted differentiation towards the myelomonocytic cells. In CFC assays, neither colony formation units
(CFU-GM) nor burst-formation units (BFU-E) were strongly
affected by knockdown of HUWE1. KRAS mutant cells
were severely impacted in BFU-E formation. Cells showing
knockdown of HUWE1 as well as the KRAS mutation
were severely impacted in both types of colony formation
units.
MMR achieved within 3 months of nilotinib treatment. One
patient needed to interrupt dasatinib therapy because of gastrointestinal bleeding, after 1 week of interruption dasatinib
started again no bleeding observed and he is still on molecular
remission.
Conclusions: These results suggest that HUWE1 has an
impact in human hematopoietic stem cell differentiation,
besides acting together with KRAS mutation in events such
as proliferation and colony formation capacity.
P-078 Clinical Study of Children with Acute
Promyelocytic Leukemia Treated with Arsenic
Trioxide: A Multicenter Study
Financial Support: FAPESP (Process 2015/12146-5)
P-077 Tyrosine Kinase Inhibitor Responses in
Pediatric CML Patients: Hacettepe Experience
İ. Yaman Bajin1 , S. Aytaç1 , B. Kuşkonmaz1 , Ş. Ünal1 , V. Okur1 , D.
Çetinkaya1 , M. Çetin1 , F. Gümrük1
1 Hacettepe
University, Department of Pediatrics- Division of Pediatric
Hematology, ANKARA, Turkey
Background/Objectives: Chronic myeloid leukemia (CML)
is a rare malignancy of childhood which is composed of 3%
of all pediatric leukemias. Tyrosine kinase inhibitors (TKIs)
revolutionazed CML treatment and made it possible to avoid
allogeneic stem cell transplant (SCT) for most of the patients.
Here, we aimed to investigate the TKI responses of patients
diagnosed CML in our department.
Design/Methods: Patients diagnosed with CML, did not
underwent SCT and is still on follow-up since 2012 in
Hacettepe University Department of Pediatric Hematology
were included. Four patients who underwent SCT between
this period were excluded. The clinical features and TKI
responses of these patients were evaluated.
Results: There were nine patients. Age at diagnoses were
median 13 years (10-16 years). Two girls and 7 boys. Treatment was started with imatinib for all of the cases. Two
patients responded imatinib and major molecular response
(MMR) was achieved in 4 and 9 months respectively. Two
patients were diagnosed within the three months and MR
have not been checked yet. The other 4 patients did not
responded imatinib therapy in 18 months, since they do not
have an eligible donor we replaced imatinib with dasatinib
therapy. One patient achieved MMR with imatinib in 3 months
but he developed leukopenia so imatinib replaced with dasatinib for this case. Patients achieved MMR with dasatinib
except one. In this case dasatinib replaced with nilotinib and
Conclusions: TKIs are effective in the CML treatment and
MMR could be achieved with the change between these drugs
when an adverse events occur or an eligible donor could not
be found and SCT is not an option.
H. Jiang1 , J. Zhu1 , J. Yang1
1 Shanghai
Children's Hospital, Hematology/Oncology, Shanghai, China
Background/Objectives: Acute promyelocytic leukemia
(APL) is rare in children. Due to the lack of long-term
follow-up, results of ATO and the concern about long-term
ATO related toxicity, the main protocol for children with
newly diagnosed APL is still a combination of ATRA and
chemotherapy. Few studies have demonstrated the efficacy of
ATO in the treatment of children with APL. In this study,
we retrospectively analyzed 25 children with newly diagnosed
APL treated with ATO in mulicenter.
Design/Methods: To evaluate the efficacy of Children with
acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO), we retrospectively reviewed 25 newly diagnosed APL patients treated mainly with all-trans-retinoic acid
(ATRA) and ATO from 2 hospitals. According to different
risk stratification by NCCN, 25 patients were separated into 2
groups, low risk group and high risk group.
Results: Overall, 24 of 25 patients achieved hematological
complete remission (HCR). In one case, the patient failed
to enter HCR, because of early death. The median duration
required to achieve HCR was 34 days (range, 26-63 days).
The median date to achieve molecular complete remission
was 56 days (range, 30-207 days). The 5-year EFS and OS of
25 patients were (88.0±6.5)% and (96.0±3.9)%, respectively.
The 5-year EFS of low risk group and high risk group patients
were (92.9±6.9)% and (81.8±11.6)% (P=0.44). ATO related
side effects were mild, including abnormal liver tests and electrocardiogram, but were invertible after supportive therapy.
At the end of each chemotherapy course, the urine arsenic
concentration remained low and no chronic arsenic toxicity or
second malignancies were found during the follow-up period.
Conclusions: The ATRA plus ATO regimen is a promising
and better treatment for childhood APL with positive PMLRARa fusion gene. It was necessary to make risk stratification
in APL patients.
SIOP ABSTRACTS
S203 of S518
HAEMATOLOGY - LYMPHOMAS
P-080 Childhood Hodgkin Lymphoma: Single
Center Experience
P-079 Superior Outcome and Lower Cumulative
Chemotherapy Doses in Adolescents and Young
Adults (AYA) with Non-Advanced Diffuse Large
B-Cell Lymphoma (DLBCL) Treated with Pediatric
Chemotherapy Regimen
E. Ataseven1 , Z. Siviş1 , B. Malbora1 , F.B. Belen1 , B. Güneş1 , S.
kamer2 , Y. Anacak2 , B. Atabay1 , M. Türker1 , H. Öniz1
Z. Afify1
1 Primary
Children Hospital, Oncology, Salt Lake City, Usa
Background/Objectives: Systematic data on the optimal treatment for AYA with DLBCL are lacking. Many
are treated by R-CHOP with favorable outcome. However pediatric based chemotherapy regimens have yielded
equal or superior results. We present a series of AYA
with DLBCL referred by medical oncologists to our children hospital in consideration for treatment on pediatric
protocol.
Design/Methods: Retrospective review of patients diagnosed with DLBCL between ages 16 and 24 years from
1/2002 to 3/2017. PMBCL was excluded. Clinical characteristics, staging, treatment details and outcome data
were collected. These were compared with published
data in young adults above 18 years of age treated by
R-CHOP.
Results: Six AYA with DLBCL were identified. Five were
male. Age at diagnosis ranged from 16-20 years. Four were
above 18 years old. Sites of presentation were bone n=4,
rectum=1, abdomen n=1. None had bone marrow or CNS
involvement. Stage was I-III Murphy/St Jude. This corresponds to Ann Arbor staging I-IV. All six patients are alive
and lymphoma free at last follow up (2-6 years, median 5
years). None received radiation therapy. All patients were
treated per FAB/LMB regimen: Group A therapy (COPAD)
n=1, Group B4 therapy (COP, COPADM1&2, CYM1&2)
n=5. Cumulative chemotherapy doses in 5 patients who
received group B therapy were Cyclophosphamide 3.3 g/m2,
Doxorubicin 120 mg/m2, Prednisone 900 mg/m2, Vincristine 6 mg, Methotrexate 12 g/m2, and Cytarabine 1000
mg/m2. There were 7 intrathecal chemotherapy administrations (methotrexate, Cytarabine, hydrocortisone). Compared to this regimen, 6 courses of R-CHOP consist of
1.2-2.5 fold cumulative doses of cyclophosphamide (4.5
grams/m2), Hydroxydaunorubicin (300 mg/m2), Vincristine
(12 mg).
Conclusions: In AYA with non-advanced DLBCL, pediatric
chemotherapy regimen provides an alternative to R-CHOP,
eliminates the use of radiation therapy and provides lower
cumulative Anthracyline and alkylating doses. Pediatric regimen may reduce risk of long term cardiac and second cancer
effects.
1 Izmir
Tepecik Research and Training Hospital, Pediatric Hematology and
Oncology, Izmir, Turkey; 2 Ege University Faculty of Medicine, Department
of Radiation Oncology, İzmir, Turkey
Background/Objectives: Childhood Hodgkin lymphoma(HL) is a type of cancer of the lymphoid system.According to the Turkish Pediatric Oncology
Group(TPOG) statistics lymphomas are the most common solid tumors of childhood(26,8%) and 9.9% of them
are Hodgkin lymphomas.With current chemotherapy and
radiotherapy regimens,most of the children with HL survive.
In this study,our aim is to evaluate the clinical characteristics
and treatment outcome of HL cases treated in our institution.
Design/Methods: We evaluated the recordings of the
patients with HL treated between 1987-2016 retrospectively.Demographic and clinical features,treatment
results,overall survival(OS) and event free survival(EFS)
rates were evaluated.
Results: 104 patients were eligible out of 133 patients(F/M=
27 /77).The mean age was 9.5±3.7 years.Most common
complaint was lump in the neck(n=82).B symptoms were
present in 42.3%(n:44).Most common B symptom was found
to be fever.Histopathologic diagnosis revealed 65.3% mixed
cellularity,19.2% nodular sclerosis.Stage distribution was
as follows:Stage-1 in 14.4%,Stage-2 in 46.1%,Stage-3 in
19.2%, Stage-4 in 20.1%.In stage 4 patients,most common
metastatic site was lung(n:12).Fifty-eight patients were
treated according to the GPOH 90/95 protocol,remaining
patients were treated with other regimens(ABVD(n:10),
MOPP/ABVD(n:25),MOPP(n:8),COPP(n:3)).Radiotherapy
was performed to the primary tumor site in 91 cases.Relapse
occurred in 16 patients,most of them were treated with
MOPLACE(n:7) chemotherapy.Remission was achieved
in 3 patients,10 patients died because of disease progression,3 patients refused treatment.Median follow-up-time
was 10 years(1 month-30 years).5-years EFS and OS
were 76%,86% respectively.Between GPOH 90/95 and
ABVD,MOPP/ABVD treatment groups no significant
difference was found in survival(p=0,882) and relapse
rates(p=0,047).
Conclusions: When our results were compared with the literature,it was seen that the most common type is mixed cellularity in accordance with the previous reports.In1970's 5-years
OS was 81%,in 2002 5-years OS increased to 90%.Our survival rates were lower than original protocols.It was thought
that it might be due to the fact that most patients in the study
belonged to the era before 90’s lowering the overall OS and
EFS.
SIOP ABSTRACTS
S204 of S518
P-081 Presentation of Burkutt's Lymphoma in a
Tertiary Hospital in Ghana
M. Barnabas1 , V. Paintsi2
1 komfo
Anokye Teaching Hospital, Cild Health Directorate, Kumasi,
Ghana; 2 komfo Anokye Teaching Hospital, Child Health Directorate,
Kumasi, Ghana
Background / Objectives Burkett's lymphoma (BL) is the
most frequent subtype of Non-Hodgkin's lymphoma seen in
childhood in sub-Sahara Africa. BL is highly aggressive with
a doubling time of approximately 24 hours. It responds favorably if diagnosed accurately and treated early. Prompt recognition and initiation of therapy are essential for improved survival. This study seeks to review the clinical presentation and
imaging findings of patents’ with Burkett's lymphoma in the
pediatric population
Design/Methods: This was a hospital-based retrospective
study which reviewed all the clinical and histopathological
records of patients with Burkett's Lymphoma at the paediatric
cancer unit - Komfo Anokye Teaching Hospital from January
2016 to December, 2016.
Results: There were 35 children diagnosed, with male to
female ratio of 3:2. The median age was 8years (Range;
2years-15years).The maximum duration of symptoms was
4 weeks. The commonest symptom was swelling with
the majority sites involved being abdomen 42.9%, jaw
25.7%, combined jaw and abdomen (14.2%) and other
body sites (17%). Other presenting symptoms include fever
(25.7%), weight loss 6(17.14%), proptosis 3(8.57%), night
sweats 2(5.7%), anaemia 1(2.85%) and difficulty in breathing
1(2.85%). Stage III was the commonest stage seen at presentation in 13(37.14%) of the patients and those with stage IV
were 5(14.3%), been the rarest. Stage I was 10(28.3%), whilst
stage II was seen in 7(28%). Intent of treatment was 71.4%
of patients for palliation and 28.6% of the patient's curative
intent.
Conclusions: Although Burkett's lymphoma is relatively
cheap and easy to treat as compared to the other cancers, most
of the patients presented with advanced disease impacting on
the survival. Increased education on early warning signs for
parents and healthcare personnel needs to be undertaken to
reduce advanced disease at presentation.
Background/Objectives: Follicular lymphoma (FL) is rare
to occur in children. Its pediatric variant (pFL) had been
recently included in the updated WHO classification of lymphoid malignancies (2016). Patients usually present with a
low stage disease, that is t(14,18) and BCL2 negative.
Design/Methods: Retrospective analysis of the cases diagnosed with FL presented to our cancer center during the
period between July 2007 to December 2016.
Results: Over a period of 9 years, 3 patients were diagnosed
with FL at our cancer center. All patients were males, presented with stage II disease, morphologically grade 3a. The
first case: 7 years old male who presented with cervical lymphadenopathy and B symptoms. Tumor was CD20, BCL6
positive, CD3, BCL2 negative, MIB-1 (80%). He received RCHOP (Rituximab immunotherapy plus cyclophosphamide,
doxorubicin, vincristine and prednisone) and is under follow
up from July 2011 till now. The second case: An 8 years old
male who had atypical lymphoid hyperplasia diagnosed 1 year
prior to the diagnosis of FL in April 2014. Tumor was positive
to CD20 and BCL6 and negative BCL2 with low expression
of Ki-67. He received R-CHOP chemotherapy and involved
field radiotherapy (IFRT) in addition and placed under follow
up since April 2015. The third case: An 12 years old male presented with bilateral cervical and parotid lymph node enlargement. Biopsy showed positive reaction to CD20 in the neoplastic cells. BCL2 diffusely highlighted the neoplastic cells.
BCL6 and CD10 were positive. Ki67 labeling index was high
(60%). He received R-CHOP chemotherapy and is currently
under follow up since June 2014.
Conclusions: Patients with pFL presented to our center had
localized disease, responded well to chemotherapy and had
durable complete remission. Trial of less intensive chemotherapy, omission of radiotherapy and inclusion of new agents
as Bendamustine with Rituximab based therapy should be
attempted to minimize the late effects.
P-083 Hodgkin Lyphoma in Children: A Single
Center Experience in Turkey
N. Eker1 , G. Tokuc1 , B. Yılmaz1 , E. Senay1 , B. Berk1 , O. Dogru1
1 Marmara
University, Pediatric Hematology and Oncology, Istanbul,
Turkey
P-082 Clinical Characteristics and Outcome of
Pediatric-Type Follicular Lymphoma: Report from
a Pediatric Cancer Center in a Developing Country
S. Eissa1 , S. Semary1 , A. Salama2 , A. Elhaddad1
1 Children's
Cancer Hospital-Egypt, Pediatric HematIology/Oncology,
Cairo, Egypt; 2 National Cancer Institute - Egypt, Pathology Department,
Cairo, Egypt
Background/Objectives: Hodgkin Lymphoma (HL) is one
of the most frequent cancers in adolescent and young adults
and is curable in more than 90% of cases. The aim of this
study was to assess the demographic, clinic data, prognostic
factors and treatment/follow-up results of children who were
diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Marmara University Medical Faculty, Istanbul, Turkey, for 20 years.
SIOP ABSTRACTS
Design/Methods: Children with HL who were diagnosed and
treated at our center between 1996 and 2016 were retrospectively analyzed.
Results: A total of 87 children with a mean age of 9,5±3,9
years were treated for HL. Fifty-eight patients (67%) were
males and 29 (33%) were females. Among them, 52% presented with advanced-stage (stages III and IV) disease, 39 %
had B symptoms, and 50,6% had mixed cellularity type of
HL. Multiagent chemotherapy was the mainstay of treatment.
All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) or COPPABV (Cyclophoshamide, Vincristine, Procarbazine, Prednisone, Adriamycin, Bleomycin, Vinblastine) chemotherapy
and also received involved field radiotherapy. During th follow
up ten patients had relapsed. The 5-year overall survival rate
was 87%, respectively. Stage, treatment risk groups, presence
of B symptoms and histopathologic subtype had no significant
effect on overall survival in univariate analysis while relapsed
disease was the only significant factor on overall survival.
Conclusions: Hodgkin lymphoma can be cured with
chemotherapy combined with low dose IFRT however
relapsed disease is still the significant factor on overall
survival.
P-084 Venous Thromboembolism in Childhood
Cancer: Hodgkin Lymphoma is a High-Risk
Diagnosis
N. El-Haj1 , B. Lau1 , J. Friderici2 , J. Luty3 , M. Richardson3 , S.
Grewal3
1 Baystate
Medical Center, Internal Medicine and Pediatrics, Springfield,
USA; 2 Baystate Medical Center, Biostatics and Epidemiology, Springfield,
USA; 3 Baystate Medical Center- D'Amour Center for Cancer Care,
Pediatric Hematology-Oncology, Springfield, USA
Background/Objectives: Venous thromboembolism (VTE)
is understudied in pediatric cancer patients. This study evaluates risk of VTE in children with cancer and identifies highrisk diagnostic groups.
Design/Methods: This single center retrospective cohort
study included patients under 21 years old diagnosed with
cancer between 1/01/2007-6/30/2016 and followed from date
of diagnosis to date of VTE, age 21, or end of study, whichever
occurred first. The institution's Tumor Registry captured a
primary diagnosis of cancer and a secondary diagnosis of
VTE was extracted using ICD codes. Patients were excluded if
they were under the care of adult providers or sub-specialists,
had insufficient documentation, or were inaccurately identified. For patients diagnosed with HL, demographic, treatment
and disease-related variables were obtained by manual chart
review.
S205 of S518
Results: The study included 181 patients split into 3 groups:
HL (n=18), ALL +T-Non-Hodgkin lymphoma (T-NHL)
(n=51), and other cancers (n=112). VTE was diagnosed in 10
patients (6%). VTE occurred among 27.8% of HL patients;
5.9% of ALL/T-NHL patients; and 1.8% of other cancer
patients; corresponding hazard ratios: HL vs. ALL/T-NHL
5.1 (95% CI 1.21, 21.3); HL vs. other cancers 17.2 (95% CI
3.3, 88.7). Patients with HL only developed VTE in major
upper body veins. Median time from HL diagnosis to VTE
was 52 days (29 to 245 days), and all VTE incidents occurred
prior to radiation. Within our cohort of patients with HL and
VTE, 60% received chemotherapy per GPOH-HD95 regimen.
Both patients with refractory HL who proceeded with autologous bone marrow transplant had prior VTE during first line
therapy for HL. All patients with HL and VTE had a negative
family history, and thrombophilia workup performed in 3/5
patients was unremarkable.
Conclusions: In our cohort, HL represented a high-risk group
for VTE. If a larger cohort confirms these results, these children may be candidates for prophylactic anticoagulation during initial treatment.
P-085 Clinical Characteristics and Outcome of
Children and Adolescents with Anaplastic
Large-Cell Lymphoma in China: A Retrospective
Study from the Chinese Children's Cancer Group
Y.J. Gao1 , M. Xie2 , H. Jiang3 , X. Guo4 , J. Yan5 , A.G. Liu6 , J. Lu7 ,
X.L. Ju8 , X.J. Yuan9 , R.M. Jin10 , J.Y. Tang1
1 Shanghai
Children's Medical Center, Department of Hematology and
Oncology, Shanghai, China; 2 Xiangya Hospital- Central South University,
Department of Pediatric Hematology & Oncology, Changsha, China;
3 Children's Hospital of Shanghai, Department of Hematology & Oncology,
Shanghai, China; 4 West China Second University Hospital of Sichuan
University, Department of Pediatric Hematology & Oncology, Chengdu,
China; 5 Tianjin Medical University Cancer Institute & Hospital,
Department of Pediatric Oncology, Tianjin, China; 6 Tongji Hospital- Tongji
Medical College- Huazhong University of Science & Technology,
Department of Pediatric Hematology & Oncology, Wuhan, China;
7 Children's Hospital of Soochow University, Department of Hematology &
Oncology, Soochow, China; 8 Qilu Hospital of Shandong University,
Department of Pediatric Hematology & Oncology, Jinan, China; 9 Xinhua
Hospital, Department of Pediatric Hematology & Oncology, Shanghai,
China; 10 Wuhan Union Hospital, Department of Pediatric Hematology &
Oncology, Wuhan, China
Background/Objectives: To provide a description review
and improve our understanding of the clinical characteristics and outcome of pediatric anaplastic large cell lymphoma
(ALCL) in China. And the results can serve as baseline data
to guide our future therapeutic protocol development.
Design/Methods: We retrospectively evaluated clinical characteristics and outcomes of 80 children (≤16 years) with
newly histopathologically-confirmed ALCL (52 boys, 28
SIOP ABSTRACTS
S206 of S518
girls) treated by ten large single institutions in China between
January 2009 and June 2014.
imaging and clinic letters were analysed, with residual disease
categorised according to formal radiology reports.
Results: Two patients (3%) had Stage I disease, 9 (11%) had
Stage II, 64 (80 %) had Stage III, and 5 (6%) had Stage
IV. Phenotyping demonstrated a predominance of T-cell phenotype in 72.5% of cases (58/80). Sixty-five patients (81%)
were treated with the CCCG-BNHL-2010 regimen (a Chinese national-wide protocol for pediatric ALCL) and 15 cases
(19%) treated with other regimens. At a median follow-up of
25.2 months (range, 7.1-74.8 months), the 3-year of eventfree survival (EFS) was 65%±6% in all patients. The 3-year
EFS was 57%±7% and 78%±11% for patients with or without B symptoms, respectively (P=0.01). Twenty-four patients
experienced disease progression or relapse. The median time
from initial diagnosis to tumor failure was 7.0 months (ranged,
1.5 -42.6 months). At the last evaluation, there were 5 patients
still alive after disease progression and relapse.
Results: 27 children aged 1 to 11 years were diagnosed with
BNHL; 23 males (85%) and 4 females (15%). 7 children had
bone marrow positivity (26%), and 4 children CNS positivity (15%). 17 children (63%) were MYC positive. 20 children
(74%) received group B treatment, and 7 (26%) group C treatment. 5 children (18%) demonstrated poor response to COP
chemotherapy and were escalated to group C.
Conclusions: The presenting features and outcome of children and adolescents with ALCL in this study were similar
to those reported by other countries. Establishment of therapeutic strategies to improve survival for patients with disease
progression or relapse should be the priority in our future clinical study.
P-086 B Cell Non-Hodgkins Lymphoma (BNHL)
and Residual Disease on Scan at Disease Assessment
in Children Under 12
K. Green1 , D. Cheng2
1 Great
Ormond Street Hospital for Children, Oncology, London, United
Kingdom; 2 Great Ormond Street Hospital for Children, Haematology,
London, United Kingdom
Background/Objectives: Children with BNHL have good
outcomes with intensive upfront chemotherapy. Disease
relapse or progression is associated with very poor outcome.
Early disease assessment and escalation of chemotherapy is
necessary when there is no clear radiological early-treatment
response. The value of post-treatment imaging surveillance
and biopsy of residual imaging abnormalities in detecting and
preventing disease relapse/progression is unclear.
We evaluated whether our patients with BNHL with residual
radiological abnormalities received follow-up imaging and
biopsies, and how these investigations affected clinical outcomes.
Design/Methods: Retrospective data of all children diagnosed with BNHL between 2012-2017 at a UK tertiary paediatric oncology centre was collected. Patient age at diagnosis, gender, histology, MYC status, and bone marrow or CNS
involvement were recorded. Chemotherapy regimes were
recorded, including escalation from Group B to C. Follow-up
At end of treatment, 5 children (19%) had “no residual disease”, and 15 children (55%) “almost certainly had no residual
disease”. 6 children (22%) had abnormal findings; 4 underwent biopsy to exclude active disease. None of the children
undergoing follow up imaging demonstrated disease relapse.
One child died during treatment without achieving remission.
Conclusions: None of our patients with residual imaging
abnormalities at treatment completion had disease relapse or
progression, questioning the clinical need for long term imaging, particularly if involving radiation. Biopsy provided reassurance without altering patient management.
P-087 Risk Factors for Relapse in Children with
Hodgkin Lymphoma Treated with Chemotherapy
Alone Protocols
V. Gupta1 , R. Sonowal1 , T.B. Singh2 , S.K. Gupta3
1 Institute
of Medical Sciences- Banaras Hindu University, Pediatrics,
Varanasi, India; 2 Institute of Medical Sciences- Banaras Hindu University,
Statistics, Varanasi, India; 3 Institute of Medical Sciences- Banaras Hindu
University, Surgery, Varanasi, India
Background/Objectives: Hodgkin lymphoma displays characteristic epidemiological, clinical and pathological features
in different geographical areas. Objective was to analyze
demographic profile, disease characteristics, event free survival (EFS), overall survival (OS) and risk factors for
relapse in patients with Hodgkin lymphoma (HL) treated with
chemotherapy only protocols.
Design/Methods: Retrospective observational study was carried out in a university teaching hospital. Children below the
age of 15 years diagnosed with Hodgkin lymphoma between
Jan 2005 to Dec 2014 were included in the study.
Results: 90 patients with mean age of 8.13 ± 2.65 years
(median age 8 years; range 4.5-15 years) were diagnosed
and treated for HL during study period. Male to female ratio
was 7.2:1. 12.2% and 87.8% patients had early and advanced
stage disease respectively. B symptoms were present in 87.8%
patients. Mean duration of symptoms was 9.66 ± 6.30 months
(median 8 months; range 2-36 months). Mixed cellularity was
commonest histologic type. Overall survival (OS) and event
free survival (EFS) was 88.8% and 84.5% respectively. OS
in early stage and advanced stage disease was 90.0% and
SIOP ABSTRACTS
89.0% respectively. In patients with or without bulky disease
it was 53.3% and 92.2%. The EFS in early stage and advanced
stage disease was 90.0% and 83.8% respectively. It was 59.3%
for patients with bulky disease and 86.5% for those without bulky disease. Older age (≥10 years), bulky disease, low
hemoglobin (≤7.0 g/dl), high leucocyte count (≥12000/mm3 )
at the time of diagnosis and protocol used (COPP) were risk
factors for relapse.
Conclusions: Our patient population had younger age,
advanced disease, more B symptoms and bulky disease. Still,
we achieved good OS and EFS with chemotherapy alone protocols. Patients with bulky disease had poor overall and event
free survival. If radiotherapy is included in the protocol for
bulky disease, the survival rates can be improved further.
P-088 Treatment of Paediatric Hodgkins
Lymphoma- An Experience from a Paediatric
Tertiary Centre
Y. Gupta1 , D. Hobin1
1 Birmingham
Children's Hospital, Pediatric Oncology, Birmingham, United
Kingdom
Background/Objectives: We present a retrospective analysis
of 39 pediatric patients with HL who received treatment at our
center over a period of 4 years from 2013 to 2016 and aim to
study the response to chemotherapy in pediatric patients with
HL.
Design/Methods: Patients diagnosed with HL were divided
into 3 treatment groups depending on the stage of disease (1).
The patients in group 1 received 2 cycles of vincristine, etoposide, prednisolone, doxorubicin (OEPA), group 2 received 2
cycles of OEPA and 2 cycles of either cyclophosphamide, vincristine, prednisolone, dacarbazine (COPDAC) and group 3
received 2 cycles of OEPA and 4 cycles of COPDAC. Patients
with inadequate response received radiotherapy. Early PET
response to treatment was analyzed.
Results: Of the 39 patients, 21 were in group 1, 4 in group 2
and 14 in group 3.
Of the 21 (53.8%) patients in group1, Complete metabolic
response (CMR) was seen in 16 (76.1%) and partial response
in 2 (9%) patients PET was not done in 3(%). 3 (14.2%)
patients had a relapse. There were no deaths. Event free survival (EFS) and Overall survival (OS) for group 1 patients was
85.7% and 100%
Of the 4(10.2%) patients in group 2, CMR was seen in 4
(100%) patients. 1(25%) patients had a relapse. EFS and OS
for group 2 patients was 75% and 100%.
Of 14(35.9%) patients in group 3, CMR was seen in 13(92.8%)
patients and partial response in 1 (7.1%) patients. 1 (7.1%)
S207 of S518
patients had a relapse. EFS and OS for group 3 patients was
92.8% and 100% respectively.
Conclusions: EFS for all patients treated for HL is 84.5% and
overall survival is 100%. This study emphasizes the excellent
outcome for pediatric HL to treatment. However, a study with
a larger cohort of patients who are followed up for a longer
time is required.
P-089 Retrospective Analysis of Outcomes to
Different Chemotherapy Regimens in Pediatric
Hodgkins Lymphoma
Y. gupta1 , D. Hobin1
1 Birmingham
Children's Hospital, paediatric oncology, Birmingham,
United Kingdom
Background/Objectives: Retrospective analysis of 81 pediatric patients with Hodgkins Lymphoma who received treatment over a period of 10 years from 2006 to 2016 and study
the response to different chemotherapy regimens and hence
identify the regimens with best outcomes.
Design/Methods: Patients with HL were divided into 3 treatment groups depending on the stage. The patients in group
1 received 2 cycles of vincristine, etoposide, prednisolone,
doxorubicin (OEPA) or 3 cycles of cyclophosphamide, vincristine, prednisolone (CVP), group 2 received 2 cycles each
of OEPA and either cyclophosphamide, vincristine, prednisolone, dacarbazine (COPDAC) or cyclophosphamide, vincristine, procarbazine, prednisolone (COPP) or cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) and
group 3 received 2 cycles of OEPA and 4 cycles of COPDAC
or COPP.
Results: Of the 25 patients in group1, 21 patients treated with
2 cycles of OEPA 3 relapsed (EFS and OS, 85.7% and 100%)
and 4 with 3 cycles of CVP, 2 relapsed (EFS and OS, 50% and
100%).
Of the 11 patients in group 2, 4 treated with 2 cycles each
of OEPA and COPDAC, 1 relapsed (EFS and OS, 75% and
100%), 4 treated with 2 cycles of OEPA and 2 cycles of
COPP (100 % EFS and OS), 3 treated with 2 cycles each
of OEPA and CHOP, 1 relapsed and 1 died (EFS and OS
6.6%).
Of 45 patients in group 3, 14 treated with 2 cycles of
OEPA and 4 cycles of COPDAC, 1 relapsed (EFS and OS,
92.8% and 100%), 31 treated with 2 cycles of OEPA and 4
cycles of COPP, 6 relapsed, 4 died (EFS and OS, 80.6% and
87%).
Conclusions: For group 1 patients treatment with OEPA x2
chemotherapy, group 2 patients OEPA X 2, COPP X2, and
for group 3 patients OEPA X 2, COPDAC X 4 have shown to
have a better outcome.
SIOP ABSTRACTS
S208 of S518
P-090 Evaluation of Musculoskeletal Complaints
and Skeletal Involvements in Children with Newly
Diagnosed Lymphoma and Solid Tumors
D. Ince1 , M. Erdem1 , F. Yenigurbuz1 , D. Kizmazoglu1 , E.
Ataseven1 , H. Guleryuz2 , K. Mutafoglu1 , and N. Olgun1
1 Dokuz
Eylul University Institute of Oncology, Dept. of Pediatric Oncology,
Izmir, Turkey; 2 Dokuz Eylul University Faculty of Medicine, Dept. of
Radiodiagnostics, Izmir, Turkey
Background/Objectives: To evaluate patients who had musculoskeletal complaints at admission and/or skeletal involvement at diagnosis in our center.
Design/Methods: Medical records of whole patients with
diagnosis of lymphoma and solid tumors were analyzed retrospectively. Patients who admitted with musculoskeletal
complaints and who had skeletal involvement at diagnosis
were selected for analysis. Patient characteristics, complaints,
skeletal involvement sites, misdiagnoses, differantial diagnosis diffuculities were analyzed.
Results: There was 1061 patients with diagnosis of lymphoma and solid tumor in our clinic between 1988-2016.
One hundred ninetyfour of them admitted with musculoskeletal system complaints and/or skeletal involvement at diagnosis. The median age at diagnosis for these 194 patients
was 9yrs(4mos-17.8yrs), M/F:1.3. The median duration of
complaints was 2mos (1day-2yrs). Before definitive diagnosis was done, patients had been admitted mean 2 times (1-6)
to doctors. Oncologic diagnosis were as follows Ewing sarcoma 21.6%, LHH 15.5%, neuroblastoma 14.5%, osteosarcoma 13.9%, lymphoma 11.4%, rhabdomyosarcoma 8.2%.
Misdiagnosises were as follows artiritis 8%(n:16), artralgia
3%(n:5), myalgia 6%(n:11), muscle spasm 3%(n:5), lymphadenitis 5%(n:10), growth pain 2%(n:4), JRA 3%(n:6),
osteomyelitis 2%(n:4), bone edema 1%(n:2), ARF 2%(n:4),
trauma 7%(n:14), avascular necrosis 0.5%(n:1), FMF 1%(n:2),
scoliosis 0.5%(n:1). Dominant complaints: skeletal63%,
constituonal26%, others: pain64%, swelling42%, walking
impairement31%, fever20%, weight loss26%, night sweating9%, anorexia19%, weakness28%. Skeletal system pain:
articular16%, nonarticular25%, artricular+nonarticular21%.
Other symptoms: Headache3%, neckache4%, backache11%,
extremity pain38%, leg weakness12%, sensory impairment5%, sphincter disfunction5%, spinal cord compression8%. Physical examination: artritis10%, artralgia32%,
nonartricular bone sensitiveness19%, rash %4, petechia0.5%,
ecchymosis1%, hepatomegaly8%, splenomegaly4%, lymphadenopaty20%. Blasts in peripheral blood smear1.5%, bone
marrow aspiration13%, blood count cytopenia20%, ESR36%,
LDH >500U/L 25%, CRP >5mg/dl 27%, ANA(+)0.5%.
Abnormal findings on: graphy44%, BT46%, MRI39%, bone
sintigraphy50%.
Conclusions: Musculoskeletal complaints and rheumatic
diagnoses with atypical clinical features should be reevaluated because of possible underlying malignancy. Suspicion of
malignancy must be ruled out by simple investigations. Medical history, through physical examination, laboratory, radiological evaluations are important for diagnosis.
P-091 Hodgkin's Lymphoma in Paediatric
Population: Analysis of Short Term Outcomes with
ABVD and Non ABVD Based Treatment Protocols
N. Jadhav1 , B. Dubashi1 , S. Kayal1 , P. Madasamy1 , J. Pattnaik1 , J.
Singh1 , M. Paramanandhan1 , E. Jafa1
1 Jawaharlal
Institute of Post graduate Medical Education and Research,
Medical Oncology, PONDICHERRY, India
Background/Objectives: Hodgkin's Lymphoma is one of the
success stories in modern oncology. Cure rates as high as 90%
are possible with the current modalities of treatment. ABVD
has established itself as standard of care in adults. Contrary,
there is no standard of care for paediatric Hodgkin's. Also
there is no randomized trial comparing ABVD verses non
ABVD regimens.
Design/Methods: Consecutive patients diagnosed with
Hodgkin's lymphoma, treated at Regional Cancer Center
JIPMER were analyzed retrospectively. Data was retrieved
from the records section and patients were analyzed for
clinical profile and outcomes with ABVD and non ABVD
based treatment protocols.
Results: A total of 47 patients were registered from October
2009 till January 2017. Median age of presentation was 12
years with male to female ratio of 3.27. Most common presenting complain was neck mass, seen in 63.82% of patients.
Median symptom duration was 12 months prior to first contact with an Oncologist. B symptoms were seen in 44.68%
of patients and bulky disease in 42.55%. Extra-nodal involvement was seen in 12.76% of patients. 53.19% patients presented in early stage with 60% being early stage unfavorable.
Most common histology was classical Hodgkin's mixed cellularity (55.31%) with 86.95% and 58.69% positivity for CD30
and PAX5. 57.44% patients were treated with ABVD and
23.4% with non-ABVD protocols. 42.55% patients received
RT, 45% each for bulky disease and as a part of combined
modality treatment. Toxicity was seen in 42.55% of patients
with febrile neutropenia in 21.27% and bleomycin lung in
11.76%. Overall till date 76.56% of patients on regular follow
up are in CR
Conclusions: Outcomes for pediatric Hodgkin's are promising despite late presentation to an Oncologist in our setup.
Response rates with ABVD and non ABVD regimens are
comparable but associated with different toxicities.
SIOP ABSTRACTS
P-092 Burkitt Lymhoma in a Boy with Cryptogeneic Cirrhosis: What is the Best Way to Treat?
Z. Karakas1 , D. Tugcu1 , A. Karagenc1 , S. Cantez2 , P. Odalı1 , G.
Atay3 , S. Hancerli4 , S. Karaman1
1 Istanbul
University - Istanbul Medical Faculty, Pediatric
Hematology/Oncology, Istanbul, Turkey; 2 Istanbul University - Istanbul
Medical Faculty, Pediatric Gastroenterology, Istanbul, Turkey; 3 Istanbul
University - Istanbul Medical Faculty, Pediatric Intensive Care, Istanbul,
Turkey; 4 Istanbul University - Istanbul Medical Faculty, Pediatric Infection,
Istanbul, Turkey
Background/Objectives: To describe an uncommon
occurence of Burkitt lymphoma in a boy with cryptogeneic
cirrhosis and discuss the treatment of lymphoma in the
presence of liver failure.
Design/Methods: A fifteen-year-old-boy was first referred for
a cervical mass.Medical history revealed that he has been
under regular follow-up with the diagnosis of idiopathic cirrhosis for about 9 years.The pathologic diagnosis was Burkitt
lymphoma(BL).He was evaluated as stage II and BFM NHL
2012 study protocol was began.
Results: Hepatic failure developed after full dose prophase
and two days 50% reduced AA block, and chemotherapy could not be continued. On 14 th day,he was transferred to Pediatric Intensive Care Unıt due to hepatic and
respiratory failure,massive ascites with diagnoses of sinusoidal obstruction syndrome,and sepsis.Klebsiella Pneumoniae was detected in hemoculture. After an effective treatment, he was re-transferred to our clinic on 28 th day
of therapy.Considering life threatening complications even
after reduced dose chemotherapy,he was discussed at local
tumor council and decided to continue with single six rituximab therapy.Complete remission was achieved just after
the first course of rituximab. After the first cure,liver functions impaired and next rituximab could be given one month
later.He is still in remission for BL with stable signs of chronic
liver failure.He is a candidate for liver transplantation. He had
alive donor for liver transplantation. The liver transplant council decided to follow up until the end of chemotherapy because
the patient was stable.
Conclusions: Burkitt lymphoma is very chemo-sensitive
tumor with successful results with chemotherapy. But as
in our case,in the presence of comcomitant liver failure,
treatment of this well-known tumor could be very difficult.
Targeted therapies might be an effective alternative instead
of conventional treatment protocols in such extraordinary
presentations.
P-093 Evaluation of Metabolic Tumor Volum and
Total Lesion Glicolysis in Pediatric Hodgkn
Lymphomas at Diagnosis and After 4
Chemotherapy Courses
S209 of S518
D. Massano1 , E. Carraro1 , M.P. Boaro1 , M.S. Buzzaccarini2 , G.
Scarzello2 , A. Zanella3 , G. Basso1 , M. Pillon1 , P. Zucchetta3
1 University
Hospital of Padua, Pediatric Onco-Hematology Unit, Padua,
Italy; 2 IOV Istituto Oncologico Veneto, Nuclear Medicine and Radiation
Therapy Unit, Padua, Italy; 3 University Hospital of Padua, Nuclear
Medicine Department, Padua, Italy
Background/Objectives: Recent studies demonstrated how
qualitative and semi-quantitative measures, obtained with ad
interim evaluation with positron emission tomography (PET),
could predict the clinical response in patients with Hodgkin
Lymphoma (HL). The aim of our study was to evaluate some
semi-quantitative PET measures to predict the response in
pediatric patients with HL.
Design/Methods: We measured the Standard Uptake Value
(SUV)-max, SUV-peak, Metabolic Tumor Volume (MTV)
and Total Lesion Glicolysis (TLG) in the PET imagings obtained at staging and after 4 chemotherapy courses
COPP/ABV or ABVD. Patients were treated according to
the AIOEP-LH-2004 protocol. Patients were defined good
responders (GR) if they were in complete remission (CR)
at the end of follow-up, otherwise they were defined as noresponders (NR). Statistical analysis was performed with the
Mann-Whitney test.
Results: Ninety-four PET datasets of 47 children were analyzed. Mean follow-up was 44 months. At the end of the
follow-up 41 patients were in CR and only 6 were NR. All
relapsed patients, or refractory to the first line therapy, suffered of Nodular Sclerosis HL stage III or IV.
The PET imagings done at diagnosis showed a higher burden
of disease in NR patients compared to GR patients: MTV (223
vs. 127, p =0.03) and TLG (891 vs. 614, p=0.04). Also SUVmax and SUV-peak were higher but without statistical significance. After 4 chemotherapy courses only TLG remain higher
in PR group (9.3 vs. 5.1, p=0.04) while MTV was slightly
higher in GR group (1.7 vs. 1.6, p=0.04).
Conclusions: The MTV and TLG are two semi-quantitative
parameters that could predict the clinical response in patients
with HL. A larger cohort study is needed to confirm these preliminaries data.
P-094 Factors Associated with Time to Diagnosis
of Childhood and Adolescent Non-Hodgkin
Lymphoma in Peru
M. Oscanoa1
1 hospital
Nacional Edgardo Rebagliati, Oncology, Lima, Peru
Background/Objectives: Time to diagnosis (TD) or “lag
time” is the time between a patient's first symptom recognition
to a diagnosis of cancer. Delayed TD allows tumor progression and poor outcome in Non-Hodgkin Lymphoma (NHL)
in some studies, although it remains controversial.
SIOP ABSTRACTS
S210 of S518
Objectives
The aim of this study was to define clinical and sociodemographic factors associated to TD, which includes “Parents delay” (PD) and “Medical delay” (MD) in children and
adolescents diagnosed with NHL in Lima, Peru.
Design/Methods: A total of 46 patients younger than 18 years
of age diagnosed with NHL between January 2012 and October 2016 were retrospectively evaluated. Clinical and demographic variables such as type of diagnosis, clinical stage,
sex, age and parental characteristics were analyzed to evaluate
their effects on TD, PD and MD.
Results: Forty-six patients were included in the study. The
median age was 10 years (range 3-17) and 68.5% were
male. Histological subtypes were mature B-cell NHL in
40%, lymphoblastic NHL in 31.4%, T/NK lymphoma in
14.3%, anaplastic large cell lymphoma in 5.7% and hydroavacciniforme-like lymphoma in 5.7%. Stage III and IV tumors
were seen in 77.2% of cases. The TD ranged between 2 weeks
and 17.5 months (median, 8 weeks), with a median of PD and
MD of 2 and 6 weeks, respectively. Among histological subtype, we could not found significant differences in TD. Age,
parental age or level of education, metastatic disease, clinical
stage and sex did not affect significantly TD.
Conclusions: In our country, median TD was comparable to
described in developing countries, where index of suspicion
of childhood cancer remains low. It is necessary to establish
strategies for optimizing early diagnosis based on associated
factors.
P-095 Epigenetic Silencing of the Tumor
Suppressor Genes SPI1, PRDX2, KLF4, DLEC1,
and DAPK1 in Childhood and Adolescent
Lymphomas*
F.G. Pinarli1 , F. Alpaslan Pinarli2 , I. Ozdemir3 , A. Okur1 , P. Uyar
Gocun4 , N. Baran Aksakal5 , C. Karadeniz1
1 Gazi
University Medical Faculty, Pediatric Oncology, Ankara, Turkey;
Yildirim Beyazit Research Hospital, Medical Genetics, Ankara,
Turkey; 3 Gazi University Medical Faculty, Pediatrics, Ankara, Turkey;
4 Gazi University Medical Faculty, Pathology, Ankara, Turkey; 5 Gazi
University Medical Faculty, Public Health, Ankara, Turkey
2 Diskapi
Background/Objectives: The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and
adolescent lymphomas.
Design/Methods: A total of 96 patients with Hodgkin Lymphoma (HL, n=41), Non-Hodgkin Lymphoma (NHL, n=15),
and reactive lymph node proliferation (n=40, as controls) who
were followed-up between the years 2000-2015 at the Department of Pediatric Oncology are included in the research.
The expression status of CDKN2A, SPI1, PRDX2, DLEC1,
FOXO1, KLF4 and DAPK1 genes were measured with QPCR
method after the RNA isolation from paraffin blocks of tumor
tissue and cDNA conversion. DNA isolation was performed
from samples with low gene expression followed by methylation PCR study specific to promotor regions of these genes in
order to investigate the methylation patterns.
Results: We found that SPI1, PRDX2, KLF4, DLEC1 and
DAPK1 genes are significantly less expressed in the patients
than the control group (p=0.0001). However, expression of
CDKNA2 and FOXO1 genes in the patient and control groups
were not statistically different. The methylation ratios of
all genes excluding the CDKN2A and FOXO1 were significantly higher in the HL and NHL groups than the controls
(p=0.0001).
Conclusions: We showed that SPI1, PRDX2, DLEC1, KLF4
and DAPK1 genes are epigenetically silenced via hypermethylation in the tumor tissue samples of children with HL
and NHL. Due to our finding that CDKN2A gene was not
expressed in both of the patient and control groups, we concluded that it is not specific to malignancy. As FOXO1 gene
was similarly expressed in both of the patient and control
groups, its relation with malignancy could neither be found.
Future studies may show if these genes will be candidates for
biomarkers or therapeutic targets in childhood and adolescent
lymphomas.
*This study has been supported by a research grant of Turkish
Pediatric Oncology Group (TPOG)
P-096 Expert Consensus for Waldeyer's Ring
Involvement in Pediatric Hodgkin Lymphoma
J. Seelisch1 , J. Flerlage2 , K. Kelly3 , L. Kurch4 , C. Mauz-Koerholz5 ,
K. McCarten6 , M. Metzger2 , S. Voss7 , A. Punnett1
1 The
Hospital for Sick Children, Hematology/Oncology, Toronto, Canada;
Jude Children's Research Hospital, Oncology, Memphis, USA;
3 Roswell Park Cancer Institute, Hematology/Oncology, Buffalo, USA;
4 University Hospital of Leipzig, Nuclear Medicine, Leipzig, Germany;
5 Martin-Luther-University Medical Center, Hematology/Oncology, Halle,
Germany; 6 Hasbro Children's Hospital, Pediatric Radiology, Providence,
USA; 7 Boston Children's Hospital, Radiology, Boston, USA
2 St.
Background/Objectives: Waldeyer's Ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is a rare phenomenon of unclear definition. International pediatric HL
specialists formed the WR working group of CAYAHL
(Childhood, Adolescent, Young Adult HL). Existing literature
was reviewed, cases were collected and consensus recommendations for WR involvement were established.
Design/Methods: A systematic review was conducted for literature involving WR and HL.
Results: 1499 titles/abstracts were reviewed, 75 papers at full
text, and 24 included (8 pediatric). Nineteen further pediatric
cases were collected from the group.
SIOP ABSTRACTS
Conclusions: Historically involvement of WR was determined by examination, ideally by ENT with biopsy confirmation. There are currently no standard clinical criteria to define
involvement, rendering clinical evaluation highly subjective.
Diagnostic, contrast-enhanced CT and FDG-PET are the standard of care for newly diagnosed HL. Review of both modalities is required to determine disease presence in WR given that
normal/reactive lymphoid tissue may be avid on PET alone.
Abnormality or asymmetry of both anatomy and metabolic
activity should be assessed. Where PET avidity of WR structures approaches that of the primary mass, involvement should
be considered. MRI is excellent for assessing head and neck
tissues and should be considered for further delineation of
PET-CT findings.
Indeterminate PET findings on initial staging that cannot
be confirmed with CT/MRI should be reviewed with early
response assessment. If metabolic activity normalizes at early
response assessment, involvement is likely and should be considered in ongoing treatment.
Tonsils can demonstrate physiologically increased metabolic
activity making response assessment with FDG-PET challenging. Thus, standard Deauville criteria cannot be applied.
We suggest that the disappearance of asymmetric uptake and
a symmetric uptake in palatine tonsils that does not markedly
exceed (20%) the uptake of the adenoid region be considered
adequate response.
In clinical trials, final involvement should be determined by
central review and a prospective database of WR involvement
maintained.
S211 of S518
followed by lymphoblastic lymphoma (LL) (30%), anaplastic large cell lymphoma (ALCL) (14%) and diffuse large B
cell lymphoma (DLBCL) (13%). Most patients (81%) had
advanced disease at diagnosis. Bone marrow (BM) and CNS
involvement were more frequently observed in BL and LL.
The 5-year overall survival and event-free survival (EFS)
rates were 89% and 84%, respectively at a median 50.5
months of follow up. 5-year EFS rates were excellent in BL,
LL and DLBCL (88, 88, 89%, respectively), and lower in
ALCL and PTCL (71, 56%, respectively) (P<0.001). CNS
involvement, high LDH (>250 IU/mL) and advanced disease at diagnosis were associated with significantly poorer
outcomes (P<0.05). Ninety one patients (12%) experienced
relapse at median 8 months after diagnosis. Patients with
ALCL and PTCL relapsed more frequently than other subtypes (P<0.001). Patients relapsed within 12 months from
diagnosis, and relapsed BL and LL showed significantly
poorer outcomes.
Conclusions: The clinical characteristics and treatment outcomes of pNHL in East Asian countries were similar to those
observed in Western countries, but some peculiar clinical
aspects were observed as well. This international study is
expected to provide a platform for future collaborative study
on NHL in East Asia.
P-098 ZUCH-S3, An Antibody Targeting B
Lymphocytes, Is a Potential Therapeutic Agent for
B-Lineage Malignancies
H. Shen1 , S. Li1 , Q. Shu1
1 Children's
P-097 Clinical Characteristics and Treatment
Outcome of Pediatric Non-Hodgkin Lymphoma in
East Asia
J.J. Seo1
1 Asan
Medical Center, Pediatrics, Seoul, Republic of Korea
Background/Objectives: Pediatric non-Hodgkin lymphoma
(pNHL) comprises a heterogeneous group of lymphoid neoplasms, and is known to have different aspects from adult disease and geographical differences in incidence. We performed
this study to delineate the characteristics and outcomes of
pNHL in East Asia.
Design / Methods: Medical records of 749 patients with
pNHL treated in 4 participating institutions of Beijing, Shanghai, Nagoya, Seoul, and in TPOG centers of Taiwan from
January 2008 to December 2013 were reviewed retrospectively. Demographic and clinical features, survival outcomes
and putative prognostic factors were analyzed.
Results: Median age at diagnosis was 8 years. The most common pathologic subtype was Burkitt lymphoma (BL) (36%)
Hospital - Zhejiang University School of Medicine,
Hematology-Oncology, Hangzhou, China
Background/Objectives: Monoclonal antibody (mAb)based targeted therapy is one of the most promising strategies
to cure cancers. ZUCH-S3mAb was a novel antibody
generated using hybridoma technique with human B lymphoma Raji cells immunogens in our laboratory, which
presented potential to be a therapeutic agent for hematologic
malignancies.
Design/Methods: We investigated the reactivity profile of
ZUCH-S3mAb and identified the targeting antigen by flow
cytometry. The internalization of ZUCH-S3mAb was studied
by the method applying papain digestion and flow cytometry.
The capacity of ZUCH-S3mAb specifically binding to S3Ag
and activating complement was determined by complement
dependent cytotoxicity (CDC).
Results: The results showed that the antibody ZUCH-S3mAb
(murine IgG1�) was a new clone of anti-CD79a. It reacted
with extracellular portion of CD79a protein. ZUCH-S3 antigen was strictly expressed on B-lineage lymphoma cells such
as Burkitt's lymphoma, DLBCL and CLL cells from patients.
SIOP ABSTRACTS
S212 of S518
ZUCH-S3mAb was quickly internalized into the target cells
once binding to the antigen. When the antibody was incubated
with targeting cell Raji at 37◦ C, the degrees of internalization
at different time points were 5.9% (0.25h), 9.5% (0.5h), 34.8%
(1h), 64.8% (2h) and 74.6% (3h), 75.1% (4h), respectively.
ZUCH-S3mAb VL and VH gene was inserted into plasmid
pcDNA3.1, and the recombinant plasmids encoding ZUCHS3mAb were transfected into CHO cells. The Western blotting
analysis showed the culture supernatants bound to the extracts
from Raji cells. The activities of CDC on Raji cells were in a
dose dependent manner and the inhibition rates of Raji cells
were 15.3%, 40.9%, 68.6% and 75.2% at the concentrations of
0.05�g/ml, 0.1�g/ml, 1�g/ml, 5�g/ml, respectively.
Conclusions: ZUCH-S3mAb is a novel antibody targeting
extracellular portion of CD79a, which has the potential to be
a therapeutic agent for B-lineage malignancies.
57.1% vs 11/20 or 55%), and location in the intestine allograft
(4/7 or 57.1% vs 11/20 or 55%).
All subjects were treated with immunosuppression reduction.
Within the alemtuzumab group, treatment also included rituximab in 4 and chemotherapy (with combination of cyclophosphamide and steroids) in 2 children, and enterectomy in 4 (3
from rejection/graft failure, 1 from PTLD). PTLD resolved
in all of these subjects. One child died of infection. Within
the rATG group, treatment included rituximab in 11 and
chemotherapy in 6 children, and enterectomy in 7 (5 from
rejection/graft failure, 2 from PTLD). Six children died: 3 due
to PTLD, 2 of infection and 1 of renal failure.
Conclusions: rATG induction is associated with a trend
toward lower PTLD incidence compared with alemtuzumab.
P-100 Minimal Disseminated Disease Evaluation
in T-Cell Acute Lymphoblastic Lymphoma
P-099 Lymphocyte Depleting Induction Agents
and Posttransplant Lymphoproliferative Disorder
(PTLD) in Children with Intestinal Transplants
(ITX)
K. Stanley1 , K. Soltys2 , G. Bond2 , G. Mazariegos2 , S.
Ranganathan3 , R. Sindhi2
1 Children's
Hospital of Pittsburgh of UPMC, Department of Pediatric
Hematology Oncology, Pittsburgh, USA; 2 Children's Hospital of Pittsburgh
of UPMC, Department of Transplant Surgery, Pittsburgh, USA; 3 Children's
Hospital of Pittsburgh of UPMC, Department of Pathology, Pittsburgh, USA
Background/Objectives: Lymphocyte depleting induction
immunosuppression decreases rejection severity and reduces
maintenance immunosuppression requirements after ITx
alone or with liver (L-ITx) in children. Whether PTLD rates
vary with induction agent is unknown.
Design/Methods: Retrospective chart review of subjects who
received ITx from January 2000 through present at the Children's Hospital of Pittsburgh of UPMC.
Results: Of 193 ITx, 25 underwent alemtuzumab induction
and 147 underwent rabbit anti-thymocyte globulin (rATG)
induction. Alemtuzumab-induced subjects were older, compared with rATG-induced subjects with median age of 5 years
(range <1-24) vs 3 years (range <1-22) (p=0.5, NS), experienced lower incidence of early (60-day) acute cellular rejection (13/25 or 52% vs 96/147 or 65.3%, p=0.262, NS, Fisher's
exact) and higher incidence of PTLD (7/25 or 28% vs 20/147
or 13.6%, p=0.078, NS, Fisher's exact).
The alemtuzumab and rATG groups were similar with regards
to liver containing grafts (4/25 or 16% vs 22/145 or 15%),
PTLD onset during the first post-transplant year (5/7 or 71.4%
vs 16/20 or 80%), association with EBV (6/7 or 85.7% vs
18/20 or 90%), incidence of monomorphic PTLD (4/7 or
G.K. Viswanathan1 , P. Tembhare1 , S. Gujral1 , N. Patkar1 , Y.
Badrinath1 , S. Ghogale1 , N. Deshpande1 , M. Rajotiya1 , S.D.
Banavali2 , G. Narula2 , G. Chatterjee1 , D. Dhaliwal1 , P.G.
Subramanian1
1 Advanced
Centre for Treatment- Research and Education in Cancer
ACTREC- Tata Memorial Centre TMC, Hematopathology Laboratory,
Mumbai, India; 2 Tata Memorial Hospital TMH-Tata Memorial Centre
TMC, Pediatric Hemato-Oncology, Mumbai, India
Background/Objectives: T-lymphoblastic lymphoma (TLBL) with minimal disseminated disease (MDD) is defined
as T-LBL with <25% morphologically identifiable blasts
in peripheral blood (PB) and/or bone marrow (BM) along
with presence of BM involvement detected by flowcytometric
immunophenotyping (FCM-IPT). Published literature of this
rare subgroup is sparse. This study aims at identifying MDD
in T-LBL using 10-colour FCM-IPT and study their clinical
features.
Design/Methods: A retrospective analysis of 40 children of
T-LBL (diagnosed on mediastinal and/or lymph node biopsy)
with predominantly lymphomatous presentation and <25%
blasts in PB/BM was done. Clinical and laboratory and FCMIPT data were studied. FCM-IPT was performed on a 10-color
flowcytometer.
Results: Mean age was 10.2 years (range:2-18 years). M:F
ratio was 2.1:1. Mean hemoglobin, WBC count and platelet
count were 12.7g/dl, 11.7x10^9/L and 411x10^9/L (142-875)
respectively. CSF examination was negative in all cases indicating rarity of CNS involvement in this subgroup. MDD
was seen in 14 cases (35%) and ranged from 0.007% to
18.5% (mean:1.4%; median:1.2%). Mean (range) morphologically identifiable bone marrow blast/hematogones count in
the group without MDD was 2.7% (1-4%) and in the group
with MDD was 3.7% (0-15%). Seven(50%) cases of T-LBL
with MDD showed <5% blasts in BM indicating sensitivity
SIOP ABSTRACTS
and necessity of FCM-IPT. PET-CT was insensitive to identify MDD.
Conclusions: MDD is present in one-third(35%) of T-LBL
with <25% blasts in PB/BM. This underlines the importance
of performing FCM-IPT in cases with <25% blasts and even
in cases of <5% blasts on morphology. Identification of minimal disseminated disease in T-LBL is important as (1) limited published data are available, (2) these studies show inferior event free survival in T-LBL with MDD as compared
to patients without MDD and (3) there is a need for postinduction BM examination for residual disease detection in
MDD positive cases and intensification of therapy if positive.
P-101 Improved Outcome of Newly Diagnosed
Childhood Mature B-Cell Lymphoma/Leukemia
with High Tumor Burden Treated with Rituximab
Combining BFM95-Based Protocol: A Report from
Shanghai, China
Y. Fu1 , H. Wang1 , X. zhai1 , X. Qian1
1 Children's
Hospital of Fudan University, Hematology and oncology,
Shanghai, China
Background/Objectives: Rituximab has become a standard
medicine in the treatment of adult patients with DLBCL. Currently, there was a limited number of clinical trials in children
showing that rituximab can be combined with BFM and other
protocols safely with good efficacy. The absence of similar
study in China for childhood patients with newly diagnosed
B-NHL/B-ALL encouraged us to study the efficacy of rituximab in the Chinese population.
Design/Methods: In this study, we explored the efficiency of
rituximab in childhood B-NHL. We found that 46 newly diagnosed mature B-NHL which were stage III and stage IV/B-AL
children were treated with BFM95-based protocol combined
with rituximab. Compared with historical data of BFM90based protocol.
Results: Our study recuited 35 males and 11 females with an
average age of 6.9 years who were treated with R+BMF95
chemotherapy. Among the historical control of 23 patients
treated with BFM90 chemotherapy, 5 were female. Compared with patients treated with BFM90 protocol, the 5-year
EFS of patients under R+BMF95 was higher (83.7±5.7%
vs 69.6%±9.6% in R+BMF95 and BFM-90 respectively)
(P=0.11). Among subgroups of our patients, the 5-year EFS
of patients with stage III was 87.3±6.1% vs 77.8±9.8%
(P=0.30), stage IV/B-AL was 72.7%±13.4% vs 40.0±21.9%
(P=0.09) between patients treated with R++BMF95 and
BFM-90 respectively, these difference were not statistically
significant neither. Among patients whose LDH level were
<500 U/L at diagnosis, R+BFM95 protocol reached 100%
survival during our follow-up, nevertheless the 5-year EFS
S213 of S518
of patients in this group was not statistically different from
that of patients treated with BFM90 (92.3±7.4%, P=0.2994).
Among patients had LDH >500 U/L at diagnosis, the 5-year
EFS in R+BFM95 group was 77.2±7.7% and significantly
higher than that of BFM90 group (40.0±15.5%, P=0.005).
Conclusions: We found that rituximab has improved the
event-free survival (EFS) of childhood B-NHL/B-AL with
LDH > 500 U/L in China.
P-102 Hemophagocytic Lymphohistiocytosis
(HLH) Associated ALK-Positive Anaplastic Large
Cell Lymphoma (ALCL) with Leukemic
Involvement and Central Nervous System (CNS)
Disease: A Single Institution Case Series
L. Amos1 , N. Wood1 , M. Hetherington1 , A. Hays1
1 Children's
Mercy Hospital, Hematology/Oncology/BMT, Kansas-City, USA
Background/Objectives: ALCL is a form of non-Hodgkin's
lymphoma which represents 10-15% of childhood lymphomas. Leukemic and CNS involvement in ALCL is
extremely rare. In addition, ALCL has rarely been reported in
association with HLH. HLH is a life-threatening disorder of
immune dysregulation involving macrophage and T-cell activation with cytokine release causing multi-organ dysfunction.
The objective of this case series is to report the disease course
of two patients with fulminant HLH secondary to ALCL with
leukemic and CNS involvement.
Design/Methods: Here we present two patients that were
admitted to our pediatric intensive care unit (PICU) with
multi-organ system failure requiring intubation and continuous renal replacement therapy (CRRT) due to metabolic acidosis. Both met diagnostic and laboratory criteria for HLH.
Both had bone marrow and peripheral blood evaluations with
FISH analysis showing an ALK gene rearrangement, consistent with ALCL in leukemia phase. Patient 1 was a 2 year
old male. He had a brain MRI done that showed numerous
enhancing lesions consistent with metastasis. Patient 2 was a
16 year old female. Her CSF analysis showed evidence of disease with ALK positive cells. In addition, she was found to
have non enhancing lesions in the deep white matter of her
brain on MRI.
Results: Both patients were treated with HLH directed therapy, followed by ALCL directed therapy. Both received additional treatment to the CNS with intrathecal chemotherapy.
Patient 2 also received craniospinal irradiation (CSI). Both
patients are off therapy and have no evidence of disease.
Conclusions: This case series highlights two patients with the
rare presentation of HLH associated ALCL with leukemic and
CNS involvement. The diagnosis of HLH should be considered in ALCL patients presenting in the leukemic phase. This
SIOP ABSTRACTS
S214 of S518
also suggests that the leukemic phase may lead to elevated
cytokines that cause HLH.
P-104 Role of Surgery in Management of
Paediatric Abdominal Lymphoma
O. Zakaria1
P-103 High Survival Rates in Hodgkin's
Lymphoma in a Developing Country: No Mortality
in Protocol Patients without A CO- MORBID
Problem
N. Yazici1 , F. Sarialioglu1 , H.C. Onal2 , A. Erbay1 , B. Hasbay3 , S.
Demir4 , A. Temiz5 , G.N. Nursal6
1 Baskent
University, Department Of Pediatric Oncology-Hematology,
Adana, Turkey; 2 Baskent University, Department Of Radiation Oncology,
Adana, Turkey; 3 Baskent University, Department Of Pathology, Adana,
Turkey; 4 Baskent University, Department Of Radiology, Adana, Turkey;
5 Baskent University, Department Of Pediatric Surgery, Adana, Turkey;
6 Baskent University, Department Of Nuclear Medicine, Adana, Turkey
Background/Objectives: Different centers use different protocols according to their physical conditions in Turkey for
Hodgkin's lymphoma. Usually choice of protocol depends on
success and superiority of survival in original regimen. However local factors are different and it is impossible to take same
results. In this study, treatment results of German Pediatric
Oncology-Hematology Hodgkin's Disease 95 (GPOH-HD95)
regimen are presented.
Design/Methods: In our department, PET/BT is routinely
used in staging of every patient before and at the end
of chemotherapy. GPOH-HD regimen is used in its original version and radiotherapy had been used in involved
fields (https://doi.org/10.1200/JCO.2012.45.3266). Patients
were hospitalized for minimum 7 days at diagnosis for adaptation to treatment. The rest of treatment was continued in outpatient basis.
Results: Between January 2006 –December 2015 there were
42 patients with Hodgkin's lymphoma. Thirty three of them
were untreated. Mean age was 11,4 years (2,8-16,6 years);
there were 23 males. Seventeen of them were mixed cellular type, There were 15 cases of risk group (RG)1; 10 of them
were RG2, and 8 of them were RG3. Median follow up was
55.6 months. A patient with RG1 and stage 2A Hodgkin disease at diagnosis had a relapse at 50th month of follow up.
He is still under follow up in second remission for a year. A
patient with ataxia telengiectasia which had been exitus with
pulmonary complications was excluded. There was no mortality in our series of protocol patients. Event-free and overall
survival for 5 years were % 95,5 and %100 respectively.
Conclusions: The results of the GPOH-HD95 protocol in
our center were as successful as the original protocol despite
local factors. We think that treatment related toxicity should
be reduced with some modifications in our patients such as
omitting radiotherapy in complete metabolic response with
PET/CT after chemotherapy without procarbazine in male
patients.
1 King
Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia
Background/Objectives: BACKGROUND: The abdomen
is one of the most frequent sites for lymphoma in children. The
role of surgery has been limited to intra-abdominal resectable
tumours or as a diagnostic procedure in case of disseminated
disease. Laparotomy without total excision of the tumour does
not improve survival; moreover, it may cause complications
and delays initiation of chemotherapy.
AIM OF THE WORK: This study was undertaken to assess
the role of surgery in the management of children and adolescents presenting with intra-abdominal lymphoma in order
to create certain criteria to select the proper surgical modality
for managing those patients.
Design/Methods: PATIENTS AND METHODS: This
case-series, retrospective study was done on 83 patients of
abdominal lymphoma over a period of seven years from 2000
to 2015. Patients’ files were reviewed regarding the full clinical examinations, laboratory and radiological investigations
as well as surgical and diagnostic procedures. Collected data
were tabulated and statistically analyzed using SPSS program
package.
Results: Twenty seven patients (32.5%) presented with huge
pelvi-abdominal mass and 27 (32.5%) had generalized lymphadenopathy beside their abdominal affection. The remaining 29 (35%) patients presented with symptoms of an acute
abdomen. A total of 38 laparotomies were done. 27 patients
underwent emergency laparotomy for acute abdomen and
10 patients had elective abdominal exploration. Lymph node
biopsies were taken in 18 patients and laparoscopy procedures
were performed in 8 patients as a diagnostic tool. Out of the
total 83, the remaining 20 patients underwent true cut needle
biopsy for diagnosis of their disease.
Conclusions: Surgery still has a role in treatment of lymphoma whether non Hodgkin or Hodgkin's. However, in disseminated metastatic disease, aggressive debulking of the
tumour should be avoided as chemotherapy is to be instituted
primarily. Surgical resection does not cause significant change
in morbidity or mortality.
P-105 Abnormalities of the Thyroid in Survivors
of Childhood Hodgkin's Disease
D. Zvyagintseva1 , S. Kuleva2 , S. Ivanova3 , T. Semiglazova3 , E.
Tsyrlina3 , S. Novikov3
1 NN
Petrov Research Research of Oncology Institute, Department of
chemotherapy and combined treatment of malignant tumors in children,
Saint - Petersburg, Russia; 2 N.N. Petrov Research Institute of Oncology,
Department of chemotherapy and combined treatment of malignant tumors
SIOP ABSTRACTS
in children, Saint - Petersburg, Russia; 3 N.N. Petrov Research Institute of
Oncology, Department of chemotherapy and combined treatment of
malignant tumors in children, St. Petersburg, Russia
Background/Objectives: Overall 5-year survival rate for
childhood Hodgkin's lymphoma (HL) is now around 90-95%,
therefore late sequelae of treatment, especially endocrine diseases, have become more important.
Aims: to investigate the late side effects of childhood
Hodgkin's lymphoma therapy on the thyroid gland among
childhood cancer survivors.
Design/Methods: This report analyzed the function of the
thyroid gland in 78 patients successfully treated in childhood
with HD, according to two different protocols of therapy.
The patients were divided into three groups depending on
the treatment: group 1 - risk-adapted therapy according DALHD protocol (n=42), group 2 - risk-adapted therapy according
SPbHL protocol (n=86), and BEACOPP + radiotherapy (RT)
(n=15). The treatment methods correlated with the appearance of thyroid dysfunction.
Results: After median follow-up of 7.5 years, thyroid dysfunction was detected in 20 of 78 patients (25.6%). The thyroid abnormalities were: hypothyroidism (n= 16, 20,5 %),
thyroid nodules (n=4, 5,1%), and thyroid malignancy (n=1,
1,28%). [С1] Сervical irradiation and 39 Gy doses of radiation
were found to constitute risk factors for thyroid abnormalities.
Conclusions: This study confirms the high incidence of thyroid abnormalities in patients treated for Hodgkin's lymphoma with combination therapy of chemotherapy with
head/neck/thorax radiotherapy and strengthens the importance of a long-term follow-up.
P-106 Treatment Outcomes of Adolescents with
Hodgkin's Lymphoma
D. Zvyagintseva1 , S. Kulyova2 , S. Ivanova2
1 NN
Petrov Research Research of Oncology Institute 2 Saint-Petersburg
State Pediatric Medical University, Department of chemotherapy and
combined treatment of malignant tumors in children, Saint - Petersburg,
Russia; 2 NN Petrov Research Research of Oncology Institute, Department
of chemotherapy and combined treatment of malignant tumors in children,
St. Petersburg, Russia
Background/Objectives: Survival rates after a diagnosis of
Hodgkin's lymphoma (HL) have improved substantially over
the past 40 years. But adolescents who are between 10 and 17
years old seem to experience poorer survivals.
Objective: To provide a descriptive review and improve our
understanding of the treatment outcome of Hodgkin's lymphoma.
Design/Methods: A retrospective review of 106 patients aged
10-17 years old with HL treated at our institution from 1996-
S215 of S518
2014 was performed. Survival analysis was performed using
the Kaplan-Meier method.
Results: Median age was 13.8 years, 44% were boys, and
56% were girls. Forty-three patients (41%) had I-II stage, 63
patients (59%) had advanced disease (III-IV stage). About half
of patients (46 or 43%) had a B-stage disease. The majority
patients (84 or 79%) had nodular sclerosis, 4 patients (4%) the lymphocyte predominance and 12 (12%) - mixed cellularity, in 6 cases (6%) morphological type was not diagnosed.
Patients were treated with risk-adapted therapy (chemotherapy and radiation) according to DAL-МD (40 or 39%) or
SPbHL (56 or 54%) protocols. Seven (7%) patients were
treated with BEACOPP. The radiation dose ranged from
20 to 35 Gy. The 5-years overall survival was 89,5±3,4%,
disease-free survival was 86±3,8%, event-free survival was
78,5±4,4%, the 10-years survival was 85,7±4%, 81±5% и
76,9±4,6%, respectively.
Conclusions: The presenting features of adolescents with
HL and efficiency in this study were better than at
young adult (overall survival was 83%) but it is worse
than at children (overall survival was 95%). Adolescent's Hodgkin's lymphoma is very curable diseases but
require a personalized management in oncohematological
units.
P-107 Prognostic Factors of Young Adults
Hodgkin's Lymphoma
D. Zvyagintseva1 , S. Kuleva2 , S. Ivanova3 , A. Karitskiy3
1 NN
Petrov Research Research of Oncology Institute 2 Saint-Petersburg
State Pediatric Medical University, Department of chemotherapy and
combined treatment of malignant tumors in children, Saint - Petersburg,
Russia; 2 NN Petrov Research Research of Oncology Institute 2
Saint-Petersburg State Pediatric Medical University, Department of
chemotherapy and combined treatment of malignant tumors in children, ST.
PETERSBURG, Russia; 3 NN Petrov Research Research of Oncology
Institute, Department of chemotherapy and combined treatment of
malignant tumors in children, St. Petersburg, Russia
Background/Objectives: Hodgkin's lymphoma is approximately 12% of all malignant tumors in patients aged 19-29.
The risk-adapted treatment program in this group is not used.
The aim of the study was to identify prognostic unfavorable
factors in young adults with HL.
Design/Methods: The study included data of 87 patients
aged 19 to 29 years (the average age was 24 ± 4 years).
Thirty-four (39.1%) was men, 53 was women (60.9%), sex
ratio 1: 1.6. Forty-seven patients (54%) had I-II stage, 40
patients (46%) had advanced disease (III-IV stage). More
than half of patients (47 or 54%) had a B-stage disease.
The majority patients (76 or 87.4%) had nodular sclerosis, 2
patients (2.3%) - the lymphocyte predominance and 5 (5.7%)
- mixed cellularity, in 4 cases (4.6%) morphological type was
not diagnosed. All patients received from 2 to 11 cycles of
SIOP ABSTRACTS
S216 of S518
primary chemotherapy (median of 4 cycles) with ABVD
(48 patients, or 55.2%), BEACOPP (36 or 41,4%), MOPP
(2 or 2.3%), and COPP (one patient) following radiation in
57 patients (65.5%). The radiation dose ranged from 20 to
51 Gy.
at 39 Gy of radiation dose on neck and thyroid gland in children and adolescents with Hodgkin's lymphoma for predictive dosimetric variables was found. The ROC curve area was
0.717 ± 0.108 (CI 0.590-0.822), p = 0.0445. The maximum
Youden index was 0.3929.
Results: Correlation matrix included 35 factors. Significant
impact on overall and event-free survival was had stage IV
disease (p = 0.035813), extranodal lesion (p = 0.002746),
the involvement of the pericardium (p = 0.039394), the value
of ESR 35 mm / h (p = 0.012357), white blood cell count
more 11,5x109 / l (p = 0.026490), the level of lymphocytes
less than 9% (p = 0.001053), fibrinogen value of more than
7.5 g / l (p = 0.048856), the effectiveness of therapy (p =
0.000789) and the volume of tumor more than 210 cm3 / m2
(p = 0.017734).
Conclusions: Total dose of 39 Gy on neck and thyroid gland
was the critical cut-off values for the development of thyroid
dysfunction.
Conclusions: Using the identified unfavorable prognostic factors, it is possible to stratified patients on risk groups and to
determine the treatment program.
P-108 Thyroid Abnormalities in Survival of
Childhood Hodgkin's Lymphoma
D. Zvyagintseva1 , S. Keuleva1 , E. Tsyrlina1 , S. Novikov-1 , T.
Semiglazova1
1 N.N.
Petrov Research Institute of Oncology, Department of chemotherapy
and combined treatment of malignant tumors in children, Saint - Petersburg,
Russia
Background/Objectives: Long-term side effects of treatment modalities for childhood Hodgkin's lymphoma (HL)
are focused in modern researches. Thyroid dysfunction
has been reported especially following head and neck
irradiation.
Aims: to determine the critical cut-off point of radiation dose
on neck and thyroid gland in children and adolescents with
Hodgkin's lymphoma for predictive dosimetric variables with
the Youden method.
Design/Methods: One hundred and forty-three patients with
proved HL (aged 2- 17 years) were included in the study.
The patients were divided into three groups depending on
the treatment: group 1 - risk-adapted therapy according DALHD protocol (n=42), group 2 - risk-adapted therapy according
SPbHL protocol (n=86), and BEACOPP + radiotherapy (RT)
(n=15). Eligibility criteria for inclusion in the current analysis were: diagnosis of the cancer at age ≤18 years, treatment
with chemotherapy and RT (neck/thorax) and a time interval
of ≥6 months after completion of the therapy. Thyroid function tests, thyroid gland ultrasound examinations were evaluated in this groups.
Results: The mean follow-up period was 7,5 years (range: 022). One hundred twenty-six patients (88.1%) of 143 received
a total dose of 15-46 Gy head/neck/thorax RT. A cut-off point
P-109 Linear Regression Model “Bulky Disease”
of Hodgkin Lymphoma in Adolescents
D. Zvyagintseva1 , S. Ivanova1 , S. Kulyova1 , A. Karitsky1
1 NN
Petrov Research Institute of Oncology- Saint-Petersburg State Pediatric
Medical University- St. Petersburg- Russia, Department of children‘s
chemoterapy and combined modality therapy, Saint - Petersburg, Russia
Background/Objectives: The predictive value of Hodgkin's
lymphoma tumor burden has been discussed for about 20
years. However, the evidence based on modern research, has
become possible to use only in recent years. The purpose of
the study was assessment of influence of relative tumor burden on long-term outcomes.
Design/Methods: The study included data on 106 patients
aged from 10 to 18 years old (middle age of 14 years)
with biopsy-proved Hodgkin lymphoma. Boys were 44%,
girls were 56%. Thirty-eight patients (35.8%) had II stage
and thirty-nine (36.8%) had III stage of the disease. B
symptoms occurred in 46 patients (43.4%). In 66 patients
(62.3%) were identified the b-stage disease. All patients
were treated according to pediatric protocols: 40 (38.8%)
patients - according to DAL-HD, and 56 (54.3%) - according to SPBLH program. Seven teenagers (6.8%) were
treated according to BEACORP scheme. Chemotherapy regimen was followed by extend- or involved-field or subtotal radiation with doses from 20 to 51 Gy in 68 patients
(66%).
Results: Overall survival at 5 years was 91% (range 8993%), disease-free survival was 88% (85-91%). The optimum cut-off level according ROC method for relative tumor
burden has been established at 122.7 cm3 /m2 . The ROC
curve area was 0.717, p = 0.00010. The maximum Youden
index was 0.4113. Overall survival in the cohort of patients
with this volume and above was 69.6%, with a tumor volume of less than 122.7 cm3 /m2 , overall survival was 97.2%
(p = 0.00002).
Conclusions: The relative tumor burden is the parameter which is significantly changing survival rates in adolescents with Hodgkin lymphoma. The determinate can
be intercorrelated and included from the final multifactor
analysis.
SIOP ABSTRACTS
HAEMATOLOGY - STEM CELL
TRANSPLANTAT ION
(HAEMATOLOGICA L
DISEASES/TECHNIQUE AND
SUPPORT IVE CA R E )
S217 of S518
P-111 Basiliximab is well Tolerated and Effective
in the Treatment of Steroid-Refractory Acute Gut
Graft-Versus-Host Disease After Pediatric
Allogeneic Stem Cell Transplantation
F. Ansari1
1 FMRI-
P-110 Acute Kidney Injury After Total Body
Irradiation: Associated Factors and Natural History
M. Abugideiri1 , M. Ferris1 , J. Switcheko2 , N. Madden1 , C. Butker1 ,
E. Butker1 , R. Cassidy1 , D. Tanenbaum1 , B. Eaton1 , N. Esiashvili1
1 Winship
Cancer Institute of Emory University, Department of Radiation
Oncology, Atlanta, USA; 2 Winship Cancer Institute of Emory University,
Department of Biostatistics & Bioinformatics, Atlanta, USA
Background/Objectives: To evaluate factors associated with
acute kidney injury (AKI) in pediatric patients after total body
irradiation (TBI) based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation (HSCT).
Design/Methods: The records were reviewed for 129 consecutive pediatric patients (range, 1-21 years) who underwent TBI-based myeloablative conditioning for hematologic
malignancies at a single institution between January 2003 and
May 2014. TBI total dose ranged from 10.5-14Gy and TBI
dose-rate ranged from 5.57-20.85cGy/min. AKI was defined
as a doubling of the baseline creatinine in the first 100 days
after TBI. Univariate and multivariable analyses were performed to determine associations between variables.
Results: AKI developed in 96 patients (74.4%). TBI total
dose (P=0.095), dose rate (P=0.680), and dose per fraction (P=0.373) were not significant predictors for AKI. For
chemotherapy, 99.2% of patients received a regimen containing Cytoxan. AKI was not increased with the additions of AraC (P=0.156), VP-16 (P=0.428), or Fludarabine (P=0.840).
Neither infection (P=0.142), nor acute GVHD (P=0.874)
were associated with increased AKI. AKI was not increased
in patients with a low pre-TBI glomerular filtration rate (GFR)
(P=0.561). The majority of patients with AKI had normalization of their creatinine after HSCT (67.9%), however, persistent renal dysfunction after TBI was associated with a higher
incidence of transplant related mortality (TRM) (P<0.001)
and worse overall survival (OS) (P<0.001), both of which
remained significant on multivariable analysis (P<0.001).
Conclusions: A high incidence of AKI was noted in this
series. Despite this, no significant factors were identified as
agents that increase the incidence of AKI in this series and
other variables must be identified as potential causes of AKI.
AKI did not appear to result in long-term renal damage in
the majority of patients; however, persistent renal dysfunction
was associated with worse OS and TRM. Additional attention
must be paid to factors that facilitate normalization of kidney
function after AKI.
Gurgaon, pediatric hematoncology and stem cell transplant,
Bhiwandi, India
Background/Objectives: Background-Anti-CD(25) monoclonal antibodies (Mabs) have been evaluated for the treatment of steroid-refractory acute graftnegativersus-host disease (GVHD) in patients undergoing hematopoietic stem cell
transplantation (HSCT) mainly in adults after matched donors
for years, but there is paucity of data in pediatric patients.
Aims and Objective- To evaluate the efficacy of the chimeric
Mab, basiliximab in pediatric patients with steroid-refractory
acute gut GVHD after matched and haploidentical HSCT.
Design/Methods: Material and Methods-Basiliximab was
evaluated in 11 patients with steroid-refractory acute gut
GVHD after matched and haploidentical SCT. Patients were
transplanted from a matched sibling (n = 3) or haploidentical (n =8) donor because of acute lymphoblastic leukemia (n
= 4), acute myeloid leukemia (n = 2), fanconi anemia (n =
2), thalassemia (n = 2) and immunodeficiency (n = 1). Basiliximab was given at a dose of 2 x 10 mg (<40kg) and 2 x
20 mg(>40kg) on 2 consecutive days after steroid-refractory
acute gut GVHD had developed. Basiliximab was repeated on
day 8 in cases of persistent GVHD. A median of four basiliximab infusions (range 2-12) were given to these patients.
Results: Results-None had infusion-associated or cytokinerelated side-effects after basiliximab. Eight of 11 patients
(72.7 %) responded to basiliximab, 5/11 (45.4%) had a complete response (CR) of acute gut GVHD and 3/11 (27.2%) had
a partial response (PR). Three of 11 patients (27%) did not
respond.
Conclusions: Conclusion-These data suggested that basiliximab was effective to treat steroid-refractory acute gut GVHD
after pediatric matched/haploidentical SCT
P-112 Bone Marrow Transplantation in Pediatric
Population; 15 Year Experience from Single Centre
S.H. Ansari1
1 National
Institute of Blood Diseases and Bone Marrow Transplantation,
Haematology- Bone Marrow Transplantation, karachi, Pakistan
Background/Objectives: Hematopoietic stem cell transplantation (HSCT) as a rescue procedure in patients with malignant & non malignant disorders treated with cytotoxic regimens in patients with aberrant, or defective hematopoietic
cells, including marrow failure and autoimmune disorders. In
SIOP ABSTRACTS
S218 of S518
both situations, however, HSCT also has therapeutic effects
to eradicate the patients disease. The objective of the study
was to assess the outcome of bone marrow transplantation in
pediatric population with malignant and non malignant hematological disorders.
University Hospital´s Medical Controlling database. Demographics, disease related parameters, medical course during
the ICU stay, short- and long-term outcome were analyzed.
Causes of death and parameters with potential impact on outcome were analyzed by uni- and multivariate analysis.
Design/Methods: A total of 205 pediatric patients underwent transplantation between January 2000 and December
2014 at National Institute of Blood Diseases and Bone Marrow Transplantation for various hematological disorders, both
malignant and non-malignant. Both Haematopoietic Stem
cells as well as peripheral blood transplantation methods were
employed. For allogenic transplantaion, HLA-matched siblings were the donors. Two years post-transplant survival was
calculated using Kaplan-Meier survival function.
Results: During the study period, 140 patients had 188 admissions to the ICU for a life-threatening medical condition. The
majority of patients (60.6%) had a hematological malignancy,
and 38.3% were post allogeneic HSCT; the median age was
10.4 years (range, 0.0– 20.5). Main reasons for ICU admission were respiratory insufficiency (85; 45.2%), cardiovascular insufficiency (52; 27.7%) and sepsis (51; 27.1%). Mortality in the ICU was 19.1% (36) and related to organ failure and
acute complications (28; 77.8%) or irreversible progress of the
underlying malignancy (8; 22.2%). Mortality rates at 30, 100
and 365 days post discharge from the ICU were 24.5%, 30.9%,
and 39.9%, respectively. Parameters significantly associated
with death in the ICU included status post allogeneic HSCT,
prior ICU admission(s), the number of days in the ICU, the
presence of infections, occurrence and number of organ failures and the number of supported organ systems.
Results: The mean follow-up period was 301 ± 265 days.
Acute episodes of graft versus host disease(GvHD) were
observed in 11% and chronic GvHD in 7% of the patients.
Overall survival among patients undergoing stem cell transplantation during past five years was 70%. Six months Disease free survival was 42% in aplastic anemia (AA), 69.1% in
Beta thalassemia major(BTM), 40% in hematological malignancies and 45.4% in Fanconis anemia.
Conclusions: In this study the overall survival among patients
undergoing stem cell transplantation during past five years
was 70% with the less incidence of acute and chronic GvHD
reported from other parts of the world.
P-113 Outcome of Children with Cancer and/or
Allogeneic Hematopoietic Stem Cell
Transplantation in the Intensive Care Unit:
Experience at a Large European Pediatric Cancer
Center
C. Barking1 , K. Masjosthusmann2 , G. Rellensmann2 , K. Ehlert1 , S.
Zöllner1 , S. Jocham1 , B. Bohnenkamp3 , A. Kremer3 , E.
Rieger-Fackeldey2 , A.H. Groll1
1 University
Children's Hospital, Pediatric Hematology and Oncology,
Muenster, Germany; 2 University Children's Hospital, General Pediatrics,
Muenster, Germany; 3 University Hospital Muenster, Medical Controlling,
Muenster, Germany
Background/Objectives: Pediatric cancer treatment and
hematopoietic stem cell transplantation (HSCT) carry considerable risks of morbidity. We analyzed intensive care unit
(ICU) admissions in children and adolescents treated for cancer or undergoing HSCT who developed life-threatening complications.
Design/Methods: Patients ≤ 21 years with hematological or
oncological disorders or status post allogeneic HSCT receiving care at the Department of Pediatric Hematology and
Oncology admitted to the ICU between 2003 and 2013 for lifethreatening conditions were identified through a search of the
Conclusions: The outcome of pediatric cancer/HSCT
patients admitted for acute, life-threatening conditions was
not as dismal as reported for some centers in the literature.
Most patients benefitted from ICU care and survival was predominantly compromised by the evolution of complications.
P-114 Various Ebstein Barr Virus Manifestation
in Children after Allogeneic Stem Cell
Transplantation from Unrelated Donors
W. Czogala1 , J. Gozdzik1,2 , M. Wozniak1 , A.
Krasowska-Kwiecien1,2 , A. Dluzniewska1 , S. Skoczen1,2 , O.
Wiecha1 , A. Sarnecka-Paruch1
1 University
Children's Hospital of Krakow, Transplantation Department,
Krakow, Poland; 2 Jagiellonian University Medical College, Department of
Immunology- Chair of Clinical Immunology and Transplantation, Krakow,
Poland
Background/Objectives: Epstein – Barr Virus (EBV) infections remain to be a considerable reason of severe complications in patients after allogeneic stem cell transplantation from
unrelated donors (MUD - HST). Clinical status of these complications vary from negligible viraemia to life – threatening
PTLD.
Design/Methods: There have been 85 MUD-HST performed
on our Transplantation Ward from 2007 to 2015 in children
aged from 1 to 20 years. Clinical infection status was examined every 7 days by real-time PCR in blood serum. Other
body fluids or/and tissues were examined in case the clinical
disease status was unclear.
Results: Escalating EBV replication was confirmed in 28
(33%) patients. EBV infection after MUD – HST devel-
SIOP ABSTRACTS
oped as: primary infection (3 patients), EBV reactivation
(17), probable EBV disease (5), confirmed EBV disease (1)
and posttransplant lympheproliferative disease (PTLD) (2).
Reduction of immunosuppressive drugs was implemented as
a first choice procedure in case of non – symptom EBV infection after MUD – HST. When subsequent replications or clinical development occured, rituximab (1 to 8 doses) was implemented. In 27 cases such treatment was successful. In 2 cases
(one with confirmed disease and one with PTLD) there was
a low DNA virus detection in blood, yet it coexisted with a
massive EBV replication in tonsil tissue. In one case of PTLD
with lymphatic tissue of the throat involvement we observed
treatment resistance and chemotherapy was added to treatment. In this case there was a non - significant and variable
viraemia detection, while tonsils remained infected. The boy
died regardless to treatment.
Conclusions: Systematic virus replication development monitoring is an effective PTLD prophylaxis. Low viraemia detection does not exlude tissue involvement and in presence of
suspected symptoms diagnostics should be enlarged.
P-115 Unmanipulated Stem Cell Transplantation
with POS Transplantation Cyclophosphamide. An
Excellent Alternative in Latinoamerican Population
M. Perez Garcia1 , A. OLAYA VARGAS1 , G. LOPEZ
HERNANDEZ1 , N. Ramirez Uribe1 , L. Vollbrechthaussen1 , Y.
Melchor Vidal1
1 Instituto
Nacional de Pediatria - Insurgentes 3700-C, bone marrow
transplantation, Mexico City, Mexico
S219 of S518
aproved by Investigation Comitee and written informed consent was obtained from parental guardians of all patients and
donors
Results: Forty patients were elegible: Age 0.6-17.9 years.
68% male and 22% female. CD34 dose were 2-12 ×10e6/kg.
Median of day for neutrophil graft was 15.7 (10-35 days). Primary failure was 10%.
Three years Overall survival was 65%, Acute Graft versus host
disease was 35% and chronic graft versus host disease 20%
Incidence of viral infection was 15%: adenovirus,
cytomegalovirus and BK virus were common and Immune
reconstitución shows a delay of CD4+ and CD8+ delay, until
1 year postransplantation
Conclusions: PTCy is an option at our country to face lack
of unrelated donor and umbilical cord blood with good dose.
It´s a factible procedure.
More studies should be achieved in order to demonstrate the
better source
P-116 Haploidentical Transplantation with T Cell
Depletion for Systemic Relapses of Aggressive
Pediatric Solid Tumors
E. Ramos Elbal1 , M. Plaza Fornieres2 , J.P. Muñoz Pérez1 , M. Del
Pozo Carlavilla1 , M.V. Martinez Sánchez3 , A.M. Galera Miñarro1 ,
M.E. Llinares Riestra1 , M.D.M. Bermúdez Cortés1 , J. Monserrat
Coll1 , A. Sánchez Salinas1 , M. Blanquer Blanquer1 , J.A. Campillo
Marquina3 , A. Minguela Puras3 , J.M. Moraleda Jiménez1 , J.L.
Fuster Soler1
1 Hospital
Background/Objectives: As the chance of finding a HLA
genotypically identical sibling donor is 25%. Unrelated donnor is not available at our country yet. Cord blood stem cell
source is limited by dose.
The use of high dose pos transplant cyclophosphamide (PTCY) introduced by the Baltimore group approximately 10
years ago has been rapidly adopted worldwide.
Manipulated haploidentical stem cell transplantation (ex vivo)
have demonstrated good results. Several studies achieved 2
year overall survival from 40-70% and 4 year OS 36-46%, and
GVHD incidence from 47%.80%
Objective: To determinate feasibility and overall survival with
pos transplantation cyclophosphamide.
Design/Methods: Prospective, longitudinal study was performed
All patients with ALL in CR2 lacked 1) Matched Sibling
Donor 2) Umbilical cord blood units with nucleated cells ≥
4×10 7 /kg recipient body weight and ≥ 4/6 HLA matched
antigen with molecular typing. The order preference of donor
selection was a) mother b) father c) brother or sister. Patients
with any severe condition were not elegible. This study was
Clínico Universitario Virgen de la Arrixaca, Stem cell
transplantation and cell therapy unit, El Palmar Murcia, Spain; 2 Hospital
Clínico Universitario Virgen de la Arrixaca, Murcia Biohealth Research
Institute, El Palmar Murcia, Spain; 3 Hospital Clínico Universitario Virgen
de la Arrixaca, Immunology service, El Palmar Murcia, Spain
Background/Objectives: The prognosis after systemic
relapse (SR) of aggressive pediatric solid tumors is poor.
After haploidentical stem cell transplantation (Haplo-SCT),
with ex vivo T depletion, alloreactive NK cells may exert
an antitumor effect. We analyzed the procedure and results
of Haplo-SCT in six patients (6 to 15 years old) with SR of
Ewing sarcoma (ES, 3), neuroblastoma (2) and osteosarcoma
(1).
Design/Methods: Three patients (2 ES, 1 osteosarcoma)
were in second complete remission (2CR) after resection of
lung metastases and second line chemotherapy and 3 had
active disease. Donor selection (parents) was based on KIR
and KIR-ligand genotyping (donor and recipient) and KIR
expression (donor) by flow cytometry. Ex vivo manipulation of the graft consisted of double CD3+/CD19+ (2) or
CD3��+/CD19+ (4) depletion. The conditioning consisted
of fludarabine, busulfan and thiotepa (5) or radioactive mIBG
followed by fludarabine, melphalan, thiotepa and ATG (1).
SIOP ABSTRACTS
S220 of S518
Prophylaxis of graftnegativersus-host disease (GVHD) was
done with mycophenolate (1) or cyclosporine and methotrexate (5).
Results: On average, 10.3 × 106 /kg CD34+, 6.75 × 106 /kg
CD3+ and 23.62 × 106 /kg CD56+ were infused. Graft failure occurred in two patients (CD3+/CD19+ depletion), and
both were rescued with matched HLA sibling allograft. No
patient died from complications of Haplo-SCT, one developed
acute grade III/IV, steroid-resistant GVHD responding to photopheresis. Four patients suffered tumor progression and died
3 to 12 months after Haplo-SCT. Two patients with ES in 2CR
at transplantation are alive and disease free 51 and 60 months
after Haplo-SCT, respectively.
Conclusions: Haplo-SCT was a safe option for these heavily
pre-treated patients with no treatment-related mortality in our
series. Graft rejection was associated with CD3+ depletion
but not with CD3��+ depletion. Only patients transplanted
in 2CR have a real chance for long-term disease-free survival.
P-117 High Dose Chemotherapy (HDCT) and
Autologous Stem Cell Transplant (ASCT) in
Childhood Cancer- Experience from the Royal
Marsden Hospital
N. Roy Moulik1 , J. Indranee1 , T. Petterson1 , S. Vaidya1
1 Royal
Marsden Hospital, Paediatric Oncology, Greater London, United
Kingdom
Background/Objectives: High dose chemotherapy and
autologous stem cell transplant (ASCT)form an integral part
of treatment protocols for some of the childhood cancers
and is being increasingly used for relapsed and refractory
solid tumours as well as brain tumours and lymphomas in
children.The clinical course and complications of autologous
transplant for childhood cancers between 2010 and 2017 is
described.
Design/Methods: In this retrospective study all children
undergoing high dose chemotherapy and autologous stem
cell transplant between January 2010 and March 2017 were
included. Relevant data were retrieved from patient records
and analysed using conventional statistics.
Results: Eighty-two children (M:F 8:9) with a mean age
of 5.2±4.4 years underwent ASCT for various cancers,
most commonly neuroblastoma (47%).Neutrophil and platelet
engraftment after ASCT were seen after 13.6±2.9 and
27.3±15.6 days respectively. Platelet recovery was longer
in patients with neuroblastoma receiving BuMel conditioning compared to other diagnosis (p<0.001).Common complications included mucositis (100%) and febrile neutropenia
(90%). Culture positive sepsis was seen in 17(20.7%) cases
whereas 42 (51%) patients needed parenteral nutrition for
mucositis. Hepatic and renal dysfunction were observed in 33
(43.4%) and 4 (4.7%) of cases respectively. Hepatic sinusoidal
obstruction syndrome (SOS) was seen in 14(17%)patients; of
which 13 had Busulfan based conditioning. Median duration
of parenteral nutrition and antibioticswere 8(0-35) and 9(028) days respectively.Twelve(14%) patients needed escalation
of care to HDU/PICU for sepsis (8) or SOS (4). Mean duration
of hospitalisation was 30.5±8.7 days and was significantly different among various conditioning regimens (p<0.001).There
was no transplant related mortality within Day+100 following
ASCT.
Conclusions: Complications of ASCT in childhood cancer
occurring during the period of cytopenia between conditioning and engraftment are frequently related to the underlying diagnosis and conditioning regimen. Despite commonly
occurring complications the immediate outcome for ASCT is
excellent with optimum supportive care.
P-118 Psycho-Affective Implications in Pediatric
Hematopoietic Stem-Cell Transplantation. A
Qualitative-Quantitative Study
F. Sinatora1 , A. Traverso1 , N. Di Florio1 , A. Porreca1 , S. Zanato1 ,
A. Marzollo1 , M. Tremolada2 , M. Pillon1 , E. Calore1 , M. Tumino1 ,
C. Mainardi1 , C. Cattelan1 , G. Basso1 , C. Messina1
1 University
of Padua, Department of Women's and Children's Health,
Padova, Italy; 2 University of Padua, Department of Developmental
Psychology and Socialisation, Padova, Italy
Background/Objectives: Only few studies have focused on
the analysis of quantitative and qualitative data in patients
undergoing HSCT during childhood (Bingen et al., 2012). The
aim of the study was to investigate the perception of illness
experience in patients, survivors and their families, and to correlate quantitative and qualitative data.
Design/Methods: Three different populations answered an
open-ended single question about disease experience by writing a brief composition. Group_A, tested before transplantation and after a year, included patients, parents and siblings.
Group_B was composed of pediatric HSCT survivors, parents
and siblings, and Group_B_over included adult survivors, at
least 5 years after pediatric transplantation. The Child Behavior Checklist 6-18 (Achenbach and Rescorla, 2001) and the
36-Item Short Form Health Survey (Ware et al, 2000) were
also administered. The T-LAB (Ver. 8.1.4, Lancia, 2012) was
used for qualitative analyses.
Results: Semantic differences in Group A indicate that the
disruption of familiar unity and the way the disease is faced
have a major impact on the mental health of family members.
Despite 5 years from HSCT, in the second group, the theme
of familiar disruption, as well as the inability to refer directly
to the disease and to the fear of death are associated with clinical scores in the scales considered. The third group shows
SIOP ABSTRACTS
significant differences with respect to gender and the type of
transplant.
Conclusions: Results seems to suggest that clinicians should
take into account the impact that the disease and HSCT could
have on mental health, during all the phases of care. Moreover, the care approach should focus attention on how the disease affects the whole family and relationships between its
members.
P-119 Pediatric Haploidentical Transplant: An
Indian Experience
N. Singh1
1 FMRI-
Gurgaon, Pediatric Hematoncology and Stem cell transplant,
Gurgaon, India
Background/Objectives: Background-Out of an estimated
20,000 patients requiring an Allogeneic HSCT in India,
only 500 odd patients receive one. Keeping in cognizance
the resource constraints, the major reason for the discordance lies in the lack of alternate donors. Whilst unrelated
donor marrow and cord suffice for the ethnic majorities in
Europe and the USA, such registries provide for less than
10% of HSCT recipients due to both cost and an available
match.
Aims and Objective-To initiate a Pediatric Haploidentical
Family Donor HSCT program in our Institute.
Design / Methods: Material and Methods-We chose a Posttransplant Cyclophosphamide (PTCY) based approach in all
except one in which TCR alpha beta CD 19 depletion was
used with PBSC as the graft source. We have carried out 22
transplants in 20 patients over the last 3 years (AML-7; ALL6; CML-BC-1; Fanconi Anemia-3; Thalassemia-2, Wiskott
Aldrich Syndrome-1). All received PBSC with PTCY on
days 3 and 4 followed by cyclosporine/tacrolimus and
MMF except one. The conditioning regimen comprised of
Fludarabine/Busulphan/Melphalan(AML),Fludarabine/Thiotepa/Melphalan(ALL),Fludarabine/Cyclo/TBI(FA), Fludarabine /Busulphan/ATG(Thalassemia).
Results: Results-16/20 patients surviving beyond 21 days had
successful engraftment with full donor Chimerism, 2 patients
undergoing a second Haploidentical HCT engrafted as well.
Acute GVHD grade 2-4 developed in 7/20 patients. Day 100
NRM was 6/20 (30%) and the overall survival at 1 year was
70%. The major cause of NRM was infection with Gram Negative Bacilli accounting for 70% of the deaths. Chronic GVHD
occurred in 14% of the evaluable patients. With stringent monitoring for CMV and preemptive therapy, none succumbed to
CMV disease
Conclusions: Conclusion-Haploidentical HCT based on
PTCY and PBSC graft is feasible and probably the most viable
form of alternate donor HCT in resource constrained settings.
S221 of S518
P-120 Allogenic Hematopoeitic Stem Cell
Transplant for High Risk Acute Pediatric
Leukemia: Single Center Experience from India
V. khandelwal1 , D. choudhary1 , S. sharma1 , D. doval1 , P. banthia1 ,
A. bakliwal1 , R. setia2 , A. handoo3
1 BLK
superspeciality hospital, haematooncology and BMT, Delhi, India;
superspeciality hospital, Transfusion medicine, Delhi, India; 3 BLK
superspeciality hospital, Haematology, Delhi, India
2 BLK
Background/Objectives: To analyze retrospectively the outcome of allogenic hematopoeitic stem cell transplant(HSCT)
for High Risk Acute Pediatric Leukemia.
Design/Methods: 42 transplants were done for 41 patients
over period of 4 years; Median age -16 years (range 3-21).
The diagnosis was: acute lymphoblastic leukemia in 26(63%)
patients, acute myeloid leukemia14(34%), and acute Promyelocytic Leukemia in one. 33% were in first remission (CR1),
40% in second (CR2), and 27 %in third or with refractory disease (CR3). Transplant type: MSD-30; Haploidentical HSCT- 10 and MUD- 2. Conditioning regimen: Cy/TBI13; BU/Cy- 13; Flu/Mel- 4; Flu/Cy/TBI- 6; Bu/flu/Cy -3; In
vitro T cell depletion and Flu/Mel/ATG/Thiotepa - 2 patients;
Flu/AraC/Ida/Mel-1. GVHD prophylaxis was Cyclosporine
and Methotrexate in 31; PTCy with Tacrolimus/MMF in 9,
and Tacrolimus/MMF in 2 patients.
Results: Out of 42 transplants, 5 received bone marrow,
37 received G- CSF mobilized peripheral blood stem cells.
A median 7 million of CD34+ cells/kg was infused. A
total of 39 transplants (93%) engrafted. Median time for
Neutrophil and platelet engraftment was 11 days and 17
days respectively. Seven patient developed hemorrhagic
cystitis.Acute GVHD (GR II – IV) was seen in 12(29%) and
chronic GVHD in 3 patients. CMV reactivation was seen in
5 patients. Chimerism at day + 100 was available in 25(60%)
cases; all of them had full donor hematopoiesis. Primary
rejection was seen in 2 and secondary rejection in 1 patient.
Fourteen patients(34%) died, the causes were; relapse (n: 7),
Infection (n: 4), GVHD (n: 3).Median follow up period was
260 days with overall survival (OS) for the whole group 66%.
Discriminated OS according to remission status was 71% in
CR1, 70% in CR2 and 54% in CR3.
Conclusions: Allogenic HSCT in pediatric high risk
leukemia shows encouraging results.PTCy based haploidentical HSCT is also one option in developing countries and is
cost effective.
P-121 Outcomes of Refractory and Relapsed
Hodgkin's Lymphoma with Autologous Stem Cell
Transplantation: A Single Institution Experience
R. Wali1 , H. Saeed1 , N. Patrus1 , S. Javed1 , S.J. Khan1
SIOP ABSTRACTS
S222 of S518
1 Shaukat
Khanum Memorial Cancer Hospital, Paediatric Oncology,
Lahore, Pakistan
Background/Objectives: Hodgkin Lymphoma (HL) is the
most common cancer in children, adolescents and young
adults with a peak incidence between the ages of 20 and
34. The overall survival (OS) rate of newly diagnosed HL is
approximately 80–90%. However, a subset of these patients
with HL has refractory disease to first line therapies or experience disease relapse. For these patients, conventional salvage
therapies and autologous stem cell transplant is often considered the standard of care.
Our analysis reports outcomes in these patients.
Design/Methods: A retrospective analysis was done on
patients with Hodgkin's Lymphoma who had refractory or
relapsed disease at Shaukat Khanum Hospital from September 2009 till December 2013 after IRB approval. Patients who
had high dose chemotherapy followed by stem cell rescue
were selected for this analysis.
Results: A total of 567 patients were registered at the Hospital. Sixty (10.6%) of the patient had either Primary Progressive/Refractory disease or Relapse after finishing with first
line chemotherapy. High dose chemotherapy followed by stem
cell was given on 25 patients (42%). Thirteen patients had PD
(40%), 5 had early relapse (22%) and 7 had late relapse (38%).
A number of salvage regimens were used which included
EPIC, DHAC and Gemcitibine/Vinorelbine. Re-evaluation
was done before taking patients to high dose and showed CR
in 17 (68%), PR in 6 (24%) and PD in 2 (8%) patients. Twenty
one patients (84%) are in remission after transplant with 2
(8%) dead due to septicemia and 2(2%) patients progressed
after treatment. Overall survival is 95% at 4 years with event
free survival of 80% at 4 years.
Conclusions: Our retrospective analysis shows good outcomes in patients who had progressive refractory and relapse
disease. Survival is superior in chemo sensitive disease.
SOLID NON B R A I N T U MO U R S NEUROBLASTOMA
P-122 Prognostic Significance of MGMT
Expression in Peripheral Neuroblastic Tumors
D. Abdallah1 , S. Fadel2 , N. Mashalli3
1 Alexandria
faculty of medicine- Egypt, pathology department, Alexandria,
Egypt; 2 Alexandria faculty of medicine, oncology, Alexandria, Egypt;
3 Alexandria faculty of medicine, Pathology, Alexandria, Egypt
Background/Objectives: Neuroblastoma is the most common extracranial solid malignancy in childhood. Disease with
favourable biologic features is curable with surgery alone,
high risk disease is essentially incurable and new treatment
strategies are needed for these patients. Temozolamide has
shown clinical activity against neuroblastoma. MGMT overexpression was a resistant factor to this drug.
Design/Methods: MGMT expression was assessed immunohistochemically on formalin fixed paraffin embedded blocks
from 32 neuroblastoma cases. It was then correlated with
clinicopathologic parameters as: age, site, histopathology and
stage as well as prognostic factors as: fate, treatment protocol,
overall survival (OS) and disease free survival (DFS)
Results: 32 neuroblastic tumors were studied, ages ranged
from 2ms to 10 years, 17 were females and 15 were males, 27
cases were abdominal and 5 cases were thoracic. No significant correlation was found between MGMT expression and
patient‘s age, tumor site, histologic type, grade of differentiation and stage.
No significant correlation was noted between MGMT expression and follow-up data: including fate, DFS and OS as well
as treatment protocol
Conclusions: MGMT expression is not a prognostic factor
in neuroblastoma. This result must be validated on a larger
number of cases.
P-123 The Relation of Microenvironment
Associated Gene Expression with Risk
Classification in Neuroblastoma
S. Aktas1 , P. Ercetin1 , E. Serinan1 , M. Aydın1 , Z. Altun1 , N. Olgun1
1 Dokuz
Eylul University, Institute of Oncology, Izmir, Turkey
Background/Objectives: Tumor microenvironment is a significant and current topic for invasion, spreading, metastasis
and survival of cancer cells. Neuroblastoma is usually poor in
terms of stroma and inflammatory elements. It shows a wide
spectrum of clinical behaviors from very aggressive forms to
spontaneous regression so tumor microenvironment should be
considered and evaluated. The aim of the study was to compare microenvironment associated gene expressions of low,
intermediate and high risk neuroblastoma with normal control cells and mature ganglioma.
Design/Methods: CFLAR, TNFSF10, BCL2L1, PIK3R1,
PPP3CA, EGFR, FGF1, FGF14, FGF23, TGFBR1, polo-like
kinase 1, CD47 expression levels were analyzed with realtime PCR from RNA and cDNA samples of fresh tumor tissues. Fold change analysis were evaluated in compare with
control group.
Results: 28 cases were included with 39 months mean
age (1-168 months) and 19 were female, 9 were male.
There were 9 high, 5 intermediate and 11 low risk cases.
Three cases were mature ganglioneuroma. When gene expression profile of high risk cases were compared with control
TNFSF10, BCL2L1, FGF1, FGF23 and CD47 expressions
were increased while CFLAR, PPP3CA, EGFR and FGF14
SIOP ABSTRACTS
were decreased. BCL2L1, FGF1 and CD47 expressions were
increased in intermediate risk cases. BCL2L1 expression
which was increased in all cases, was found to be more in
ganglioneuroma cases. High expression of EGFR stood out in
low risk cases. PPP3Ca expression was decreased in all cases.
CD47 gene which has a role in immune escape, did not show
difference in ganglioneuroma while significantly increased in
low risk cases. TGFBR1, PLR, FGF14 did not show expression difference in neuroblastoma.
Conclusions: When ganglioneuroma, low, intermadiate and
high risk neuroblastoma were considered as a spectrum
TNSF10 and FGF showed a gradient increase which suggested as candidate risk defining malignancy marker. The
increased expression of CD47 was also suggested a remarkable immune escape role for neuroblastoma.
P-124 The Effects of Rosiglitazone on Minimal
Residual Disease Model of Neuroblastoma
Z. Altun1 , M. Ayla1 , S. Aktas1 , A. Pamukoglu1 , P. Ercetin1 , N.
Olgun2
1 Dokuz
Eylul University, Basic Oncology, Izmir, Turkey; 2 Dokuz Eylul
University, Pediatric Oncology, Izmir, Turkey
Background/Objectives: The major problem in advanced
neuroblastoma is presence of minimal residual disease
(MRD).We investigated the effect of peroxisome proliferatoractivating receptor (PPR) agonist, antidiabetic rosiglitazone
(RGZ), which regulating cell proliferation and differentiation,
on neuronal stem cell differentiation by using MRD model.
Design/Methods: PPRgamma expressed and not expressed,
SH-SY5Y and KELLY neuroblastoma cells were used for
MRD model with using increasing LD90 doses of recurrent
cisplatin (CDDP) for 1.5 year. CDDP(10-400 uM), RGZ(0,1100uM) and CP-RGZ combinations were applied and viability of cells was determined with using WST-1, apoptosis
with Annexin-V/PI and differentiation with using immunohistochemically S-100 and flow cytometric Oct-3, Nestin and
Sox-2.
Results: In MRD model of SH-SY5Y cells, viabilities and
apoptosis were 37.3% and 74.5% with CDDP, 35.3 % and
82.9 % with RGZ100, 33.2% and % 83.4 with CDDP-RGZ.
S-100 expression was similar in both MRD model and normal cells. In CDDP treated KELLY cells, differentiation was
slightly increased. In CDDP-RGZ combination, differentiation was not different from CDDP. RGZ treatment to MRD
model of SH-SY5Y cells caused less differentiation. Differentiation of survivaed cells was similar both CDDP treated
and control cells. The CP-RGZ application revealed that the
remaining cells were less differentiated than CP alone. In
particular, expression of Oct-3 and Sox-2 in SH-SY5Y cells
caused reduction in CP-RGZ administration in MRD model.
S223 of S518
Conclusions: CDDP and RGZ and combinations in neuroblastoma MRD-developing KELLY cells cell death at similar levels, whereas in PPR� expressed SH-SY5Y cells, RGZ
killed more cells than CDDP and in combination. CP-RGZ
was effective in decreasing Nestin and Sox-2 expressions of
neuronal stem cell differentiation markers in SH-SY5Y MRD
model. Examination of the effects of PPRgamma-agonist
antidiabetic agents, such as rosiglitazone, in the in vivo models of metastatic neuroblastoma may provide a new perspective on neuroblastoma therapy.
Acknowledgments. This study was supported by TPOG.
P-125 Effectiveness and Toxicity of Headstart I
and II Protocols: Experience from a Low-Middle
Income Country
A. Elshahoubi1 , N. Amayiri2 , E. Khattab3 , H. Halalsheh1 , E.
Bouffet4
1 King
Hussein Cancer Center, Pediatric Hematology and oncology,
Amman, Jordan; 2 KHCC-Jordan, Pediatric Oncology Department, Amman,
Jordan; 3 King Hussein Cancer Center, Stem Cell transplantation- Pediatric
Department- KHCC- JordanE, Amman, Jordan; 4 The Hospital for Sick
Children- Canada, Neuro-oncology Division, Toronto, Canada
Background/Objectives: HeadStart protocols (HS), a highdose chemotherapy strategy for infants with malignant CNS
tumors, reported variable success and toxicity profiles. Their
benefit-risk ratio is rarely reported from low-middle income
countries (LMIC). We aimed to evaluate our HS experience
at KHCC/ Jordan.
Design/Methods: We retrospectively reviewed charts of children diagnosed with CNS tumors and treated with HS
(2006-2015). Data collected included patients’ demographics,
chemotherapy complications and cost.
Results: Eighteen patients, median age 27 months at diagnosis (10-62months), were identified (twelve HS-I, six HSII). Twelve (66%) had non-metastatic disease and four
(22%) had GTR. Pathology was ATRT (9), PNET (6) and
Medulloblastoma (4). Three patients didn't complete induction cycles (2 ATRT progressed, I PNET failed stemcell collection). Fifteen patients (83%) completed induction
chemotherapy; eleven (61%) went into CR/PR, two stabilized, two progressed. Seven patients didn't receive SCT
(tumor progression(2), financial causes(2), failed stem cell
collection(1), family decline(1) and (1)unknown. Six patients
(40%) received radiotherapy; two (residual ATRT) following
SCT, two (ATRT) with financial limitations, two (1 ATRT,
1 Medulloblastoma) upon tumor progression. Seventy-one
chemotherapy cycles were administered (median interval
23 days). Complications during induction and consolidation
phases were febrile neutropenia (75% &100%), documented
infections (11% &13%), PICU admissions (3% &0), and
mucosits (11% & 88%), respectively. Three patients (20%)
SIOP ABSTRACTS
S224 of S518
developed hearing deficit and one tubulopathy. At last follow
up, 5 patients are alive: three patients with Medulloblastoma
(9, 18, 71months); one received CSI 18/54Gy and chemotherapy at relapse. Two patients (29%) with ATRT are alive (8,
27months); both received focal radiation on residual tumor.
No chemotherapy-related deaths occurred. The median hospitalization was 78 days (71-94days).The median cost of treatment was 91,000$.
Conclusions: Toxicity of HS was manageable for LMIC, but
the financial cost was high for a limited survival. Better selection criteria (e.g. high risk medulloblastoma, HS-I, and financial support) may outbalance survival over cost.
P-126 Minimally Invasive Surgery in Children
with Intraabdominal Neuroblastoma
E. Andreev1 , T. Shamanskaya2
1 Dmitry
Rogachev National Research Center of Pediatric HematologyOncology and Immunology, pediatric surgery and oncology, Moscow,
Russia; 2 Dmitry Rogachev National Research Center of Pediatric
Hematology- Oncology and Immunology, pediatric oncology, Moscow,
Russia
Background/Objectives: One of the promising areas in pediatric oncology is MIS in children with thoracoabdominal
neuroblastoma.We investigated and comparing the result of
laparoscopy and laparotomy treatment.
Design/Methods: Radical surgical treatment was performed
in 224 patients(01.2012 - 10.2016).Laparoscopy was performed in 39(17.4%).Patients were treated according to
NB2004 protocol.Image-defined risk factors(IDRF) and size
of the tumor were used to select patients.To compare the
effects of laparotomy with those of laparoscopy in patients
with neuroblastomas without IDRFs, the following items were
retrospectively compared: largest tumor dimension, volume
of blood loss, time required to initiate postoperative feeding,
locoregional recurrence rate, survival, etc.
Results: 31 patients without IDRFs(20 at low-medium
risk and 11 at high risk) underwent laparotomy, and
39 patients without IDRFs(31 low-medium risk and 8
at high risk) underwent laparoscopy.Median age was 14
months(1 – 69) after laparotomy and 11 months(3 –
62) after laparoscopy (p=0.68).Median duration of surgery
was 120(70-200) and 135(50 - 300) min(p=0.15).Median
postoperative time required for resuming meal consumption was significantly longer in the laparotomy group(2
days; 1–4) than that in the laparoscopy group(0 days;0–
10;p=0,000005).Median blood loss was significantly higher
in the laparotomy group(20 ml;0–200) than in the laparoscopy
group(0 ml;0-100;p = 0,01).Median time of draenage removal
was higher in the laparotomy group(4 ml;0-8) than in the
laparoscopy group(2 days;0-13;p= 0,001).Median time of
analgesia was higher in the laparotomy group(4 days;2-6) than
in the laparoscopy group(2 days;1-5;p=0,000002).Median
time of antibacterial therapy was higher in the laparotomy
group(6 days;3-11) than in the laparoscopy group(5 days;110;p=0,000002).Median follow-up time was 36 months.We
have not differences in intraoperative and postoperative complications, local reccurence and mortality in postoperative
period.
Conclusions: MIS in children with intraabdominal neuroblastoma is an effective technique which enables to carry out
radical surgery in the absence of contraindications and IDRF
and provides minimally invasiveness and good cosmetic effect
without worsening oncological prognosis.
P-127 MYCN Mediates Metabolic
Reprogramming in Childhood Neuroblastoma
M. Arsenian Henriksson1 , G. Oliynyk1 , M.V. Ruiz Perez1 , J.
Dzieran1 , H. Zirath1 , H. Johassson2 , J. Lehtio2
1 Karolinska
institutet, Microbiology- Tumor and Cell Biology, Stockholm,
Sweden; 2 Karolinska institutet, Oncology/Pathology, Stockholm, Sweden
Background/Objectives: Neuroblastoma (NB), which arises
from the developing sympathetic nervous system, is one of
the most aggressive solid tumors of early childhood. Amplification of the MYCN oncogene is found in around 30% of
NB patients and is associated with rapid tumor progression
and poor prognosis. Our recent findings show that targeting
of MYCN with small molecules including JQ1 and 10058F4 results in metabolic changes including mitochondrial dysfunction leading to accumulation of lipid droplets in NB cells
(Zirath et al, PNAS 100, 10258-10263, 2013).
Design/Methods: To investigate downstream effects of
MYCN targeting we have performed quantitative proteomics
of MYCN-amplified NB cells where MYCN has been downregulated using short hairpin RNA against MYCN. We identified over 7,000 proteins of which around 2250 have been
used for identification of novel pathways involved in neuroblastoma pathogenesis. We have also performed metabolic flux
analysis.
Results: We found that primary metabolic processes including protein, lipid and nucleic acid metabolic processes were
the most significantly affected activities upon MYCN downregulation. For analysis of the impact of MYCN expression on glycolysis and mitochondrial capacity we performed
metabolic flux measurements using a Seahorse XF analyser. Our data show that MYCN-amplified NB cells have a
high metabolic potential and that they primarily use oxidative phosphorylation for their energy consumption. We also
found that MYCN not only positively regulates the respiratory
capacity but also significantly enhances glycolysis. Importantly, we demonstrate that MYCN positively regulates the
ability of NB cells to oxidize exogenous fatty acids.
SIOP ABSTRACTS
Conclusions: Taken together, our findings show that MYCN
expression enhances the bioenergetic capabilities and that
NB cells can shift their metabolic processes depending on
the available nutrition. Our data highlights the importance
of metabolic pathways for tumor aggressiveness, which may
be the basis for future cancer therapies for patients with
NB.
P-128 The Chemotherapy Response of Very Early
Stage in Neuroblastoma Patients with N-MYC
Amplification
C. huang1 , X. ma1 , Z. yue1 , M. jin1 , D. zhang1 , W. zhao1 , Q. zhao1 ,
X. wang1 , C. duan1 , T. xing1 , S. li1 , Y. chen1 , X. chai1
1 Beijing
Children's Hospital, Hematology Oncology Center- Capital
Medical University, Bei Jing, China
Background/Objectives: To summarize the clinical features
of neuroblastoma with N-myc amplification. Analyse the biofeatures and evaluate the effect of chemotherapy in early
stage
Design/Methods: The research analyzed the medical records
of 38 patients with N-myc amplification of NB from Feb 2012
to Dec 2016 in Beijing children's hospital. The regimen were
according to the protocol of our hospital, which based on the
N7 protocol. The data were reviewed for the medical history.
Analysised the viration of biomarker and the primary site, to
object the short-term effect of chemotherapy.
Results: 38 cases admitted in the research, The primary site of
tumor is retroperitoneal, adrenal area. 27 cases are positive in
bone marrow cytomorpholigic examination. The proportion
of tumor range 10-50% is 3 cases, above 50% is 14 cases. Of
all the cases, 37 reported that they had the lactate dehydrogenase (LDH) level higher than the normal. Only 1 case under
500U/L. 29 cases above 1000U/L. The diameter of tumor
lager than 10cm are 32 cases. 33 cases measure the volume. 12
cases are <100cm3, 11 cases range 100cm3 -500cm3,10 cases
larger than 500cm3. All the 38 cases have finished 2 courses
chemotherapy. 35 cases reduce to under 1000U/L. Among the
38 cases, 36 cases’ bone marrow examination reverse to negative. According to the imageological examination, the overall
response rate after 2 courses chemotherapy is 84.8%. 1 case
achieve VGPR, 21 cases achieve PR, 7 cases achieve MR, 2
cases are NR, while 2 cases show PD.
Conclusions: NB with N-myc gene amplification are sensitive to chemotherapy. Chemotherapy can minish the burden
of tumor in early stage. But because of the huge burden and
the huge size of tumor, it is not the ripe opportunity to receive
the surgery or the autologous stem cell transplantation. The
patient should go on receiving chemotherapy for remission of
disease.
S225 of S518
P-129 Characteristics of Mediastinal
Neuroblastoma Detected by Chance in Children
Older Than 18 Months in Japan
Y. Cho1,2 , A. Iguchi1 , J. Ohshima1 , M. Sugiyama1 , Y. Terashita1 , T.
Ariga1
1 Hokkaido
University Hospital, Pediatrics, Sapporo, Japan; 2 Hokkaido
Cancer Center, Pediatrics, Sapporo, Japan
Background/Objectives: Neuroblastoma is an aggressive
malignant and heterogeneous tumor in children. Cases under
18 months old, or cases with primary tumor arising from
mediastinum tend to have a better prognosis. We sometimes
detect by chance cases with mediastinal neuroblastoma when
doing an imaging examination for mild respiratory illness in
older children. Clarifying their characteristics is important for
appropriate treatment.
Design/Methods: We analyzed patients with neuroblastoma
diagnosed at Hokkaido University Hospital and Hokkaido
Cancer Center from 1989 to 2016 retrospectively. Cases under
18 months old, and cases detected by mass screening or with
apparent tumor-related symptoms were excluded. Analytical factors included primary site, detection, stage, pathology,
molecular biology, treatment and outcome.
Results: Out of 221 patients with neuroblastoma, 11 cases
were with mediastinal neuroblastoma detected by chance
over 18 months old. Nine cases were detected by X-rays for
examining pneumonia/ bronchitis, 1 by abdomen CT scan,
1 by health checkup. Serum NSE levels were from 12.4 to
26.4 (cut off; 12 ng/mL), VMA in urine from 4.3 to 37.1
(cut off; 13mcrg/mgCr), and HVA from 0.7 to 56 (cut off;
27mcrg/mgCr). Eight cases were totally resected with videoassisted thoracoscopic surgery/ open thoracic surgery. Two
were limited to partial resection even in open thoracic surgery.
One had only biopsy for diagnosis. Eight cases were in INSS
stage 1, one case in stage 2, and 2 cases in stage 3. Six
cases were ganglioneuroblastoma and 5 were ganglioneuroma. MYCN gene was not amplified in any case. Chemotherapy was performed for 2 cases before 2000. Cases after 2000
had no chemotherapy even with partial resection. All were
alive for more than 3 years after diagnosis.
Conclusions: Almost every case with mediastinal neuroblastoma detected by chance over 18 months old showed characteristics of low risk group. Good prognosis can be expected
without drastic treatment.
P-130 Minimal Residual Disease in Bone Marrow
of Patients with High Risk Neuroblastoma in 31
Patients from a Single Institution in Argentina
M. CIMOLAI1 , A. MEDINA1 , R. MITCHELL2 , P. RUBIO1 , J.
ROSSI2 , P. ZUBIZARRETA1 , W. CACCIAVILLANO1 , C.
ALONSO1
SIOP ABSTRACTS
S226 of S518
1 Hospital
de Pediatría Prof. dr. Juan P. Garrahan, Hematology and
Oncology, Buenos Aires, Argentina; 2 hospital de Pediatría Prof. dr. Juan P.
Garrahan, Immunology and Rheumatology Department, Buenos Aires,
Argentina
Background/Objectives: The outcome of neuroblastoma
(NB) is dependent on several well stablished prognostic factors. Bone marrow (BM) evaluation by conventional cytology,
at diagnosis and during treatment, has limited sensitivity and
it is not suitable for minimal residual disease (MRD) detection. PHOX2B measurment by quantitative-RT-PCR has been
described as a sensitive and specific marker for MRD analysis.
Our aim was to perform molecular MRD evaluation at different time points in order to evaluate the prognostic value of
PHOX2B in our population of high-risk patients.
Design/Methods: Quantitative RT-PCR for PHOX2B was
performed in 271 BM samples from 31 patients with highrisk-NB treated at the Garrahan Pediatric Hospital with first
or second line treatment protocols. A median of 8 samples per
patient were evaluated [range: 2-19]. Median follow-up time
was 13 [range: 3-44] months. The prognostic impact of MRD
at diagnosis (n=22), after cycle 3 (n=22), after cycle 5 (n=20),
or at any follow-up time (n=28) was evaluated using Fisher's
and Log-rank-tests.
Results: PHOX2B was detected in 21/22 evaluable samples
at diagnosis, and in 9/22 after cycle 3, and no correlation was
found between outcome and MRD status at both time points.
However, molecular BM remission (PHOX2B not detectable)
was associated with a better outcome for MRD negativity after
cycle 5 (10/20; Fisher-p=0.0364; 2-y-pEFS: 64±17% versus 33±19%; Log-Rank-p=0.0928) or MRD negativity at any
follow-up time (9/28; Fisher-p<0.0001; 2-y-pEFS: 80±18%
versus 24±11%; Log-Rank-p=0.0038).
Conclusions: Despite the limited number of patients included
in the study, negative MRD in BM samples after cycle 5,
or at every follow-up time during treatment, seems to identify a group of patients with high-risk-NB with a significant
better outcome. No association was found between PHOX2B
at diagnosis or after cycle 3 of treatment. These preliminary
results suggest that PHOX2B-could be a useful MRD marker
in our population of patients with high-risk NB.
P-131 MLN8237 Induces Cellular Senescence by
Down-Regulation of N-MYC in Neuroblastoma
A. Liu1 , L. Ding2 , Y. Yang3 , Y. Liu4 , J. Sun5 , Q. Hu5
1 Tongji
Hospital- Tongji Medical College- Huazhong University of Science
& Technology, Pediatrics, Wuhan, China; 2 Tongji Hospital - Tongji Medical
College - Hua Zhong University of Science and T, Pediatrics, Wuhan,
China; 3 Tongji Hospital-Tongji Medical College- Huazhong University of
Science & Technology, Experimental Medicine Center, Wuhan, China; 4 UT
Southwestern Medical Center, Radiation Oncology, Dallas, USA; 5 Tongji
Hospital-Tongji Medical College- Huazhong University of Science &
Technology, Pediatrics, Wuhan, China
Background/Objectives: Neuroblastoma is one of the most
common malignancy pediatric solid tumors and the prognosis
of high-risk neuroblastoma is still poor. MYCN amplification
is a risk factor and the stability of N-MYC is closely linked to
Aurora A. In this study, we investigated the effect and molecular mechanism of senescence induced by MLN8237 (Alisertib), a small molecule that selective inhibit Aurora A, in high
risk neuroblastoma.
Design/Methods: Senescence was detected by SA-�-gal
staining. The related proteins expressions were analyzed by
Western blot. In vivo experiments were carried out in tumor
xenograft model mice.
Results: MLN8237 could induce neuroblastoma cells senescence by N-MYC down-regulation via inhibiting the phosphorylation of Aurora A. It could also inhibit tumor growth and
prolong the survival time of xenograft tumor mice. However,
some senescent cells tended to recover from cell cycle arrest
during the MLN8237 treatment in vitro. We found MLN8237
activated the interleukin-6 and signal transducer and activator of transcription factor-3 (IL-6/STAT3) pathway, which
could promote the tumor progression and recurrence. When
IL-6/STAT3 of senescence neuroblastoma cells were inhibited by LLL12, a small molecule STAT3 inhibitor, senescence
reversion could be suppressed.
Conclusions: MLN8237 Induces Cellular Senescence by
down-regulation of N-MYC in Neuroblastoma and then activates the IL-6/STAT3 pathway of senescent cells. These
results provide a new relapse mechanism of neuroblastoma
and exploring novel therapeutic targets on cellular senescence
and IL-6/STAT3 signaling.
P-132 The Value of Detection of Circulating
Tumor Cell in Neuroblastoma Patients on the
Prognosis and Treatment Evaluation
K. Dong1 , X. liu1 , R. Dong1
1 Children's
Hospital of Fudan University, surgery, Shanghai, China
Background/Objectives: Circulating tumor cells (CTCs) has
been shown to be associated with prognosis and therapeutic
efficacy in many tumors. We detection the peripheral blood
circulating tumor cells in neuroblastoma and discuse its value
on the prognosis and treatment evaluation.
Design/Methods: There were 28 newly diagnosed cases of
neuroblastoma. The circulating tumor cells were collected by
the negative enrichment method combined with i-FISH. The
relationship between the number of circulating tumor cells
and the clinical factors were analyzed. In addition, the peripheral blood CTC of other types solid tumors was examined to
assess the difference with neuroblastoma.
SIOP ABSTRACTS
Results: In children with distant metastases, the number of
CTCs is higher than those in other types of tumors. The number of CTCs in the high, middle and low risk groups of children were statistically different (Mean rank diff = 8.583).
The number of CTC in children with N-myc positive was
lower than that in N-myc-negative children (p = 0.6133).
24-hour urine VMA has no relationship with CTC numbers,
but serum NSE has positive correlation with CTC numbers,
Spearman test, r = 0.463 95% CI (0.09713, 0.7186), p =
0.0131. There was significant difference between the distant
metastasis group and non-metastasis group (p <0.0001). For
those whose CTC number >10, the number is significantly
went down in 80% of the patients after the chemotherapy.
After 16 months of follow-up, The ROC curve shows AUCROC is 0.81, 95% CI (0.57, 1.04) and the cutoff was 6. The
survival time for those CTCs number>5 at the time of dignose
was shorter.
Conclusions: The number of peripheral blood CTC in children with neuroblastoma is higher than in other solid tumors.
CTC number is associated with COG classification, distant
metastasis, and serum NSE levels.
The survival time of those children with peripheral blood CTC
number> 5 is shorter than those number<5.
P-133 Combination of Micro-RNA 128A
Downregulation and TERT Overexpression
Predicts Unfavorable Outcome in Neuroblastoma
Patients
S227 of S518
were utilized for group separation in subsequent survival analysis. Median of follow-up time achieved 5.8 years.
Results: Abundant TERT expression and lack of miR128A
expression resulted in superior frequency of adverse events
(p=0.027, TL=4,7E-3 and p=0.004, TL=4.6E-2 respectively). EFS in group of patients with TERT expression above 4,7E-3 (group TERT) was 0.66SE0.07, in
patients with miR128A expression below 4.6E-2 (group
miR128A) was 0.64SE0.15, patients harboring both TERT
overexpression and lack of miR128A expression (group
miR128/TERT) had dismal outcome: EFS 0.29SE0.11, comparing to patients without these abnormalities (group neither): EFS 0.92SE0.06, p<0.001. Analogously cumulative
incidence of progression in the group TERT was 0.32SE0.07,
miR128A – 0.36SE0.15, miR128A/TERT – 0.71SE0,11, neither – 0.08SE0.06, p<0.001.
MYCN amplified (MNA) cases were accumulated in the
groups TERT and miR128/TERT (p=0.061), while gain
of chromosome 17, 9p and 14q deletions prevailed in
the group neither (p=0.014, 0.043 and 0.017 accordingly).
MNA and 14q deletion had prognostic significance in the
correspondent groups (p<0.001, p=0.022). The classifier
was proposed for distinguishing patients with unequal outcome: MNA EFS=0.25SE0.11, MYCN single copy patients
divided into groups miR128A/TERT (0.40SE0.15), miR128A
(0.60SE0.15) and TERT (0.74SE0.08). Group neither was
separated basing on presence (0.71SE0.17) or absence
(EFS=1.00) of 14q deletion, p<0.001.
Conclusions: Levels of miR128A and TERT expression
together with cytogenetic data allow discriminating patients
into groups with significantly different outcome.
A. Druy1 , G. Tsaur2 , E. Shorikov3 , A. Zaychikov4 , Y.
Olshanskaya1 , L. Saveliev5 , L. Fechina4
1 National
Scientific and Practical Center of Pediatric HematologyOncology and I, Laboratory of Cytogenetics and Molecular Genetics,
Moscow, Russia; 2 Research Institute of Medical Cell Technologies,
Laboratory of Cellular Therapeutics of Oncohematological Disorders,
Yekaterinburg, Russia; 3 PET-technology Center of Nuclear Medicine, PET
diagnostics, Yekaterinburg, Russia; 4 Regional Children's Hospital N1,
Department of Pediatric Oncology, Yekaterinburg, Russia; 5 Ural State
Medical University, Chair of Laboratory Medicine, Yekaterinburg, Russia
Background/Objectives: Clinical heterogeneity is a hallmark of neuroblastoma (NB). TERT hyperexpression was
identified as adverse prognostic marker, while significance of
microRNA expression profile in NB is undiscovered.
Aim. Investigation of prognostic significance of miR128A
and TERT expression in primary NB.
Design / Methods: RNA samples from 103 fresh-frozen NB
tissues were subjected to qRTPCR for miR128A and TERT
expression evaluation. Copy number variations were determined by MLPA and FISH. Correspondence of miR128A
and TERT expression levels to event-free survival (EFS) was
proved by ROC-analysis and established threshold levels (TL)
P-134 Magnetic Resonance Guided High
Intensity Focused Ultrasound Treatment Effects in
a Mouse Model of Neuroblastoma
A. Fahy1 , S. Papp2 , K. Piorkowska3 , A. Waspe3 , S. Pichardo4 , C.
Abraham4 , L. Curiel4 , L. Zhang5 , S. Baruchel5 , G. Somers6 , J.T.
Gerstle1
1 Hospital for Sick Children, General and Thoracic Surgery, Toronto,
Canada; 2 University of Toronto, Department of Laboratory Medicine and
Pathobiology, Toronto, Canada; 3 Hospital for Sick Children, Center for
Image Guided Innovation and Therapeutic Interventions, Toronto, Canada;
4 Thunder Bay Regional Research Institute, Image-Guided Interventions,
Thunder Bay, Canada; 5 Hospital for Sick Children, Department of
Hematology/Oncology, Toronto, Canada; 6 Hospital for Sick Children,
Department of Pathology, Toronto, Canada
Background/Objectives: Magnetic Resonance guided High
intensity focused ultrasound (MRgHIFU) is a non-invasive
technology that uses an extracorporeal focused ultrasound
transducer to converge high intensity focused ultrasound
(HIFU) energy onto a specific tissue target via MR guidance.
This focused ultrasound energy can induce localized thermal
SIOP ABSTRACTS
S228 of S518
necrosis of benign or malignant tissue while simultaneous
MR thermometry can monitor the temperatures of surrounding structures to avoid unintended thermal injuries. We aimed
to evaluate the effects of MRgHIFU in a mouse model of neuroblastoma (NBL).
Design/Methods: NOD/SCID mice (n=18) were inoculated
with a CHLA-15 NBL cell line in the left hind limb and tumor
growth monitored until size reached 5mm in largest dimension. Tumors (n=10) were treated with MRgHIFU at 42.5
acoustic Watts for 20 seconds. Control tumors (n=8) were
imaged but not treated. Immediately post-treatment, mice
were euthanized and the tumors immersion fixed in 10% neutral buffered formalin, paraffin embedded, and stained with
H&E and elastin trichrome for gross and histological evaluation.
Results: Tumors reached 5.1 +/- 1.7 mm in size (treated =
5.8 +/- 1.9 mm, untreated 4.2 +/- 0.6 mm). HIFU treatment
increased the temperature in the tumors to a range between
55◦ C and 80◦ C. Histological changes in the treated tumors
included confluent necrosis, diffuse single cell necrosis, and
large areas of intratumoral hemorrhage. Untreated tumors had
sporadic single cell necrosis and small areas of intratumoral
hemorrhage but no areas of confluent necrosis.
Conclusions: MRgHIFU can be used to cause localized thermal necrosis of tumors in a mouse model of NBL. Further
work is underway to investigate the effect of MRgHIFU on
tumor growth and mouse survival. MRgHIFU may offer a
potential additional local therapy to patients with recurrent or
refractory high risk NBL.
P-135 Does Salvage Chemotherapy Regimen
Intensity Embark on Clearance of Bone Marrow
Neuroblastoma?
A. elhemaly1 , M. fawzy1 , A. Hamoda1 , E. moussa2 , H. reda3 , S.
elmenawi4
1 national
cancer institute and children cancer hospital of egypt, pediatric
oncology, Cairo, Egypt; 2 children cancer hospital of egypt and elmonofia
university, pediatric oncology, Cairo, Egypt; 3 national cancer institute and
children cancer hospital of egypt, clinical pathology, Cairo, Egypt;
4 children cancer hospital of egypt, clinical research, Cairo, Egypt
Background/Objectives: neuroblastoma is the most common extracranial solid tumor in children. It accounts for 15%
of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at “high risk”
of treatment failure. This study aim was to evaluate the impact
of salvage chemotherapy ICE (Ifosfamide, Carboplatin, and
Etoposide) versus TC (Topotecan/Cyclophosphamide) when
administered to neuroblastoma high risk patients having residual bone marrow disease after primary tumor control on first
line treatment regimen.
Design/Methods: the present retrospective study included 2
matched groups of eligible stage 4 neuroblastoma patients
with persistent bone marrow disease. Each group consisted
of 36 patients. Group (1) patients received ICE whereas less
intensive TC was administered to Group (2). Data analysis included epidemiological variables, pathology subtype,
NMYC gene status, primary tumor response and their correlation with bone marrow disease clearance on each regimen.
Results: higher tendency of complete bone marrow clearance
was reported in patients received ICE compared to TC; 33.3%
versus 22.2%, respectively. However, the difference was not
statistically significant (p= 0.293).
Conclusions: TC regimen appears to be non-inferior to ICE
as salvage treatment in attempt to clear bone marrow neuroblastoma residual, with the privilege of being less toxic and can
be given on outpatient basis. Yet, further randomized trials of
larger study sample size and with survival impact analysis are
warranted.
P-136 Quality Indicators in Neuroblastoma
(NBL) Treatment
P. Hoogerbrugge1 , S. Dijkstra2 , M. Van Noesel1 , L. Tytgat1 , M.
Wijnen1 , K. Kraal1
1 Princess
Máxima Center for Pediatric Oncology, Ped Oncology, Utrecht,
The Netherlands; 2 Princess Máxima Center for Pediatric Oncology,
Honours Program UMCU, Utrecht, The Netherlands
Background/Objectives: To improve neuroblastoma (NBL)
treatment within a center, and compare NBL treatment
between centers, quality indicators may be helpful as surrogate markers of effective treatment. In our study, we report
data of 4 quality indicators (diagnostic work-up, thyroid protection at MIBG-scanning, treatment-delay and use of tumor
board meetings) that may correlate with treatment effectivity
and toxicity.
Design/Methods: A cross-sectional, retrospective analysis
was performed of Dutch patients treated for NBL in the
national centralized facilities of the Princess Máxima Center. Medical records were reviewed to extract information
on demographics, treatment and quality of care indicators.
The variables recorded included 1: time-interval from presentation to complete diagnosis,2: use of thyroid prophylaxis
before MIBG imaging, 3: chemotherapy intervals and 4: use
of tumor-board meetings. Analysis of surgical procedures is
topic of another study, and not included in this analysis.
Results: Data of 47 patients treated between 2014 and 2017
were available for analysis. Patients were classified INSS
stage I in 2% of cases, stage II in 11%, stage III in 19%, stage
IV in 65% and stage IVS in 2%. Sixty-six percent of patients
with NBL were stratified for DCOG-NBL high-risk treatment.
The median time between presentation and complete diag-
SIOP ABSTRACTS
nostic work-up (urinary catecholamines, pathology, MIBGscan) was 8 days (range 2-42 days). Prescription of thyroidprophylactic treatment prior to MIBG-scans was recorded in
190 of 200 MIBG-scans (95%). In only 2 patients, the interval
between diagnosis and the end of the 6th chemotherapy-course
was more than 120% of the originally planned, protocolbased interval. Finally, we found that 75% (123 of 164) of
the protocol-based evaluations were discussed in tumor-board
meetings.
Conclusions: Identification and analysis of quality-indicators
in neuroblastoma treatment is feasible, and may provide tools
to improve treatment over time and compare treatment quality
between various centers.
P-137 Individualized Risk Assessment in
Neuroblastoma: Does The Tumoral Metabolic
Activity in I-123-MIBG-SPECT Predict the
Outcome?
J. Rogasch1 , P. Hundsdoerfer2 , C. Furth1 , F. Wedel1 , F. Hofheinz3 ,
P.C. Krüger4 , H. Lode5 , W. Brenner1 , A. Eggert2 , H. Amthauer1 , I.
Schatka1
1 Charité
University Medicine, Department of Nuclear Medicine, Berlin,
Germany; 2 Charité University Medicine, Pediatric Oncology, Berlin,
Germany; 3 PET Center- Helmholtz Zentrum Dresden-Rossendorf, Institute
of Radiopharmaceutical Cancer Research, Dresden, Germany; 4 University
Medicine Greifswald, Institute for Diagnostic Radiology and
Neuroradiology, Greifswald, Germany; 5 University Medicine Greifswald,
Department of Pediatric Oncology and Hematology, Greifswald, Germany
Background/Objectives: Risk-adapted treatment in children
with neuroblastoma (NB) occurs according to clinical and
genetic factors. This study evaluated the significance of
metabolic tumor volume (MTV) and its asphericity (ASP) in
pretherapeutic I-123-MIBG-SPECT (IMS) for individualized
image-based prediction of outcome.
Design/Methods: Retrospective analysis in 23 children (f:11;
m:12; median age, 1.8 [0.3-6.8] years) with primary diagnosis of NB consecutively examined by pretherapeutic IMS.
Primary tumor's MTV and ASP were defined using semiautomatic thresholds. Cox regression, ROC analysis (cutoff determination) and Kaplan-Meier (KM) analyses with
log-rank test for event-free survival (EFS) were performed
for ASP, MTV, laboratory parameters (such as urinary
homovanillic acid-to-creatinine ratio [HVA/C]), clinical (age,
stage) and genetic factors. Predictive accuracy of the optimal
multifactorial model was determined by Harrell's C and LR
� 2.
Results: Median follow-up was 36 [7-107] months (disease
progression/relapse, n=8; death, n=4). ASP (p=0.029; hazard ratio [HR], 1.032 for one-unit increase), MTV (p=0.038;
HR, 1.012) and MYCN (p=0.047; HR, 4.67) were the only
significant predictors of EFS in univariate Cox; only ASP also
S229 of S518
in multivariate analysis (p=0.026; HR, 1.042). Mean EFS for
high (>32.0%) vs. low ASP was 21 vs. 88 months (p=0.013),
and for high (>46.7 ml) vs. low MTV 22 vs. 87 months
(p=0.023). A combined risk model of either high ASP and
high HVA/C or high MTV and high HVA/C best predicted
EFS.
Conclusions: In this explorative study, pretherapeutic imagederived and laboratory markers of tumoral metabolic activity in neuroblastoma (ASP, MTV, urinary HVA-to-creatinine
ratio) allowed to identify children with high and low risk for
progression/relapse treated according to current therapy protocols.
P-138 Interim Results of a Clinical Trial of IDRF
for Intermediate-Risk Neuroblastoma from the
Japan Neuroblastoma Study Group (JNBSG)
T. Iehara1 , I. Yokota2 , A. Yoneda3 , T. Kamijo4 , A. Nakazawa5 , A.
Kikuta6 , T. Takimoto7 , S. Teramukai2 , H. Hajime1 , A.
Nakagawara8 , T. Tajiri9
1 Kyoto
Prefectural University of Medicine, Pediatrics, Kyoto, Japan; 2 Kyoto
Prefectural University of Medicine, Biostatistics, Kyoto, Japan; 3 Osaka City
General Hospital, Pediatric surgery, Oasaka, Japan; 4 Saitama Cancer
Center, Research Institute for Clinical Oncology, Saitama, Japan; 5 National
Center for Child Health and Development, Pathology, Tokyo, Japan;
6 Fukushima Medical University, Pediatric Oncology, Fukushima, Japan;
7 National Center for Child Health and Development, Center for Clinical
Research and Development, Tokyo, Japan; 8 Saga Medical Center Koseikan,
Saga Medical Center Koseikan, Saga, Japan; 9 Kyoto Prefectural University
of Medicine, Pediatrics surgery, Kyoto, Japan
Background/Objectives: We aim to reduce the incidence
of treatment complications and improve the outcomes
for neuroblastoma in intermediate-risk patients by using
low-dose preoperative chemotherapy without myeloablative
chemotherapy, and to make the treatment decision at the
time of the operation based on the image-defined risk factors
(IDRFs).
Design/Methods: Prospective single-arm studies (JN-I-10)
were conducted. Patients with INSS stage 3 without MYCN
amplification, including children of >12 months of age
with favorable histology and 12-18 months of age with
unfavorable histology, were treated with low-dose induction
regimen B (vincristine/cyclophosphamide/pirarubicin) or
C (vincristine/cyclophosphamide/carboplatin). If no IDRFs
were present, the patient underwent surgery. The resectability of the tumors was judged based on the IDRF every
3 courses. When the response rate was insufficient, the
treatment was changed to up to 9 courses of regimen D (vincristine/cyclophosphamide/pirarubicin/cisplatin).Patients
with stage 4 without MYCN amplification, including children <12 months and 12-18 months of age with favorable
histology and a DNA index of >1, were treated with 5 to 6
courses of regimen D. When possible, surgical resection was
SIOP ABSTRACTS
S230 of S518
performed based on the IDRF after 3 courses. Target sample
size was 73.
was observed in MNA tumour samples and in patients with
A313A genotype.
Results: At the planned interim analysis, 38 eligible patients
were enrolled in this trial (stage 3, n=9; stage 4, n=29).
The median age was 8 months (range, 0–45 months). The 3year progression-free survival rates of the whole study population, the stage 3 patients and the stage 4 patients were
84.4% (99.99%CI: 35.5-97.3), 88.9% (99.99%CI: 0.2-99.8),
and 82.5% (99.99%CI: 22.6-97.5), respectively. Ten percent
of the whole study population showed ileus, while 20%
showed pleural effusion and ascites as early complications
after surgery; however there were no long-term complications
of surgery. The trial was decided to continue.
Analysing 3-year overall survival (OS) we established that
patients with G313G genotype had significantly lower OS
(11.4% vs 45.8% - A313A, P=0.03; vs 37% - A313G,
P=0.04). With ROC-analysis we assessed the optimal criterions for patients distribution according to GSTP1 EL (p=0.04,
AUC: 0.64) and analysed OS according to GSTP1 polymorphism and EL. OS was significantly higher in patients
with A313G and low GSTP1 EL comparing to other groups
(P<0.05).
Conclusions: Our treatment strategy did not increase the incidence of long-term complications. This trial was decided to
continue.
Conclusions: GSTP1 G313G genotype was associated with
unfavourable prognosis in neuroblastoma, while patients with
A313G and low GSTP1 EL had higher OS. Analysis of GSTP1
polymorphism and expression along with other biomarkers is
an important step to improve neuroblastoma risk stratification.
P-139 GSTP1 Gene Expression and A313G
Polymorphism Can Affect Neuroblastoma Outcome
P-140 Immunohistological Characterization of
Intra-Tumor Hypoxia Biomarkers in
Neuroblastomas
M. Inomistova1 , N. Khranovska1 , O. Skachkova1 , G. Klymniuk2 , S.
Pavlyk2
S. Jannier1 , M. Luc2 , L. Benoit2 , L. Marie3 , D. Aurélie3 , E.W.
Natacha1
1 National
Cancer Institute, Laboratory of Experimental Oncology, Kiev,
Ukraine; 2 National Cancer Institute, Department of Pediatric Oncology,
Kiev, Ukraine
1 Hopitaux
Background/Objectives: Neuroblastoma - malignant paediatric tumour of sympathetic nervous system and is often
accompanied with MYCN amplification (MNA). Study of
glutathione-S-transferase P1 (GSTP1) which affects the
chemotherapy efficiency can help to understand the mechanism of neuroblastoma progression.
Background/Objectives: Neuroblastoma is the second most
frequent pediatric solid tumor. In high risk neuroblastoma,
Nmyc amplified and/or metastatic patients’ overall survival
is only 40% and there is no hope of cure in case of relapse.
Intra-tumor hypoxia appears to be correlated with an aggressive phenotype and resistance to chemotherapy as recently
described in neuroblastoma, but no specific study described
precisely the Pi3K/AKT/mTor/HIF-1a pathway involvement.
The pathway activation seems to be linked to poor prognostic
tumors. Recently, ATRX mutations has also been described in
association with high-risk neuroblastoma and possibly linked
to their hypoxia.
Design/Methods: Case group comprised of 144 children
with neuroblastoma and control group of 158 healthy donors.
A313G GSTP1 polymorphism was detected with allelespecific PCR in DNA from peripheral blood of patients and
healthy donors. GSTP1 expression level (EL) was analysed
with qRT-PCR in tumour samples using TaqMan primers and
probes.
Results: Polymorphism distribution in patients with neuroblastoma (A313A – 51.4%, A313G – 38.9%, G313G –
9.7%) complied with Hardy-Weinberg equilibrium (P=0.46).
G313G genotype was observed in patients with advanced
stages (8.8% - III and 12.2% - IV stages) and earlier occurrence age of neuroblastoma (median - 18 months, A313A –
28 months, A313G – 34 months). Most patients with MNA
had A313A genotype (63.1%) while most G313G patients had
non-MNA neuroblastoma (77%).
The highest GSTP1 EL was observed in tumours with
unfavourable clinical features (early occurrence age;
advanced stages; recurrent and metastatic foci). Lower EL
Universitaires de Strasbourg, Oncology, Strasbourg, France;
Universitaires de Strasbourg, Pathology, Strasbourg, France;
3 University of Strasbourg, EA3430, Strasbourg, France
2 Hopitaux
Design/Methods: A retrospective study was designed to
characterize to target by immunohistochemistry (IHC) Pi3K,
AKT, mTor and ATRX in neuroblastomas in 26 patients of
Strasbourg's center, who have signed with their parents an
informed consent.
Results: Six biomarkers were analyzed by IHC: HIF1-a,
HIF2-a, pAKT, pERK, pS6RP and ATRX. All patients were
negative for HIF1-a. HIF2-a was overexpressed in 16 patients
out of the 26, which among those 10 patients were high risk
patients. Among the 4 pAKT positive patients, 3 out of 4 were
also HIF2-a positive and 2 out of 4 had a pERK, pS6RP and
HIF2-a co-expression. Positivity for pERK (9 patients) and
pS6RP (9 patients) were mainly localized in vessels and only
SIOP ABSTRACTS
5 patients had concomitant pERK and pS6RP positive stainings. Loss of ATRX was observed in 8 patients without any
correlation with the other markers.
Conclusions: This preliminary study shows the implication
of hypoxia signaling pathway, and mainly HIF2-a in neuroblastomas.
P-141 Treatment Of Intermediate-Risk
Neuroblastoma: Experience of Russian Federal
Center
D. Kachanov1 , T. Shamanskaya1 , E. Andreev2 , D. Shevtsov1 , N.
Merkulov2 , A. Kazakova3 , S. Talypov2 , G. Tereschenko4 , V.
Roschin5 , D. Konovalov5 , A. Nechesnyuk6 , Y. Olshanskaya3 , E.
Feoktistova4 , Y. Likar7 , S. Varfolomeeva1
1 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Clinical Oncology, Moscow, Russia; 2 Federal Research
Center of Pediatric Hematology - Oncology - Immunology, Surgery,
Moscow, Russia; 3 Federal Research Center of Pediatric Hematology Oncology - Immunology, Cytogenetics, Moscow, Russia; 4 Federal Research
Center of Pediatric Hematology - Oncology - Immunology, Radiology,
Moscow, Russia; 5 Federal Research Center of Pediatric Hematology Oncology - Immunology, Pathology, Moscow, Russia; 6 Federal Research
Center of Pediatric Hematology - Oncology - Immunology, Radiation
Oncology, Moscow, Russia; 7 Federal Research Center of Pediatric
Hematology - Oncology - Immunology, Nuclear Medicine, Moscow, Russia
Background/Objectives: The aim of the study was to analyze
the clinical characteristics and results of therapy of patients
with intermediate-risk neuroblastoma treated in Russian federal center.
Design/Methods: 270 patients with neuroblastoma were
treated for the period 01.2012-06.2015 (42 months). The
diagnosis has been established on the basis of the international criteria. FISH was done to assess the status of 1p
and 11q. Patients were stratified and treated according to
the German NB2004 protocol. 19 (7.1%) patients were stratified to the intermediate-risk group. Therapy consists of 6
cycles of multiagent chemotherapy, surgery, radiation therapy to the MIBG-avid residual primary tumor after induction
chemotherapy, 4 cycles of maintenance therapy and 9 cycles
of 13-cis-retinoic acid.
Results: Male:female ratio was - 0.58:1. The median age was
10.4 months (range 1.6-91.5). The most common site of primary tumor was retroperitoneum - 12 (63.2%). Stage distribution: stage 4 - 12 (63.2%) cases, stage 3 - 6 (31.5%),
stage 2 - 1 (5.3%). 3 (15.8%) had segmental chromosomal aberrations. 17 (89.4%) patients received per protocol
therapy, 2 were treated with protocol modification because
of treatment-related complications. Surgery was done in 18
patients, macroscopic residual tumor was observed in 16
(88.8%). Radiation therapy was done in 3 (15.7%). After
induction therapy 12 (63.2 %) patients achieved complete
and very good partial response. There was no difference in
response rate between stage 4 and stage 2/3 (р = 0.65). Median
S231 of S518
follow-up was 37.0 months (range – 20.4–57.3). Progression/relapse was observed in 4 (21.0 %) cases. 4-year OS was
100%. 4-year EFS of the whole cohort was 78.9 ± 9.3 %. EFS
in patients treated without protocol violations was 93.7 ± 6.0
%.
Conclusions: Intensification of therapy in patients with
intermediate-risk neuroblastoma, compared with patients in
the observation group, allows achieving satisfactory results
given that therapy was provided without violations.
P-142 CNS Relapses of High-Risk
Neuroblastoma: Analysis of Risk Factors and
Clinical Outcomes
T. Shamanskaya1 , D. Kachanov1 , S. Ozerov2 , G. Tereschenko3 , Y.
Likar4 , V. Roschin5 , Y. Olshanskaya6 , A. Kazakova6 , A.
Nechesnyuk7 , S. Varfolomeeva1
1 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Clinical Oncology, Moscow, Russia; 2 Federal Research
Center of Pediatric Hematology - Oncology - Immunology, Surgery,
Moscow, Russia; 3 Federal Research Center of Pediatric Hematology Oncology - Immunology, Radiology, Moscow, Russia; 4 Federal Research
Center of Pediatric Hematology - Oncology - Immunology, Nuclear
Medicine, Moscow, Russia; 5 Federal Research Center of Pediatric
Hematology - Oncology - Immunology, Pathology, Moscow, Russia;
6 Federal Research Center of Pediatric Hematology - Oncology Immunology, Cytogenetics, Moscow, Russia; 7 Federal Research Center of
Pediatric Hematology - Oncology - Immunology, Radiation Oncology,
Moscow, Russia
Background/Objectives: CNS relapses in patients with highrisk neuroblastoma are an extremely unfavorable clinical
event. The aim of the study was to analyze the frequency of
occurrence and the factors predisposing to the development
of the CNS involvement in patients with high-risk neuroblastoma at the time of the first relapse.
Design/Methods: Patients with high-risk neuroblastoma who
received treatment for the period 01.2012 - 12.2015 were
included in the analyses. Patients were stratified to risk
groups and treated according to German NB2004 protocol. High-dose preparative regimens included melphalan/etoposide/carboplatin (MEC) (till June 2013) and treosulfan/melphalan (TreoMel) (since July 2013).
Results: 111 patients were analyzed. 58/111 (52.3%) had progression/relapse, CNS involvement was observed in 10/58
(17.2%). Isolated CNS involvement was noted in 7/10 (70%).
Median age at the time of the neuroblastoma diagnosis in
patients with CNS involvement was 27.3 months (range 1,843,5). Male: female ratio was 1.5:1. The primary tumor
located in the abdomen in 9/10 cases, unknown primary in
1/10. All 10 patients had stage 4 disease. MYCN amplification was detected in 8/10 (80%). Median time from diagnosis till progression/relapse was 15.2 months (range 5.9-20.0).
Comparison between two groups of relapsed patients (CNS
involvement/ lack of CNS involvement) by sex, age, site of
SIOP ABSTRACTS
S232 of S518
the primary tumor, MYCN gene status, skull metastases, bone
marrow involvement at the onset of the disease, the number of metastatic compartments, response to induction therapy before auto-HSCT, type of preparative regimen (CEM
vs Treo/Mel) showed no statistically significant difference. 2year overall survival after the development of CNS-relapse in
the study group was 13.1 ± 12.1%.
systems. ALKI1171T -expressing PC12 cells showed ligandindependent ALK activation, neurite outgrowth and downstream signaling activation. Further, ALKI1171T mediated
foci formation in NIH3T3 transformation analysis. Finally,
second-generation ALK-inhibitor ceritinib/LDK378 showed
14-fold better ability to abrogate ALKI1171T compared with
crizotinib.
Conclusions: CNS involvement at the time of relapse is
a frequent event in high-risk neuroblastoma. The introduction of CNS MRI into the standard work-up at the time of
relapse/progression will allow timely detection of metastases
to optimize the therapeutic strategy.
When life-threatening platinum-induced toxicity with
multiorgan complications had been handled/subsided
targeted treatment with ceritinib/LDK378 (450mg/m2 540mg/m2 ) was started as compassionate use. Elevated
urinary catecholamine-markers were normalized after the
first 4-week-treatment cycle. Hemoglobin normalized and
platelets improved to stable levels (>100). Metastatic disease gradually resolved and MRI showed 1/3-reduction
of the primary tumor that was then radically removed
after 6 months’ treatment. Complete radiological work-up
(MRI/CT-scan/mIBG), urinary catecholamines and bonemarrow investigations confirmed complete response after
21 months of ALK-inhibitor treatment without significant
side-effects (only mild GI-symptoms were noted).
P-143 Complete Clinical Response in High-Risk
Neuroblastoma After ALK-Inhibitor
Mono-Therapy Specifically Targeting the Novel
Activating I1171T ALK Mutation
P. Kogner1 , D. Treis1 , J. Siaw2 , S. Fransson3 , J. Guan2 , P.
Svenberg1 , M. Hansson4 , S. Wessman5 , L. Gordon6 , J. Stenman7 ,
P.J. Svensson7 , J.I. Johnsen1 , T. Martinsson3 , R.H. Palmer2 , B.
Hallberg2
1 Karolinska
Institutet, Childhood Cancer Research Unit, Stockholm,
Sweden; 2 Gothenburg University, Medical Biochemistry and Cell Biology,
Göteborg, Sweden; 3 Gothenburg University, Clinical Genetics, Göteborg,
Sweden; 4 Gothenburg University, Pathology, Göteborg, Sweden;
5 Karolinska Institutet, Oncology Pathology, Stockholm, Sweden;
6 Karolinska Institutet, Pediatric Radiology, Stockholm, Sweden;
7 Karolinska Institutet, Pediatric Surgery, Stockholm, Sweden
Background/Objectives: Personalized medicine and implementation of successful targeted therapies requires understanding of complex molecular mechanisms. Activating
ALK-aberrations are important genetic factors in neuroblastoma development and aggressiveness, and have been suggested for novel targeted therapies. Embryonal childhood
tumors with underlying Fanconi anemia are not available for
conventional chemotherapy and have a very poor outcome.
Design/Methods: A 15 month-old patient with 11qdeleted HR-neuroblastoma with bonemarrow, multiple
bone and intracranial metastases, was started on SIOPEN
COJEC-induction with severe long-lasting multi-organ
toxicity already after second chemotherapy-course found
to be due to underlying Fanconi anemia confirmed with
chromosome-breakage analysis and germline FANCAmutations
(c.2728C>T/c.4161-2A>C).
Subsequently
tumor sequencing revealed a novel somatic neuroblastoma
ALK(c.3215T>C; I1171T) mutation. In search for therapeutic opportunities the biological nature of this ALK-mutation
was characterized preclinically.
Results: We show here that this novel ALK tyrosine kinase
domain mutation of I1171 to threonine generates a potent
gain-of-function mutant, as observed in cell culture model
Conclusions: Here we show that the ALK(I1171T)-mutation
is activating and promotes neuroblastoma aggressiveness.
Monotherapy with ALK-inhibitor ceritinib induced complete
response in a child with metastatic high-risk neuroblastoma
unable to receive conventional treatment.
P-144 Exome Sequencing to Identify Novel
Neuroblastoma Predisposition Genes
C. Derpoorter1 , K. Vandepoele2 , A. Diez-Fraile1 , K.
Vandemeulebroecke1 , N. Van Roy3 , B. De Wilde1 , T. Lammens1 ,
G. Laureys1
1 Ghent
University Hospital, Department of Pediatric Hematology-Oncology
and Stem Cell Transplantation, Ghent, Belgium; 2 Ghent University
Hospital, Department of Laboratory Medicine, Ghent, Belgium; 3 Ghent
university Hospital, Center for Medical Genetics Ghent CMGG, Ghent,
Belgium
Background/Objectives: Genetic susceptibility to cancer has
been the subject of considerable interest in unraveling the etiology and natural history of cancer and plays an essential role
in understanding the molecular biology of cancer. Familial
clustering of childhood cancers is among the strongest suggestive situation of a genetic susceptibility.
Design/Methods: Exome sequencing was used to identify
novel cancer predisposition genes in a family with a boy
affected by neuroblastoma and his second cousin by a ganglioneuroma. Interestingly, we previously identified a de novo
constitutional translocation t(1;17)(p36.2;q11.2) in the boy,
which was absent in the affected second cousin (Laureys et al.,
1995; Laureys et al, 1990).
SIOP ABSTRACTS
Results: Predisposing variants were put forward as candidates through selection of non-synonymous, rare/novel variants, shared by the affected second cousins and mothers
(being first cousins) and not found in the spousal controls. Amongst others, we identified a deleterious mutation in CLEC12B (c.790A>G; p.E264K) located at the Cterminal end of the lectin C-type domain in a highly conserved region and potentially interferes with ligand interaction or homodimerization. Interestingly, Hoffmanns and colleagues, have shown that CLEC12B (12p13.2) binds PTPN11
and PTPN6. Interfering with this interaction protects against
natural killer cell-mediated cytotoxicity, indicating that mutations within CLEC12B may affect immune surveillance. Both
PTNP11 and PTNP6 are well-known cancer predisposition
genes (Hoffmann et al., 2007; Seishima et al., 2007; Jongmans et al., 2011). In silico analysis revealed that somatic
mutation frequencies for CLEC12B vary from 2.2% in medulloblastoma to 0.4% in head and neck carcinoma.
Conclusions: This and ongoing work highlights the value of
using index families with multiple children affected by cancer,
as a valuable source to identify novel cancer predisposition
genes.
*TL and GL are shared senior authors
P-145 External Beam Radiotherapy is not
Associated with the Incidence, Severity or Duration
of Sinusoidal Obstruction Syndrome
J. Lucas Jr.1 , S. Braunstein2 , V. Tolbert3 , A. Sunkara4 , G. Kang4 , R.
Goldsby3 , M. Krasin1 , S. Federico5 , C. Dvorak3 , V. Santana5 , W.
Furman5 , K. Matthay2 , L. Cunningham6
1 St
Jude Children's Research Hospital, Radiation Oncology, Memphis,
USA; 2 University of California San Francisco, Radiation Oncology, San
Francisco, USA; 3 University of California San Francisco, Pediatrics, San
Francisco, USA; 4 St Jude Children's Research Hospital, Biostatistics,
Memphis, USA; 5 St Jude Children's Research Hospital, Oncology,
Memphis, USA; 6 St Jude Children's Research Hospital, Bone Marrow
Transplantation and Cellular Therapy, Memphis, USA
Background/Objectives: Sinusoidal Obstruction Syndrome
(SOS) is a morbid complication of High Risk Neuroblastoma
(HRNB) therapy. We evaluated associations between external beam radiotherapy (EBRT), I131-MIBG, chemotherapy,
and clinical factors on SOS incidence, duration and severity
in HRNB patients.
Design/Methods: 98 newly diagnosed HRNB patients treated
from 1997 to 2016 at multiple institutions with induction
and consolidation chemotherapy, autologous stem cell transplant, radiotherapy and maintenance therapy[FS1] were retrospectively reviewed. We examined patient, laboratory, and
treatment characteristics up to 100 days post-transplant. SOS
prophylaxis, treatment, and complications (intubation, multiorgan failure, etc.) were documented. Generalized linear
S233 of S518
regression was used to assess the associations of covariates
with the incidence, duration and severity of SOS.
Results: Sixteen patients were diagnosed with SOS (median
time from transplant to SOS, 22 days [range, 9-130]). The
median duration of SOS was 13 days (range, 3-63). All
but 2 cases of SOS preceded EBRT. The median time to
EBRT from transplant in patients with and without SOS was
8.6 and 5.3 weeks respectively (p<0.001). Earlier time to
EBRT, prescription dose (Gy), and liver dose (Dmean, D25,
D50, D75) did not impact the incidence, duration, recurrence or severity of SOS. Induction (ANBL0532 vs. other,
p=0.005), and consolidation [(MEC vs. BuMel, �=-1.6263,
p=0.005), (MEC vs. MEC-PT, �=-3.0, P<.001)] chemotherapy impacted the duration of SOS. SOS-associated death
occurred in one patient who received I131-MIBG during consolidation. SOS incidence and complications were not different across I131-MIBG (N=8) and non-I131-MIBG (N=90)
treated patients (p=0.6). However, 2/2 I131-MIBG treated
patients who developed SOS required ICU support, compared
to 4/14 (29%) non-MIBG treated patients (p=0.12).
Conclusions: In this modern-treatment cohort, EBRT dose,
volume and timing after transplant did not impact the incidence, severity, recurrence or duration of SOS. Induction and
transplant conditioning impacted the duration and severity of
SOS.
P-146 Studies of the Mechanism in
Epithelial-Mesenchymal Transition Induced by
TGF-B1 in Neuroblastoma Cells
J. Shao1 , Z. Lu2
1 Shanghai
2 Shanghai
Children's Hospital, Hematology/Oncology, Shanghai, China;
Children's Hospital, Surgery, Shanghai, China
Background/Objectives: Neuroblastoma is the second most
common extracranial malignant solid tumor that occurs in
childhood. Metastasis is one of the major causes of death in
neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. This study
investigated the mechanism in EMT induced by transforming
growth factor (TGF)-�1 in SK-N-SH human neuroblastoma
cells.
Design/Methods: The present study focused on the regulatory effects of TGF-�1 on the EMT in human neuroblastoma SK-N-SH cells and the correlation with transcription
factor Gli using quantitative RT-PCR, western blot analysis,
immunocytochemistry, cell transfection, etc.
Results: We identified that the mRNA and protein expression
levels of E-cadherin were significantly decreased while �SMA were significantly increased after SK-N-SH cells were
treated with different concentration of TGF-�1. A scratch test
SIOP ABSTRACTS
S234 of S518
and transwell migration assay revealed that cell migration was
increased significantly with increasingly higher concentrations of TGF-�1. Which means TGF-�1 can induce the EMT
in SK-N-SH cells to increase SK-N-SH cell migration. Interference the expression of Smad2/3 did not affect the expression of the key molecules in the EMT. Further investigation
found the expression of transcription factor Gli increased significantly in EMT induced by TGF-�1 in SK-N-SH cells.
Interfering with the expression of Gli1/Gli2 can inhibit the
EMT induced by TGF-�1 in SK-N-SH cells. GANT61, which
target to inhibitors transcription factor Gli1 and Gli2, can
reduce the proliferation of cells, promote cell apoptosis.
Conclusions: The authors conclude that TGF-�1 can induce
the EMT in SK-N-SH cells to increase SK-N-SH cell migration. EMT induced by TGF-�1 in SK-N-SH cells may does
not depend on the Smad signaling pathway. Transcription factor Gli participates in the EMT induced by TGF-�1 through
Smad independent signaling pathways.
P-147 Synergistic Effect of Curcumin and
Nanoceria in the Treatment of Childhood
Neuroblastoma
J. Mazar1 , A. Rosado1 , T. Westmoreland1 , C. Neal2 , I.
Kalashnikova2 , S. Das3 , S. Seal2
1 Nemours
Children's Hospital, Biomedical Research, Orlando, USA;
of Central Florida, Materials Science and EngineeringAdvanced Materials Processing Center, Orlando, USA; 3 University of
Central Florida, Nanoscience Technology Center, Orlando, USA
2 University
Background/Objectives: MYCN-amplification is associated
with poor prognosis in human neuroblastoma, reflective of a
low overall survival rate in children with this gene amplification. As a result, we are investigating novel molecular formulations of nanoceria and dextran-nanoceria with curcumin,
each demonstrated to have anti-cancer properties, synthesized
and applied as a treatment for neuroblastoma. Anti-cancer
activities of these formulations were explored in neuroblastoma cells that were both MYCN-amplified and MYCN-nonamplified.
Design/Methods: To test these formulations, we utilized the
MYCN-amplified neuroblastoma cell lines IMR-32 and SMSKAN, as well as the non-amplified cell lines SK-N-AS and
LA-N-6. The effects induced in neuroblastoma cells by these
nano-formulations with curcumin were examined by MTS,
Caspase 3/7, ROS, and TUNEL assays, as well as by qRTPCR and Western blot analysis for changes in gene expression. HUVEC cells served as control cells to evidence the
cyto-protective effects of ceria nanoparticles.
Results: Ceria nanoparticles, coated with dextran and loaded
with curcumin, were found to induce substantial cell death
in neuroblastoma cells while producing no or minor toxicity
towards healthy cells. Death of neuroblastoma cells was con-
firmed to be due to apoptosis induced via BCL-2/BAX ratio
disruption and reactive oxygen species accumulation. Additionally, expression of HIF-1� was analyzed and shown to be
up-regulated in samples treated with ceria due to ceria's oxygen buffering capacity.
Conclusions: Treatment of human neuroblastoma cells,
both MYCN-amplified and MYCN-non-amplified, with ceria
nanoparticles successfully induced cell death. The additional
coating of the nanoceria with dextran appeared to further
enhance this phenotype. An analysis of the cause of cell death
suggested that apoptosis was induced due to the stabilization
of HIF-1�, indicating induction of hypoxic conditions and
significant accumulation of reactive oxygen species. Overall,
ceria treatments showed a more pronounced effect in MYCNamplified cells, which are traditionally more resistant to drug
therapies.
P-148 Stage IV Neuroblastoma Treatment,
Eleven Years Experience Hospital De Ninos Ricardo
Gutierrez Buenos Aires Argentina
A. Oller1 , M.F. Gutierrez1 , M. Urbieta1 , G. Puppa1 , S. Colli2 , M.
Garcia Lombardi1 , S.M. Acosta1 , R. Ramirez1
1 Hospital
de Niños Ricardo Gutierrez, Oncology Unit, Capital Federal,
Argentina; 2 Hospital de Niños Ricardo Gutierrez, Pathology, Capital
Federal, Argentina
Background/Objectives: To describe clinic, biologic and
histological features and overall survival(OS) of patients(p)
with stage IV (SIV) NBL treated at Hospital de Niños
Ricardo Gutiérrez (HNRG) Oncology Unit, Buenos Aires
Argentina.
Design/Methods: A retrospective and descriptive analysis of
medical records from p with SIV NBL admitted between
April 1st 2004 to December 31st 2015. Variables evaluated
were sex, age, primary site, tumor size, histology, N-myc
status, urinary catecholamines status, treatment, and overall
survival. After diagnosis p received chemotherapy induction
with cyclophosphamide, vincristine, doxorubicin, cisplatin,
VP-16. Local resection was performed follow by high doses
chemotherapy with autologous stem cell transplantation; primary tumor-bed radiotherapy and retinoic acid as maintenance. Kaplan-Meier method analysis was used to determine
overall survival(OS)
Results: Sixty-six p were diagnosed with NBL, 29(44%) were
stage IV NBL. Average age at presentation was 14.4 month,
ratio men:women 3:1. Primary site was adrenal gland (86%),
tumor size >0.10m in 75.8%. Most common histology was
poorly differentiated NBL (24%), N-myc status by fish was
performed in twenty tumor samples, amplified in 50%. Thirteen (44,8%) p completed treatment, 6/12p (46.1%) are alive.
Sixteen p did not complete treatment and die due tumoral
SIOP ABSTRACTS
progression during induction (55.1%) or to infectious complications (31.2%), which most take place before 2008. Relapsed
get 51%, from which bone marrow represented 20%.
Conclusions: Results obtained indicate that 50% of studied
patients with stage IV NBT presented N-myc amplification.
Global OS is 17.3% For patients who reach complete treatment OS is 46.1%, comparable with results of international
cooperative groups. In addition, an improvement in survival
is observed associated with an amelioration in healthcare in
the last years.
P-149 Exploring the Genomic Profiles of
Neuroblastomas by Comparative Analysis of Exome
Sequencing Versus aCGH Data
S235 of S518
Conclusions: Our project represents the first exome sequencing approach on NB in Norway. We have compared array
and sequencing data to the expression of relevant genes and
will enlarge our cohort with samples during different time
points of treatment. We expect that these data will reveal novel
insights into the genomics of NB and finally pave the way
towards genetic-clinical cancer platforms for actionable gene
targets.
P-150 Cytotoxic Activity of
Difluoromethylornithine Compared with
Fenretinide in Neuroblastoma Cell Lines
M. Makena1 , H. Cho1 , T. Nguyen1 , B. Koneru1 , D. Verlekar1 , A.
Hindle1 , B. Rodriguez1 , M. Kang1 , C.P. Reynolds1
W. Przybyla1 , G. Trøen2 , K. Beiske2,3 , L.O. Baumbusch1
1 Texas
1 Oslo
USA
University Hospital Rikshospitalet, Department of Pediatric
Research- Division of Pediatric and Adolescent Medicine, Oslo, Norway;
2 Oslo University Hospital Radiumhospitalet, Department of Pathology,
Oslo, Norway; 3 University of Oslo, Medical Faculty- Institute of Clinical
Medicine, Oslo, Norway
Background/Objectives: Next generation sequencing will
contribute to personalized pediatric oncology in the near
future, in particular for biologically and clinically heterogeneous diseases requiring multi-modal therapeutic approaches
like neuroblastoma (NB) - one of the major challenges in pediatric oncology. In NB specific copy number variations and
rearrangements of single genes have been reported including amplification of MYCN (20%) and mutations of the ALK
gene. We hypothesize that comparative genomic analysis of
mutations and copy number variations will provide novel
information about genes and signalling pathways relevant for
the heterogeneity and relapse in high-risk NB.
Design/Methods: Samples of tumor and normal DNA from
high-risk NB patients (n=20) are available from an existing
diagnostic biobank. Clinical and pathological information like
age and histopathology are known from routine diagnostics.
Additionally, FISH analyses have determined MYCN amplification status and possible chromosomal losses of 1p and 11q,
and gain of 17q. Samples of the primary tumors were analyzed
by whole exome sequencing using the Illumina HiSeq2500
platform with a mean coverage of 300. Additionally, the
same DNA samples were investigated by array comparative
genomic hybridization (aCGH) applying the Affymetrix SNP
platform (CytoScan HD array).
Results: Preliminary results reveal a high concordance
between aCGH profiles and copy number information provided by sequencing. Detailed studies were performed to
investigate specific genomic biomarkers. Further, we studied
cancer mutation hotspots or predicted driver mutations and
mutational signatures in these samples.
Tech University Health Sciences Center, Cancer Center, Lubbock,
Background/Objectives: Maintenance therapy with 13-cisretinoic acid and immunotherapy (given after completion
of intensive cytotoxic therapy) improves outcome for highrisk neuroblastoma patients. The synthetic retinoid fenretinide (4-HPR) achieved multiple complete responses in
relapse/refractory neuroblastoma in early-phase clinical trials, has low systemic toxicity, and has been considered for
maintenance therapy clinical trials. Difluoromethylornithine
(DFMO, an irreversible inhibitor of ornithine decarboxylase
with minimal single agent clinical response data) is being used
for maintenance therapy of neuroblastoma. We evaluated the
cytotoxic activity of DFMO and fenretinide in neuroblastoma
cell lines.
Design/Methods: We tested sixteen neuroblastoma cell lines
in bone marrow level hypoxia (5% O2 ) using the DIMSCAN cytotoxicity assay. Polyamines were measured by
HPLC-mass spectrometry and apoptosis by TUNEL flow
cytometry.
Results: At clinically achievable levels (100 �M), DFMO significantly decreased (P < 0.05) polyamine putrescine (measured by HPLC-mass spectrometry) and achieved modest
cytotoxicity (< 1 log (90% cytotoxicity). Prolonged exposures
(7 days) or culture in 2% and 20% O2 did not enhance DFMO
cytotoxicity. At clinically achievable levels (30 �M) fenretinide induced multi-log cell kills (> 3 logs (99.9% cytotoxicity) in all neuroblastoma cell lines tested. Even at lower concentrations (10 �M) fenretinide induced > 1 log cytotoxicity
in fourteen cell lines tested. DFMO did not show a significant
increase (P > 0.05) in apoptosis (TUNEL assay). Apoptosis
by fenretinide was significantly higher (P < 0.001) compared
to DFMO or controls.
Conclusions: DFMO as a single agent has minimal cytotoxic
activity for neuroblastoma.
SIOP ABSTRACTS
S236 of S518
P-151 Evolving Biopsy Techniques for
Neuroblastoma in Children
E. Rosenfeld1 , G. Campagna1 , Y. Yu1 , S. Vasudevan1 , J. Nuchtern1 ,
E. Kim1 , S. Commander1 , B. Naik-Mathuria1
1 Baylor
College of Medicine, Surgery, Houston, USA
Background/Objectives: In order to obtain adequate tissue
for diagnosis and tissue banking of neuroblastoma, surgical
wedge biopsy is commonly performed. In the past decade, our
experience with percutaneous needle core biopsy has evolved.
The purpose of this study was to compare the adequacy and
safety of biopsy techniques.
Design/Methods: Following IRB-approval, we retrospectively reviewed patients who underwent biopsy for intermediate or high-risk neuroblastoma at our institution between
2011-2016 (recent cohort). Procedure details and outcomes
were collected. Statistical analysis was performed using
Wilcoxon rank tests with a p-value<0.05 considered significant. Data from the recent cohort was compared to previously
published data from 2002-2010 (historic cohort).
Results: Since 2011, percutaneous ultrasound-guided needle
core biopsy has been more commonly utilized (47% [16/34]
recent cohort vs 34% [11/32] historic). The majority (94%)
of percutaneous biopsies were performed by a surgeon with
intravenous access port placement under the same anesthetic.
The number of needle core samples obtained increased from
median 7 (historic cohort) to 25 (recent cohort). Of the surgical cases, 61% were laparoscopic (previously all were open),
and one patient had laparoscopic-assisted percutaneous needle core biopsy. Biopsy adequacy in the recent cohort was
similar in percutaneous and surgical specimens (94% percutaneous vs 89% surgical; p=1), with improved adequacy of percutaneous specimens compared to historic cohort (71% percutaneous vs 100% surgical). Transfusion requirements (13%
percutaneous vs 28% surgical, p=) and other complications
(0% percutaneous vs 17% surgical, p=) were higher following
surgical biopsy. Operative time, hospital length of stay, and
time to chemotherapy initiation were similar. Larger tumors
were more likely to have a percutaneous biopsy (82±37 cm
percutaneous vs 47±29 cm surgical; p=0.04).
Conclusions: When multiple cores are obtained, surgeonperformed percutaneous needle core biopsy is adequate for
complete tissue diagnosis of neuroblastoma and can be safely
performed. This can be considered as an alternative to surgical
wedge biopsy.
P-152 Is Reck Gene Polymorphism is Linked with
Predisposition and Prognosis of Wilms’ Tumor? A
Case Control Study
M.R. Safarinejad1
1 Clinical
center for urological disease diagnosis and private clinic
specialized in urological and andrological genetics- Tehran- Iran, Urology,
Terhran, Iran
Background/Objectives: The reversion-inducing-cysteinerich protein with Kazal motifs (RECK) gene is a new transformation suppressor gene that was linked to some malignancies.
We examined the association between RECK gene polymorphisms and the clinicopathologic characteristics of Wilms’
tumor.
Design/Methods: Two single nucleotide polymorphism
(SNP) (rs10972727 and rs11788747) were analyzed using
PCR-RFLP protocol. The study subjects included 87 patients
with Wilms’ tumor and 174 healthy subjects as controls (1:2
ratio). We gathered patients with Wilms’ tumor within last 2
decade.
Results: For rs10972727 polymorphism, the genotype frequency distributions were in Hardy-Weinberg equilibrium in
patients (� 2 = 3.2, P = 0.062, P = 0.72) and controls (� 2 =
2.2, P = 1.77, P = 0.84). A significant alteration in both genotype distribution and allele frequency between Wilms’ tumor
patients and healthy controls were detected for rs10972727
SNP. There was a statistically significant association between
the presence of C allele and the Wilms’ tumor (OR = 5.02,
95% CI: 2.87 –8.31; P = 0.001). According to the logistic
regression analysis, Wilms’ tumor patients with RECK TC
and CC genotype have a 3.82-fold, and 3.73-fold increased
risk for Wilms’ tumor (OR = 3.82, 95% CI: 2.42–7.71; P =
0.006, and OR = 3.73, 95% CI: 2.83 –7.63; P = 0.002, respectively.
rs11788747 polymorphism: Both the patients and control subjects were in Hardy-Weinberg equilibrium for the
rs11788747 SNP polymorphism (� 2 = 2.2, P = 0.056, P =
0.73; � 2 = 2.2 = 0.054, P = 0.61). In single locus analysis, genotype distribution and allele frequency did not demonstrate a statistically significant difference between the cases
and controls. We did not find a significant association between
the rs11788747 polymorphism genotypes and the Wilms’
tumor.
Conclusions: We found statistically significant differences
in genotype distribution and allelic frequencies in RECK
gene between Wilms’ tumor patients and controls for the
rs10972727 SNP.
P-153 Primary Yolk SAC Tumor of the Prostate
in Children
M.R. Safarinejad1
1 Clinical
center for urological disease diagnosis and private clinic
specialized in urological and andrological genetics- Tehran- Iran, Urology,
Terhran, Iran
SIOP ABSTRACTS
Background/Objectives: Primary yolk sac (endodermal
sinus) tumors (ESTs) are rare malignancies that most commonly driven from the testes or ovaries. To our best knowledge, only six cases of prostatic ESTs have been reported until
now in the literature.
Design/Methods: In the last 2 decade, we have had six cases
of prostatic ESTs. In this manuscript we report our experiences with this rare neoplasms and a brief literature review has
also be done. All of the cases have underwent six courses of
cisplatin-based combination chemotherapy followed by same
session retroperitoneal lymph node dissection, cystoprostatectomy and ileal conduit urinary diversion.
Results: None of the cases had a history of previous testis
cancer and all of them were primary.
At the presentation 4 (66.6%) of patients had metastatic disease, most commonly to the liver. When patient had on localized tumor in the lung or liver, they were also removed surgically. The median free of tumor survival was 36±4.6 months.
Two patients died rapidly within 6-month of diagnosis. Both
of them had metastatic diseases during presentations.
Conclusions: Despite significant advances in imaging and
treatment modalities during the last two decade, yolk sac
tumor of the prostate remained a significant challenge for
physicians dealing with these children.
P-154 Hemorrhagic Brain Metastases in
Neuroblastoma
S. Sorrentino1 , C. Manzitti1 , M. Conte1 , G. Morana2 , A. Piccardo3 ,
A. Garaventa1
1 G.Gaslini
Institute, Oncology, Genoa, Italy; 2 G.Gaslini Institute,
Neuroradiology, Genoa, Italy; 3 Galliera Hospital, Nuclear Medicine,
Genova, Italy
Background/Objectives: In 70% of the cases, neuroblastoma (NB) presents with metastases mostly at skeletal and
bone marrow level. Involvement of the central nervous system (CNS) is rare and usually associated with metastases of
theca, skull base and orbit. The occurrence of CNS parenchymal localizations is an exceptional event with dismal prognostic outcome.
Design/Methods: We have recently observed two cases of
stage 4 MYCN-amplified NBs who have developed parenchymal CNS metastases during the clinical course.
Results: Both were treated according to HR-NBL-01 protocol. Symptoms at relapse were severe headache and vomiting
for both patients. Magnetic Resonance Imaging (MRI) and
Computed Tomography (CT) performed at time of relapse
suggested the hemorrhagic nature of the lesions, that were
localized in the temporal and cerebellar lobes, respectively.
CNS relapses were documented at stop therapy in the former
patient, three months later in the latter. The hemorrhagic char-
S237 of S518
acteristics of the lesions made difficult to immediate recognize
their tumoral nature, as several causes (i.e., vascular malformation, post-traumatic lesion, iatrogenic damage) may have
the identical imaging features. 18F-DOPA-PET/CT was performed in both patients showing intense peripheral uptake of
the tracer at the level of the hemorrhagic lesions. In the former patient surgery was avoided in favor of chemotherapeutic
approach consisting of multiple subsequent regimens that did
not prohibit slow disease progression with death ensuing nine
months later. In the latter the relapse was confirmed histologically following incomplete neurosurgical removal of the
mass. She is alive on Temozolomide treatment two months
after surgery.
Conclusions: The detection of CNS parenchymal metastases
in NB patients, both at diagnosis and during the clinical
course, is rare. MRI is the method of choice for studying brain
lesions. In case of hemorrhagic lesions, 18F-DOPA-PET/CT
appears a more sensitive tool as it may help to clarify earlier
their tumoral nature.
P-155 Synchronous Neoplasias in Patients
Diagnosed with Peripheral Neuroblastic Tumors
S. Sorrentino1 , C. Manzitti1 , M. Conte1 , G. Erminio2 , M.L. Garrè3 ,
C. Milanaccio3 , P. D'Angelo4 , A. Di Cataldo5 , C. Consarino6 , E.
Viscardi7 , M. Nantron1 , L. Amoroso1 , A. Garaventa1
1 G.Gaslini
Institute, Oncology, Genoa, Italy; 2 G.Gaslini Institute,
Biostatistic and Epidemiology, Genoa, Italy; 3 G.Gaslini Institute,
NeuroOncology, Genoa, Italy; 4 G. Di Cristina Hospital, Onco-hematology
Unit, Palermo, Italy; 5 Policlinico - Vittorio Emanuele, Pediatric
Onco-hematology Unit, Catania, Italy; 6 Pugliese-Ciaccio Hospital,
Pediatric Oncology and Hematology Unit, Catanzaro, Italy; 7 Padova
University, Pediatric Onco-hematology Unit, Padova, Italy
Background/Objectives: Patients diagnosed with a Peripheral Neuroblastic Tumor (PNT) may occasionally develop
a secondary tumor. Instead, the detection of a synchronous
malignancy in these patients is much rarer and mainly occurs
in subjects harboring a cancer predisposition condition, such
as Beckwith-Wiedemann (SBW) or Li-Fraumeni syndromes.
Design/Methods: In the period 1976-2016, a total of 3942
NPTs cases have been enrolled in the Italian Neuroblastoma
Registry. Of them, 35 developed a secondary tumor and other
6 had a synchronous tumor.
Results: Histology of PNT in the latter 6 cases was neuroblastoma in 3, intermixed ganglioneuroblastoma in 2 and
ganglioneuroma in one. Synchronous tumors include acute
lymphoblastic leukemia (ALL) in 3, acute myeloid leukemia
(AML), pilocytic astrocytoma and pancreatoblastoma (PB)
in one case each. SBW was present in the patient diagnosed
with PB. All patients had localized PNT disease. Five underwent tumor resection as only therapy, while in the sixth one
tumor regressed spontaneously. The 4 children diagnostic
with leukemia were treated according to specific protocols,
SIOP ABSTRACTS
S238 of S518
while radical tumor surgery was performed in patients with
PB and astrocytoma. All these 6 patients are presently in complete remission with a median follow-up of 38 months (range,
2-114).
Conclusions: The observation of these 6 cases illustrates a
clinical condition of rare occurrence but worth of being better
understood. More information may derived through retrospective and/or studies on larger patient populations, as SIOPEN
might offer.
P-156 Immunotherapy in the Treatment of
Pediatric Patients with High Risk Neuroblastoma
“An Education Program for Patients and Their
Parents”
A. van Rooijen1 , M. Kortlandt1 , M.M.P. van Noesel1 , M.P. van
Grotel1 , K.C.J.P. Kraal1
1 Princess
Máxima center, Pediatric Oncology, Utrecht, The Netherlands
Background/Objectives: Since August 2016, the PMC has
started with the anti-GD2 therapy for patients with high risk
neuroblastoma (NB).
Immunotherapy;
combining
anti-GD2
antibody
(CH14.18/Dinutuximab), GM-CSF, IL-2 and ISOT [1]
has significant side effects such as pain, hypotension, fever,
hypersensitivity reactions and capillary leak syndrome.
Pediatric oncology nurses make a significant contribution in
the treatment, including education of families and patients
receiving this therapy.
Design/Methods: This study investigates which aspects are
important for education about immunotherapy and whether
this education is appropriate for children between the age of 1
and 8 years old. Based on analysis of studies regarding education of young children, existing educational materials of the
DCOG are evaluated and several points of improvement are
proposed.
Results: Additionally, a brochure has been developed which
includes aspects of treatment, logistics and side effects and the
issuance of an extensive and informative film for young children undergoing the immunotherapy is scheduled for October
2017.
Conclusions: Clear communication with patients about the
expected toxicities, as well as proactive and comprehensive
supportive care, are integral components to ensure successful completion of antibody infusions[2]. Well-informed parents and children experience less stress, which enhances the
collaboration between parents, their children and the medical
team. For this reason, proper education of patients and their
families in this intense anti-GD2 therapy is crucial.
[1] Alice, L., Yu, M., Andrew, L., Gilman, M., & al, e.
(2010, September 30). Anti-GD2 antibody with GM-CSF,
Interleukin-2, and Isotretinoin for Neuroblastoma. The New
England Journal of Medicine, 1324-1334.
[2] Bartholomew, J et al (2016), Dinutuximab: a novel
immunotherapy in the treatment of pediatric patients with
high risk neuroblastoma. Journal of Pediatric Oncology Nursing, 1-8
P-157 Elevated Urinary 3-Methoxytyramine at
Diagnosis is Correlated with High Risk Disease and
is Associated with Poor Clinical Outcome in
Neuroblastoma Patients
I. Verly1,2,3 , A. van Kuilenburg2 , N. Abeling2 , S. Goorden2 , M.
Fiocco4,5 , F. Vaz2 , M. van Noesel3,6 , M. Zwaan7 , G.J. Kaspers3,8 , H.
Merks1,3 , H. Caron1 , G. Tytgat1,3
1 Academical
Medical Center, Pediatric hemato-oncology, Amsterdam, The
Netherlands; 2 Academical Medical Center, Laboratory Genetic Metabolic
Diseases, Amsterdam, The Netherlands; 3 Princess Máxima Center for
Pediatric Oncology/Hematology, Pediatric Oncology/Hematology, Utrecht,
The Netherlands; 4 Leiden University Medical Center, Medical Statistics and
Bioinformatics, Leiden, The Netherlands; 5 Leiden University, Mathematical
institute, Leiden, The Netherlands; 6 University Medical Center Utrecht,
Pediatrics, Utrecht, The Netherlands; 7 Sophia Children's Hospital/Erasmus
Medical Center, Pediatric Oncology/Hematology, Rotterdam, The
Netherlands; 8 VU University Medical Center, Pediatric
Oncology/Hematology, Amsterdam, The Netherlands
Background/Objectives: Prognosis of patients with neuroblastoma is diverse, indicating the need for more accurate
prognostic parameters. Most neuroblastomas excrete catecholamine metabolites, however, their correlation with prognosis has hardly been investigated. Therefore, we performed
an in-depth analysis of a panel of elevated urinary catecholamine metabolites and their correlation with prognosis.
Design/Methods: Retrospective study of a panel of 8 urinary
catecholamine metabolites in test (n = 96) and validation (n
= 205) cohorts of patients with neuroblastoma (all stages) at
diagnosis.
Results: Multivariate Cox regression model analyses revealed
that 3-methoxytyramine (3MT) was an independent risk factor for Event-free survival (EFS) and Overall survival (OS).
EFS and OS of stage 4 patients with non-elevated 3MT were
significantly better compared to stage 4 patients with elevated
3MT [5-years EFS: 47.4%±7% versus 17.7%±4%; 5-years
OS: 67.0%±7% versus 26.8%±5%, both p < 0.001]. Also in
other clinical subgroups, elevated 3MT was associated with
poor survival outcome. In multivariate-analyses for high risk
patients (stage 4 and older than 1 year or any patients with
MYCN amplification), only age and 3MT were independent
risk factors for EFS and OS, and thus independent of the
given therapy. Among high risk patients, those with elevated
3MT and age ≥ 18 months had an extremely poor prognosis
compared to patients with non-elevated 3MT and age < 18
[5-years EFS of 15.2%±4% and 62.2%±18%, respectively, p
SIOP ABSTRACTS
S239 of S518
= 0.005; 5-years OS of 23.4%±5% and 87.5%±12%, respectively, p = 0.002].
Conclusions: elevated 3MT-levels at diagnosis are associated with high risk disease and poor prognosis. For high risk
patients, age and elevated 3MT at diagnosis are the most significant risk factor for EFS and OS. 3MT was also able to
identify subgroups of high risk patients with favorable and
extremely poor prognosis.
did not. Catecholamine excretion was also detected in SKNBE
cells with ADRN phenotype, however, it stopped once transition to mesenchymal phenotype was induced. Enzyme profiling revealed that all the excreting cell lines expressed the TH
protein, which was absent in all the non-excreting cell lines.
Conclusions: Catecholamine excretion was absent in MEStype neuroblastoma cells and seems to be an exclusive feature
of the ADRN-cells with TH expression.
Acknowledgements: this study was supported by the Villa
Joep Foundation.
Acknowledgements: this study was supported by a grant
from the Villa Joep Foundation.
P-158 Epithelial to Mesenchymal Transition in
Patients with Neuroblastoma – The Mechanism
Underlying Catecholamine Negative
Neuroblastoma?
P-159 Efficacy of Ultrasonography in Diagnosis in
Neonatal Adrenal Neuroblastoma
1,2,3
3
3
3
I. Verly , A. van Kuilenburg , D. Goedkoop , R. Meinsma , R.
Leen3 , T. van Groningen4 , M. Broekmans4 , J. Koster4 , R.
Versteeg2,4 , J. van Nes4 , G. Tytgat1,2
1 Academical
Medical Center, Pediatric hemato-oncology, Amsterdam, The
Netherlands; 2 Princess Máxima Center for Pediatric
Oncology/Hematology, Pediatric Oncology/Hematology, Utrecht, The
Netherlands; 3 Academic Medical Center, Laboratory Genetic Metabolic
Diseases, Amsterdam, The Netherlands; 4 Academic Medical Center,
Oncogenomics, Amsterdam, The Netherlands
Background/Objectives: Catecholamine measurements in
urine of patients with neuroblastoma is standard practice.
When a panel of 8 markers is used, 5% of the patients
have no elevated catecholamines at diagnosis (catecholamine
negative), and 20% of the patients is negative at time of
relapse. Recently, two cell types in neuroblastoma were identified, adrenergic (ADRN)-type cells expressing markers of
adrenergic-lineage differentiation, and mesenchymal (MES)type cells lacking these markers (van Groningen et al., submitted). This phenotypical duality might regulate catecholamine
excretion and explain the switch of catecholamine positive
to catecholamine negative patients. In this study, we investigated in vitro catecholamine excretion in relation to MESand ADRN cell types.
Design/Methods: We studied catecholamine excretion in
neuroblastoma cell lines (6 MES and 23 ADRN), including
two pairs of ADRN-MES cell lines (SY5Y-SHEP2 and 691B691T). Additionally, SKNBE cells, in which mesenchymal
transition can be induced were also used. Subsequently, the
presence of the catecholamine biosynthetic enzymes: tyrosine
hydroxylase (TH), dopa-decarboxylase (DDC) and dopamine�-hydroxylase (DBH) in these cell lines was determined by
qRT-PCR and Western-blot.
Results: Among the 23 ADRN cell lines, 10 cell lines (44%)
excreted catecholamines. MES cell lines did not excrete catecholamines. In the ADRN-MES pairs, the ADRN cell lines
excreted catecholamines, while their MES cell lines partner
J. Yu1 , J. Ye1 , X. Li1 , X. Yang1 , J. He1 , J. Wang2
1 Children's
Hospital - Zhejiang University School of Medicine, Department
of Ultrasound, Hangzhou, China; 2 Children's Hospital - Zhejiang
University School of Medicine, Department of Surgical Oncology,
Hangzhou, China
Background/Objectives: To investigate the efficacy of ultrasonography in diagnosis and follow-up in neonatal adrenal
neuroblastoma (NB).
Design/Methods: Twenty-eight neonatal adrenal neuroblastoma confirmed by pathology in our center from November
2004 to February 2017 were included in this study, including 16 boys and 12 girls. All cases were unilateral. Ultrasonographic image data were analyzed retrospectively.
Results: All cases were detected by ultrasound firstly, aged
from 34w gestational age to 28 days postpartum, 13(46.43%)
cases detected during prenatal routine examination. Major
ultrasonographic characteristics: border clear, size of mass
from 2.7cm * 1.7cm * 1.7cm to 12.0cm * 11.0cm * 7.5cm, 24
cases were parenchymal masses (19 cases with calcification,
5 cases without calcification), 2 cases were cystic masses, 2
cases were cystic solid masses. NB was considered as the first
diagnosis in 27 cases (96.4%). Only 1 case of cystic adrenal
neuroblastoma was misdiagnosed as mesenteric cyst.
Conclusions: Ultrasound can be used as a preferred imaging
method for fetal and neonatal adrenal neuroblastoma, which
contributes to early diagnosis and management.
P-160 Paraneoplastic Syndromes – A
Retrospective Clinical Analysis of 8 Cases in
Children
S. Wang1 , Z. Lu1 , C. Li1 , C. Yang1 , L. Lv1 , Z. Zhao1
1 Children's
Hospital of Chongqing Medical University, Department of
Pediatric Surgical Oncology, Chongqing, China
Background/Objectives: Paraneoplastic Syndromes (PSs)
are the kinds of rare syndromes, the clinical characteristics
SIOP ABSTRACTS
S240 of S518
have rarely been discussed in children. We analyzed data on
the clinical manifestations, diagnoses, treatments, and prognosis in children with PSs to investigate how diagnosis and
treatment could be improved.
Design/Methods: Eight patients with PSs were enrolled from
July 2011 to February 2017. A range of examinations were
used to evaluate the patients. Pathological examinations were
performed on all of the patients. In addition to either complete tumor resection or puncture biopsy, chemotherapy, corticosteroid therapy and other supportive treatments were also
applied in the different patients.
Results: Three patients suffered from paraneoplastic neurologic syndromes (PNSs), 3 presented with Ectopic Cushing's syndrome, 1 patient with respiratory failure and 1 had
vasoactive intestinal polypeptide (VIP)-induced intractable
diarrhea. Two patients were confirmed as ganglioneuroblastoma (GNB), 4 had neuroblastoma (NB) and 2 had ganglioneuroma(GN). In 6 patients the tumors were completely
resected, 2 had puncture biopsy of the tumors. Six patients
received chemotherapy, 4 received futher supportive treatments, and 4 received futher corticosteroid therapy. Except
for 2 patients who discontinued therapy, the 3 patients who
suffered from PNSs achieved complete remission, and the
remaining 4 patients who completed follow-up were classified as having “very good partial remission”.
Conclusions: When children present with PNSs such as
Opsoclonus-Myoclonus Syndrome (OMS) and Cerebellar
Ataxia, Ectopic Cushing's syndrome, dyspnea and unexplained intractable diarrhea, hypokalemia and dysplasia, clinicians should consider the possibility of neuroblastoma.
P-161 A Double-Conditioning Regimen with
Thiotepa and Melphalan is Effective for
MYCN-Amplified High-Risk Neuroblastoma
1,2
3
4
4
regimen in patients with high-risk neuroblastoma in two
Japanese institutions.
Design/Methods: The medical records of consecutive 34
patients with high-risk neuroblastoma who received the
double-conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were
reviewed.
Results: The median patient age at diagnosis was 35 months.
MYCN-amplified tumors were observed in 19 patients. Thirtytwo patients had stage 4 tumors. All patients underwent surgical resection of the primary lesion and radiotherapy against
the residual lesion. The regimen of induction chemotherapy
and timing of surgery varied depending on the institution.
The median follow-up period was 8.6 years (range, 4.8–14.1).
Nine patients subsequently received planned tandem HDC
with cord blood transplantation. Fifteen patients, including
2 of the 9 patients treated with tandem HDC, have survived
without recurrence. The event-free survival (EFS) rate and
the overall survival (OS) rate at 5 years from diagnosis was
47.1% ± 8.6% and 52.9% ± 8.6%, respectively. Three patients
died from regimen-related toxicity. None of the patients developed secondary malignancies. Notably, both the EFS and OS
rates at 5 years in patients with MYCN-amplified tumors were
68.4% ± 10.7%, which were significantly superior to those
with MYCN-nonamplified tumors (P < 0.01 and P = 0.014).
In a multivariate analysis, increased probability of EFS was
demonstrated in patients with MYCN-amplification and good
remission status during HDC.
Conclusions: The double-conditioning regimen comprising
thiotepa and melphalan is an effective regimen for patients
with high-risk neuroblastoma with MYCN amplification.
P-162 Yap Promotes Tumorigenesis and Cisplatin
Resistance in Neuroblastoma
C. yang1 , W. shan2
4
F. Yamazaki , C. Kiyotani , K. Yamasaki , C. Nitani , K. Okada ,
H. Fujisaki4 , Y. Shioda3 , J. Hara4 , K. Matsumoto3
1 Keio
University School of Medicine, Department of Pediatrics, Tokyo,
Japan; 2 National Cancer Center Research Institute, Department of Clinical
Genomics, Tokyo, Japan; 3 National Center for Child Health and
Development, Children's Cancer Center, Tokyo, Japan; 4 Osaka City
General Hospital, Department of Pediatric Hematology and Oncology,
Osaka, Japan
Background/Objectives: Appropriate combinations of
induction chemotherapy and high-dose chemotherapy (HDC)
regimens for patients with high-risk neuroblastoma remain
unestablished. Previously, we reported the feasibility and
efficacy of a double-conditioning regimen using two cycles of
thiotepa (total 800 mg/m2 ) and melphalan (total 280 mg/m2 )
with a single grafting for neuroblastoma. In the present
study, we analyzed the outcomes of the double-conditioning
1 Children's
Hospital of Chongqing Medical University, Department of
Pediatric surgical oncology, Chongqing, China; 2 hildren's Hospital of
Chongqing Medical University, Department of Pediatric surgical oncology,
chongqing, China
Background/Objectives: The transcriptional co-activator
Yes-associated protein (YAP) is essential for Hippo pathwaydriven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive.
Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced
tumor staging.
Design/Methods: We examined the expression of YAP in
clinical tumor specimens and adjacent tissues, and analyzed
the relationship between them and tumor staging. The cell viability assay, colony formation assay and Invasion assay were
SIOP ABSTRACTS
perfomed after siRNA interfering. The expression of YAP and
possibly related downstream proteins was detected by westerblot. Human SH-SY5Y and SH-SY5Y-R xenografts were
established, low concentration of cisplatin, high concentration
of cisplatin, low concentration of cisplatin + peptid 17 was
treated for each group. Tumor volume was calculated. After
mice were sacrificed, the tumor were peeled off and weighted,
YAP expression and apoptosis was performed.
Results: Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro.
Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors. Additionally, less proliferative and more apoptotic cells were found in
the Peptide 17 treatment group. Furthermore, YAP inhibition
significantly inhibited cisplatin-resistant neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The combination of Peptide 17 with low-dose cisplatin efficiently impaired
cisplatin-resistant NB subcutaneous tumor growth, being as
effective as high-dose cisplatin. Notably, the combination
therapy caused lesser liver toxicity in mice compared to the
high-dose cisplatin treatment group.
Conclusions: Collectively, this work identifies YAP as a
novel regulator of neuroblastoma proliferation, tumorigenesis, and invasion and indicates that YAP is a potential therapeutic target for cisplatin-resistant neuroblastoma.
S241 of S518
adrenal, two mediastinal and one cervical neuroblastomas.
Four tumors showed intraspinal extension. The surgical complications were two nephrectomies, one renal atrophy, one
bowel obstruction, one ejaculation disorder, one Horner syndrome and one resection of the internal jugular vein. All
tumors were resected at least 95% in group A, including 5
complete resections, whereas there were 2 complete resections, three 90% and 50%-90% resections each and 1 patient
without surgery in group B. Five of the six patients in group
A and five of the nine patients in group B had tumors with
image-defined risk factors (IDRFs). Only one tumor in group
B changed from ‘IDRFs present’ to ‘not present’ after preoperative chemotherapy. All patients were alive without disease
after a median follow-up 143 months (range: 13-242 months).
Conclusions: More than 95% resection and the presence
of preoperative IDRFs seems to be surgical risk factors in
intermediate-risk neuroblastoma. As all patients are alive
without disease, conservative surgery to avoid complications
may be acceptable, even if residual tumor remains after
surgery.
P-164 The Role of UBE4B in Neuroblastoma
Differentiation
P. Zage1 , J. Lesperance1 , D. Subramonian1 , S. Woodfield2 , R.
Guo3 , A. Bean4 , D. Lopez-Terrada5 , M. Ittmann5 , S. Hakim1
1 University
P-163 An Evaluation of The Risk Factors in the
Surgical Treatment of Intermediate-Risk
Neuroblastoma
A. Yoneda1 , K. Santo1 , S. Nishimoto1 , Y. Tsukazaki1 , M.
Kamiyama1 , T. Nakaoka1 , T. Nakamura2 , J. Hara3
1 Osaka
City General Hospital, Pediatric Surgery, Osaka, Japan; 2 Osaka
General Medical Center, Pediatric Surgery, Osaka, Japan; 3 Osaka City
General Hospital, Pediatric Hematology and Oncology, Osaka, Japan
Background/Objectives: With improvement in the treatment
results for intermediate-risk neuroblastoma, minimizing treatment complications should be the top priority. We retrospectively evaluated the risk factors in the surgical treatment of
intermediate-risk neuroblastoma in order to minimize surgical complications.
Design/Methods: Of 148 neuroblastoma patients treated
at our institute between 1995 and 2016, 15 classified as
intermediate-risk according to the COG risk classification
were selected. We divided these patients into two groups
according to the presence (group A, n=6) or absence (group
B, n=9) of surgical complications.
Results: The median age at diagnosis was 7 months (range:
5 days-3 years). There were 13 INSS stage 3 patients,
2 stage 4 and 1 stage 4S. Eight had retroperitoneal, five
of California - San Diego - Moores Cancer Center, Pediatrics,
San Diego, USA; 2 Baylor College of Medicine, Pediatric Surgery, Houston,
USA; 3 University of Alabama-Birmingham, Pathology, Birmingham, USA;
4 University of Texas Health Science Center - Houston, Neurobiology &
Anatomy, Houston, USA; 5 Baylor College of Medicine, Pathology, Houston,
USA
Background/Objectives: UBE4B is an E3/E4 ubiquitin ligase involved in growth factor receptor (GFR) trafficking
whose gene is found in the chromosome 1p36 region commonly deleted in high-risk neuroblastoma tumors. We have
previously observed associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and neuroblastoma tumor histology. However, the functional roles
of UBE4B in neuroblastoma tumor differentiation are not
known.
Design/Methods: We screened cell lines and neuroblastoma
tumor samples for UBE4B protein expression using Western blot and quantitative immunohistochemistry and analyzed
the association of UBE4B gene expression with expression of
known markers of neuroblastoma tumor differentiation using
publicly available databases. We measured UBE4B expression by Western blot in cell lines before and after induction
of differentiation with retinoic acid treatment and determined
the effects of UBE4B overexpression and depletion on retinoic
acid-induced differentiation using continuous live-cell imaging of neurite morphology, immunohistochemistry, and
SIOP ABSTRACTS
S242 of S518
Western blot for markers of differentiation. Effects on signaling through the Ras/MAPK pathway were measured using
Western blots.
cycle is similar to the A1 cycle, however the only difference
is that on day 4, 30 mg/m2 of doxorubicin is substituted for
etoposide.
Results: UBE4B expression was associated with differentiation in patient tumor samples, and UBE4B gene and protein
expression were associated with expression levels of known
markers of neuroblastoma differentiation. Retinoic acid treatment resulted in increased UBE4B expression in retinoic acidsensitive, but not -resistant, neuroblastoma cells, and UBE4B
depletion was associated with increased phosphorylation of
ERK, increased proliferation, and inhibition of retinoic acidinduced neuroblastoma differentiation.
Results: Between 2008 to 2011, a total of 51 patients were
enrolled, 15 patients were excluded from the study. Of
the remaining thirty-six patients, twenty-eight patients had
completed consolidation chemotherapy. They were finally
enrolled. Fifteen patients were long term event-free survivors.
Five patients were alive with tumor whilst eight patients died.
The 3-year EFS and OS were 53.6% (95%CI, 26.74% to
66.12%) and 71.4% (95%CI, 53.59% to 89.27%) respectively.
Conclusion: We have demonstrated associations between
UBE4B expression and tumor cell differentiation in gene
expression databases and in neuroblastoma tumor samples,
and our data suggests that UBE4B expression is required
for retinoic acid-induced differentiation, potentially through
effects on ERK activation. These associations between
UBE4B and neuroblastoma differentiation combined with the
established role of UBE4B in GFR trafficking suggest that
UBE4B-mediated receptor trafficking may contribute to the
responses of neuroblastoma tumors to therapy and to the outcomes of patients with neuroblastoma.
Conclusions: A high rate of survival among patients with
high-risk neuroblastoma was achieved with delayed intensification chemotherapy without the occurrence of a second
malignancy. This study warrants further investigation into the
long-term outcomes and EFS in patients with high-risk neuroblastoma.
P-166 PLK4 Promotes Neuroblastoma Invasion
and Metastasis Through PI3K/AKT Signaling
Pathway
Q. Zhao1
1 Tianjin
P-165 Treatment of High-Risk Neuroblastoma
Over One Year of Age with Intensive and a Novel
Delayed Intensification Chemotherapy
Y.T. Zhang1 , J. Chang1 , X.D. Zhong1
1 First
Hospital of Jilin University, Department of pediatric oncology,
Changchun, China
Background/Objectives: Current “standard” therapy for
patients with high-risk neuroblastoma consists of intensive
induction chemotherapy and surgery, myeloablative consolidation chemotherapy, autologous stem cell transplantation,
local irradiation and immunotherapy. However, autologous
stem-cell transplantation is expensive. Until recently, antiGD2 antibody was not easily accessible in China. What should
we do to improve the survival rate of patients with high-risk
neuroblastoma in developing countries? On the basis of these
considerations, we designed this study to test the feasibility
of adding a novel delayed intensification chemotherapy to a
dose-intensive induction regimen.
Design/Methods: Patients enrolled in this study received
chemotherapy in accordance with the design of the NB97
trial. At the end of the therapy, patients received three cycles
of delayed intensification chemotherapy. The delayed intensification chemotherapy consists of two A1 and one A2 cycle.
The A1 cycle consists of 1.5 mg/m2 of vincristine on day 1,
1.2 g/m2 of cyclophosphamide on day 2, 100 mg/m2 of cisplatin on day 3, and 160 mg/m2 of etoposide on day 4. The A2
Medical University Cancer Institute and Hospital, Department of
Pediatric Cancer, Tianjin, China
Background/Objectives: Neuroblastoma (NB) is the most
common malignant tumor in infancy and the most common
extracranial solid tumor in childhood. With the improvement
of diagnosis and treatment, the survival rate of patients with
low-risk and intermediate-risk NB can reach up to 90%. But
for high-risk NBs, the long-term survival rate is still less than
40%. The pathogenesis of NB is still not explicit, therefore it is
of great significance to explore the mechanism of NB tumorigenesis and discovery new therapeutic targets for NB. PLK4,
one of the Polo-like kinase family members, is an important
regulator of centriole replication. The abnormal expression of
PLK4 was found in several cancers and a recent study has
unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela cell lines. However, the function
of PLK4 in NB development and progression remains to be
elucidated.
Design/Methods: We evaluated the expression level of PLK4
in NB tissues and detected the function of PLK4 in NB
through a series of experiments in vitro and in vivo.
Results: The expression level of PLK4 in NB tissues was
remarkably up-regulated and high expression of PLK4 was
negatively correlated with the survival rate of NBs, which
suggesting that PLK4 was a potential tumor promoting factor of NB. Functional studies indicated down-regulation of
PLK4 suppressed cell proliferation and invasion in SK-NSH and SK-N-BE(2) cells. And down-regulated PLK4 in NB
SIOP ABSTRACTS
cell lines inhibited epithelial-mesenchymal transition (EMT)
through the PI3K/Akt signaling pathway. Animal experiments
demonstrated that PLK4 down-regulation in SK-N-BE(2)
cells dramatically suppressed tumorigenesis and metastasis.
Conclusions: PLK4 promotes cell proliferation, invasion and
metastasis in NB cells and it induces epithelial-mesenchymal
transition by activation of PI3K/Akt signaling pathway. PLK4
may be a promising therapeutic target for NB.
SOLID NON B R A I N T U MO U R S R E NA L T U M O U R S
P-167 Outcome of Wilms Tumor Treated
According to the SIOP- PODC Approach: Early
Experience in a Tertiary Referral Hospital in the
Philippines
J.P. Caneba1 , A. Moreno2 , E. Yturralde3 , C.V. Villafuerte III4 , J.M.
Avila3 , W. Baltazar2 , A. Catangui2 , N. Cupino4 , P. Fajardo1 , A.P.
Alcasabas1
1 University
of the Philippines - Philippine General Hospital, Pediatrics,
Manila, Philippines; 2 University of the Philippines - Philippine General
Hospital, Surgery, Manila, Philippines; 3 University of the Philippines Philippine General Hospital, Pathology, Manila, Philippines; 4 University of
the Philippines - Philippine General Hospital, Radiology, Manila,
Philippines
Background/Objectives: At Philippine General Hospital, the
country's national referral center, Wilms tumor (WT) survival
was low at 26% largely due to treatment delays and abandonment from inoperable tumors and infections. In March 2014,
the pediatric surgery, pediatric oncology, pathology, and radiology group adopted the SIOP-PODC WT treatment approach
and guidelines.
Design/Methods: Review of medical records of newlydiagnosed patients from March 2014 to August 2016 with
study endpoint at December 2016.
Results: There were 22 patients with mean age of 2.5 years
(0.33-11). M:F ratio of 1:2.3. Eighteen patients (82%) had
localized disease and 4 (18%) were metastatic. All were
given neoadjuvant chemo for mean of 6 weeks, (4-11) and
9 weeks (8-11), respectively. Only 20 patients had nephrectomy due to abandonment (1) and progressive disease (1).
19 patients (95%) had lymph node sampling and 2 (9%) had
tumor spillage. Surgical staging were: Stage I: 6; Stage II:
2; Stage III: 6; Stage IV: 4. Pathology risk grading were:
Low: 1; Intermediate: 8; and High: 5. Three were reported as
Favorable histology, and 3 were misdiagnoses: neuroblastoma
(1), Angiomyolipoma (1) and Multicystic renal dysplasia (1).
Thirteen WT patients received SIOP risk-stratified adjuvant
treatment, 4 were off protocol due to poor response (N=3)
and progressive disease (N=1), and 1 abandoned treatment.
S243 of S518
Six patients underwent radiation. At study endpoint, for WT
patients: 9 (47%) completed treatment; 3 (16%) on treatment;
5 (26%) abandoned therapy; 1 (5%) relapsed (local); and 1
died due to gastroenteritis 12 months off treatment. The 2 year
EFS is 57%, and 2 year OS and abandonment sensitive OS are
89% and 63%, respectively.
Conclusions: The adoption of the SIOP-PODC WT multidisciplinary protocol and guidelines has markedly improved
survival in our setting and addressed diagnostic and treatment
delays. However, efforts are still needed to curb abandonment,
and improve protocol adherence and misdiagnosis.
P-168 Outcome of Wilms’ Tumor in Children: A
10 Year Experience From King Faisal Specialist
Hospital and Research Center-Riyadh
A. Ali1 , M. Ayas1 , T. AlHussain2 , A. Alkofide1 , Z. Habib3 , V.
Mohammed1 , D. Bushnak4 , I. Abosoudah5 , A. Nadeem1 , A.
Abbas1 , S. Khan1 , M. AlQaisi4 , A. Ahmad4 , S. Mohammad2 , I.
Alfawaz1
1 King
Faisal Specialist Hospital & Research Centre, Pediatric
Hematology/Oncology, Riyadh, Saudi Arabia; 2 King Faisal Specialist
Hospital & Research Centre, Pathology & Laboratory Medicine, Riyadh,
Saudi Arabia; 3 King Faisal Specialist Hospital & Research Centre,
Pediatric Surgery, Riyadh, Saudi Arabia; 4 King Faisal Specialist Hospital
& Research Centre, Nursing, Riyadh, Saudi Arabia; 5 King Faisal Specialist
Hospital & Research Centre-Jeddah, Oncology, Jeddah, Saudi Arabia
Background/Objectives: Wilms’ tumor (WT) is the most
common renal malignancy in children. Outcome data for
WT in our region is limited. A retrospective study to evaluate clinical outcomes of pediatric patients (pts) with WT at
King Faisal Specialist Hospital and Research Centre, Riyadh
(KFSH&RC-Riyadh) was conducted.
Design/Methods: Data of WT pts (ages 0 to 14 years) diagnosed and treated at KFSH&RC-Riyadh from 2001-2011
was reviewed. Only histopathology confirmed cases were
included.
Results: Out of 137 cases identified, 7 cases were excluded
due to insufficient data. Median age at diagnosis was 3.4
years (0.3-13). with 73(56%) females and 57(44%) males.
Unilateral disease was observed in 119(91.5%)pts and bilateral in 11(9.5%). Presenting features included: abdominal distension,85%; abdominal pain,41.5%; hematuria,13%; and vascular thrombosis,4%. 66% of pts were stage III,57(44%) and
IV,29(22%). Relapse was seen in 34(26%); of which 23(68%)
were Stage III and IV. Five-year OS for all pts was 90.5%
[(Stage I(94%); II(89.5%); III(93%); IV(82%); and V(100%)]
and EFS 70%[(Stage I(88%); II(68%), III(76%);IV(48%);
V(57%)], P value of <0.05 for EFS in pts based on staging. Our results corroborate previously presented data from
the Saudi Arabian Pediatric Hematology/Oncology Society(SAPHOS) where a national 5-year OS and EFS of
86% and 74% respectively (n=67) was reported. Favorable
SIOP ABSTRACTS
S244 of S518
histology was seen in 119(91.5%) while 7(5%) had anaplasia.
P value for both OS and EFS was <0.05 for pts comparing
favorable histology with anaplasia. For pts <5years, OS and
EFS were 93% and 71.6%, and 82% and 65.6%, for >5years
of age, respectively.
Conclusions: Despite variability in healthcare services and
referral patterns, and given that over half of the pts being
referred to our center have advanced disease, not amenable
to upfront resection, our outcomes for WT are comparable
tothe national data as well as to international reports. Further review including specifications of relapsed patients and
molecular studies are warranted and underway.
P-169 Bilateral Wilms Tumors: Treatment
Results from a Single Center with Turkish Pediatric
Oncology Group Wilms Tumor Study
B. Aydin1 , C. Akyuz1 , B. Yalcin1 , S. Ekinci2 , A. Varan1 , N.
Kurucu1 , M. Buyukpamukcu1 , T. Kutluk1
1 Hacettepe
University Cancer Institute, Pediatric Oncology, ANKARA,
Turkey; 2 Hacettepe University Faculty of Medicine, Pediatric Surgery,
ANKARA, Turkey
Background/Objectives: The outcome of patients with BWT
has improved due to both preoperative chemotherapy and
operative techniques in preservation of renal parenchyma. In
this study the results of TPOG Wilms tumor regimen for BWT
and outcome of patients from a single center were retrospectively reviewed.
Design/Methods: From 1990 to 2016, 33 patients with synchronous BWT were treated with preoperative chemotherapy
with vincristine and actinomycine. Chemotherapy was continued until safe nephron sparing surgery (NSS) could be performed as long as radiological tumor response continued or
chemotherapy was intensified with adding doxorubicin (D)
alternating with VA every 6 weeks.
Results: The median follow-up of non-failure patients was 68
months (7-297 months). The median duration of preoperative
chemotherapy was 85 days ranged between 14 days and 216
days. Preoperative chemotherapy was modified in 7 patients
(21%) with VAD regimen. 6 patients received VAD regimen
due to metastases, thrombi in vena cava and possible spontaneous tumor rupture at diagnosis. 24 patients had radical
nephrectomy for greater tumor and NSS for the contralateral
kidney. Eight patients (24%) had bilateral NSS. EFS and OS
rates for VA and VAD was not statistically different. Postoperative tumor stages for stage I, II and III were 55%, 15% and
17%. The 5-year OS rates were 100%, 90% and 70% for stages
I, II and III (p=0.06). Unfavorable histology and nephroblastomatosis were reported in 18% and 27% of patients. 5-year
OS and EFS rates were 50% and 25% in patients with anaplasia, while same rates were 96% and 96% in patients with FH
tumors (p=0.03 and p<0.001). 10-year OS and EFS rates for
all patients were 84% and 80%. Only one patient died after
bilateral nephrectomy.
Conclusions: Our results are comparable with literature.
VA is effective for BWT as initial preoperative treatment.
VAD combination might help better local control for selected
advanced staged tumors.
P-170 Review of Phase I and II Trials for Wilms
Tumour – Can We Optimise the Search for Novel
Agents?
J. Brok1 , K. Pritchard-Jones1 , J.I. Geller2 , F. Spreafico3
1 University
College Great Ormond Street Institute of Child Health, Cancer
section, London, United Kingdom; 2 Cincinnati Children's Hospital Medical
Center- University of Cincinnati- Cincinnati- Ohio, Division of Pediatric
Oncology, Cincinatti, USA; 3 Fondazione IRCCS Istituto Nazionale dei
Tumori- Milan- Italy, Department of Hematology and Pediatric
Onco-Hematology, Milano, Italy
Background/Objectives: Survival rates for patients with
Wilms’ tumour (WT) approximate 90% with refined use of
currently available interventions. However, a subgroup of
patients with initial high-risk histopathology or relapsing disease have a poor prognosis and it is a challenge to identify and
prioritise the development of new innovative approaches for
these subgroups.
Design/Methods: We conducted a systematic literature
search for published phase I and II clinical trials that registered
patients with WTs, and characterised the early-phase trial
activity, quantified response rates and highlighted avenues for
further development.
Results: We identified 63 trials (48 phase I, three phase I/II,
and 12 phase II trials) enrolling 214 patients with WTs, alongside other malignancies. The number of annually recruited
WTs did not change significantly and was less than 20%
of the potential candidates. The vast majority of the trials
were conducted in North America and 56 different interventions were investigated, including conventional chemotherapy
and biologically-targeted therapies. Overall, 33 WTs revealed
some degree of tumour control. Of these, five patients demonstrated complete remission (2%), 15 patients partial response
(7%) and 13 patients stable disease (6%). None of the included
novel biologically-targeted therapies emerged as promising
interventions and only conventional chemotherapy was able
to induce a complete and partial response.
Conclusions: We conclude that early phase trial recruitment
of WTs is below expected and the clinical outcome of the
included patients is dismal. Improvement of the availability
and recruitment to early-phase trials for WTs, especially in
Europe, is needed.
SIOP ABSTRACTS
P-171 Single Center Study: Retrospective Study
of 12 Cases of Malignant Rhabdoid Tumour of the
Kidney (MRTK) in Children
H.Y. Cheng1
1 Beijing
Children's hospital, surgical oncology, Beijing, China
Background/Objectives: To investigate the clinical characteristics and prognostic factors of malignant rhabdoid tumour
of the kidney (MRTK) in children.
Design/Methods: Twelve patients with MRTK were diagnosed and treated in Our hospital from January 2007 to
December 2015. Variables examined were tumor stage,
sex, age at diagnosis, surgical radicality, radiotherapy and
chemotherapeutic regimens.
Results: The median age of all cases was 15.5 months (4
to 42 months) at the time of diagnosis, 75% of patients
were male. The most common presenting complaint was
intra-abdominal mass or pain(75%),gross hematuria (33.3%),
tumor rupture(25%).8(75%)had positive lymph nodes or distant parenchymal metastases. The median follow-up was 22.2
months (rang 14-55 months),9 died and 3 survived.The 1-and
3-year survival rates were 50% and 25%.the whole patients
underwent surgery and chemotheropy,3 patients treated combining with radiation therapy, no significant improvement in
efficacy. There were no differences in survival between males
and females, or younger and older children. 3 cases survived
include one of stageⅠ,2 cases of stage Ⅲ.One of stage III
patient only underwent one cycle chemotherapy after surgery,
she survived disease-free for 43 months.
Conclusions: In infants and children has a dismal prognosis, Surgical radicality seems to be of prognostic value in
MRTK. Molecular diagnostics and research is warranted to
refine diagnostics and classifying prognostic relevant MRTK
subtypes.
P-172 Malignant Paediatric Abdominal Tumors;
Experience at the Children Hospital, Lahore
M. Faizan1 , M. Saleem2 , S. Anwar1 , N. Talat2 , P. Najam-ud-din3
1 The
Children's Hospital and Institute of Child Health, Paediatric
Haematology/Oncology, Lahore, Pakistan; 2 The Children's Hospital and
Institute of Child Health, Paediatric Surgery, Lahore, Pakistan; 3 The
Children's Hospital and Institute of Child Health, Paediatric Radiology,
Lahore, Pakistan
Background/Objectives: To determine the demographics,
Presentation, need of any Surgical intervention and Etiology
in Paediatric patients with histologically proven Malignant
abdominal masses in children.
Design/Methods: A retrospective observational Study carried out in the Hematology and Oncology Department
at The Children's Hospital and Institute of Child Health,
S245 of S518
Lahore,Pakistan. All children with Histologically proven
malignant abdominal masses from January 1st 2016 till
December 31st 2016 were included. Data regarding age, gender, any surgical intervention required and final diagnosis
were analyzed. Neonates, Patients with relapse and in whom
diagnosis was not confirmed histologically were excluded
form the study. Consecutive sampling technique was used and
data analyzed using SPSS 21.
Results: Total 191 children diagnosed with malignant
abdominal tumor were eligible for study. Majority were
male 120(63%), 1-4years of age 101(53%), and 5-9yrs
of age 58(30%). Commonest presentation was abdominal
distension and palpable abdominal mass 186 (97%), In
majority mothers 175(91%) only noted abdominal distension while mass was clinically palpable as noted by the
oncologist. Abdominal pain was present in 43(22.5%) and
fever 23(12%). Diagnosis was made on trucut biopsy in
177(93%) while primary surgical intervention required in
13(7%). Etiology of malignant abdominal masses was Wilms
tumor 66(34.6%), neuroblastoma 52(27.2%), Non Hodgkin
Lymphoma 34(17.8%), Germ cell tumor 16(3.1%), Rhabdomyosarcoma 6(3%), Hepatoblastoma 7(3.7%), hepatocellular carcinoma 3(1.5%),renal synovial cell carcinoma and
adrenocortical tumor in 2(1%)patients each while papillary
renal cell carcinoma, undifferentiated synovial sarcoma liver
was diagnosed in one patient each.
Conclusions: Wilms tumor followed by Non Hodgkin Lymphoma is the most common solid Abdominal Malignancy in
paediatric age group. Presentation is mostly in advanced stage
with a palpable abdominal mass. Need of surgery was avoided
by trucut biopsy at presentation for diagnosis. There is a need
to train pediatricians and family physicians along with mothers early recognition of abdominal distension and mass for
early diagnosis and better prognosis.
P-173 Treatment of Extra-Cranial Malignant
Rhabdoid Tumor: Results from the Children's
Oncology Group AREN0321 Study
J. Geller1 , Y.Y. Chi2 , J. Kalapurakal3 , N. Daw4 , F. Hoffer5 , E.
Perlman6 , P. Ehrlich7 , E. Mullen8 , A. Warwick9 , A. Paulino10 , Z.
Tochner11 , K. Gow12 , P. Grundy13 , E. Gratias14 , D. Ward15 , J.
Anderson16 , C. Fernandez17 , J. Dome18
1 Cincinnati
Children's Hospital Medical Center, Pediatrics, Cincinnati,
USA; 2 Children's Oncology Group, Biostatistics, Gainsville, USA; 3 Ann
and Robert H Lurie Children's Hospital of Chicago, Radiation Oncology,
Chicago, USA; 4 MD Anderson Cancer Center, Pediatrics, Houston, USA;
5 Quality Asasurance Review Ctr, Radiology, Lincoln, USA; 6 Ann and
Robert H Lurie Children's Hospital of Chicago, Pathology, Chicago, USA;
7 C S Mott Children's Hospital, Surgery, Ann Arbor, USA;
8 Dana-Farber/Harvard Cancer Center, Pediatric, Boston, USA; 9 Walter
Reed National Military Medical Center, Pediatric, Bethesda, USA; 10 MD
Anderson Cancer Center, Radiation Oncology, Houston, USA; 11 Childrens
Hospital of Philadelphia, Radiation Oncology, Philadelphia, USA;
12 Seattle Children's Hospital, Surgery, Seattle, USA; 13 University of
Alberta Hospital, Pediatrics, Edmonton, Canada; 14 eviCore Healthcare,
SIOP ABSTRACTS
S246 of S518
Oncology, Bluffton, USA; 15 St Jude Children's Research Hospital,
Pharmacy, Memphis, USA; 16 Merck, Oncology, North Wales, USA; 17 IWK
Health Centre, Pediatric and Bioethics, Halifax, Canada; 18 Children's
National Medical Center, Pediatrics, Washington DC, USA
Background/Objectives: In National Wilms Tumor Studies
1-5, 4-year overall survival (OS) for patients with advanced
malignant rhabdoid tumor (MRT) was 23%. AREN0321
evaluated a more intensive regimen containing vincristine,
doxorubicin, cyclophosphamide alternating with cyclophosphamide, carboplatin, etoposide (Regimen UH-1), with radiotherapy, with the goal to improve event-free survival (EFS)
and OS.
Design/Methods: Patients with stages I-IV extra-cranial
MRT were eligible. The study was designed to detect an OS
of 42%, using the historical OS of 25% as a fixed standard for
comparison. Patients with stage IV measurable disease had
the option to receive vincristine in combination with irinotecan (VI) in an upfront window.
Results: 39 patients with MRT were enrolled (30 with renal,9
with extra-renal primary tumors). Median age was 11.7
months (range, 1.1-109.6 months). Stage distribution was I
(2), II (5), III (23), and IV (9). No tumor response was seen
in the 3 patients who received VI window therapy. Among
those with relapse/progression, median time to progression
was 5.6 months. The 4-year EFS and OS estimates for the
entire cohort were both 35.9% (95% CI: 18.1%-53.7%). EFS
estimates according to stage were 100% each for stage I and
II, 26.1% (95% CI: 0.7%-51.5%) for stage III and 11.1% (95%
CI: 0%-31.6%) for stage IV. EFS estimates were 43.3% (95%
CI: 22%-64.6%) for renal tumors and 11.1% for extra-renal
tumors. Impact of age, radiotherapy, germline INI1 status and
toxicity will be evaluated.
Conclusions: Regimen UH1 did not improve survival for
the collective group of patients with MRT, though it may
have improved outcomes for patients with low-stage disease..
There was no salvage for patients with relapse or progression. For advanced-stage MRT, novel therapeutic strategies
such as integration of targeted biologics in combination with
chemotherapy are needed.
P-174 Clear Cell SARCOMA of the Kidney
(CCSK) in Pediatric Patients: A 28 Years Study
from One Institution in Brazil
F.N. Gutierrez1 , F. Rebelo1 , R. Carvalho1 , S. Nogueira1 , S.
Coelho1 , F. Lima2 , S. Ferman2 , M. Grabois2
1 Instituto
2 Instituto
Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil;
Nacional de Câncer, Pediatric Oncology, Rio de Janeiro, Brazil
Background/Objectives: To retrospectively analyze pediatric patients with clear cell sarcoma of the kidney admitted
to our institution from February 1987 to December 2015.
Design/Methods: Case report forms of pediatric patients (age
range: 10 months-6 years) were retrospectively analyzed. Collected data included demographics, clinical presentation, surgical and oncology management and Follow up. Patients data
were updated on March 2017.
Results: Among 51 patients diagnosed with non Wilms renal
tumors, 24 patients (11 boys, 13 girls) had histopathological diagnosis of CCSK. The median age at diagnosis was 29
months (range: 9 months to 6 years). Presenting symptoms
included abdominal mass first noticed by the family in 70,8%
of cases, 3 patients had hematuria, 1 patient had abdominal pain. The median time from initial symptoms to suspected diagnosis was 60 days (range: 1 day to 270 days). The
mean tumor volume was evaluated pre-chemotherapy in 8/24
patients and was 644 cm3 (range: 213 to 918 cm3). No patient
presented metastasis at diagnosis. Twenty four patients had
radical nefrectomy either upfront (14 cases) or after neoadjuvant chemotherapy (10 cases). In 21/24 patients there was free
surgical margins and in 3 cases without report. Lymphadenectomy was performed in 15 cases, of which 6 were positive.
Surgical stage was: I (n=7), II (n=7) and III (n=10).Overall
survival in 7 years was 73.7%. Survival by stage was: 83.3%
for stage I, 62.5% for stage II was and 71% stage III. Eight
patients had disease relapse: bone (n=4), brain (n=1), lung
(n=1), local (n=1), bone and lung (n=1) and 5 of 8 patients
died of disease.
Conclusions: With multidisciplinary care, treatment result
was good. There was no significant difference in survival in
relation to initial stage.
P-175 Surgical Management and Outcomes of
Renal Tumors Among Children with
IVC/Intracardiac Extension
H. Halepota1 , M. Arshad1 , S. khan1
1 Aga
Khan university, Paediatric Surgery, Karachi, Pakistan
Background/Objectives:
Determine
outcomes
of
renal tumor with inferior vena cava(IVC)and intracardiac(IC)extension in our institute. These subset of patients,
presents a technical challenge to surgeon especially with
constrained resources.
Design/Methods: Retrospective cross sectional study.All
patients from 1-16 years of age from January 1998 till June
2016 included
Results: During the study period 60 patients with renal
tumors were managed. 18 (30%)patients presented with IVC
and /or IC extension majority involving right kidney (13/18),
most common age at presentation ranged between 1-5 years.
Out of 18 children 55%were male and 45% were female. The
level of Tumor extension into IVC was below the diaphragm
in 10 (55.5%), above the diaphragm in 8 (44.44%) out of which
SIOP ABSTRACTS
5 extending into IC (27.8%).Wilms tumor (83%) was the most
common tumor type followed by renal cell carcinoma. Most
patients 9(60%) with Wilm's tumor had IVC extension below
diaphragm. 7 out of these 9 patients had no recurrence after
5 years of follow up. One had lung metastasis due to tumor
spillage and one patient with stage 5 disease expired. Most
(5/9) of the patients had received preoperative chemotherapy,
3 underwent direct thrombectomy. 5 patients had intra-atrial
extension; all received preoperative chemotherapy 2 showed
no recurrence after 5 years. 2 patients had Renal cell carcinoma and 1 had Rhabdoid tumor.
Conclusions: In our study 30% incidence of IVC and
or IC Tumor extension is much higher than the reported
series.This high incidence can be explained that many of these
patients were referred from other institutions.2 patients in
our study had surgical complications: In our study no patient
required cardiopulmonary bypass as preoperative chemotherapy reduced the thrombus to IVC., most patients received preoperative chemotherapy as well as preoperative radiotherapy
in case of metastatic disease. 61% of these patients are disease
free on five years of follow up.
P-176 Clinical Outcomes of Children with Wilms
Tumor Treated on a Modified SIOP WT 2001
PROTOCOL and Comparison with A Historic
Cohort Treated with Upfront Surgery
R. John1 , J. Kurian2 , L.G. Mathew1 , S. Sen2
1 Christian
Medical College, Pediatric Hematology Oncology, Vellore,
India; 2 Christian Medical College, Pediatric Surgery, Vellore, India
Background/Objectives: To analyze the clinical profile of
children with Wilms tumor treated by the modified SIOP
protocol and compare with historical patients treated on the
NWTS protocol
Design/Methods: Clinical, radiological and biopsy data of
59 children diagnosed to have Wilms tumor from 2004 to
2014 and treated using the SIOP WT 2001 protocol, with
a minor modification of pre-operative posterior flank core
biopsy, were collected from their medical records. The outcome of this cohort was compared with 62 children treated
from 1985 – 1995 on the NWTS protocol from two centres,
including our centre and reported by Sen et al.
Results: The median age at diagnosis was 36 months. M:
F was1:0.7. 31% had metastatic disease, 18% had renal
vein/IVC thrombosis and 10% had bilateral tumour. 97%
had favourable histology. Mean tumour volume reduced from
523ml to 315ml following neoadjuvant chemotherapy. 55
children underwent surgery and 52 completed treatment. 2
children had tumour spill and one had recurrence at biopsy
site.
S247 of S518
After a mean follow up of 42 months, 43 are in CR1 and 4
in CR2. The OS was 80% and EFS was 73%. Comparing this
data with the historical cohort: OS 80 vs 55%, stage I- 100
vs 81%, II-90 vs 75%, III- 80 vs 42% IV- 53 vs 14%, V- 67
vs 50%. OS for localized disease 97 vs 80% and metastatic
disease 50 vs 18%.
Conclusions: There is significant improvement in OS of all
stages of Wilms tumour treated on SIOP-WT-2001 protocol
compared to historic cohort treated with upfront surgery followed by chemotherapy. In centres where patients present
with large tumours, use of neoadjuvant chemotherapy followed by surgery is preferable. The outcome of the cohort
treated on SIOP-WT-2001 protocol for localised disease is
comparable with data from developed countries, however it
is less for metastatic disease.
P-177 Bilateral Wilms Tumor, Demographic
Characteristics, Treatment and Outcome: A
Multicenter Study
R. Kebudi1 , D. Tugcu2 , F. Akici3 , T. Celkan4 , S. Vural5 , G. Tokuc6 ,
G. Aydogan3 , Z. Karakas2 , B. Zulfikar1 , S. Bay7 , S. Yilmaz8 , A.
Irıbas9 , A. Celik10 , C. Buyukunal11 , F. Gun Soysal10 , S. Kuroglu12 ,
I. Adaletli12 , B. Bilgic13 , E. Darendeliler9
1 Istanbul
University Cerrahpasa Medical Faculty & Oncology Institute,
Pediatric Hematology-Oncology, Istanbul, Turkey; 2 Istanbul UniversityIstanbul Medical Faculty, Pediatric Hematology-Oncology, Istanbul,
Turkey; 3 Kanuni Sultan Suleyman Education and Research Hospital,
Pediatric Hematology-Oncology, Istanbul, Turkey; 4 Istanbul UniversityCerrahpasa Medical Faculty, Pediatric Hematology-Oncology, Istanbul,
Turkey; 5 Sisli Etfal Education and Research Hospital, Pediatric Oncology,
Istanbul, Turkey; 6 Marmara University- Pendik Education and Research
Hospital, Pediatric Hematology-Oncology, Istanbul, Turkey; 7 Istanbul
University Oncology Institute, Pediatric Hematology-Oncology, Istanbul,
Turkey; 8 Yeditepe University, Pediatric Hematology-Oncology, Istanbul,
Turkey; 9 Istanbul University- Oncology Institute, Radiation Oncology,
Istanbul, Turkey; 10 Istanbul University- Istanbul Medical Faculty, Pediatric
Surgery, Istanbul, Turkey; 11 Istanbul University Cerrahpasa Medical
Faculty, Pediatric Surgery, Istanbul, Turkey; 12 Istanbul UniversityCerrahpasa Medical Faculty, Radiology, Istanbul, Turkey; 13 Istanbul
University- Istanbul Medical Faculty, Pathology, Istanbul, Turkey
Background/Objectives: Bilateral Wilms tumor (BWT)
comprise 5% of all Wilms tumor in children. The outcomes
of children with BWT are reported to be inferior than for children with unilateral tumors at diagnosis.
Design/Methods: In this multicentric study, patients with
BWT treated in seven centers in Istanbul were retrospectively
evaluated for demographic characteristics, treatment and outcome.
Results: Thirty one patients (19 female, 12 male) with a
median age of 22.5 months (4-63) treated between 1990-2017
were evaluated. Nine patients had various congenital conditions. Eight patients (26%) had metastasis (lung, liver) at diagnosis. Eighteen patients had a biopsy (58%), 8 patients unilateral nephrectomy (26%) at diagnosis. Five (16%) patients
SIOP ABSTRACTS
S248 of S518
were diagnosed as BWT only radiologically. Anaplasia was
found in 4 patients. All received chemotherapy (vincristine,
actinomycine D±adriamycine (VAD) initially). Radiologic
response to VAD given the same day was better. Twenty five
patients underwent surgery (8 unilateral nephrectomy; 8 unilateral nephrectomy+partial contralateral nephrectomy; 4 unilateral nephrectomy+contralateral tumor excision; 2 bilateral
partial nephrectomy; 1 unilateral partial nephrectomy+ contralateral tumor excision; 1 bilateral tumor excision; 1 unilateral tumor excision). Fifteen patients (48%) received radiotherapy. Three patients (9.6%) who never had surgery are alive
with no disease (14-36 months from diagnosis). Two patients
(6.5%) developed chronic renal failure. Four patients died due
to progressive disease. Overall survival was 79% and event
free survival 73%, at a median follow up of 57 months (3-322).
Survival was significantly lower in metastatic patients (95 vs
48%) (p=0.04) and in those with anaplasia in histopathology
(95 vs 0%) (p=0.001).
Conclusions: Treatment of BWT is a challenge and the goal is
to have a good survival and to spare normal renal parenchyma
from unnecessary surgical resection, when possible. In this
series, the survival in nonmetastatic patients with favorable
histology is quite high with most of the surviving patients having adequate renal function.
were diagnosed as stage III, 10 cases (21.7%) as stage IV.
Stage I was diagnosed in 5 patients (10.9%) and stage II in
10 children (21.7%). Four cases with bilateral disease (stage
V) were observed with dominant tumour referring to stage III.
The neoadjuvant vincristin-dactinomycin chemotherapy regimen was used as standart with no upfront surgeries (nephrectomy or biopsy) performed in majority of cases. Unfavourable
histological type (including clear cell sarcoma) was revealed
in 17.4%. Adjuvant high risk chemotherapy and use of radiotherapy was considered in 43.5% of children mostly due to
massive tumour spread at diagnosis. The 3-year overall survival (OS) and event free survival (EFS) rates were 87% and
83%, respectively. Primary tumour stage was the most statistically significant factor that influenced the overall survival.
Conclusions: The approach of neoadjuvant chemotherapy of
nephroblastoma is more feasible compared to upfront surgery
in the realms of developing country, considering statistically
larger amount of advanced stage tumours at presentation.
P-179 Wilms Tumor: A Retrospective Study of a
Single Institute
T. Mehmood1
1 Shaukat
P-178 Outcomes of Nephroblastoma (Wilms
Tumor) Treatment in Western Ukraine, A 10 Year
Report from a Retrospective Cohort Analysis
R. Kizyma1 , Z. Kizyma1 , I. Lukavetskyi1 , B. Romanyshyn1 , B.
Kotsay2 , A. Kuzyk2 , A. Synyuta1 , M. Zakharus1 , I. Shchurovska3 ,
R. Sobko3
1 Western
Ukrainian Specialized Children's Medical Centre,
Surgery/Pediatric Oncology, Lviv, Ukraine; 2 Lviv National Medical
University, Pediatrics, Lviv, Ukraine; 3 Western Ukrainian Specialized
Children's Medical Centre, Intensive Care Department, Lviv, Ukraine
Background/Objectives: The objectives of the analyses
study were to review the clinical presentation and management of children with Wilms tumor and the factors influencing
the outcome in Lviv region. Despite the good overall prognosis in patients with nephroblastoma, most children in the
developing country present with advanced stage of disease at
diagnosis.
Design/Methods: A retrospective chart review of 46 children with renal tumours mostly from western part of Ukraine
treated and observed at surgery department of our institution from 2005 to 2015 was performed. Diagnosis was confirmed by conventional CT, MRI and sonography, that were
performed according to the site of involvement. The treatment
protocol was based on SIOP recommendations.
Results: More than a half of patients presented with large primary tumour or metastatic spread of disease: 17 cases (37%)
Khanum Memorial Cancer Hospital and Research Centre,
Radiation Oncology, Lahore, Pakistan
Background/Objectives: To compare our results to SIOP 9
study.
Design/Methods: We retrospectively reviewed 45 children
with Wilms Tumor (WT) treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore, Pakistan
from January 2001 to December 2010. Kaplan Meier method
with Log-Rank testing was employed for survival analysis.
Results: The mean age was 3.5 years old, with a sex ratio 0.48.
Eighty percent of the children presented a painless abdominal tumor as a first sign. The tumor was mainly unilateral
(93%), right for 56% of them. Ultrasounds, computed tomography showed a heterogeneous tumor in 52%, with a medium
size of 16.5 cm, developed in 48% in the lower pole of the
kidney. Venous thrombosis was diagnosed in 6.5% of the
patients. 23% of the patients had metastatic disease at presentation. Most of the patients received preoperative chemotherapy (98.3%) followed by nephrectomy. Postoperative stage I,
II, III were respectively 39%, 41%, 20% and according to SIOP
9 risk classification, there were 28%, 62%, 10% of low, intermediate and high histological risk. Postoperative chemotherapy was received in 84% while adjuvant radiotherapy was
given to 16% of the patients. The five-year overall survival was
68%, 80% in localized stages and 46% in metastatic stages.
Thirty-four percent relapsed in an average of 9 months. No
late treatment related side effects were seen.
SIOP ABSTRACTS
Conclusions: This study shows less overall survival then the
SIOP 9, due to a bigger rate of metastatic forms and late
diagnosis.
P-180 Renal Tumors in Children: A 25-Year
Single Center Experience
M. Moschovi1 , A. Zampogiannis1 , A. Athanasiadou1 , I. Nikas2 , K.
Stefanaki3 , G. Chrousos1
1 University
of Athens Medical School, 1st Pediatric DeptHematology/Oncology Unit, Athens, Greece; 2 University of Athens Medical
School, Imaging Department- “AGIA SOPHIA” Children's Hospital,
Athens, Greece; 3 University of Athens Medical School, Pathology
Department- “AGIA SOPHIA” Children's Hospital, Athens, Greece
Background/Objectives: Nephroblastoma, or Wilms’
tumor, is the most common renal malignancy in childhood. The median age at diagnosis is approximately
3.5 years. The occurrence in infancy and adolescence is
quite rare. Other less frequent tumors include mesoblastic nephroma, clear cell sarcoma, rhabdoid tumor and
adenocarcinoma.
Design/Methods: We reviewed all children with renal
tumors treated in our center in the last 25 years and evaluated demographic features, histopathologic results and
outcome.
Results: Out of a total of 91 cases with renal tumor, there
were 85 cases of nephroblastoma (34M, 51F), three cases
of mesoblastic nephroma, one of clear cell sarcoma, one of
rhabdoid tumor, and one of anaplastic sarcoma. Specifically
regarding nephroblastoma, the age at diagnosis ranged from
4mo-14yrs (mean: 4.2yrs): 2 children (2,5%) were <6mo, 35
children (41%) were 6mo–3yrs, 41 children (48%) were 310yrs and 7 children (8,5%) were >10yrs old. In three cases,
nephroblastoma developed in the context of a genetic syndrome, specifically two cases of Denys-Drash syndrome and
one of WAGR syndrome. 35 patients resided in large urban
centers and 48 resided in the province. Relapse was observed
in two cases, 12 (M) and 17 (F) years after the initial diagnosis, respectively, with the relapse in the second case occurring two years after pregnancy. Now, both cases are in second remission. One case with Denys-Drash syndrome remains
in remission ten years after diagnosis. Three cases died: two
with nephroblastoma-one from the disease and the other with
Denys-Drash syndrome from renal failure- and one with rhabdoid tumor.
Conclusions: Nephroblastoma is nowadays a curable disease. We observed a higher mean age at diagnosis than those
recorded in international data. This may denote a delay in
diagnosis and thus a need for a higher level of awareness.
Since relapse can occur decades after the initial diagnosis, a
long-term follow-up is required.
S249 of S518
P-181 Single and Tandem High-Dose
Chemotherapy Followed by Autologous Stem Cell
Rescue in Wilms Tumors: A Single-Institution
Report on Feasibility and Toxicity Profile
M. Delafoy1 , C. Pasqualini1 , C. Dufour1 , I. Hezam2 , G. Goma3 , V.
Lapierre4 , D. Valteau-Couanet1
1 Gustave
Roussy, Children and Adolescent Oncology Unit, Villejuif,
France; 2 Gustave Roussy, Clinical Research Operations Department,
Villejuif, France; 3 Gustave Roussy, Biostatistic and Epidemiology Unit,
Villejuif, France; 4 Gustave Roussy, Cell Therapy Unit, Villejuif, France
Background/Objectives: Very few data have been reported
yet on high-dose chemotherapy (HDC) with autologous stem
cell rescue (ASCR) in Wilms tumors (WT). We aim to define
the feasibility and the safety profile of HDC with ASCR in a
pediatric cohort of WT.
Design/Methods: We analysed data from patients with WT
treated with HDC and ASCR from 2000 to 2016 in the Children and Adolescent Oncology Unit at Gustave Roussy. Toxicity is reported according to CTCAE v4.0.
Results: Ten patients received HDC with ASCR, 5 as single
(Melphalan-Etoposide Carboplatine (MEC), n=4; Thiotepa
900mg/m2 , n=1), and 5 as a tandem HDC (Thiotepa
720mg/m2 with ASCR, followed after 6 weeks by Etoposide 1.8g/m2 -Melphalan 140mg/m2 , n=4; tandem Thiotepa
900 mg/m2 , n=1). The median age at ASCR was 5.6 years
(2.6-21.2). HDC was performed at relapse for 9 patients and
as first-line in 1 patient with stage 4 high-risk WT. Most
observed toxicity was digestive with grade ≥ 3 mucositis
and diarrhoea in 6 and 3 patients, respectively. One grade 3
renal toxicity was displayed after MEC. No neurological toxicity was observed nor sinusoidal obstruction syndrome. The
median duration of neutrophil recovery and hospitalisation
was 10 (2-13) and 24 days (21-36), respectively. No toxicityrelated death was observed. Toxicity profile was similar in single and tandem HDC. Whenever needed, the treatment could
be completed by lung and/or liver radiotherapy, with no significant delay. At the last follow-up, 4 patients were alive in
complete remission (CR1 n=1; CR2 n=3), while 6 patients
died of progressive disease.
Conclusions: Single and tandem HDC seems to be feasible
and with an acceptable toxicity profile in WT. Prospective
national and international studies are needed to define the best
condition regimens and to evaluate the role of HDC in this setting.
P-182 Consolidation Therapy with Autologous
Hematopoietic Stem Cell Transplant in Patients
with Relapsed Wilms Tumour. Experience of A
Single Mexican Pediatric Hospital
SIOP ABSTRACTS
S250 of S518
A. Castellanos1 , H. Pena1
1 Instituto
Nacional de Pediatría, Oncology, Mexico City, Mexico
Background/Objectives: To determine the experience of a
therapeutic arm with autologous hematopoietic stem cell rescue in wilms tumour's patients at National Institute of Pediatrics (INP) in Mexico City
Design/Methods: We performed a retrospective study with
the analysis of 10 years of experience at INP of patients with
Wilms Tumour. We only analized patients with relapse
Results: A total of 9 relapses (8%) were diagnosed, including 5 patients (55%) with wilms tumour relapse who received
treatment with intense chemotherapy, radiation therapy and
autologous hematopoietic stem cell transplantation. The mean
age at diagnosis was 38 months with a mean relapse time from
diagnosis of 18 months. Favorable histology was reported
in 2 patients, and all the cases were metastatic at diagnosis, all cases with lung metastasis and one patient also liver.
All patients received intense chemotherapy with ifosfamide
1.8grm2scdose / 5 days, etoposide 100mgm2scdose / 5 days
and carboplatin 450mgm2scdose / 1 day (ICE) as well as
abdominal/pulmonary radiation therapy for the treatment of
relapse.The 5-year overall survival is 57% (95% CI 2.46-9.00).
The cause of death was progression of disease in both cases.
No transplant-related mortality was reported
Conclusions: Treatment of relapse in wilms tumor with combination therapy (radiation, chemotherapy and stem cell transplant) is effective. Morbi-mortality related to intensive treatment was no reported in our cases
2001 protocol at INCA (Brazil) were reviewed by pathologist who defined areas of blastema and normal renal cortex
tissues. Prognostic factors (age, gender and risk classificaion)
and relapse were explored regarding LINE-1 methylation as
defined by pyrosequencing. Average methylation of 5 CpG
sites located in LINE-1 were used for analyzes.
Results: Comparing WT blastemal (median of 65%, 47.473.2%) to normal kidney (median of 71.8%, 51.5-77.5%)
samples revealed that LINE-1 is hypomethylated in WT
(p<0.0001). Age, gender, stage and risk classification showed
no relation with methylation levels within WT samples.
Nevertheless, tumors from patients who relapsed (60.5%,
47.4-71.30%) presented lower methylation levens than those
patients without relapse (66.5%, 52.8-73.30%, p=0.0005). A
ROC curve analysis using a cut-off value of 62.71% for LINE1 methylation levels showed that the area under the curve
(AUC) was 0.80, with a sensitivity of 76.5% and a specificity
of 83.3% (p=0.0005).
Conclusions: We suggest that LINE-1 methylation levels
evaluated in the blastemal component of WT can be used as a
marker for patients, with WT that presented relapse reporting
hypomethylation compared to patients without relapse
P-184 Challenges and Implications of
Histopathology Diagnosis of ‘Non-Wilm's’ Tumours
of Kidney in Children
M. Ramadwar1 , A. Sali1 , B. Rekhi1 , S. Qureshi2 , G.
Chinnaswamy3 , T. Vora3 , N. Khanna4 , S. Medhi5
1 TATA
P-183 Association Between Long Interspersed
Nuclear Element-1 Methylation Levels and Relapse
in Blastemal Component of Wilms Tumors
B. Pereira1 , R. Montalvao-de-Azevedo1 , P. Faria2 , P. Nicolau Neto3 ,
M. Maschietto4 , B. de Camargo1 , S. Coelho Soares Lima3
1 Instituto
Nacional de Cancer, Pediatric Hematology Oncology Programa,
Rio de Janeiro, Brazil; 2 Instituto Nacional de Cancer, Patholgy Division,
Rio de Janeiro, Brazil; 3 Instituto Nacional de Cancer, Carcinogenesis
molecular Program, Rio de Janeiro, Brazil; 4 Brazilian Biosciences National
Laboratory LNBio-, Brazilian Center for Research in Energy and Materials
CNPEM-, Campinas, Brazil
Background/Objectives: Risk stratification of Wilms tumors
(WTs) is largely based on tumor stage and histology, with
the blastemal component predominance in chemotherapy pretreated WT classifying patiets as high risk. WTs present an
hypomethylation profile compared to matched normal kidney.
We aimed to explore the relation between global DNA methylation, represented by LINE-1 (17% of the human genome) in
WT blastemal component and prognostic factors
Design/Methods: Samples from 47 FFPE sporadic unilateral WTs from patients treated according to the SIOP WT
Memorial Hospital, Pathology, Mumbai, India; 2 TATA Memorial
Hospital, Paediatric Surgery, Mumbai, India; 3 TATA Memorial Hospital,
Medical Oncology, Mumbai, India; 4 TATA Memorial Hospital, radiation
oncology, Mumbai, India; 5 TATA Memorial Hospital, Radiolgy, Mumbai,
India
Background/Objectives: ‘Non-Wilm's’ tumour category
constitutes several rare benign and highly aggressive tumours
of kidney in children. We aim to review histopathology of
‘non-Wilm's’ tumours with emphasis on diagnostic challenges
and clinical relevance of the precise diagnosis.
Design/Methods: We reviewed histopathology and immunohistochemistry (IHC) of 55 patients diagnosed with ‘nonWilm's’ renal tumours from period 2011- 2016. Clinical
details were noted from electronic medical records.
Results: Various non-Wilm's renal tumours in our series of
55 patients were rhabdoid tumour (20), clear cell sarcoma
(11), congenital mesoblastic nephroma (4), Ewing's sarcoma/
PNET (3), Translocation associated renal cell carcinoma (5),
cystic partially differentiated nephroblastoma (2), Papillary
RCC (1),Burkitt's lymphoma (1), granulocytic sarcoma (1).
All rhabdoid tumours showed loss of INI1 on IHC. Remaining 8 tumours posed diagnostic problems. Distinction between
clear cell sarcoma and Wlim's tumour could not be resolved
SIOP ABSTRACTS
(2). Undifferentiated round cell tumours posed a problem of
differentiation between PNET, Wilm's tumour and synovial
sarcoma respectively (5), Teratoid Wilm's and teratoma could
not be distinguished.
11 of 20 patients with rhabdoid tumour underwent resection post-chemotherapy. 3 patients presented with extensive
brain and lung metastasis. Rest were inoperable tumours. 7 of
11 patients with clear cell sarcoma could undergo resection.
Relapses were in the form of bone and brain metastasis.
Conclusions: Rhabdoid tumour and clear cell sarcoma were
commonest ‘non-Wilm's‘ tumours in our series (31/55). CMN
represented benign tumours. Rhabdoid tumours were the most
aggressive tumours. Tumours with undifferentiated round cell
morphology posed diagnostic problem. Clear cell sarcoma
also posed a diagnostic problem due to its non-discrete morphology and lack of specific immunoprofile. Diagnosis of
rhabdoid tumours was facilitated by its distinctive morphology and loss of INI-1 expression on IHC. Thus our study
emphasises the need of precise diagnosis on biopsy due to
its impact on treatment decisions of wide variety of different
tumour entities.
P-185 Tumor Inferior VENA CAVA (IVC)
Thrombosis in Children with Nephroblastoma
M. Rubanskaya1 , K. Anatoliy1 , K. Polad1 , R. Mikhail1
1 Cancer
research instutute N.N. Blokhin RAMS, children oncology,
Moscow, Russia
Background/Objectives: Nephroblastoma is one of the most
common solid tumors in childhood (about 7%). The incidence
of tumor thrombosis in nephroblastoma according to various
large studies is 3 to 6%. In the literature there are rare individual descriptions of cases of thrombosis of children with
nephroblastoma with the spread of thrombus to the atrium.
Design/Methods: In our clinic from 1990 to 2016 were
treated 24 children with nephroblastoma, with IVC thrombosis. Age of children ranged from 1 year to 15 years. In
2 of these, the thrombus reached the right atrium. Treatment included preoperative chemotherapy, surgery (nephrectomy, thrombectomy) and postoperative radiation therapy and
chemotherapy.
Results: Survival in stage III nephroblastoma does not differ
from survival in nephroblastoma with tumor IVC thrombosis. With preoperative chemotherapy, complete regression of
the tumor thrombus can be achieved in 57.9% of cases, partial regression in 21.1%. Preoperative chemotherapy reduces
intraoperative blood loss and the frequency of surgical complications. Under the condition of radical operation, the localization of lesions of different sections of the IVC does not
affect survival. Currently, 22 children were alive without evidence of recurrence and disease progression.
S251 of S518
Conclusions: Complex therapy allows to achieve a good overall survival of children with nephroblastoma with IVC thrombosis.
P-186 The Outcome of Ruptured Wilms Tumor:
Single Institution Experience
T. sarrawi1 , T. ISMAEEL1 , H. HALALSHEH1 , R. DEEBAJAH1 ,
K. ghandoUr1 , F. AJLOUNI1 , I. SULTAN1
1 King
Hussein Cancer Center, Pediatric, Amman, Jordan
Background/Objectives: Patients with Wilms tumor (WT)
can present with ruptured tumors with no specific symptoms.
Radiologic diagnosis, pathological confirmation and optimal
management are necessary to improve the outcome of these
patients.
Design/Methods: We conducted a retrospective chart-review
of all pediatric patients who were diagnosed with WT between
2003-2016. Ruptured Wilms Tumor was diagnosed based on
radiological and/or pathological findings
Results: Twenty seven patients (Males, 52%) were analysed. Median age at diagnosis was 4.5 years (range, 1.615.8). Pathological local stages, irrespective of rupture, were
as follows: I (n=3, 11%), II (n=7, 26%), III (n=17, 63%).
The median duration of symptoms before presentation was 2
weeks (range, 0-17). Twenty three (85%) patients had favorable histology. Distant metastasis was found in 8(29.6%)
patients at presentation. Upfront nephrectomy was done for
9(33.3%) of patients. Ruptured WT was identified radiologically in 21(78%) patients and intraoperatively in 6 patients
(22%). Rupture was pathologically confirmed in 13 patients
(48%). Twenty five (93%) patients received postoperative
radiotherapy, whether flank or whole abdomen. Relapse
developed in 8(30%) patients, and 6 of them died. One of
the relapsed patients was not upstaged and 2 of them did not
receive radiotherapy. The 3-year OS and EFS were 69±11%
and 66±9.9%, respectively. Univariate analysis showed relatively worse EFS for patients with age less than 4 years
(p=0.059). In further analysis, no difference in outcome was
observed according to duration of symptoms, use of radiotherapy or upfront nephrectomy.
Conclusions: Similar to previous reports, we showed that
majority of patients with rupture can be cured with a 3drug regimen and abdominal radiation. Clinico-radiologicalpathological correlation is important to diagnose these
patients. The current staging system is not optimal to capture
these patients and needs to be revised.
P-187 Presentation and Outcomes of Wilms
Tumour in a Paediatric Oncology Unit in Ghana
L.G. Tagoe1 , E. Nyarko1
SIOP ABSTRACTS
S252 of S518
1 Korle
Bu Teaching Hospital, Child Health, Accra, Ghana
Background/Objectives: Wilms tumour is the fourth commonest childhood malignancy in Ghana. The survival of
Wilms tumour in sub-Saharan Africa is reported to be below
50%. The objective of this study is to describe the presentation
of Wilms tumour, extent of spread at presentation and patient
outcomes.
Design/Methods: In this retrospective study, clinical notes,
including results of investigations of children diagnosed with
Wilms tumour at the Paediatric Oncology Unit of the Korlebu Teaching Hospital, Accra, from January 2011 to December 2015 were reviewed. Data was then analysed for time lag
between symptom onset, presentation and start of treatment,
evidence of metastases, histopathological features and patient
outcomes.
Results: Fifty-one case notes (54%) were retrieved out of the
ninety-four cases seen over the period. Majority of the patients
(37%) were between three to five years old with a male: female
ratio 1:1.7. Five (10%) had bilateral disease. The commonest
presenting complaint was a painless abdominal mass (47%).
Most patients delayed in seeking medical help with 53% presenting after a month. In majority (98%) of the patients, maximum tumour diameter was >8cm by imaging. 11 cases (22%)
had metastases at presentation, to the lungs and/or liver. 96%
of patients received treatment, which in all cases, except two,
involved neoadjuvant chemotherapy prior to nephrectomy.
35% of cases were found to be Stage III at surgery. 57% were
classified as intermediate risk at histopathology and 20% high
risk. 33% received adjuvant radiotherapy. 9 patients (18%)
abandoned treatment, whilst 55% completed treatment and are
currently alive. 8 patients (16%) relapsed after treatment completion. 7 patients (14%) died either before, during treatment
or after relapse.
Conclusions: Although most children with Wilms tumour in
our setting present with advanced stage disease (stages III to
V), with the appropriate treatment including radiotherapy, the
outcomes are encouraging.
P-188 Intussusception After Renal Tumor
Surgery in Children: Two Cases and an Overview of
Literature
S. van Peer1 , C. van de Ven1 , S. Terwisscha van Scheltinga1 , J.
Hol1 , M. van Grotel1 , M. van den Heuvel-Eibrink1
1 Princess
Máxima Center for Pediatric Oncology, Pediatric Oncology,
Utrecht, The Netherlands
Background/Objectives: To further optimize survival rates
as well as quality of cure for pediatric kidney tumors,
attention for treatment related morbidity and mortality has
become increasingly important. Intussusception is a rare but
important complication after tumornephrectomy in children,
causing morbidity, mortality and prolonged hospitalization.
In this study, we describe two recent cases in our institute and
provide a comprehensive review of the literature.
Design/Methods: For our narrative review, we searched for
all reported cases of post tumornephrectomy intussusception
published until November 2016, using Pubmed and Embase
libraries.
Results: A total of 52 pediatric renal tumor cases who developed intussusception after tumornephrectomy were identified.
Median age was 23 months (range 5-84). Median time of
onset was postoperative day 6 (range 3-37). Of 41 patients
described in detail, 37 suffered from a ileoileal intussusception, 4/41 were ileocolic. Most frequent presenting symptom
was bilious vomiting. Preceding treatment approach could
was documented in 45 cases; i.e. preoperative chemotherapy was administered to 10/45 patients. In 29 of 30 well
documented cases successful manually reduction through relaparotomy was described and only 1 patient needed resection.
All patients survived without recurrence of intussusception.
Conclusions: In pediatric renal tumor patients small bowel
obstruction seems to reflect most postnephrectomy intussusception cases in contrast to the ileocolic idiopathic intussusceptions that are observed in healthy children. Symptoms of
intussusception mimic chemotherapy related toxicity and general post-surgical symptoms, thereby initiating a significant
delay in diagnosis. Awareness of intussusception after renal
tumor surgery is warranted.
P-189 Evaluation of Preoperative Tace in
Children with Advanced Wilm's Tumor
C. Lai1 , J. Wang2 , Q. Shu2 , M. Li2
1 Children's
Hospital - Zhejiang University School of Medicine, Department
of Radiology, Hangzhou, China; 2 Children's Hospital - Zhejiang University
School of Medicine, Department of Surgical Oncology, Hangzhou, China
Background/Objectives: To evaluate the efficacy of preoperative TACE in children with advanced Wilm's tumor.
Design/Methods: In the late 62 cases of advanced Wilms
1 tumor diameter> 10cm or medial
tumor, inclusion criteria: ○
border over midline;○
2 imaging studies suggest tumor invasion of adjacent organs, have abdominal aortic lymph node
3 inferior vena cava tumor thrombometastasis or ascites;○
sis; ○
4 the lung, liver, bone and other distant metastases; ○
5
bilateral Wilms tumor. Study groups:○
1 Preoperative arterial chemoembolization group (31 cases), ○
2 Preoperative
intravenous chemotherapy group (20 cases), ○
3 Early surgery
group (11 cases).
Results: Preoperative TACE group average reduction of
32.4% of tumor, preoperative chemotherapy tumor shrinkage
of 20.3%, the tumor volume reduction rate between the two
SIOP ABSTRACTS
groups was statistically significant.Three groups of patients
with complete resection rate was 87.1%, 70.0% and 18.2%,
preoperative TACE group with preoperative chemotherapy
group, the difference was statistically significant.
Conclusions: Preoperative TACE has higher tumor shrinkage
rate, shorter peroperatin treatment time, less systemic toxicity,
higher rate of complete tumor resection. TACE is safe and
effective in advanced Wilm's tumor.
P-190 Evaluation of Preoperative Transarterial
Chemoembolization in Wilms’ Tumor
Z. Sun1 , D. Hu1 , J. Chen1 , H. Jin1 , X. Guo1 , X. Fang1 , J. Wang2
1 Jinhua
Municipal central hospital, Department of pediatric surgery,
Jinhua, China; 2 Children's Hospital - Zhejiang University School of
Medicine, Department of Surgical Oncology, Hangzhou, China
Background/Objectives: To evaluate the efficacy of transarterial chemoembolization (TACE) combining with surgery in
the treatment of Wilms’ tumor in children.
Design/Methods: Twenty-four cases of wilms’ tumor were
admitted to the department of pediatric surgery in Jinhua
municipal central hospital between January 2010 and December 2016. Three cases of bilateral tumor and 1 case of solitary tumor were excluded, 20 cases of unilateral wilms’ tumor
were randomly allocated to preoperative TACE group ( preoperative TACE + surgery, n = 10) and control group (preoperative chemotherapy + surgery, n = 10). The shrinkage
volume of tumor between pre- and post-chemotherapy, blood
loss during surgery, intra-operative tumor spillage, operative
time and postoperative complications were analyzed.
Results: Comparing with control group, the shrinkage volume of tumor is higher in the preoperative TACE group
(476.9±156.75cm3 vs. 577.5±138.35cm3 , P<0.05), blood
loss during surgery was less (97.5±21.63ml vs. 119±26.23ml,
P<0.05), myelosuppression rate was lower (0 vs. 5, P<0.05).
The number of Less intra-operative tumor spillage in TACE
group, but there was statistical diffence between two groups.
The mean follow-up time was 34.15 months, no tumor recurrence or distant metastasis was observed.
Conclusions: Preoperative TACE combining with surgery is
a safe and effective modality in the treatment of wilms’ tumor
in children.
P-191 Clinical Characteristics of Renal Cell
Carcinoma Associated with XP11.2
Translocation/TFE Gene Fusion in Children: An
Experience of A Single Institution
W. Yao1 , K. Li1 , K. Dong1 , X. Xiao1 , S. Zheng1
1 Children's
China
Hospital of Fudan University, Pediatric Surgery, Shanghai,
S253 of S518
Background/Objectives: To investigate the clinical features,
prognosis of renal cell carcinoma (RCC) associated with
Xp11.2 translocation/TFE gene fusion in children.
Design/Methods: A retrospective review of 10 cases between
Jan 2010 and Dec 2016 were evaluated and the clinical data
were collected and analyzed.
Results: Xp 11.2 translocation RCCs were identified in 7
males and 3 females with a mean age of 5.2 years (range: 1.212.9 years). The clinical symptom included painless hematuria in 3 cases, abdominal pain with microscopic hematuria
in 3 cases and as an incidental finding in 4 patients. According
to the TNM staging system, there were 3 patients in stage I,
2 patients in stage II, 4 patients in stage III and 1 patients in
stage IV with lumber metastasis. The tumor side is between
5.11- 745.05 cm3 (mean 197.17cm3 ). Radical nephrectomy
and lymphadenectomy were performed in 8 patients and lymphatic invasion was confirmed in 4 cases, while tumor biopsy
was performed in 2 patients. Only one patient received postoperative chemotherapy, while 7 patients just observed after
surgery and of the 2 patients with biopsy, one received radiotherapy and the other one gave up treatment. All patients
were followed up for an average of 24.2 months (range: 2- 74
months), and 7 were still alive and 3 had died after surgery.
Conclusions: Xp 11.2 translocation RCC is rare subtype
of renal tumor in children associated with poor prognosis
and lymphatic metastasis. Radical nephrectomy and lymphadenectomy is the main treatment for these patients.
S O LID NO N BRAIN TUM O URS BON E T U M O U R S
P-192 In Vivo Prevention Local Effect of
Cadmium of Local Recurrence in Xenograft Model
of Osteosarcoma
D. Demirkiran1 , S. Aktas1 , P. Ercetin1 , E. Kolatan1 , O. Yilmaz2 , H.
Havitcioglu3 , N. Olgun1
1 Dokuz
Eylul University, Institute of Oncology, Izmir, Turkey; 2 Dokuz Eylul
University, Experimental Animal Sciences, Izmir, Turkey; 3 Dokuz Eylul
University, Orthopedics, Izmir, Turkey
Background/Objectives: Osteosarcoma usually occurs in
childhood and young adulthood and is very aggressive.
These tumors were achieved great success in limb salvage
surgery. However, residual tumor may remain at the microscopic level increases the likelihood of recurrence. Apart
from surgery, the residual tumor is observed despite the highdose methotrexate, cisplatin chemotherapy regimens, therefore, new approaches are needed for the treatment of osteosarcoma. In this study, the cadmium in cement was placed locally
SIOP ABSTRACTS
S254 of S518
after surgical resection to evaluate its preventive efficacy on
residual tumor and recurrence in in vivo animal model.
Design/Methods: K7M2 tumorigenic osteosarcoma cell line
was cultivated in vitro. Then, the xenograft tumor model was
formed by giving the tumor cells subcucateously to athymic
nude mice. After the tumor growth, control tumor, near total
resected tumor group, near total resected group with serum
in cement and near total resected group with cadmium in
cement group was conducted randomly with 7 animals in each
group. Animals were observed for 15 days for recurrences in
tumor site. After the sacrification, the presence of residue was
checked histopathologically in each group.
Results: Tumor was formed within one month after subcutanous injection. REcurrent tumor was formed in all animals
in near total resected group, near total resected group with
serum in cement. No or small tumor formation was observed
in cadmium group. No systemic toxic effect was observed.
Conclusions: Our data suggest that local application of cadmium in cement might help local therapy of osteosarcoma
after surgery. Postoperative local treatment with agents within
orthopedic biyomechanic substances might be an option of
additive treatment to overcome the recurrences in osteosarcoma. Our next step is to test chemotherapoetic agents
(methotrexate, cispatin) in cemnent in vivo animal model.
P-193 Successful Re-Treatment of an
Unresectable Sacral Giant Cell Tumour of Bone
with Denosumab after a Pregnancy-Induced Hiatus
S. Wilson1 , S. Pratap2 , E. Blanco1 , B. Hassan3
1 Oxford
University Hospitals NHS Foundation Trust, Paediatric
Haematology/Oncology, Oxford, United Kingdom; 2 Oxford University
Hospitals NHS Foundation Trust, Oxford Sarcoma Service, Oxford, United
Kingdom; 3 University of Oxford, Oxford Sarcoma Service, Oxford, United
Kingdom
Background/Objectives: Giant cell tumours of bone
(GCTB) are benign, locally aggressive tumours predominantly treated surgically. More recently, neoadjuvant
treatment with the RANK-L monoclonal antibody Denosumab has enabled surgery in unresectable cases to be
considered. Denosumab disturbs the RANK-RANKL
interaction, inhibiting osteoclastic-induced bone lysis and
promotes osteogenesis. RANK-L is overexpressed on GCTB
stromal cells driving bony destruction associated with the
tumour.
The Oxford Sarcoma Service selectively utilises Denosumab
to optimise operability and reduce surgical – associated morbidity.
Design/Methods: We present the case of a patient undergoing
Denosumab treatment for an unresectable sacral GCTB who
became pregnant on treatment.
Results: The patient presented with cauda equina syndrome.
Biopsy of an extensive S2-S5 vertebral lesion confirmed a
sacral GCTB. Resection would require sacrifice of S2-3 nerve
roots and the loss of bowel and bladder function. Denosumab
was commenced with an excellent metabolic, radiological and
neurological response after 1 cycle. PET/CT demonstrated a
reduction in SUVmax from 16.3 to 4.4, with resolution of the
presacral soft tissue mass and sacral ossification. Complete
metabolic response was seen after 6 cycles of Denosumab.
After 17 cycles, treatment was stopped because of pregnancy.
During this time the patient's symptoms were stable despite
the tumour increasing by greater than 15mm in the sagittal
axis. A normal baby was born by elective Cesarean section,
without skeletal or metabolic abnormalities.
Denosumab was recommenced with a rapid radiological
response after 1 cycle, peaking at cycle 13 when dose frequency was reduced to 6-weekly. Alterations in bone mineralisation density has necessitated planning definitive local
therapy with proton beam therapy.
Conclusions: Denosumab provides excellent tumour control
for unresectable GCTB. We report objective evidence that retreatment is effective after an hiatus and the risk of resistance
is low. Consideration of long-term toxicity and definitive management remain important considerations.
P-194 A DNA Methylation-Based Classifier for
Accurate Molecular Diagnosis of Bone Sarcomas
P. Wu1 , B. Cooper1 , F. Bu2 , C. Bowman2 , K. Jonathan3 , J.
Serrano2 , S. Wang4 , T. Jackson4 , D. Gorovets2 , R. Gorlick5 , M.
Ladanyi3 , K. Thomas2 , M. Snuderl2 , M. Karajannis6
1 NYU
Langone Medical Center, Radiation Oncology, New York, USA;
Langone Medical Center, Pathology, New York, USA; 3 Memorial
Sloan Kettering Cancer Center, Pathology, New York, USA; 4 NYU Langone
Medical Center, Pediatrics, New York, USA; 5 Montefiore Medical Center,
Pediatrics, New York, USA; 6 Memorial Sloan Kettering Cancer Center,
Pediatrics, New York, USA
2 NYU
Background/Objectives: Pediatric bone sarcomas present a
unique diagnostic challenge because of the considerable morphologic overlap between different entities. The choice of
optimal treatment, however, is dependent upon accurate diagnosis. Genome-wide DNA methylation profiling has emerged
as a powerful new diagnostic tool in brain tumors, with diagnostic accuracy exceeding standard histopathology. We developed and validated a methylation based classifier to differentiate between osteosarcoma (OS), Ewing's sarcoma (ES), and
synovial sarcoma (SS).
Design/Methods: DNA methylation status of 482,421 CpG
sites in 15 OS, 10 ES, and 11 SS samples were measured using
the Illumina HumanMethylation450 array. From this training
set of 36 sarcoma samples we developed a random forest classifier from the 400 most differentially methylated CpG sites
SIOP ABSTRACTS
S255 of S518
(FDR q value < 0.001). This classifier was then validated
in 10 SS samples from The Cancer Genome Atlas (TCGA),
86 OS samples from TARGET-OS, and 15 ES samples from
a recently published series (Huertas-Martinez et al., Cancer
Lett. 2016).
Results: DNA methylation profiling revealed three distinct
molecular clusters, each enriched with a single sarcoma subtype. Within the validation cohorts, all samples from TCGA
were accurately classified as synovial sarcoma (10/10, sensitivity and specificity 100%). All but one sample from
TARGET-OS were classified as OS (85/86, sensitivity 98%,
specificity 100%) and all but one sample from the ES series
was classified as ES (14/15, sensitivity 93%, specificity
100%). The single mismatch, an osteosarcoma sample which
was classified as a ES, was later determined to be a misdiagnosed ES based on RNA-seq data demonstrating high EWRS1
and ETV1 expression. An additional clinical sample that was
misdiagnosed as a SS based on initial histolopathology, was
accurately recognized as OS by the methylation classifier.
Conclusions: OS, ES and SS have distinct epigenetic profiles. Our validated methylation-based classifier provides
increased diagnostic accuracy, including in cases where standard histopathology is inconclusive.
P-195 Extrapulmonary Metastasis is an
Important Prognostic Factor in Patients with
Osteosarcoma Accompanied by Pulmonary
Metastasis
1
1
1
1
Results: Twenty-eight patients had lung metastases. Thirteen
out of these 28 patients had extrapulmonary metastasis(EPM).
Metastatic sites were bones, soft tissue, the diaphragm and
brain. The 5-year survival rate was 96% in patients without
metastasis, compared to 50% with pulmonary metastasis. In
28 patients with pulmonary metastasis, the 5-year survival
rate of patients without EPM was 76%, 15% in patients with
EPM. In patients without EPM, 90% of 5-year survival rate
was achieved by surgical metastasectomy compared to 60%
without metastasectomy. In patients with EPM, the 5-years
survival rate achieved by surgical metastasectomy was 25%
compared to 0% without.
Conclusions: Our results suggested that pulmonary metastasis was the most important prognostic factor in patients with
osteosarcoma, and EPM was also a contributing factor. In
patients without EPM, pulmonary metastasectomy is recommended. However, in patients with EPM, the prognosis was
still poor even when metastasectomy was performed. Some
form of new strategy is needed.
P-196 Mechanical Damage of Knee
Endoprosthesis in Children with Malignant Bone
Tumors
V. Kobys1 , V. Konovalenko2
1 Kiev
City Oncology Center, Pediatric Oncology, Kiev, Ukraine; 2 Institute
of Experimental Oncology, Department of Osteology, Kiev, Ukraine
1
N. Kitagawa , M. Shinkai , K. Mochizuki , H. Usui , E. Osawa ,
K. Yoshizawa1 , J. Machida2 , H. Goto3 , K. Nozawa4 , M. Tanaka5 , Y.
Tanaka5
1 Kanagawa
Children's Medical Center, Department of Surgery, Yokohama,
Japan; 2 Kanagawa Children's Medical Center, Department of Orthopedic
Surgery, Yokohama, Japan; 3 Kanagawa Children's Medical Center,
Department of Hematology / Oncology and regenerative medicine,
Yokohama, Japan; 4 Kanagawa Children's Medical Center, Department of
Radiology, Yokohama, Japan; 5 Kanagawa Children's Medical Center,
Department of Pathology, Yokohama, Japan
Background/Objectives: Distant metastasis is one of the
most important prognostic factors in osteosarcoma. Metastases usually occur in the lung. We have performed aggressive
pulmonary metastasecomy, but prognosis of these patients are
still unsatisfactory. The aim of this study is to find prognostic factors in patients with osteosarcoma accompanied by pulmonary metastasis.
Design/Methods: Retrospective chart reviews of 50 patients
with osteosarcoma were performed. All patients underwent
neoadjuvant, adjuvant chemotherapy and surgery for the primary lesion. Each metastatic lung lesion was removed mainly
by wedge resection through an open thoracotomy, sometimes
lobectomy if tumor was too large.
Background/Objectives: Due to the growth of the child
and the increase of body mass, the mechanical load on the
endoprothesis significantly increases, and extension of the
prosthesis increases the arm of force on the endoprosthesis
stem. Over time this leads to fracture of the femoral endoprosthesis stem and the need for reoperation to replace the
endoprosthesis.
Design/Methods: During the period from 2000 to 2016, we
operated 50 patients with malignant femur bone tumors aged
7 to 18 years, the average age was 11.5 years. 16 (31%) of
them had a fracture of the femoral bone endoprosthesis stem
in the period from 3 to 10 years after the arthroplasty. The
material was titanium endoprosthesis or kobal-chromiummolybdenum alloy. Rod diameter femoral stem was 10 to 12
mm.
Results: All patients with a fracture of the femoral endoprosthesis stem had reimplantation of the stem, mostly with a
stem of a larger diameter. There was no deterioration of limb
function. In cement endoprosthesis the stems were removed
without cutting the bone containing the fragments of the
stem. In the cement-free prosthesis, longitudinal osteotomy
was performed to extract fragments of the endoprothesis
stem.
SIOP ABSTRACTS
S256 of S518
Conclusions: When implanting knee endoprotheses in children, preference should be given to cement endoprosthesis because of the high risk of fracture endoprosthesis legs.
They are much less traumatically removed when replacing
endoprosthesis stems. Later, when the patient stops growing,
cement-free endoprosthesis can be implanted.
P-197 Serum Adhesion Molecules Levels in Bone
and Soft Tissue Sarcoma and Prognostic
Significance
N. Kurucu1 , C. Sonmez2 , N. Sarı3 , M. Yıldırım3 , İ. Ilhan3
1 Hacettepe
University Faculty of Medicine, Department of Pedatric
Oncology, Ankara, Turkey; 2 A.Y Ankara Oncology Research and Traning
Hospital, Department of Biochemistry, Ankara, Turkey; 3 A.Y Ankara
Oncology Research and Traning Hospital, Department of Pediatric
Oncology, Ankara, Turkey
Background/Objectives: Adhesion molecules are involved
in carcinogenesis and metastases. The aim of this study is
to analysis the serum levels of some adhesion molecules and
their relationship with clinical, laboratory and prognostic factors.
Design/Methods: Forty-four patients diagnosed with bone
and soft tissue sarcomas and 31 healthy controls were
included in the study. Serum CD44, ICAM-1, VCAM-1,
selectin and cadherin levels were analyzed with ELISA
method at diagnosis, after induction and at the end of treatment. The mean AM levels of patients at different time were
compared with each other and those of control groups. The
relationship between serum AM levels and presence of metastases, percentage of necrosis and course of disease were evaluated.
Results: There were 19 males, 21 females with a median age
of 13 (1-21) years. The diagnoses were osteosarcoma in 21,
Ewing sarcoma in 15, rhabdomyosarcoma in six, synovial
sarcoma in two. Tumor location was long bones in 70% of
patients. Twenty patients (45.5%) had metastatic disease at
diagnosis. The mean CD44, selectin and cadherin levels of
patients at diagnosis were significantly (p<0.001) higher than
those of control group. Patients’ CD44 and selectin levels
were higher compared to controls in each diagnostic group.
In osteosarcoma and Ewing sarcoma, significant decrease
inCD44 and cadherin levels were observed at the end of treatment as compared to levels at diagnosis. The CD44 levels of
patients with pulmonary metastasis had higher levels of CD44
than non-metastatic patients (p:0.020). VCAM-1 levels were
significantly higher in relapsed disease (p:0.017). There was
no relationship between adhesion molecules levels and mean
percentage of necrosis.
Conclusions: CD44, selectin levels were observed in bone
and soft tissue sarcoma and they may be used as markers for
diagnosis and follow-up. Our findings suggest that elevated
levels of CD44 and VCAM-1 were associated with metastatic
and relapsed disease, respectively.
P-198 An Economical Analysis for the Care of
Pediatric Osteosarcoma Patients
T. Kutluk1 , C. Akyüz1 , A. Varan1 , B. Yalçın1 , N. Kurucu1 , B.
Aydın1
1 Hacettepe
University Cancer Institute & Faculty of Medicine, Department
of Pediatric Oncology, Ankara, Turkey
Background/Objectives: Survival rates in childhood cancer
improved significantly during the last several decades. For further improvement at global level, economical analysis are critically important. The cost of diagnosis, treatment and followup of patients with osteosarcoma was investigated on this
study.
Design/Methods: Thirty-two pediatric osteosarcoma cases
sequentially diagnosed in 2009-2014 were included. The
direct costs of ambulatory and inpatient care starting from
diagnosis to December 2016 for each patient were analyzed in
detail including examination, imaging, laboratory, operation,
pathology, medicines, medical supplies, hospital accommodation and other service costs both for inpatient and outpatient
care.
Results: Thirty-two patients (with a mean, median, minimum, maximum age, M/F ratio was 13.01, 13.58, 6.17,
17.83 years, M/F=17/15 respectively) were included. 22
patients had local and 10 had metastatic diseases at diagnosis.
Three-year overall survival (OS) was 58% for 32 patients.
Three-year OS was 75% for 22 patients with local disease
and 20% for 10 patients with metastatic diseases. Median
follow-up time was 40 months. Total costs for 32 patients
1.257.549,74 USD including 1.176.401,53 USD for inpatient
costs (%93.5) and 81.148,21 USD for outpatient costs (% 6.5)
with an average cost of 39.298,43 USD per patient. The distribution of costs (as USD) to different groups were; operation
68.766,64 (%5.47), services 115.947,44 (%9.22), medicine
223.672,80 (%17.79), laboratory examinations 41.464,84
(%3.30), examination 13.157,17 (%1.05), pathology 2635,27
(%0.21), supplies 688.401,48 (%54,74), imaging 46.478,02
(%3.70), hospital accommodation-bed fees 57.026,08
(%4.53).
Conclusions: To better understand the cost of care in pediatric cancers for investment purposes, detailed economical
analysis are needed. As an example, the cost of care for
pediatric osteosarcoma patients were calculated in this study.
The average cost per patient found in this study seems reasonable for a middle-income country. These kinds of analysis will help to plan the childhood cancer care for countries, which are planning to invest on the childhood cancer
control.
SIOP ABSTRACTS
P-199 Mechanisms of Drug Resistance to
Like-EURAMOS1 Chemotherapy in Childhood
Osteosarcoma: Preliminary Results
A. Levashov1 , E. Senzhapova1 , D. Khochenkov2
1 Pediatric
Hematology and Oncology Institution FSBI «N.N. Blokhin
Russian Cancer Research Center», Pediatric Hematology and Oncology
Institution, Moscow, Russia; 2 Experimental Diagnostic and Treatment of
Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center»,
Experimental Diagnostic and Treatment of Tumor Institution, Moscow,
Russia
Background/Objectives: The aim of this study was to estimate ERCC1, TOP2a, RFC1 and MGMT proteins expression
in 27 biopsy specimens and 38 tumor tissue samples with poor
response (grade I and II of tumor cells necrosis rate) to neoadjuvant chemotherapy after surgery of the primary site.
Design/Methods: Proteins expression was assessed by
immunohistochemical method using anti-ERCC1 (clone
8F1, Abcam), anti-TOP2a (Ki-S1, Dako), anti-RFC1
(SCL19A1ab, Genetex), anti-MGMT (MT3.1, Thermo).
ERCC1 and MGMT positive specimen was defined as weak
(+), moderate (++), strong (+++) colouring of the tumor
nuclei and cytoplasm (for ERCC1 and MGMT) with number
of positive tumor cells above 10% (for ERCC1), 25% (for
MGMT). TOP2a and RFC1 positive specimen was defined as
moderate (++), strong (+++) colouring of the tumor nuclei
and cytoplasm (for TOP2a), membrane (for RFC1) with
number of positive tumor cells above 25%.
All 38 patients were treated according to like-EURAMOS1
chemotherapy. Primary metastatic osteosarcoma was diagnosed in 15 out of 38 patients and localized disease in 23.
Results: TOP2a positive samples were revealed in 70.4% of
biopsy specimens, in 26% of postoperative specimens (6.7%
for group with metastases, 39.1% for group without metastases, p = 0.026), ERCC1 in 51.9% and 34.2%, RFC1 in 55%
and 23.1%, MGMT in 85.7% and 88.5%, ERCC1 positive /
TOP2a negative variant in 11.1% and 28.9%, ERCC1 positive
/ TOP2a negative / RFC1 negative variant in 0% and 26.9%,
TOP2a negative / RFC1 negative variant in 10% and 65.4% (p
< 0.05).
Conclusions: These data suggest that basic mechanisms of
drug resistance were presented by decreased TOP2a and
RFC1 expression and constant MGMT expression, increased
number of ERCC1 positive / TOP2a negative variant, ERCC1
positive / TOP2a negative / RFC1 negative variant and TOP2a
negative / RFC1 negative variant in postoperative specimens.
S257 of S518
1 National
Hospital Abuja, nursing serivces, Abuja, Nigeria
Background/Objectives: Cancer is one the major causes of
death in children and adolescents, accounting for about 4% of
deaths in children below 5years in Nigeria. The nursing care of
these patients often does not receive adequate attention. This
report highlights challenges in nursing care of these children
in a low resource setting and is aimed at raising awareness to
influence advocacy and action.
Design/Methods: A retrospective review of 38 children
treated for cancers in an inpatient children's ward over a oneyear period (November 2015 – November 2016). In the same
period, a total of 992 children were admitted into the same
ward. The nursing care of the patients has been reviewed
Results: Children with cancers accounted for 3.8% of admissions on the ward. In addition to the nursing workload of
these patients, several important challenges and limitations
were encountered requiring attention and efforts of the nursing staff, including; financial burden on parents and their
inability to cope with costs, psychological issues involving
parents and patients (aggression, anxiety, depression, withdrawal) and difficulties with communicating disease course,
treatment and complications of treatment. These challenges
significantly increased the nursing burden of the patients,
which were often not part of patient treatment plan.
Conclusions: It's important to include these identified challenges in the counseling and treatment plan of children with
cancers, particularly in low resource settings where the burden
of nursing care is enormous. Development and implementation of a careful multidisciplinary care plan should help in
addressing these challenges
P-201 Retinoblastoma, Osteosarcoma and
Unusual Sites of Tumor Recurrence: A Case Report
K. O'Halloran1 , M.R. Wollman2
1 Childrens
Hospital of UPMC, Pediatrics Residency Program, Pittsburgh,
USA; 2 Childrens Hospital of UPMC, Pediatric Hematology/Oncology,
Pittsburgh, USA
Background/Objectives:
Osteosarcoma
following
retinoblastoma is known to occur, however, patterns of
osteosarcoma recurrence in this subset of patients are not
well described. We report the case of a patient with a history
of bilateral germline retinoblastoma and osteosarcoma with
unusual sites of soft tissue osteosarcoma recurrence.
Design/Methods: Case Report.
P-200 Challenges in the Nursing Care for
Children with Cancer: Report of Experience from
Nigeria
N. Mary1
Results: At 6 months of age the patient was diagnosed with
bilateral germline retinoblastoma despite no family history.
He underwent chemotherapy with vincristine, carboplatin and
etoposide. Given disease progression, however, he underwent
enucleation of the right eye. He remained in remission for
SIOP ABSTRACTS
S258 of S518
12 years at which time he developed knee pain found to be
an osteosarcoma tumor. No metastatic disease was noted on
chest CT. He underwent 29 weeks of doxorubicin, cisplatin
and methotrexate as per AOST0331. Less than 1 year later pulmonary metastases were found and following metastasectomy
he was started on dinutuximab (phase II trial). Two weeks following initiation of dinutuximab he presented with an antebcubital fossa mass found on biopsy to represent soft tissue
recurrence of osteosarcoma. PET scan subsequently revealed
T12 vertebral, left popliteal soft tissue and right lower lobe
lung lesion. Genetic testing was positive for TP53 mutation
and CSF1R. He was subsequently started on ifosfamide. Due
to mixed response and poor prognosis, however, he is now
undergoing palliative radiation therapy and oral sorafenib.
Conclusions: This case suggests survivors of germline
retinoblastoma who develop a second primary malignancy
and subsequent relapse may have more unusual sites and
patterns of recurrence. This case furthermore illustrates that
underlying genetic mutations such as Rb gene mutations may
impact response to therapies including chemotherapy.
P-202 Dose Intensity of Neoadjuvant
Chemotherapy in the Treatment of Paediatric
Patients with Osteosarcoma at Hospital Infantil De
Mexico
M.A. Palomo Colli1 , A. Perez Bañuelos2 , M. Mier-Cabrera3 , J.F.
Gaytan Morales1 , C. Cicero Oneto1 , I. Castorena Villa1
1 Hospital
Infantil de México, Oncology, México, Mexico; 2 Hospital de
Especialidades del Niño y la Mujer, Pediatrics, Queretaro, Mexico;
3 Hospital Regional de Alta Especialidad Ixtapaluca, Pediatrics, Ixtapaluca,
Mexico
Background/Objectives: Osteosarcoma is the most common
bone malignancy, which is more frequent in children and adolescents. Neoadjuvant chemotherapy for osteosarcoma offers
a series of advantages, such as treatment of microscopic
metastases or shrinking the primary tumor with possibility of limb-sparing surgery. Preoperative treatment allows in
vivo evaluation of the treatment and postoperative treatment
adjustment according to histological response.
Design/Methods: We conducted a retrospective study based
in medical records of all patients with osteosarcoma who
had received neoadjuvant treatment at Hospital Infantil de
México Federico Gómez (HIMFG) between 2009-2014. The
aim of this study was to evaluate the dose intensity (DI),
which is calculated as dose per unit of time. For the purpose of this analysis, “time” was set as “days”, starting at
“Day 1” of chemotherapy according to 2 different treatments.
The MAP treatment consisted of pre-operative administration of two 5-week cycles of cisplatin (120 mg/m2 ), doxorubicin (75mg/m2 ) and methotrexate(2x 12g/m2 ). The second one consisted of four cycles of cisplatin(120mg/m2 ), and
doxorubicin(75mg/m2 ) administrated every three weeks. The
neoadjuvant DI was calculated for each drug administrated.
Results: Thirty-four medical records were collected during
this period of time. However, eleven of them were eliminated
since chemotherapy information was incomplete or treatmentrelated death prior to day and follow-up ended before day 7084. The information from the remaining 23 medical records
was analyzed. The study population were 12 females and
22 males. Regarding the age at diagnosis, the median was
11.5 years(4-17y). Metastases at diagnosis was observed in
15 patients(44.1%). The average time between diagnosis and
surgery was 14.08± 1.2 weeks for MAP protocol and 23.21±
1.96 weeks for Cisplatin/Doxorubicin.
The relative DI was 0.65 for doxorubicin, 0.68 for Cisplatin
and 0.75 for Methotrexate.
Conclusions: DI is inadequate in many cases because of toxicity and the lack of sufficient beds in hospital, which results
in delay on surgery.
P-203 Clinical Outcome of Osteosarcoma in
Children: Experience from a Developing Country
A.S.B. Syed1 , H. Saeed1 , A.A. Arshad1 , R. Mohammad Wali1 , S.
Javed Khan1
1 Shaukat
Khanum Memorial Cancer Hospital & Research Center, Pediatric
Oncology, Lahore, Pakistan
Background/Objectives: Osteosarcoma is the most common
bone tumor in children. There is limited information about
outcome for pediatric osteosarcoma in Pakistan. We conducted this study to determine the outcome of children with
osteosarcoma who were diagnosed and treated in our institution over 10 years.
Design/Methods: We conducted a retrospective chart review
of patients with osteosarcoma who received treatment at
our institution between January 2005 and December 2014.
Kaplan-Meier analysis was used for survival analysis using
SPSS version 19.
Results: Osteosarcoma was diagnosed in 225 patients out of
which 77 patients (34.2%) abandoned treatment within first 3
months of diagnosis. The final study population was 147. All
patients received treatment with Cisplatin, Doxorubicin and
Methotrexate as per Euromos 1 protocol. Mean age at diagnosis was 13.6 years (SD +/- 3.2). Male to female ratio was 1.7:1.
120 patients (81.6%) had non-metastatic disease. 131 (89%)
had lower extremity, 14 (9.5%) upper extremity and 2 (1.4%)
had axial involvement. There were 28 (19%) mortalities (16
from disease progression, 8 from infectious complications and
4 from cardiac complications). 29 patients (19.7%) had disease progression during treatment while 24(16.3%) relapsed
after end of treatment.
SIOP ABSTRACTS
The overall survival (OS) and event free survival (EFS) for
entire population at eight years was 70% and 40% respectively
with median follow-up of 43 months. For metastatic and nonmetastatic cases the OS and EFS were 57% and 72% and 19%
and 52% respectively. None of the patients with axial tumor
survived. For upper extremity and lower extremity tumors OS
and EFS were 92% and 68% and 59% and 41 % respectively.
There was no difference in survival based on gender.
Conclusions: Survival for osteosarcoma is about 70%
but EFS is lower than expected. Measures to improve
care for infections and cardiac complications can improve
these outcomes. Efforts to reduce abandonment are also
needed.
P-204 Treatment Abandonment in Patients with
Osteosarcoma: Experience from a Developing
Country
H. Saeed1 , S.A.S. Baqari1 , A.A. Arshad1 , R. Mohammad Wali1 , S.
Javed Khan1
1 Shaukat
Khanum Memorial Cancer Hospital & Research Center, Pediatric
Oncology, Lahore, Pakistan
Background/Objectives: Treatment abandonment is a common cause of cancer related mortality in developing countries
especially in conditions that require mutilating surgery. We
conducted this study to determine the patterns of treatment
abandonment in patients of Osteosarcoma treated at our institution over 10 years.
Design/Methods: We conducted a retrospective chart review
of patients diagnosed with Osteosarcoma at our institution
between January 2005 and December 2014. We compared
characteristic of patients that continued treatment and that
abandoned. SPSS version 19 was used for analysis.
Results: Osteosarcoma was diagnosed in 225 patients out of
which 77 patients (34.2%) abandoned treatment. Thus, about 8
patients a year did not complete treatment. About half of these
(38 patients) abandoned prior to start of chemotherapy while
the remaining 39 left following neo-adjuvant chemotherapy.
The mean age of treated group was 13.6 (SD+/-3.2) and abandonment group was 14.4(SD+/-2.6). Of the total 134 male
patients 40 (30%) abandoned while 37 of 90 females (41%)
abandoned. The likelihood ratio for abandonment for females
was 3 (p= 0.056). None of the patients from Afghanistan
abandoned, while 25% from Sindh and Baluchistan, 32.7%
from KPK and 37.4 from Punjab abandoned treatment. 34%
of patients with non-metastatic and 37% with metastatic disease abandoned. Follow-up information was only available for
8 (10%) patients. 3 patients died of disease progression and 5
patients came back with progressive disease and were lost to
follow-up again.
S259 of S518
Conclusions: There is high rate of treatment abandonment
in Osteosarcoma patients at our institution. Half of the
cases occur at time of surgery so better counseling and
preparation of patients for amputation may reduce abandonment rates. Females also show a higher trend for abandonment. Disease prognosis and geographic distance from
institution don't affect abandonment. There is need for better follow-up of patients who abandoned to know their
outcomes.
P-205 Epiphysis Growth after
Epiphyseal-Preservation Surgery for Childhood
Osteosarcoma Around the Knee Joint
A. Takeuchi1 , N. Yamamoto1 , K. Hayashi1 , T. Higuchi1 , K. Abe1 ,
Y. Taniguchi1 , H. Aiba1 , Y. Araki1 , H. Tsuchiya1
1 Kanazawa
University Graduate School of Medical Sciences, Orthopaedic
Surgery, Kanazawa, Japan
Background/Objectives: Osteosarcoma usually occurs in
metaphyseal locations and must be excised with the adjacent
joint and replaced by an endoprosthesis. Recently, advanced
imaging, accurate tumor excision and rigid fixation using a
locking plate have been used in epiphysis-preserved tumor
excision for selected patients. To reconstruct the defect after
epiphysis-preserved tumor excision, various methods, including allograft, distraction osteogenesis, tumor-devitalised autograft, vascularised fibular graft and custom-made implants,
have been applied. Tumor-devitalised autograft treated with
liquid nitrogen procedure was introduced in 1999 and its usefulness has since been reported. The advantages of frozen
autografts include simplicity and the possibility of preserving proteins, including bone morphogenetic protein (BMP).
We investigated postoperative epiphysis growth following
epiphyseal-preservation surgery for childhood osteosarcoma
around the knee joint.
Design/Methods: We retrospectively reviewed 13 patients
with osteosarcoma who underwent epiphysis-preserved tumor
excision (transmetaphyseal, transphyseal and transepiphyseal
excision) and reconstructed by using tumor-devitalized autograft treated with liquid nitrogen. The mean patient age was
11 (range, 6 to 15) years. The mean follow-up periods were
59 (range, 30 to 93) months. Nine tumors were in the distal
femur, and four were in the proximal tibia. Epiphysis transverse growth rate, epiphysis-width discrepancy (EWD) and
collapse of epiphysis were evaluated by using pre- and postoperative whole standing leg radiographs. Functional outcome, complications and oncological status were also investigated.
Results: The mean epiphysis growth rate was 9.7% (range,
0.5 to 28.0 %), mean EWD was 0.1mm (range, –1.7 to 3.2
mm), mean LLD was–29mm (range, –1 to –48 mm) and two
SIOP ABSTRACTS
S260 of S518
patients underwent limb lengthening. There was no apparent
collapse of the residual epiphysis. The mean MSTS score was
27.7 (range, 18 to 30).
S O LID NO N BRAIN TUM O URS SOFT TISSUE SARCOMAS
Conclusions: Epiphysis transverse growth continued after
epiphyseal-preservation surgery in childhood osteosarcoma.
Epiphyseal-preservation surgery in children should be
considered.
P-207 Treatment Outcome in Patients with
Orbital Rhabdomyosarcoma- Clinical Experience
from a Regional Cancer Centre in North India
A. Biswas1 , N. Adhikari1 , S. Bakhshi2 , S. Sen3 , S. Kashyap3 , R.
Meel4 , B. Mohanti1
P-206 Prognostic Impact of Diagnostic and
Treatment Delay in Children with Osteosarcoma
L. Vasquez1 , A. Zapata2 , S. Chavez2 , R. Diaz2 , F. Tarrillo1 , M.
Oscanoa1 , I. Maza1 , J. Geronimo1
1 Rebagliati
Hospital, Pediatric Oncology, Lima, Peru; 2 National Institute of
Neoplastic Diseases INEN, Pediatric Oncology, Lima, Peru
Background/Objectives: The aim of this study is to evaluate the relationship between latency to diagnosis (LD) and
medical/non-medical treatment delay (TD) and survival outcomes in children with osteosarcoma.
Design/Methods: A retrospective analysis of all consecutively treated patients at the two major tertiary centers in childhood cancer of Peru (between January 2008 and December
2015) with diagnosis of osteosarcoma was performed. LD
was measured as the time between start of symptoms and
definitive diagnosis. TD was defined as any delay in weeks
of the frontline treatment protocol. All causes of TD were
evaluated as medical (neutropenia or severe infection) and
extra-medical (lack of available beds, surgical prosthesis or
social problems). Overall survival (OS) and event-free survival (EFS) were estimated and compared according to LD,
TD and known prognostic factors.
Results: A total of 113 patients were included in the study.
Median LD was 17 weeks (range, 3-53.3). No association
between clinical stage, tumor size and LD were detected. Children of parents without a formal job had significantly longer
LD (p=0.018). Delayed LD was not associated to worse outcome. Multivariate analysis confirmed that OS and EFS were
significantly worse for a TD longer than 4 weeks with a hazard
ratio of 2.70 (95%CI, 1.11-6.76, p=0.003) and 1.13 (95%CI,
1.00-1.26, p=0.016) respectively. Only 15% of patients completed the treatment protocol in the initially established
time. Most TD (85%) was caused by extra-medical reasons,
with no differences in survival rates between both groups
(p=0.081).
Conclusions: Longer LD in children with osteosarcoma did
not seem to influence OS and EFS. A delay from any cause
in the oncological treatment is independently associated with
poor prognosis. Based on these results, further efforts are
needed to decrease treatment delay in our country.
1 All
India Institute of Medical Sciences, Radiation Oncology, New Delhi,
India; 2 All India Institute of Medical Sciences, Medical Oncology, New
Delhi, India; 3 All India Institute of Medical Sciences, Ocular Pathology,
New Delhi, India; 4 All India Institute of Medical Sciences, Ophthalmology,
New Delhi, India
Background/Objectives:
Orbital
Rhabdomyosarcoma(RMS) is a favourable prognostic tumour, where
cure rates of more than 90% can be achieved with combination chemotherapy and local radiotherapy in trial setting.
We intend to report the treatment outcome of patients with
orbital RMS treated at our institute.
Design/Methods: The treatment plan for patients diagnosed with orbital RMS was induction chemotherapy
(VAC regimen-Vincristine,Actinomycin D, Cyclophosphamide) for 3 courses followed by orbital radiotherapy
(45Gray/25fractions/5weeks) followed by further chemotherapy (VAC regimen) up to a total of 12 courses. Clinical data
was collected by retrospective chart review from 2010-17.
Overall survival (OS) and progression free survival (PFS)
were analyzed by Kaplan-Meier method.
Results: Twenty five patients met the study criterion (male:
female=13:12). Median age at presentation was 13 years. The
common symptoms (median duration 4 months) were proptosis, visual disturbance, ocular pain, eyelid swelling and ptosis
in 80%,64%,28%,28% and 20% patients respectively. Orbital
biopsy revealed embryonal and alveolar RMS in 21(84%)
and 4(16%) patients respectively. After staging work-up,
5(20%),17(68%) and 3(12%) patients had IRS clinical group
II, III and IV disease respectively. Systemic chemotherapy(VAC) was administered in all patients (median-6
courses). Orbital radiotherapy was given in 19(76%)
patients(median dose 45 Gray;18-curative;1-palliative).
After a mean follow-up of 18.11 months, 10(40%) patients
had disease progression(local-8,regional-1,distant-1). Two
patients could be successfully salvaged with chemotherapy(ICE regimen-Ifosfamide,Carboplatin,Etoposide) and
orbital exenteration. At last follow-up, 8(32%) patients had
died- 4 due to progressive disease and 4 due to chemotherapy
related toxicity. Median PFS was 20.03 months and median
OS was not reached. The actuarial rate of PFS and OS were
respectively 46.9% and 64.6%(at 2 years) and 46.9% and
53.8%(at 3 years).
SIOP ABSTRACTS
S261 of S518
Conclusions: Combination chemotherapy (VAC) and orbital
radiotherapy (45Gy) led to modest clinical outcome in
patients with orbital RMS at our centre possibly due to high
incidence of alveolar RMS(16%), metastatic disease(12%),
poor treatment compliance(20%) and toxic death(16%).
are alive in first CR. Molecular analysis for the 25 remaining
patients are ongoing (CGH array, FISH, RT-PCR and if all
negatives RNAseq). 29(81%) infants did not present any grade
III or IV toxicities. 31 infants received ifosfamide, among (24
with aged less than 6 months). One tubular toxicity and 3
neurologic toxicities were recorded for infants treated with
ifosfamide.
P-208 Rhabdomyosarcoma in Infants Under 6
Months: A Clinical, Histological and Molecular
Analysis of the French Cohorts SIOP MMT 89-95,
RMS 2005 and National Cancer Registry
Conclusions: Our results suggest that a subtype of neonatal RMS does exist, with specific a clinical, histological
(S/ScRMS) and/or molecular presentation (VGLL2, NCOA2
fusions).
T. Butler1 , D. Ranchère-Vince2 , G. Pierron3 , D. Orbach4 , L.
Galmiche5 , B. Lacour6 , C. Bergeron7 , A. Coulomb8 , H. Martelli9 ,
D. Anne-Sophie10 , D. Cecile11 , J.C. Gentet12 , C. Vérité13 , D.
Sophie14 , L. Mansuy15 , N. Cozic16 , M.P. Castex17 , H. Brisse18 , V.
Minard-Colin1
1 Institut
2 Centre
Gustave Roussy, Pediatric, Villejuif, France;
Léon Bérard,
Biopathology, Lyon, France; 3 Institut Curie, Biopathology, Paris, France;
4 Institut Curie, Pediatric, Paris, France; 5 Necker Hospital, Biopathology,
Paris, France; 6 Nancy Hospital, French National Registry Center, Nancy,
France; 7 Centre Léon Bérard, Pediatric, Lyon, France; 8 Trousseau
Hospital, Biopathology, Paris, France; 9 Bicêtre Hospital, Pediatric
Surgery, Kremlin-Bicêtre, France; 10 Centre Oscar Lambert, Pediatric,
Lille, France; 11 Rouen Hospital, Pediatric, Rouen, France; 12 Hôpital de la
Timone, Pediatric, Marseille, France; 13 Bordeaux Hospital, Pediatric,
Bordeaux, France; 14 Nantes Hospital, Pediatric, Nantes, France; 15 Nancy
Hospital, Pediatric, Nancy, France; 16 Institut Gustave Roussy, Biostatistics,
Villejuif, France; 17 Hôpital des enfants, Pediatric, Toulouse, France;
18 Institut Curie, Radiology, Paris, France
Background/Objectives: Rhabdomyosarcoma (RMS) is the
most common soft tissue tumor in childhood with 2
major subtypes: alveolar and embryonal tumors. RMS in
infants, ∼4-10% of RMS, is a particular entity with specific clinical presentation and outcome. Recently, molecular rearrangement involving NCOA2 or VGGL2 genes
have been described in congenital spindle cell RMS
(S/ScRMS).
Design/Methods: Our retrospective study reviewed all clinical, histological and molecular data from infants aged less
than 6 months at diagnosis and treated in France for a RMS
(registered in MMT89, MMT95, RMS2005 or recorded in the
French National Cancer Registry). A histological centralized
review and molecular analysis were performed on tumoral tissue of each patient.
Results: 45 infants were included with a median age of 2.4
months at diagnosis. 6(13%) were metastatic and 7 patients
(16%) had congenital malformations. Considering only survivors, the median follow-up was 6.2 years. OS and EFS rates
for all patients were 59.8% (95%CI, 47-77) and 47% (95%CI,
34-65). 24 infants (53%) experienced treatment failures: 14
relapsed (31%), mostly loco-regional, and 9 (20%) progressed
early. a PAX-FOXO1 translocation was identified in 2 patients.
2 VGLL2-related RMS were recorded, both localized and
with a common spindle cell histologic appearance. The two
P-209 Role of PET-CT in Evaluation of Therapy
Response for Pediatric Rhabdomyosarcoma
E. Elnadi1 , M. Mohamed S Zaghlol1,2 , G. Taha3 , H. Hafez4 , S.
Abdel Hamid5 , E. Elkholy6 , A. Younes7 , N. Elkinaai8 , M. Khalaf9 ,
E. Khaled10
1 Benisuif
University - Egypt And Children's Cancer Hospital Egypt,
Children Cancer Hospital Of Egypt, Cairo, Egypt; 2 Nci- Egypt And
Children's Cancer Hospital Egypt, Radiotherapy, Cairo, Egypt; 3 Helwan
University- Children Cancer Hospital Of Egypt, Surgical Oncology, Cairo,
Egypt; 4 National Cancer Institute- Children Cancer Hospital, Pediatric
Oncology, Cairo, Egypt; 5 National Cancer Institute - Children Cancer
Hospital, Pediatric Oncology, Cairo, Egypt; 6 Nci- Children Cancer Hospitl,
Nuclear Medicine, Cairo, Egypt; 7 Nci- Children Cancer Hospital, Surgical
Oncology, Cairo, Egypt; 8 National Cancer Institute- Children Cancer
Hospital, Pathology, Cairo, Egypt; 9 National Cancer Institute- Children
Cancer Hospital, Radiology, Cairo, Egypt; 10 Children Cancer Hospital Of
Egypt, Research, Cairo, Egypt
Background/Objectives: PET-CT has been used to evaluate
RMS and other sarcomas in adults and children. Role of PETCT in staging pediatric RMS has not been clearly established,
this study aimed to investigate the role PET in evaluation of
response to treatment and its correlation with survival in pediatric patients with RMS.
Design/Methods: A retrospective study included children
with intermediate risk RMS presented to CCHE period from
Jan, 2010 to June, 2016. They were stratified and treated based
on COG protocol study ARST0531. The patients did initial
PET scan and then at w 4 and at w 15.
Results: We reported 138 patients who had initial PET, 18
excluded with negative PET and 120 patients were analyzed.
Age ranged from 0.02 years to 14 years old with median 4.095.
Eighty seven cases had embryonal pathology and 33 were of
alveolar type. Fifty one patients did PET CT on week 4, 36
patients were negative and 15 patients were positive. Sixty six
patients did PET CT at W 15, 58 patients were negative PET
and 8 patients were still positive. OS% for negative patients at
W4 was 86.6% ± 0.143 at 5 years in comparison to 33.8% ±
0.509 IN PET positive cases(P Value: 0.089). EFS% for negative patients was 69% ± 0.199 and positive patients was 33%
± 0.407 (P Value: 0.357). OS% for negative patients at W15
was 60.7% ± 0.186 and was 66.7% ± 0.533 in PET positive
SIOP ABSTRACTS
S262 of S518
patients at W15 (P Value: 0.604). EFS% for negative patients
at W15 was 52.9% ± 0.152 and EFS% for positive patients
was 41.7% ± 0.401 (P Value: 0.452).
Conclusions: Patients with negative PET at W4 had better
outcome. Results was insignificant due to small number of pet
negative patients. PET scan can be a tool to predict outcome
in RMS
P-210 Outcome of Vaginal Tumors in Pediatric
Age Group; Children's Cancer Hospital Egypt
(CCHE) 57357 Experience
M. Elsherif1 , E. Mohsen2 , S. Ahmed3 , M. Elwakeel4 , H. Taha5 , M.
Elshafiey6 , G. Taha6 , M. Saad7 , D. Elgalaly8 , E. Khaled8 , A.
Elhaddad9
1 Pediatric
Oncology Fellow at CCHE-57357, pediatric oncology, Cairo,
Egypt; 2 Assistant professor of pediatrics at faculty of medicine beni-souef
university- consultant of pediatric oncology at CCHE-57357, pediatric
oncology, Cairo, Egypt; 3 Lecturer of pediatric oncology at NCI - consultant
of pediatric oncology at CCHE-57357, pediatric oncology, Cairo, Egypt;
4 Professor of radiology at NCI- consultant of radiology at CCHE-57357,
Radio-diagnosis, Cairo, Egypt; 5 Professor of clinical pathology at NCIhead of clinical pathology department at CCHE-57357, Clinical pathology,
Cairo, Egypt; 6 Consultant of surgery at CCHE-57357, surgical oncology,
Cairo, Egypt; 7 Professor of Radiotherapy at NCI- Consultant of
radiotherapy at CCHE-57357, Radiation-Oncology, Cairo, Egypt; 8 Clinical
Research Specialist at CCHE-57357, Clinical Research, Cairo, Egypt;
9 Professor of Pediatric Oncology at NCI - Head of pediatric oncology
department at CCHE-57357, Pediatric Oncology, Cairo, Egypt
Background/Objectives: Childhood vaginal tumors are rare
comprising less than 5% of all pediatric cancers. Rhabdomyosarcoma (RMS), germ cell tumors and adenocarcinoma are the most common malignancies of the vagina.
To analyze the outcome of children with vaginal tumors who
were treated at a single institution.
Design/Methods: A Retrospective chart review of all pediatric patients with vaginal tumors treated at CCHE-57357
from June 2007 till June 2016.
Results: Nineteen patients (median age, 2.7 years; range, 0.72
- 12.15 years) were studied. Three different histological subtypes were identified; RMS in 11 patients, germ cell tumor
in 7 cases, and clear cell adenocarcinoma in one patient.
Vaginal Bleeding was the most common clinical presentation, reported in (65%) of the patients. Surgery was done for
6 patients (33%) (4 with uterine salvage and 2 underwent
hysterectomy).Thirteen patients (72.2%) remain disease-free
with median follow-up of 36 months. Only one patient with
RMS died out of disease progression. The 3- year OS and
EFS for patients with RMS were 88.9% and 80% respectively,
while for those with germ cell tumors the OS was 100% and
EFS was 66.7%.
Conclusions: Vaginal tumors are rare in the pediatric population and generally have a good prognosis. Treatment with
chemotherapy only or with either conservative surgery or
brachytherapy may achieve an excellent outcome in germ cell
tumors and rhabdomyosarcoma.
P-211 Radiotherapy in the Local Management of
Aggressive Fibromatosis: Efficacy is Inversely
Proportional to Age
J. Bates1 , C. Morris1 , N. Iovino1 , M. Rutenberg2 , R. Zlotecki1 , C.P.
Gibbs3 , M. Scarborough3 , D. Indelicato2
1 University
of Florida College of Medicine, Radiation Oncology,
Gainesville, USA; 2 University of Florida College of Medicine, Radiation
Oncology, Jacksonville, USA; 3 University of Florida College of Medicine,
Orthopaedics and Rehabilition, Gainesville, USA
Background/Objectives: Aggressive fibromatosis, also
called desmoid tumor, is a locally aggressive non-malignant
disease affecting patients across all ages. Although radiotherapy has an established role in disease management,
cross-study comparison suggests effectiveness is inversely
proportional to patient age. Our goal was to comprehensively describe local control across all ages using a large
single-institution cohort.
Design/Methods: We retrospectively analyzed all patients
treated with radiotherapy for desmoid tumor at a single institution from 1975–2015. Demographic, tumor-related, and
treatment-related information was abstracted from patient
charts. Kaplan-Meier analysis, logistic regression, and Cox
proportional hazards models were used to analyze the effect
of various factors on local control following radiotherapy.
Results: A total of 101 patients were identified with a median
follow-up of 14.3 years (range, 0.3–41.5). At 5 and 10 years,
the overall survival rates were 98% and 94% and overall
local control rates were 82% and 78%. Most patients were
female (66%) and white (66%); 15% were <20 years old at
diagnosis, 47% were 20 to <40, and 39% were 40 years or
older. The cohorts were split evenly between patients with initial versus recurrent disease at the time of radiotherapy. On
univariate analysis, the only factors predicting for increased
risk of local recurrence was young age at diagnosis (<20,
72% 5-year local control; 20-<40, 73% 5-year local control; ≥40, 97% 5-year local control; p = 0.008) and use of
twice-daily fractionation as compared to once-daily radiotherapy fractionation (73% versus 90% 5-year local control; p =
0.008). Logistic regression confirmed a relationship between
increasing age and increasing probability of local control
(p = 0.004).
Conclusions: Younger patients with aggressive fibromatosis exhibit more frequent local failures than older patients,
suggesting that tumor biology and radio-responsiveness
may differ with age. Younger patients may benefit from
alternate approaches to local therapy or radiation-dose
escalation.
SIOP ABSTRACTS
P-212 Kaposi Sarcoma, Oral Malformations,
Mitral Dysplasia, and Scoliosis (KOMS Syndrome)
Associated with 7Q34-Q36.3 Heterozygous
Terminal Deletion
C. Jackson1,2,3 , A. Lefèvre-Utile4 , A. Guimier5 , V. Malan5 , J.
Bruneau6 , A. Gessain7 , O. Cassar7 , J. Amiel5 , A. Cobat8,9 , V.
Rattina8,9 , L. Abel1,8,9 , J.L. Casanova1,4,8,9,10 , S. Blanche4
1 The
Rockefeller University, St. Giles Laboratory of Human Genetics of
Infectious Diseases- Rockefeller Branch, New York, USA; 2 Weill Cornell
Medical Center, Division of Pediatric Hematology-Oncology, New York,
USA; 3 Memorial Sloan Kettering Cancer Center, Department of Pediatrics,
New York, USA; 4 Necker-Enfants Malades Hospital, Pediatric
Immunology-Hematology-Rheumatology Unit, Paris, France;
5 Necker-Enfants Malades Hospital, Genetics Department, Paris, France;
6 Necker-Enfants Malades Hospital, Pathology Unit, Paris, France; 7 Institut
Pasteur, Unit of Epidemiology and Physiopathology of Oncogenic Viruses,
Paris, France; 8 Necker-Enfants Malades Hospital, Laboratory of Human
Genetics of Infectious Diseases- Necker Branch- INSERM U1163, Paris,
France; 9 Paris Descartes University, Imagine Institute, Paris, France;
10 Howard Hughes Medical Institute, Howard Hughes Medical Institute,
New York, USA
Background/Objectives: The meiotic pathway is conserved
in humans and chromosomal crossover errors during meiosis
can cause chromosomal deletions. Chromosome 7 germline
terminal macrodeletions have been implicated in human congenital malformations and developmental delays. We herein
decipher a novel cancer predisposition phenotype (endemic
Kaposi sarcoma) attributable to a heterozygous macrodeletion of 7q34-q36.3 in a 16-year-old girl originally from West
Indies.
Design/Methods: Comparative genomic hybridization
(CGH) array in the patient was significant for 7q34-q36.3
macrodeletion of 16 megabase pairs (Mbp). To investigate
the mode of inheritance, Affymetrix Genome-Wide Human
SNP (single nucleotide polymorphism) Array 6.0 was performed in the patient and her mother (father not available),
and data were analyzed using PennCNV Software. Human
herpesvirus-8 (HHV-8) genotype was performed by nested
polymerase chain reaction (PCR), and comparative sequence
analysis was utilized to demonstrate the origin of HHV-8
viral strain.
Results: We herein describe a novel de novo heterozygous
macrodeletion of 7q34-q36.3 (7:142,883,341-159,127,004;
Reference genome b37/hg19) associated with endemic
Kaposi sarcoma predisposition. The HHV-8 viral strain
belongs to the Sub-Saharan African B subtype, and clustered with strains previously characterized from Cameroon
and Uganda. Similar to previously reported cases of germline
chromosome 7q terminal deletions, our patient has dental malposition, and developmental (growth and intellectual) delay.
Novel phenotypic features include Kaposi sarcoma, oral malformations (furrowed tongue), scoliosis (thoracolumbar), and
mitral valve dysplasia (KOMS).
S263 of S518
Conclusions: The occurrence of HHV-8-driven Kaposi sarcoma, in a child otherwise normally resistant to other infectious agents and without any other tumoral lesion, points to
a very selective immunodeficiency. While defects in organogenesis have been described with chromosome 7 terminal
macrodeletions, this is the first report of immunodeficiency
and cancer predisposition syndrome (KOMS Syndrome) associated with this chromosomal region.
P-213 Local Control for Non Metastatic
Genito-Urinary Rhabdomyosarcoma (RMS). A
Single Centre Experience
J. Lopes1 , K. Parashar1 , L. McCarthy1 , A. Robb1 , M. Pachl1 , P.
Kearns2 , D. Ford2 , S. Arul1
1 Birmingham
Children's Hospital, Paediatric Surgery and Urology,
Birmingham, United Kingdom; 2 Birmingham Children's Hospital,
Paediatric Oncology, Birmingham, United Kingdom
Background/Objectives: Recent studies show 5-year survival of localized genito-urinary RMS patients of 77%.
Though recent publications have advocated more conservative surgery, in our surgical centre emphasis is placed on
achieving complete local control of disease with surgery if at
all possible. Our principle behind considering radical surgery
was the belief of the importance of clear margins and avoidance of radiotherapy.
Design/Methods: We reviewed the notes of all patients identified by the pathology database with RMS treated at our center over the last 15 years.
Results: From 2001 to 2016 we treated 12 patients for localized genito-urinary RMS. 7:5 M:F, median age 1.7y (2mo
to 6.7 yrs), with origin in uterus(1), vagina(2), bladder/
prostate(9).
All patients had pre-operative chemotherapy. Surgery decisions were based on pre-operative imaging, examination
under anaesthesia, laparoscopy and cystoscopy. One team of
two surgeons performed: radical hysterectomy (2), vaginectomy (1), pelvic exenteration (1), partial cystectomy (2), total
cystectomy (1), cysto-prostatectomy (4). 3/6 patients have had
urinary undiversion. Two patients did not have surgery - 1
with an unresectable tumour; 1 with near total resolution of
his bladder neck tumour. Four patients had radiotherapy - 1
with an unresectable tumour and 3 with positive resection
margins.
Mean follow up is 6 years (9mo – 13.3 years) with 100% survival. Two patients suffered local recurrence. A patient post
partial vaginectomy, later required pelvic exenteration and
post-operative radiotherapy, and is now 10 years recurrence
free. A patient post partial cystectomy, had chemotherapy post
relapse, and is now 4.5 years recurrence free.
SIOP ABSTRACTS
S264 of S518
Conclusions: In our series survival was 100%. The 2
local recurrences had conservative surgery initially. Radical
surgery was performed in 8/10 patients.
Although there is a trend for conservative surgery we believe
this should be judged against the high survival rates that come
with good surgical local control. We reserve radiotherapy for
those with incomplete resections.
P-214
Orbit
Alveolar Soft Part Sarcoma of Paediatric
N. Pushker1 , R. Meel1 , S. Kashyap2 , S. Sen2 , M. Bajaj1
1 All
India Institute of Medical Sciences, Dr Rajendra Prasad Centre for
Ophthalmic Sciences, New Delhi, India; 2 All India Institute of Medical
Sciences, Dept of Ocular Pathology- Dr Rajendra Prasad Centre for
Ophthalmic Sciences, New Delhi, India
Background/Objectives: Alveolar soft-part sarcoma (ASPS)
is a translocation-associated sarcoma that constitutes 1% of all
sarcomas. It occurs most commonly in the lower extremities
and rarely in orbit. It is commonly misdiagnosed due to its
rarity and nonspecific clinical findings
Design/Methods: Retrospective review of medical records,
histopathology and imaging findings of all cases of ASPS of
paediatric orbit that were treated at our centre between Jan
2001 and Dec 2016 (16 years).
Results: Four cases of ASPS of orbit presenting in childhood were analysed. The median age of presentation was 8.5
months (range 3.5 -12 years). There were 2 male and 2 female
patients. All 4 patients presented with proptosis of left eye.
The median duration of symptoms was 8 months (range 3
months – 1 year). The initial clinical and imaging diagnosis
was low flow vascular malformation (capillary haemangioma)
in 3 cases and pseudotumor in 1 case. Imaging revealed a well
defined lesion in all 4 cases. There was no bone erosion or
extraorbital extension in any case. The lesion involved lateral
orbit in 2, superior orbit in 1 and inferior orbit in 1 case. Ultrasound revealed a homogeneous lesion with regular internal
architecture. One case underwent exenteration, while 3 underwent orbitotomy for tumor excision.
Conclusions: Orbital ASPS is a rare malignancy of childhood, and may masquerade other benign tumors of orbit.
P-215 Treatment Outcome of Four-Drug Versus
Three-Drug Regimen for Osteosarcoma: A Single
Institute Experience
H.Y. Ju1 , P. Byung-Kiu1 , P. Seog Yun2 , K. June Hyuk3 , K. Hyun
Guy3 , Y. Jong Hyung4 , K. Mimi1 , P. Hyeon Jin1
1 National
Cancer Center, Pediatric Oncology Center, Goyang-si, Republic
of Korea; 2 National Cancer Center, Department of Pathology, Goyang-si,
Republic of Korea; 3 National Cancer Center, Orthopaedic Oncology Clinic,
Goyang-si, Republic of Korea; 4 Hallym University Chuncheon Sacred
Heart Hospital, Department of Pediatrics, Chuncheon, Republic of Korea
Background/Objectives: In osteosarcoma treatment, extent
of tumor necrosis at the time of surgery following preoperative chemotherapy is known to be strongly associated with
survival rate. We conducted a retrospective study to see if difference in tumor necrosis and treatment outcome comes from
addition of ifosfamide to conventional three-drug regimen.
Design/Methods: Patients who had been treated at the
National Cancer Center from 2002 to 2015 were evaluated.
As a four-drug regimen, 2 courses of neoadjuvant chemotherapy included intravenous methotrexate 12 g/m2 , cisplatin 120
mg/m2 , doxorubicin 75 mg/m2 , and ifosfamide 9g/m2 . Adjuvant chemotherapy was tailored according to tumor necrosis:
good responders received 2 courses of doxorubicin 90 mg/m2 ,
ifosfamide 9g/m2 , methotrexate 12 g/m2 , and cisplatin 120
mg/m2 ; poor responders received an additional course of ifosfamide 9g/m2 , methotrexate 12 g/m2 , cisplatin 120 mg/m2 . As
a three-drug regimen, 7921 or AOST 0331 regimen was performed.
Results: Total 26 patients were included in the study. Median
age at the time of diagnosis was 15.9 (10.3-36.7) years.
Twelve (46.2%) patients were treated with three drugs from
2002 to 2012. Remaining 14 (53.8%) patients were treated
with 4 drugs from 2009 to 2015. Four-drug regimen yielded
higher proportion of good responder when compared to threedrug-regimen (71.4% vs. 41.7%) (OR 3.5, P=0.233). 5 year
survival rate of the former group was 76.2%, and that of latter group was 50% (P=0.64). Event-free survival of the former group was 64.3%, and that of latter group was 33.3%
(P=0.348).
Conclusions: There was no difference between four- and
three-drug regimens with regard to necrosis rate, overall survival, and event-free survival. However, small sample size
could have precluded statistical difference, considering the
apparent difference in treatment results between two groups.
Further study in a larger scale is warranted to reach a solid
conclusion.
P-216 Prognostic Value of Molecular Alterations
in Infantile Spindle Cell Rhabdomyosarcoma
E. Pozzo1 , M. Debiec-Rychter2 , R. Sciot3 , M. Renard4 , A.
Uyttebroeck4 , H. Segers4
1 KU
Leuven, Department of Development and Regeneration, Leuven,
Belgium; 2 KU Leuven and University Hospitals Leuven, Department of
Human Genetics, Leuven, Belgium; 3 KU Leuven and University Hospitals
Leuven, Department of Pathology, Leuven, Belgium; 4 University Hospitals
Leuven, Department of Paediatric Hemato-Oncology, Leuven, Belgium
Background/Objectives: Childhood rhabdomyosarcoma
(RMS) is classified as embryonal (ERMS), alveolar (ARMS),
SIOP ABSTRACTS
or spindle cell (SRMS). SRMS is an uncommon subtype
of RMS with age-dependent genetic characteristics. Recent
molecular analyses have described NCOA2 and/or VGLL2
rearrangements in the majority of infantile SRMS and their
overall good prognosis. Here, we sought to identify the
presence of these molecular aberrations in infantile SRMS
patients and investigate their correlation with observed
clinical outcome.
Design/Methods: The samples from children diagnosed with
RMS between 1990 and 2016 at our hospital (n=84) were analyzed with fluorescence in situ hybridization (FISH), arrayCGH and assessed for clinicopathological characteristics and
survival. Patients who were diagnosed with RMS before 12
months of age were considered for this study.
Results: Nine patients were diagnosed with infantile RMS,
and three of them were histologically identified as infantile
SRMS. Sites of primary disease of infantile SRMS patients
included paravertebral, gluteal and periscapular muscles, with
FISH analysis revealing absence of NCOA2 and/or VGGL2
rearrangements. Patients were allocated to RMS 2005 subgroup D treatment; following chemotherapeutic course, 2/3
patients underwent surgical removal with 0/3 patients requiring radiotherapy and one patient receiving 4 months of maintenance therapy (cyclophosphamide and vinorelbine) to avoid
mutilating effects of radiotherapy. Two patients out of three
had treatment-related toxicities including nephrotoxicity and
temporary neurotoxicity. Compared to infantile ERMS and
ARMS patients (66.7% survival, 54.3 months median followup), all patients with SRMS at follow-up were alive and well,
with one long-term follow-up of 55 months. To date, no
patients developed local recurrence nor distant metastases.
Conclusions: Although patients with infantile SRMS were
negative for NCOA2 or VGGL2 rearrangements, the good
prognosis and event-free survival were not affected. Further
studies are needed to identify novel molecular aberrations in
infantile SRMS that could correlate with prognosis and eventfree survival.
P-217 Promising use of Rapamycin in an
INFANT with Rare Smooth Muscle Cell Tumor of
Nose and Upper LIP
M. Ramzan1 , S. Katewa1
1 Manipal
Hospital, Pediatric Hematology Oncology & BMT, Jaipur, India
Background/Objectives: Smooth muscle tumor (SMT) are
rare in children and very difficult to treat. mTOR inhibitors
like rapamycin (sirolimus) are a type of targeted therapy that
stops the protein that helps cells divide and survive. mTOR
inhibitors are being studied to treat perivascular epithelioid
cell tumors (PEComas) and epithelioid hemangioendothe-
S265 of S518
lioma. Use of rapamycin has not been mentioned in literature
for treatment of SMT.
Design/Methods: We report a 5 month old infant first product
of non-consanguineous marriage who had swelling over tip of
nose and face since birth.
Results: CT scan showed lobulated soft tissue mass of
22x39mm. PET CT revealed localized FDG avid lobulated,
heterogeneous, enhancing mass of 34x37x41.6mm involving right side of nose, upper lip and adjoining cheek in
the pre maxillary region with calcification. Histopathology
showed of spindle cell with fusiform nuclei and indistinct
eosinophilic cytoplasm arranged in fascicles, was suggestive
of spindle cell sarcoma, likely to be embryonal rhabdomyosarcoma. However, immunohistochemistry was strongly positive for SMA and negative for desmin, myogenin, caldesmon,
S-100, CD34 with Ki 67 of 5% (low to intermediate grade
smooth muscle tumor). He was started on vincristine, actinomycin and cyclophosphamide (VAC) chemotherapy. At 6
weeks, mass reduced in size clinically so another 6 weeks of
VAC given. After 12 weeks of chemo CT scan still showed
mass of 31x21x26 mm. He was then started on only rapamycin
0.5 mg daily. After 8 weeks his facial swelling has significantly reduced clinically. CT showed residual mass of
21×12×21mm. Currently this infant is on rapamycin and
doing well.
Conclusions: Rapamycin treatment was promising in this
case of SMT. Further role of this drug has to be investigated
in large clinical trial in SMT.
P-218 Does Extent of Surgery Affect
Fibrosarcoma Outcomes?
K. Rao1 , J. Sola1 , O. Picado1 , E. Perez1
1 University
of Miami Miller School of Medicine/Jackson Memorial
Hospital, Pediatric Surgery, miami, USA
Background/Objectives: To determine whether surgery type
has any prognostic indications for survival in fibrosarcomas.
Design/Methods: We reviewed patients <20 years of age
diagnosed with fibrosarcomas from 1973-2013, who had any
type of surgery, in the Surveillance Epidemiology and End
Results (SEER) database. Kaplan-Meier analyses demonstrated disease-specific survival (DSS) for clinical and pathologic variables. Significant covariate predictors of DSS as
determined by univariate analysis were analyzed using Cox
regression.
Results: We identified 1,163 pediatric patients. The mean
age at diagnosis was 12 ± 6 years. There was no gender
predilection, with a male-female ratio of 1:1. Most (54%)
were White and 18% were Black. The majority (59%) were
classified as localized tumors, 28% had regional involvement,
and 3% had distant metastases. The majority of patients
SIOP ABSTRACTS
S266 of S518
required surgery (93%), and only 8% required radiation.
Overall DSS was 91% at 5 years, 90% at 10 years, and 89% at
15 years. Of the 639 patients who had surgery, site of tumor,
grade, SEER stage, and radiation were all significant using
univariate Kaplan-Meier survival analyses. Multivariate
Cox regression showed that tumor stage was an independent
determinant of survival, however surgical procedure type
(local versus aggressive resections) showed no significance.
Conclusions: Fibrosarcomas are rare in pediatric populations.
Although stage is an independent determinant of survival, surgical procedure type (local versus more aggressive resections)
did not show significance in a multivariate model. Aggressive surgical resection of fibrosarcomas is not associated with
increased survival.
P-219 Lymph Node Ratios Predict
Disease-Specific Mortality in Pediatric
Rhabdomyosarcoma
K. Rao1 , J. Tashiro1 , J. Sola1 , H. Neville1 , A. Hogan1 , E. Perez1
1 University
of Miami Miller School of Medicine/Jackson Memorial
Hospital, Pediatric Surgery, miami, USA
Background/Objectives: Lymph node involvement is associated with increased local recurrence rates and decreased
survival rates in pediatric rhabdomyosarcoma. We sought to
determine whether lymph node ratio (LNR) predicts diseasespecific mortality (DSM).
Design/Methods: We identified patients <20 years of
age diagnosed with rhabdomyosarcoma from 1988-2013 in
the Surveillance Epidemiology and End Results (SEER)
database. We calculated LNR's by taking the number of nodes
positive/ total number of nodes examined. We used KaplanMeier estimates to plot DSM for clinical and pathologic variables and Cox regression to evaluate LNR in models.
Results: Our study presented 188 cases with both lymph node
data and greater than three nodes examined. Median age at
diagnosis was 9.5 years (2-15), 64% were male and 74% were
White. The stage at presentation was 36% localized, 42%
regional, and 16% distantly metastasized. Forty-eight percent of patients received radiation therapy after surgery. The
median number of nodes examined was 7 (4-14) and mean
LNR was 0.13 ± 0.26. The mean survival was 89 ± 76 months.
Overall 5-year DSM was 13% for 5 years, and 18%, for 10,
15, and 20 years. The largest threshold for LNR associated
with DSM was 0.75. Five-year survival was 82% for LNR
< 0.75 versus 15% for LNR ≥ 0.75 (p<0.003). Lymph node
status, stage and LNR were significant determinants of DSM
on univariate analysis. Using Cox regression with all significant covariates, LNR and stage remained independent determinants of DSM.
Conclusions: Pediatric rhabdomyosarcomas are rare. LNR is
an independent determinant of DSM. Using 0.75 as a threshold may offer further value in DSM prognostication.
P-220 Clinicopathologic Spectrum of a Series of
Rhabdomyosarcomas Diagnosed at a Tertiary
Cancer Referral Centre, Mumbai, India
B. Rekhi1 , C. Gupta1 , S. Qureshi2 , G. Chinnaswamy3 , T. Vora3 , J.
Bajpai3 , N. Khanna4 , S. Laskar4
1 tata
memorial hospital, Surgical Pathology, mumbai, India; 2 tata
memorial hospital, Surgical Oncology, mumbai, India; 3 tata memorial
hospital, Medical Oncology, mumbai, India; 4 tata memorial hospital,
Radiation Oncology, mumbai, India
Background/Objectives: Spindle cell/sclerosing rhabdomyosarcoma (RMS) is a relatively newly recognized
subtype of RMS. Immunohistochemically; high myogenin
expression is associated with alveolar RMS (ARMS) and an
aggressive clinical course.
Design/Methods: This study was aimed at evaluating clinicopathologic and immunohistochemical features of 300 cases
of RMS. Immunohistochemical expression of myogenin and
MyoD1 was graded, based on percentage of tumor cells displaying positive intranuclear immunostaining, such as grade
1(1-25%); grade 2(26-50%); grade 3(51-76%) and grade
4(76-100%). Follow-up details were available in 272(90.7%)
patients. Various clinicopathologic parameters were correlated with 3-year disease-free and overall survival.
Results: Most cases, including various subtypes, except
pleomorphic RMS, occurred in the first two decades (228
cases)(76%), in males and in the head and neck region
(126)(42%), followed by extremities (59)(19.7%). The most
common subtype was ARMS (140 cases)(46.7%), followed
by embryonal RMS (90)(30%); spindle cell/ sclerosing RMS
(61)(20.3%) and pleomorphic RMS (9)(3%). Immunohistochemically, desmin was expressed in 292/299(97.6%) tumors,
myogenin in 238/267(89.1%) and MyoD1 in 192/266(72.2%)
tumors. High myogenin expression (more than, equal to
51% positive tumor cells) was significantly associated with
cases of ARMS (95/121,78.5%), as compared to other subtypes(48/117, 41%).(p<0.001). High MyoD1 expression was
seen in more cases of pure sclerosing, combined with spindle
cell/ sclerosing RMSs(10/10, 100%), as compared to the other
subtypes(91/141, 67.4%)(p=0.032) There was no significant
difference between high myogenin expression and diseasefree survival and/ or 3 year overall survival. Children, especially in first decade; patients with tumor sizes less than 5cm;
without metastasis and at an early tumor stage, showed significantly better survival outcomes.
Conclusions: There was significant association between high
myogenin expression and cases of ARMSs and high MyoD1
expression and cases of spindle cell/sclerosing RMS. Children
SIOP ABSTRACTS
in first decade, with smaller sized tumors, presenting at early
stage had relatively better outcomes. High myogenin expression was not found to be related with aggressive clinical outcomes.
P-221 Radachlorin-Based Photodynamic
Therapy of Soft Tissue Sarcoma in Children
N. Rostovtsev1 , S. Kovalenko1
1 Regional
Children Hospital, Surgery department, Chelyabinsk, Russia
Background/Objectives: The aim of our research was to
assess the effectiveness and the period of intraoperative phototoxicity of radachlorin mediated photodynamic therapy
(PDT). To treat malignant tumors characterized by far and
near infrared absorption band (650-800 nm) in children we
used the second-generation photosensitizer radachlorin (654662 nm absorption band). This agent is non-toxic, shows a
high photodynamic activity, and has a good contrast ratio (to
10:1) and a fine clearance.
Design/Methods: During a ten-year period (2007-2017), seventeen patients with primary soft tissue sarcoma (10 cases
of embryonal rhabdomyosarcoma, 3 cases of mixed rhabdomyosarcoma, and 4 cases of alveolar fibrosarcoma) were
treated. PDT was predominantly inpatient (intraoperative). In
one case of alveolar fibrosarcoma, PDT was performed on an
outpatient basis. All children were admitted to hospital with
an advanced stage of disease (tumors ranged from 10 to 20 cm
in diameter and were mainly T3-4, sometimes T2).
Results: Treatment based on chlorin photosensitizer mediated
PDT did not cause systemic or local events and was well tolerated by all patients including children with a concomitant
disease. Due to fast accumulation of radachlorin in tumor,
it was possible to use laser in 1-4 hours after intravenous
administration of the agent. Therapeutic effect was observed
in all patients including complete tumor resorption in 19 cases
(58.8%) and partial resorption in 7 cases (41.2%).
Conclusions: Chlorin photosensitizers have a high photodynamic activity and fine therapeutic effects; they are quickly
excreted from the body and, due to a fast clearance, do not
induce the prolonged light sensitivity. This erases the problem of the long-term cutaneous phototoxicity. Thanks to a fast
accumulation in tumor with a high contrast gradient between
tumor and normal tissues, chlorin photosensitizers make it
possible to reduce the number of PDT sessions and to achieve
positive therapeutic outcomes.
P-222 Prognostic Impact of Circulating
Endothelial Cells and Endothelial Progenitor Cells
on Treatment Response and Survival of Pediatric
Patients with Solid Tumors
S267 of S518
H. Sayed1 , A. Zahran2
1 South
Egypt Cancer Institute, Pediatric Oncology, Assiut, Egypt; 2 South
Egypt Cancer Institute, Clinical Pathology, Assiut, Egypt
Background/Objectives: Neoangiogenesis plays an important role in growth and spread of pediatric solid tumors. The
levels of circulating endothelial cells (CECs) and endothelial
progenitor cells (EPCs) have been documented as indicators
of the vascular function in cancer. Here, we evaluated the role
of these cells in pediatric solid tumors and their prognostic
impact.
Design/Methods: A prospective study included 70 patients
with different pediatric solid tumors treated with different
types of chemotherapy in addition to 20 age and sex matched
healthy children as controls. Blood samples collected at diagnosis then at day 7 and day 21 after chemotherapy. Samples
assessed for CECs and EPCs using the flowcytometry.
Results: The mean levels of CECs and EPCs of patients
at diagnosis were significantly higher than controls
(85.29±24.78 and 26.1±9.11 versus 20.08±6.65; and
EPCs; 2.78±1.48 respectively; p < 0.001 for both). The
highest levels of CECs was observed in patients with rhabdomyosarcoma (RMS). An overall increase was reported
in CECs and after the first cycle of chemotherapy, that was
significantly correlated to treatment response and overall
survival.
Conclusions: As the highest levels of CECs was observed in
our patients who respond to therapy, the magnitude of increase
of CECs at day 7 after chemotherapy might be used as very
early predictor of response to therapy and outcome but further
study on larger population is necessary to confirm that.
P-223 Alveolar Soft Part Sarcoma in Children
and Adolescents: Treatment Results of the Five
Cooperative Weichteilsarkom Studiengruppe Trials
(CWS)
M. Sparber-Sauer1 , G. Seitz2 , T. von Kalle3 , C. Vokuhl4 , I.
Leuschner4 , M. Scheer1 , M. Münter5 , S.S. Bielack1,6 , B.
Kazanowska7 , R. Ladenstein8 , F. Niggli9 , T. Klingebiel10 , J.
Fuchs11 , E. Koscielniak1,12
1 Stuttgart
- Olgahospital- Stuttgart Cancer Center- Zentrum für Kinder–
Jugend- und Frauenmedizin, Pediatrics 5 Oncology- HematologyImmunology, Stuttgart, Germany; 2 University Children´s Hospital
Marburg, Department of Pediatric Surgery, Marburg, Germany; 3 Klinikum
Stuttgart- Zentrum für Kinder– Jugend- und Frauenmedizin- Olgahospital,
Institute of Radiology, Stuttgart, Germany; 4 University of Kiel, Institute of
Paidopathology, Kiel, Germany; 5 Klinikum Stuttgart, Institute of
Radiotherapy, Stuttgart, Germany; 6 University of Muenster, Department of
Pediatric Hematology and Oncology, Münster, Germany; 7 University of
Wroclaw, Department of Pediatric Hematology/Oncology and BMT,
Wroclaw, Poland; 8 St. Anna Kinderspital, Pediatric Oncology, Wien,
Austria; 9 University of Zurich, Department of Pediatric Oncology, Zürich,
Switzerland; 10 University of Frankfurt, Hospital for Children and
Adolescents, Frankfurt, Germany; 11 University Children´s Hospital,
Department of Pediatric Surgery and Urology, Tuebingen, Germany;
S268 of S518
SIOP ABSTRACTS
12 University
NF-1. The reported incidence of MPNST among individuals
with NF-1 varies, and there is little information regarding the
risk factors for developing MPNST in this patient population.
Children´s Hospital-, Department of Pediatric Hematology
and Oncology, Tübingen, Germany
Background/Objectives: Alveolar soft part sarcomas
(ASPS) are mesenchymal tumours characterized by
t(X;17)(p11;q25) leading to ASPSL-TFE3.
Design/Methods: The clinical data of 61 children and adolescents with ASPS, treated according to recommendations
for “adult type” NRSTS in five prospective trials of the Cooperative Weichteilsarkom Studiengruppe (CWS) (1987-2015),
were analyzed.
Results: Median age was 14 years [range: 3–20]. The tumour
was mainly located in the extremities (75%). 46 patients had
localized (LD) and 15 metastatic disease (MD). 34/46 patients
with LD and 3/15 with MD received primary resection (LD:
RO n=37, R1 n=6, R2 n=2 and MD, primary tumour: R0
n=8, R1 n=1, R2 n=3), 7 of the LD patients received RT
additionally. All 37 patients are alive, 30/37 patients in complete remission (CR). CHT after primary resection (n=17) or
biopsy (n=7) was given in 12/46 patients with LD and 12/15
MD. In 7 patients response was assessable: 2 partial, 4 stable disease and 1 progression. In 12/24 patients a secondary
resection was performed, in 3 RT was added: 8/12 patients
were in CR in comparison to 4/12 patients without secondary
resection. After a median follow-up of 6 years (range: 0.2–
16.5), 45/46 patients with localized and 8/15 patients with MD
were alive: 36/45 and 2/8 in complete remission, the others
mostly in stable disease. 10 yr overall survival (OS) and event
free survival (EFS) were 88% and 65% respectively. Age<10
years, IRS I-III, size ≤5cm, T1 and R0 or R1 (primary or
delayed) resection correlated with favorable prognosis concerning EFS and OS.
Conclusions: Prognosis of patients with ASPS when treated
in prospective trials is comparable to prognosis of patients
with rhabdomyosarcoma. Primary or delayed complete
tumour resection correlates with long term survival.
P-224 Family History of MPNST Among
Individuals with NF-1 IS Associated with Increased
Incidence and Earlier Development of MPNST
M. Spira1 , F. Malbari2 , P. Knight3 , C. Zhu4 , M. Roth4 , J. Gill4 , I.
Abbott5 , A. Levy4
1 Albert
2 Children's
Einstein College of Medicine, Bronx, USA;
Hospital at
Montefiore, Department of Neurology, Bronx, USA; 3 Children's Tumor
Foundation, Research & Medical Programs, New York, USA; 4 Children's
Hospital at Montefiore, Department of Pediatric Hematology/Oncology and
Marrow and Blood Cell Transplantation, Bronx, USA; 5 Children's Hospital
at Montefiore, Department of Neurosurgery, Bronx, USA
Background/Objectives: Neurofibromatosis type 1 (NF-1)
is a relatively common autosomal dominant tumor predisposition syndrome. Malignant peripheral nerve sheath tumors
(MPNST) are the leading cause of death in young adults with
Design/Methods: Individuals with NF-1 registered with the
Children's Tumor Foundation's Neurofibromatosis Registry
were emailed an anonymous 15-minute survey regarding personal and family history of NF-1 and MPNST, ages of onset,
and symptomatology. Participation was voluntary and information was self-reported and not verified by individual health
records.
Results: The survey was sent to 4801 registrants and had
878 responses (18.3% response rate). Among all respondents
having at least one blood relative diagnosed with MPNST,
19.4% developed MPNST themselves. This was significantly
higher than the incidence of MPNST among respondents
who reported a negative family history of MPNST (7.5%,
p=0.021). The presence of a positive family history for
MPNST was found to be a risk factor for development of
MPNST (OR-2.975; 95% CI 1.232-7.187). In addition, NF1
patients with MPNST and a positive family history of MPNST
were significantly more likely to have developed the disease
prior to age 10 than those with a negative family history of
MPNST (42.9% vs 7.0%, p=0.029), These patients were also
more likely to develop MPNST before age 20, however the
difference was not significant (71.4% vs 32.6%, p=0.089).
Conclusions: These results suggest that a positive family history of MPNST represents a risk factor for the development of
MPNST. This data supports consideration for implementing
enhanced screening for this at-risk population. Furthermore,
since the results also suggest an earlier onset of disease in individuals with a positive family history of MPNST, screening
should be carefully considered particularly for patients less
than 10 years.
P-225 Prognostic Factors and Survival in
Children with Rhabdomyosarcoma: Experience at
the Instituto Nacional De Enfermedades
Neoplasicas and Hospital Rebagliati
C. Ugaz Olivares1 , J. Montoya1 , C. Perez1 , L. Vasquez2 , L. Rios2
1 Instituto
2 Hospital
Nacional de Enfermedades Neoplásicas, Lima, Lima, Peru;
Rebagliati, Lima, Lima, Peru
Background/Objectives: Rhabdomyosarcoma (RMS) is still
one of the neoplasms with poor prognosis in our country
despite the improvement in the worldwide cure rate. The aim
of this study is to determine survival and associated prognostic factors of this entity.
Design/Methods: Retrospective cohort study. All infants and
children younger than 14 years with RMS treated at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Hos-
SIOP ABSTRACTS
pital Rebagliati between May 1990 and December 2016 were
reviewed.
Results: A total of 252 children were identified, 124 patients
(49.2%) were male and 128 (50.8%) female. The median age
was 5 years (range, 1 month - 14 years). The most frequent histological type was embryonal (76.9%) and 41.5% of patients
had metastatic disease at onset. With a median follow-up of
26 months, the 5-year overall survival (OS) rate for localized
and metastatic RMS was 69.3% (standard error, SE 5.32%)
and 21.8% (SE 6.29 %) respectively. Five-year event-free survival (EFS) for localized and metastatic RMS was 48.0% (SE
5.45%) and 12.3% (SE 4.32%), respectively. Eleven patients
had no survival data. In the multivariate analysis, the presence of metastases (P=0.001), histological type (P=0.014),
positive surgical margins (P=0.046), risk group (P=0.001),
clinical-surgical group (P=0.001) and stage (P=0.001) significantly affected OS. There was a significant improvement in
5-year OS according to decades (30.5% in 1990 - 1999, 40.0%
in 2000 - 2009 and 54.5% in 2010 - 2016, P=0.001). Age, gender, provenance, tumor size and histological subtype did not
affect significantly OS.
Conclusions: Survival rates in patients with RMS are lower
than those reported in developed countries, although there is
evidence of improvement in recent years. It is necessary to
optimize the multidisciplinary management of this disease.
P-226 Pencil-Beam Scanned Protons for the
Treatment of Ewing's Sarcoma Patients: Results
from the Paul Scherrer Institute
D.C. Weber1 , F. Murray1 , D. Antunes Correia1 , U. Kliebsch1 , M.
Walser1 , A. Bolsi1 , A. Lomax1 , R. Schneider1
1 Paul
Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland
Background/Objectives: Few data exist regarding the clinical outcome of patients with Ewing's sarcoma (EWS) treated
with pencil-beam scanning proton therapy (PT). We report
the local/distant control rates, survivorship and late toxicity
of children, adolescents and young adults (AYA) treated at
the Paul Scherrer Institute.
Design/Methods: Thirty-eight patients (median age, 9.9
years) were identified. A total of 24 male and 14 female
patients received a median dose of 54.9 GyRBE (range, 45.069.6). Size of the tumor ranged from 1.7 to 24 cm (median,
6.7). Most common primary site was axial/pelvic (n=27;
71%). Four patients (11%) presented with metastasis at diagnosis. Twenty (53%) patients had chemo-PT only. Median follow up was 49.6 months (range, 9.2-131.7).
Results: The 5-year actuarial rate of local control (LC),
metastasis-free survival (MFS) and overall survival (OS) were
81.5%, 76.4% and 83.0%, respectively. All local recurrences
occurred in field and in patients with non-extremity primaries.
S269 of S518
Six patients died, all of tumor progression. Age < 10 years was
a favorable factor for LC (p=0.05) and OS (p=0.05) of borderline significance but was significant for MFS (p=0.003).
Tumor volume < 200 ml were favorable prognostic factors
for DFS (p=0.03) and OS (p=0.07). Acute toxicity was limited to grade 1-2 skin erythema or mucositis. Only 2 (6.9%)
grade 3 late toxicities were observed. The 5-year actuarial rate
of grade 3 toxicity-free survival was 90.9%.
Conclusions: These preliminary data suggests that the outcomes of children and AYA with EWS were good and PT was
well tolerated with very few late adverse events. The local
and distant tumor control for older patients with large prePT tumor volumes remains problematic in these challenging
patients.
P-227 Clinical Characteristics and Prognosis of
Pediatric Rhabdomyosarcoma in SCMC
H. yali1 , G. yijin1
1 Shanghai Children's Medical Center
SCMC Affiliated to Shanghai Jiaotong
University School of Medicine, Hematology/Oncology, Shanghai, China
Background/Objectives: The objective of this study was to
determine treatment outcomes in pediatric patients with rhabdomyosarcoma treated at the Shanghai Children's Medical
Center (SCMC).
Design/Methods: A retrospective chart review of 108 pediatric patients (< 19 y old) with Rhabdomyosarcoma(RMS)
diagnosed between 2005 and 2014 was performed. According to the pathological subtype, TNM stage and postoperative
pathologic staging, the patients were divided into four groups:
low-risk group, intermediate-risk group, high-risk group and
distant metastatic group. The Kaplan-Meier survival analysis
and Cox regression multivariate analysis were used to assess
prognostic factors for overall survival (OS) and event-free survival (EFS).
Results: The median age at diagnosis was 65.5 months. The
median follow-up for living patients was 44.3 months and
the median follow-up for all patients was 36.9 months. The
most common primary sites arose in the others (includes
abdomen, trunk, retroperitoneum, etc.) (32.4%). The 5-year
OS and EFS for all patients were 86.1% and 72.2% and for
metastatic disease were 58.8% and 29.4%, respectively. On
multivariate analysis, metastatic disease at presentation, ≤1y
or≧10y, tumor size ≧ 5cm were associated with worse EFS
(P < 0.05). Metastatic disease at presentation was associated
with worse OS (P < 0.05). The estimated 5-years EFS rate for
four groups (low-risk group, intermediate-risk group, highrisk group and distant metastatic group) were 71.4%, 85.1%,
75.7%, and 29.4%, respectively (P < 0.001). The estimated 5years OS rate for four groups was 85.7%, 95.7%, 86.5% and
58.8%, respectively (P < 0.001).
SIOP ABSTRACTS
S270 of S518
Conclusions: RMS patients with distinct groups have different outcomes in the SCMC, which is quite similarly to
the worldwide data. However, this study need for long-term
follow-up of RMS survivors for analysis of prognosis factors.
SOLID NON B R A I N T U MO U R S RETINOBLASTOMA
P-228 Clinico-Demographic Profile of
Retinoblastoma Patients Seen in Tertiary Referral
Centers in MANILA, Philippines (2014-2016)
1
2
3
4
A.P. Alcasabas , B. Gepte , G. Mercado , A. Goleta-Dy , E.
Domingo3 , P. Fajardo1 , J. Lecciones2
1 University
of the Philippines - Philippine General Hospital, Paediatrics,
Manila, Philippines; 2 Philippine Children's Medical Center, Pediatrics,
Manila, Philippines; 3 University of the Philippines - Philippine General
Hospital, Opthalmology, Manila, Philippines; 4 St. Luke's Medical Center,
Pediatrics, Quezon City, Philippines
Background/Objectives: Retinoblastoma has a high incidence in the Philippines (16.5 per million children 0-4 years).
In Luzon, the country's largest island, 90 cases are expected
annually. Two government pediatric cancer units in Manila
started a retinoblastoma program in October 2013 involving
adoption of a uniform stage-based protocol, patient navigation, data management and community-based health worker
education on early warning signs. We report the clinicodemographic profiles of children diagnosed from January 1,
2014 – December 31, 2016.
Design/Methods: Prospective data collection of all consecutive patients and review
Results: A total of 119 cases were seen. Eighty-two had
unilateral retinoblastoma, 35 bilateral, and 2 trilateral. Mean
age (months) at diagnosis: unilateral 29 (3-108); bilateral:
19 (2-51); and trilateral 13 (12-14). M:F ratio 1.4:1. Average lag time from initial symptoms to diagnosis was 12
months (1 - 46). Reasons for delay include financial constraints (N=67, 56%), ignorance of disease (N=27; 23%), misdiagnosis (N=11; 9%), multiple referrals (N=4; 3%) and fear
(N=4; 3%). Only 16 % (N=19) of patients came from Metro
Manila, with most 40% (N=47) from Southern Luzon (16,700
km2 area). Chief complaints were leukocoria in 42% (n=50),
orbital mass 37% (n=44), buphthalmos 10% (N=12), post
enucleation in 8% (N=9), strabismus 1% (N=1), blindness
1% (N=1), no data 2% (N=2). Majority had extra-ocular disease (50%) with International Retinoblastoma Staging System
Stage 0: N=1; Stage 1: N=45; Stage II: N=2, Stages III N=33;
Stage 4: N=24; and unknown: N=13.
Conclusions: To address delayed diagnosis and low detection
rates, a nationwide educational campaign should tackle both
the early warning signs of retinoblastoma and the availability of government financial aid, including the national health
insurance coverage for enucleation, chemotherapy and radiation. A patient referral system from communities and local
hospitals to retinoblastoma treatment centers should be established.
P-229 Impact of Simple Lifestyle Intervention
Yoga/Meditation on Improvement in the Quality of
Life and Semen Quality in Fathers of Children
Affected with Retinoblastoma
S. Bisht1
1 All
India Institute of Medical Sciences, ANATOMY, New Delhi, India
Background/Objectives: Retinoblastoma (RB) is the most
common childhood intraocular malignancy and its incidences
has increased by 30% in the past 5 years which is believed
to be due to the effect of environmental factors causing
oxidative stress (OS). Sperm DNA integrity is essential
for fertilization, proper embryonic development and birth
of healthy offspring. Sperm is highly vulnerable to oxidative damage to both nuclear and mitochondrial DNA due
to minimal cytosolic anti-oxidants and deficient DNA damage repair mechanism. Yoga/meditation are being increasingly used as adjunct to modern medicine in treatment of
several clinical conditions. In the present study, we analyzed the effects of yoga/meditation on seminal OS and
sperm DNA integrity in fathers of children affected with
RB.
Design/Methods: A total of 50 men were recruited for the
study. Semen samples were collected at base line (day 0),
1 month, 3 months and after 6 months of yoga/meditation
intervention. Reactive oxygen species (ROS), DNA fragmentation index (DFI) and 8-hydroxy-2’-deoxyguanosine (8OHdG) levels were estimated at day 0, 1 month, 3 months and
6 months.
Results: There was reduction in mean DFI levels at 1 month
(p=0.63), 3 months (p=0.046) and 6 months (p=0.032),
seminal mean ROS levels at 1 month (p=0.74), 3 months
(p=0.039) and 6 months (p=0.006), 8-OHdG levels at 1
month (p=0.68), 3 months (p=0.043) and 6 months (p=0.022)
with respect to the base line levels (day 0) of yoga/meditation
intervention.
Conclusions: Yoga/meditation may significantly lower OS
and oxidative DNA damage, and levels of mutagenic base
8-OHdG in the sperm DNA. Thus yoga/meditation are simple lifestyle interventions which are therapeutic for maintaining/restoring sperm DNA integrity and hence, can reduce
the prevalence of childhood cancers where poor sperm DNA
integrity could be one of the reason.
SIOP ABSTRACTS
P-230 “Where does this Come From?”
Understanding How Survivors and Parents of
Children with Retinoblastoma Conceptualize
Genetics
H. Dimaras1 , A. Gedleh1 , A. Lee1 , J. Hill1 , K. Hougham1 , J.
Kabiru2 , K. Kimani3 , L. Njambi3
1 Hospital
for Sick Children, Ophthalmology & Vision Sciences, Toronto,
Canada; 2 Kikuyu Eye Unit, Ophthalmology, Kikuyu, Kenya; 3 The
University of Nairobi, Ophthalmology, Nairobi, Kenya
Background/Objectives: Genetic testing and counselling
have become integral parts in the management of heritable
cancers, like the childhood eye cancer retinoblastoma. This
study aimed to determine the attitudes, knowledge and experiences - concerning retinoblastoma genetics - among survivors
and parents of children with retinoblastoma in Canada and
Kenya.
Design/Methods: Data was collected through focus groups
and a brief demographic questionnaire. Study settings were
in Canada (The Hospital for Sick Children) and Kenya (Kenyatta National Hospital and Kikuyu Eye Unit). Thematic analysis was used to identify key themes from discussions in each
setting.
Results: Three focus groups were conducted in Toronto (n =
15) and five in Kenya (n = 31). Themes that were common
to both Canadian and Kenyan populations included: (a) there
is significant confusion about the genetics and heritability of
retinoblastoma; (b) there is a need for improved communication from healthcare teams about genetics; and (c) there is a
need for improved access to psychosocial support to help with
coping. Unique themes included: (a) genetic diagnosis can
cause significant interruption to family relationships (Kenya);
and (b) genetic testing and counselling are valued by families
(Canada).
Conclusions: Even in Canada, where genetic testing and
counselling are well established, retinoblastoma survivors and
parents were found to have significant gaps in their knowledge of genetics. Similarly in Kenya, participants were confused about the genetics and heritability of retinoblastoma.
Improving communication from healthcare teams, and providing psychosocial support, could help enhance information uptake and understanding by families in both Canada
and Kenya. The patient perspective from each population also
revealed context-specific issues that are useful for the refinement of cancer genetic services in each setting.
P-231 Enhancing Communication about
Retinoblastoma Clinical Encounters Using a Novel
Global Data Repository
B. Gallie1 , K. Houghham1 , T. Truong2 , L. Justin2 , T. Viet2 , Y.
Gavrylyuk2 , S. Soliman1 , C. Zhang3
S271 of S518
1 The
Hospital for Sick Children, Ophthalmology and Vision Science,
Toronto, Canada; 2 Techna Institute- University Health Network, Health
Informatics Research, Toronto, Canada; 3 Beijing Children's Hospital,
Ophthalmology, Beijing, China
Background/Objectives: Communication plays a critical
role in effective retinoblastoma care. Yet communication of
details from clinical encounters to all members of a patient's
circle of care (individuals that provide or support retinoblastoma patient care including parents / legal guardians) remains
complex and onerous. Despite best intentions, poor communication (i) wastes time and money, (ii) results in misunderstandings about the retinoblastoma treatments and prognosis,
and (iii) contributes to family stress in the face of devastating
diagnoses and difficult choices.
Design/Methods: We set out to develop an innovative IT
solution to enhance retinoblastoma circle of care communication. The prototype point-of-care retinoblastoma data repository, developed by 2005, has been tested extensively by care
providers and iteratively refined for more than a decade at
SickKids. We showed in 2009, 2015 that the cornerstone
of this database, a language-independent timeline, enhances
understanding by parents of children with retinoblastoma concerning purposes and quality of care.
Results: The Internet version of the repository, now
called Disease-specific electronic Patient Illustrated Clinical
Timeline for RetinoBlastoma (DePICTRB), is ready for
global deployment. With consent, at diagnosis a new
retinoblastoma patient is given a DePICTRB account by their
treatment centre. Identifiable disease-specific summary data
about each clinical encounter is entered at the point of care,
into the patient's DePICTRB account on a secure Telus server.
Included in DePICTRB are drawings mapping the tumours
and treatments in each eye, selected images key to understanding and cancer prognostic staging based on algorithms. “Write
access” is securely assigned to clinical members of the circle of care; parents and others have “read access”, supporting
effective dialogue with care-givers.
Conclusions: Anecdotal feedback suggests that DePICTRB
enhances communication. By modulating communication
within retinoblastoma circles of care, DePICTRBhas potential
to reduce waste, improve understanding of the retinoblastoma
treatment course and empower parents/legal guardians to be
informed decision makers.
P-232 The Canadian Retinoblastoma Research
Registry
K. Hougham1 , H. Dimaras1 , C. Moses1
1 The
Hospital for Sick Children, Ophthalmology and Vision Sciences,
Toronto, Canada
SIOP ABSTRACTS
S272 of S518
Background/Objectives: Retinoblastoma is an aggressive
childhood eye cancer. Retinoblastoma patients (individuals
affected by retinoblastoma, including parents/legal guardians)
indicate they are deeply incentivized to keep abreast of
research and help co-create it.
Design/Methods: We initiated the Canadian Retinoblastoma
Patient Engagement Strategy, in response to the keen interest of the patient community to be involved in research. As
part of this strategy, we created the Canadian Retinoblastoma Research eRegistry. The purpose of the eRegistry is to
engage Canadian retinoblastoma patients with the research
community. Registrants are invited to give permission to (Part
A – Passive Participation) receive general information about
retinoblastoma (e.g., lay summaries); and (Part B – Active
Participation) be contacted about specific research studies for
which they (or their children) might be a suitable subject or
team member (e.g., research assistant).
Results: Since it launched (November, 2016), 35 people
have agreed to participate in the Canadian Retinoblastoma
Research Registry. All registrants enrolled in Parts A and B
of the registry. Thirty-seven percent (n = 13) of the registrants are retinoblastoma survivors and 74% (n=26) of the registrants are the parent/legal guardian of someone diagnosed
with retinoblastoma. All of the registrants are 30 years of age
and older. Forty-five percent (n =16) of the registrants are
from large urban centers. As part of enrollment, registrants are
invited to share research topics of interest. A quarter (n = 9) of
the registrants provided suggested research topic(s), including
second cancers, genetics and psychological side effects.
Conclusions: These initial data indicate: (i) registrants are
keen to receive both general information as well as invitations for specific research studies; (ii) targeted recruitment efforts may be required to reach younger people
affected by retinoblastoma and retinoblastoma survivors;
and (iii) although interested in retinoblastoma research,
some retinoblastoma patients do not have specific research
priorities.
P-233 Development of Beagle Retinoblastoma
Model: Mimicking Tumor Microenvironment
Surrounding Vitreous Seeds
1
2
2
2
1
1
D.H. Jo , J.H. Kim , H.O. Jun , C.S. Cho , E. Bak , J.H. Kim
1 Seoul
National University College of Medicine, Department of
Ophthalmology, Seoul, Republic of Korea; 2 Seoul National University
Hospital, Fight against Angiogenesis-Related Blindness FARB LaboratoryClinical Research Institute, Seoul, Republic of Korea
Background/Objectives: This study aims to develop a novel
orthotopic transplantation model of retinoblastoma model
in beagles which mimics vitreous seeds. In patients with
retinoblastoma, there is no definite method to investigate the
characteristics of vitreous seeds because biopsy is absolutely
prohibited.
Design/Methods: SNUOT-Rb1 and Y79 cells (2 x 107 cells)
from 2 different retinoblastoma cell lines were intravitreally
injected into the eyes of beagles. At 6 weeks after the injection, the enucleated eyes were processed for further analyses. Retinoblastoma cells isolated from the vitreous cavity were evaluated for proliferation and characteristics as
retinoblastoma cells. Furthermore, RNA sequencing was performed to investigate the overall patterns of gene expression
in retinoblastoma cells isolated from the vitreous cavity.
Results: At 6 weeks after the injection of retinoblastoma cells,
the clumps of retinoblastoma cells were observed in the vitreous cavity of beagles. The isolated cells from the clumps
demonstrated similar shapes to their parental cells and the viability was over 98%. Further analyses also showed that isolated cells possessed their characteristics as retinoblastoma
cells. In addition, differentially expressed genes which could
be valuable therapeutic targets were identified by comparison
of gene expression between retinoblastoma cells isolated from
the vitreous cavity and their parental cells.
Conclusions: This beagle retinoblastoma model mimics vitreous seeds in patients with retinoblastoma. Because there is
no method to identify the characteristics of vitreous seeds, this
model will be valuable to investigate them.
P-234 Mitochondrial Complex V (ATP 6 and
ATP 8) in Retinoblastoma Tumor and ITS
Association with Clinicopathological Parameters
S. Kashyap1 , L. Singh1 , M. Singh2 , N. Pushker3 , S. Sen1 , B.
Chawla3 , R. Meel3
1 All
India Institute of Medical Sciences, Ocular Pathology, Delhi, India;
India Institute of Medical Sciences, Ocular pathology, New delhi,
India; 3 All India Institute of Medical Sciences, Ophthalmology, Delhi, India
2 AII
Background/Objectives: Mitochondrial defects play an
important role in the development and progression of cancer. Genetic defects of OXPHOS have been recognized as an
important cause of human disease. The objective of this study
is to elucidate the role of ATP 6 and ATP 8 proteins and its
prognostic significance in retinoblastoma (Rb).
Design/Methods: Immunohistochemistry was performed
with primary antibodies against ATP 6 and ATP 8 on 45
formalin-fixed retinoblastoma tissues and their expression
were confirmed by western blotting on fresh tissues. Expression were then correlated with clinical, histopathological
parameters and tumor staging.
Results: ATP6 and ATP8 proteins were expressed in 35%
and 45% cases of primary retinoblastoma cases by immunohistochemistry. Histopathological high risk factors including massive choroidal invasion, scleral invasion and optic
nerve cut end were identified in 42.2% cases. Expression of
ATP 6 and ATP 8 were statistically significant with various
SIOP ABSTRACTS
histopathological high risk factors and tumor invasion (>1
HRFs)(p<0.05).
Conclusions: This is the first study predicting a relevant role
of ATP 6 and ATP 8 protein and might be used as a therapeutic
marker in retinoblastoma. This may be used as an attractive
future anticancer target in primary retinoblastoma tumors.
P-235 Changing Strategies in the Approach to
Treatment of Bilateral Retinoblastoma,
Demographics, Genetics, Outcome: 26-Years
Experience
R. Kebudi1 , S. Tuncer2 , S. Bay Buyukkapu3 , S. Sencer4 , O.
Gorgun1 , H. Yazıcı5 , D. Akdeniz Odemis5 , B. Tuncer5 , F. Yaman
Agaoglu6 , I. Ayan3 , E. Darendeliler6
1 Istanbul
University Cerrahpasa Medical Faculty and Oncology Institute,
Pediatric Hematology-Oncology, Istanbul, Turkey; 2 Istanbul UniversityIstanbul Faculty of Medicine, Department of Ophthalmology- Ocular
Oncology Service-, ISTANBUL, Turkey; 3 Istanbul University- Oncology
Institute, Pediatric Hematology-Oncology, Istanbul, Turkey; 4 Istanbul
University- Istanbul Faculty of Medicine, Department of Radiology,
ISTANBUL, Turkey; 5 Istanbul University- Oncology Institute, Cancer
Genetics, Istanbul, Turkey; 6 Istanbul University- Oncology Institute,
Radiation Oncology, Istanbul, Turkey
Background/Objectives: Treatment decision in bilateral
retinoblastomas (BRB) depends on tumor burden, potential
for vision, status of the contralateral eye. Ocular salvage and
late effects are important issues. This study evaluates demographic features, genetics, treatment modalities, late effects in
BRB.
Design/Methods: Patients with BRB treated in the Istanbul University, Oncology Institute and Opthalmology Department between 1990-2016 were retrospectively assessed. All
patients were multidisciplinarily evaluated for chemotherapy (CT-chemoreduction /adjuvant), local opthalmic therapies (transpupillary thermotherapy, cryotherapy, plaque),
radiotherapy, enucleation. The chemotherapy protocol used
had vincristine, cisplatin, etoposide, cyclophosphamide until
2009; vincristine, etoposide, carboplatin since then. Since
2011, intraarterial, intravitreal CT was used. Genetic testing
was done by Sanger DNA sequencing and MLPA analysis.
Results: 114 BRB (56 male, 58 female) (228 eyes) with a
median age of 9 months (0,5-42) were evaluated. Three had
extraocular disease, two trilateral RB. Seventeen had a family history of retinoblastoma. The kind of mutations most
observed were nonsense, frameshift, splice site. According to
ICRB classification, 67 eyes were in group E, 43 group D, 27
group C, 45 group B, and 19 group A. Enucleation was done in
68 eyes, mostly group E. Radiotherapy was used for 30 eyes,
most before 2000. Bone-soft tissue deformities, cataracts
were observed in irradiated patients. Five developed a second
cancer (4 sarcomas, 1 meningioma) at a median of 11 years,
four in irradiated sites. The 5 yr survival was 93.5%.
S273 of S518
Conclusions: Chemoreduction (systemic, intraarterial) and
local ophtalmic therapies enable preservation of vision in
most group A, B, C tumors and some D tumors. Most group
E tumors require enucleation. Radiotherapy can be avoided in
most cases. Intra-arterial chemotherapy is promising in maintaining ocular salvage. Patients should be followed up for late
effects, genetic counseling should be done.
The genetic work was supported by Scientific Research
Projects Coordination Unit, Istanbul University, Project numbers BYP20546/2016 and 23070”.
P-236 Intraarterial Chemotherapy (IAC) for
Patients with Retinoblastoma (RB) Treated in One
Center
B. Dembowska-Baginska1 , O. Rutynowska-Pronicka1 , A.
Kolodziejczyk-Gietka1 , K. Cieslik2 , A. Olechowski2 , W. Hautz2 ,
M. Pedich3 , E. Jurkiewicz3 , U. Pasik3
1 The
Children's Memorial Health Institute, Oncology, Warsaw, Poland;
Children's Memorial Health Institute, Ophthalmology, Warsaw,
Poland; 3 The Children's Memorial Health Institute, Radiology, Warsaw,
Poland
2 The
Background/Objectives: Intraarterial chemotherapy for
retinoblastoma is accepted as an effective treatment method.
Since 2015 this method has been introduced in our center.
Aim: to present tumor control and complications following
IAC for Retinoblastoma.
Design/Methods: Material and methods: 37 patients with
intraocular RB (unilateral - 29, bilateral-8) were treated with
IAC, 4 as primary treatment and 33 after systemic chemotherapy. In general all patients with bilateral disease and group
E unilateral disease received systemic chemotherapy prior
IAC. Patients who did not achieve complete tumor control
after both treatments underwent laser therapy and intravitrous
melphalan injections when needed. A total of 43 eyes were
treated. IAC consisted of melphalan as a single agent or with
topotecan or carboplatin. Doses of drugs were determined by
the patients’ age and angioanatomy. Success of treatment was
defined as tumor inactivation and ocular survival.
Results: Results; catherization was successful in 90% of procedures. There were 122 injections of chemotherapy (melphalan alone- 17, with topotecan - 13, with topotecan and
carboplatin- 89, topotecan and carboplatin - 3). Each eye
received a median of 3 intaarterial chemotherapy courses. Eye
preservation was feasible in 41 out of 43 eyes. There were
no hematological toxicities. One cerebro - vascular event and
3 episodes of optic neuritis were observed. One patient with
tumor progression on systemic chemotherapy and IAC developed distant metastases.
Conclusions: Conclusions IAC allowed eye globe preservation in our RB patients’ series.
S274 of S518
SIOP ABSTRACTS
P-237 Retinoblastoma: A Curable Childhood
Malignancy- Experience in a Tertiary Care
Hospital of Bangladesh
Mexico, Pathology, Mexico City-DF, Mexico; 6 Columbia UniversityMailman School of Public Health, Epidemiology, New York, USA;
7 Hospital de Pediatría IMSS Siglo XXI, Unidad de Investigación, Mexico
City- DF, Mexico
B. Mamtaz1 , J. Islam2 , F. Begum1 , S. karim3
Background/Objectives: Retinoblastoma is one of few pediatric malignancies whose incidence varies geographically.
Prior ecologic studies suggested that UV exposure through
sunlight might contribute to increased incidence, though individual level exposure was never examined. Previously sunlight in infancy was recommended to prevent Vitamin D
(VitD) deficiency. Rodent models of retinoblastoma suggest
VitD inhibits angiogenesis.
1 National
institute of cancer research & hospital, Paediatric Oncology,
Dhaka, Bangladesh; 2 National institute of cancer research & hospital,
Cancer Epidemiology, Dhaka, Bangladesh; 3 Bangabandhu Sheikh Mujib
Medical University, Paediatric Haematology and Oncology, Dhaka,
Bangladesh
Background/Objectives: Retinoblastoma (RB) is the most
common intraocular malignancy of childhood. It accounts for
3% of all childhood malignancies and 11% of malignancies
develop in the first year of life. RB is curable if diagnosed early
and treated appropriately. But in Bangladesh many children
with RB die due to delayed diagnosis and treatment. National
Institute of Cancer Research and Hospital (NICRH) is the only
tertiary care specialized cancer hospital in government sector
in Bangladesh. Most of the children with RB are referred here
for management from all parts of the country.The aims of the
study were to see the prevalence of RB among the children
attended the out patient department of Paediatric Oncology
of NICRH and also the proportion of patients those were able
to take treatment.
Design/Methods: It was an observational study conducted
from January 2008 to December 2016 in Paediatric Oncology
Department of NICRH, Mohakhali, Dhaka, Bangladesh. Children with RB, age less than18 yrs of both sexes were included
in the study. Data were collected from patients’ registry.
Results: Total patients attended the outpatient department of
Pediatric Oncology during the study period were 2,687 and
among them 537 (20%) were cases of RB. Male were 66%,
female were 34% and most common age group was 1.5 to
3.0 years. Unilateral cases were 422(79%) and Bilateral were
115(21%). Only 236 (43% ) patient of RB took treatment.
Most (95%) of attended children with RB were in advanced
stage.
Conclusions: Awareness about the importance of early diagnosis and treatment of RB is very important. This awareness
can save valuable lives as well as vision of many children.
P-238 Sunlight Exposure Prior to Diagnosis of
Sporadic Retinoblastoma, Risk and Extent of
Intraocular Disease
M. Orjuela-Grimm1 , M. Ramírez-Ortiz2 , A. Medina-Sanson3 , X.
Liu4 , M.L. Cabrera5 , J.P. Medina-Paez6 , J. Romero-Rendón7 , S.
Bhatt-Carreño6 , A. Ruiz6 , V. Ponce-Castañeda7
1 Columbia
University- Mailman School of Public Health, Epidemiology &
Pediatric Oncology, New York, USA; 2 Hospital Infantil de Mexico,
Ophthalmology, Mexico City-DF, Mexico; 3 Hospital Infantil de Mexico,
Oncology, Mexico City-DF, Mexico; 4 Columbia University- Mailman
School of Public Health, Biostatistics, New York, USA; 5 Hospital Infantil de
Design/Methods: In EpiRbMx, mothers of children with
retinoblastoma are interviewed at diagnosis and report their
child's daily & weekly sunlight exposure during 3 age periods (0-6 months, 6.1-12 months, 12.1-23 months). We examined whether duration of sunlight exposure varied between
216 unilateral and 101 bilateral retinoblastoma cases,and 152
similarly aged healthy controls. In 158 unilateral (’unilaterals’) and 75 bilateral (’bilaterals’) cases we examined whether
extent of disease varied with reported duration of sun exposure (’sun’).
Results: Sun increased with age in cases and controls. Within
each age group, cases had less sun than controls. Greater
maternal education was associated with less sun, particularly
after age 6 months (p<0.05). Controlling for maternal education, cases had less sun than controls. Compared with controls,
Unilaterals had less sun at each age (p<.05), while Bilaterals had less sun after age 12 months (p<.0001), and at earlier
ages (p=0.08). Controlling for maternal education, unilaterals
had more sun than bilaterals, especially at age >12 months
(p<0.01).
In unilaterals, maternal education was inversely associated with International Intraocular Retinoblastoma Classification (IIRC), and St. Jude stage, and Sun. Sun was
positively associated with IIRC in unilaterals >12 months
(p=0.03), though less so after adjusting for maternal education (p=0.06); there was no association with St Jude stage. In
bilaterals, sun was unrelated to extent of intra or extraocular
disease.
Conclusions: In central Mexico, sun exposure is inversely
associated with incidence of retinoblastoma. In unilateral
retinoblastoma, sun exposure in the 2nd year of life appears
positively associated with extent of intraocular disease.
P-239 Clinical-Epidemiological Characteristics of
Bilateral Retinoblastoma in Children at the
Edgardo Rebagliati Martins Hospital (HNERM)
and Oncosalud - Clinic in Lima-Peru During the
Period 1999-2016
SIOP ABSTRACTS
S275 of S518
C. alvarez1,2 , G. paredes2,3
1 rebagliati
2 oncosalud
hospital, oncology pediatric, lima, Peru;
clinic,
oncology pediatric, lima, Peru; 3 rebagliati hospital, oncology pediatric,
lima, Peru
Background/Objectives: Bilateral Retinoblastoma: current
multimodal treatment reduces the tumor to the maximum and
prevents blindness.
Design/Methods: Descriptive, retrospective study of children
with bilateral retinoblastoma Rebagliati Hospital-Oncosalud
Clinic.
Results: Twenty-five cases in a population of 3263 oncological children of Rebagliti Hospital and 30,000 early detection
cancer children program in Oncosalud Clinic. Mean age was
16.8 months ( newborn – fortyeigth months ), Male / Female
sex ratio 1.08, boys thirteen and twelve girls. Pre-school 52%,
infants 44% and schoolers 4%. One case with family history of
bilateral Retinoblastoma and RB1 gene (+). Clinical: leukocoria 100%, proptosis 12.5%, headache 12.5%, seizures 4.1%.
Three cases (12.5%) had metastasis: bone marrow; brain and
a sphenoid case and cervical nodes. International stage of the
right eye: A (4%), D (44%), E (52%) and left eye: B (8%), C
(12%), D (8%), E (72%). Reese's clasification of the right eye:
I (4%), IV (36%), V (60%) and left eye: I (4%), III (12%), IV
(8%), V (76%). Enucleation at debut was in 3 cases (12.5%),
and 24 cases (96%) received systemic chemotherapy. From
2003 onwards, focal therapy was added, preserving unilateral
vision in 11 (44%) of 25 cases, of whom 10 (90.9%) received
chemotherapy more focal therapy (four cryotherapy (16%),
three received laser (12%);one received brachytherapy (4%),
one thermotherapy and one intraarterial- chemotherapy melphalan); one thermotherapy alone (9.09%). At the time of this
report, twenty one cases in remission (84%) and four deaths
(16%) due to denial of bilateral enucleation by persistent postsystemic chemotherapy. Overall survival of 104.29 months
and disease free survival of 119.25 months.
Conclusions: Bilateral Retinoblastoma was more prevalent
in preschoolers and males, leukocoria was the most frequent
sign. The introduction of focal treatment from 2003 together
with surgery and systemic chemotherapy has helped to preserve vision in the less compromised eye, avoiding blindness.
tumor activity against a variety of adult and childhood solid
tumors. The CSF penetration of the active lactone form of
topotecan and no significant neurologic toxicity was observed.
To determine the efficacy of intrathecal topotecan in patients
with advanced Rb.
Design/Methods: Patients newly diagnosed for orbitary and
CNS metastatic Rb were enrolled in this study. Treatment was based on ifosfamide 1.8grm2scdose/5 days,
etoposide 100mgm2scdose/5 days and carboplatin (AUC
6 or 450mgm2scdose/day 1) each 21 days concomitant
with intrathecal topotecan (0.4mg/dose) administered twice
weekly during the 6 cycles of intense chemotherapy.
Results: We enrolled 6 patients with unilateral extraocular Rb
with mean age of 32 months, with a metastasic CNS disease
by cerebral magnetic resonance (MR) in 3 of them and nonmetastatic patient with advanced orbital disease. 2 patients
were found to have positive CFS for neoplasic cells, achieving CSF response (negativization on patology study) after one
and two cycles with intrathecal topotecan and chemotherapy.
All were submitted to enucleation after 2 cycles of treatment.
2 patients (33%) presented progression to CNS confirmed by
MRI, both died with tumor activity. Four of them are free of
disease mesured clinically and by imagen and CSF. No one
presented any sign of neurological toxicity. One patient presented hematological and infectious grade IV toxicity.
Conclusions: Remission of the disease was achieved in four
patients, without severe or irreversible adverse events. Complete response, measured by imaging and CSF negativization,
were confirmed after two cycles of treatment. Topotecan must
be evaluated in a large study to prove the efficacy.
P-241 Associations of RB1 Genetic Variants with
Clinical Traits in Retinoblastoma Patients from a
Brazilian Service (INCA - Rio de Janeiro)
B. Pinto Nasr1 , M.C. Silva de Miranda Gomes1 , B. Palma Matta1 ,
V. Lima1 , M.A. Moraes Moreira1 , C. Rodrigues Bonvicino1 , L.
Leontina Couto1 , V. Mendonça1 , M.A. Faria Domingues de Lima2 ,
F. Regla Vargas3 , A.C. Evangelista dos Santos1
1 Instituto
Nacional do Cancer INCA, Oncogenetic, Rio de Janeiro, Brazil;
do Grande Rio, Oncogenetic, Rio de Janeiro, Brazil;
3 Hospital Universitário Gafrée-Guinle HUGG, Oncogenetic, Rio de
Janeiro, Brazil
2 Universidade
P-240 Efficacy of Intrathecal Topotecan in
Patients with Advanced Retinoblastoma.
Preliminary Report
C. Leal1 , A. Perez1 , H. Pena1
1 Instituto
Nacional de Pediatría, Oncology, Mexico City, Mexico
Background/Objectives: Retinoblastoma (Rb) is the most
commun intraocular neoplasia, with high mortality in
advanced disease. Topotecan is a topoisomerase I with anti-
Background/Objectives: Estimate frequency of variants in
RB1 gene and test associations with different clinical traits in
patients with Retinoblastoma (RB).
Design/Methods: Retrospective chart review of 206 patients
was performed. We reviewed three continuous traits – age of
diagnosis (DX), age of first symptom (1S), lag-time between
1S and DX (LAG) – and the categorical traits: laterality,
survival, family history, intra/extraocular tumors, treatment,
SIOP ABSTRACTS
S276 of S518
secondary tumors. We performed complete Sanger sequencing and Multiplex Ligation-dependent Probe Amplification
(MLPA) of RB1 gene from blood samples of 127 patients. RB1
molecular diagnosis was defined as Positive or Inconclusive.
To test effects of RB1 molecular diagnosis, laterality and survival on square root (SQRT) of each continuous trait we used
three-way ANOVA. Chi-square tests were used to test associations between pairs of categorical traits
Results: ANOVA of SQRT age data showed patients with
bilateral RB have significant earlier diagnosis (DX = 11.5m
± 0.3) and first symptom (1S = 4.7m ± 0.3) than unilateral (DX = 26.4m ± 0.2; 1S = 15.7m ± 0.4); P < 0.01.
Patients with pathogenic variants presented earlier DX average (11.0m ± 0.3) than inconclusive ones (23.2m ± 0.3); P
< 0.05. Significant effect of survival was found for LAG time
(P < 0.01), which deceased patients had greater LAG average (10.3m ± 0.4) than living/non-determined (4.7m ± 0.1).
Chi-square tests were non-significant for all pairs of categorical traits (alpha = 0.01), except for: RB1 molecular diagnosis (M) × laterality; M × family history of RB; survival ×
intra/extraocular tumors. Pathogenic variants were associated
with higher frequency of bilateral (31) than unilateral (18).
Most frequent types of pathogenic RB1 variants were nonsense (20) and splicing (9). All patients with splicing variants
had bilateral tumors.
Conclusions: Frequencies of RB1 variants were similar to literature. A possible trend which patients with splicing variants
develop bilateral RB was detected.
Results: Thirty-six of 266 physicians submitted responses.
Pediatricians were more likely than non-pediatricians to correctly identify the red reflex exam technique (odds ratio
(OR)=6.0, 95% confidence interval (CI)=1.0-34.8, p=0.029)
and to report being very confident in performing the red reflex
exam (OR=11.3, CI=1.9-68.1, p=0.003). Only 6 respondents
reported performing the red reflex exam all/most of the time
in children <6 years. More than half of respondents reported
having access to a working ophthalmoscope only some of the
time or never. Physicians working in the private/mission sector were more likely than Ministry of Health (MOH) physicians to have reliable access to a working ophthalmoscope
(OR=6.6, CI=1.1-39.3, p=0.026). The most frequently selfreported barriers to performing the red reflex exam included
time constraints, no access to an ophthalmoscope, and no
training/lack of confidence in performing the red reflex exam.
Conclusions: Although the disparity in survival is likely multifactorial, improved screening may lead to better outcomes
by increasing early detection. Multiple opportunities for intervention to improve retinoblastoma screening in Botswana
were identified, including physician education, particularly
among non-pediatricians with pediatric patients, and access
to ophthalmoscopes among MOH physicians.
P-243 First Prospective National Registry for
Pediatric Eye Cancer in Germany and Austria
M. Reschke1 , M. Borowski2 , S. Johannes3 , P. Sovinz - Ritter4 , W.
Sauerwein5 , S. Goerike6 , A. Eggert3 , N. Bornfeld7 , D. Lohmann8 ,
P. Temming1
1 University
P-242 Retinoblastoma Screening Practices
Among Physicians in Botswana
H. Reed1 , P. Mehta1 , J. Slone1
1 Baylor
College of Medicine, Pediatrics, Houston, USA
Background/Objectives: Retinoblastoma is a rare but highly
treatable childhood malignancy with cure rates >90% in highincome countries. Since 2007, the sole childhood cancer treatment center in Botswana, located at Princess Marina Hospital (PMH) in Gaborone, has been operated by Baylor College
of Medicine and Texas Children's Cancer and Hematology
Centers. PMH records indicate that 16 patients were diagnosed with retinoblastoma with only 10 (62.5%) surviving
despite the availability of many appropriate treatment options.
The study assessed retinoblastoma screening practices among
physicians in Botswana in order to identify opportunities for
improving early detection.
Design/Methods: A questionnaire assessing demographics,
retinoblastoma screening knowledge, and barriers to performing the red reflex exam was distributed to physicians practicing in Botswana using REDCap online data-capture software.
Hospital Essen, Department of Pediatric Hematology and
Oncology, Essen, Germany; 2 University of Muenster, Institute of
Biostatistics and Clinical Research, Muenster, Germany;
3 Charité-University Hospital Berlin, Department of Pediatric Hematology
and Oncology, Berlin, Germany; 4 University Hospital Graz, Department of
pediatric Hematology and Oncology, Graz, Austria; 5 University Hospital
Essen, Department of Radiotherapy, Essen, Germany; 6 University Hospital
Essen, Department of Diagnostic and Interventional Radiology and
Neuroradiology, Essen, Germany; 7 University Hospital Essen, Department
of Ophthalmology, Essen, Germany; 8 University Hospital Essen, Institute of
Human Genetics, Essen, Germany
Background/Objectives: Retinoblastoma is the most frequent malignant, intraocular tumor in childhood. Five year
overall survival rate is high in developed countries; however,
secondary primary malignancies and compromised vision
still complicate follow-up. Clinical trials and multicenter
prospective data are rare.
Design/Methods: RB-registry is a prospective multicenter
observational clinical study for patients with newly diagnosed
pediatric eye cancer in Germany and Austria. It collects data
about the results of genetic analysis, stage of disease at first
diagnosis (TNM, IRSS and ICRB staging systems), choice
of therapy and outcome. Reference evaluations for neuroradiology, genetics, cytology, radiotherapy, and histopathology
SIOP ABSTRACTS
were established to improve the comparability of the investigations performed at different participating centers.
Results: The recruitment rate exceeded the expected registration. In 3 years, 154 patients with 146 retinoblastoma (91 unilateral, 52 bilateral), three uveal melanomas, two medulloepithelioma of the ciliary body, two retinal astrocytoma, and one
heritable retinoblastoma predisposition with non-penetrance
for retinoblastoma were included. In total, 193 eyes were
affected by retinoblastoma. Most frequent ICRB group was
E (n=66, 34.2%), and most frequent IRSS stages were IRSS 0
(n=64, 44.1%) and I (n=69, 47.6%). Most ICRB E eyes were
primarily enucleated (n=59, 90.8%), whereas all 16 ICRB A
eyes were treated focally. Overall eye survival remained at
48.2% after 16 months and was associated with ICRB grouping (p<0.001, logrank test); 100 of 193 eyes were enucleated.
Conclusions: RB registry is a well-established clinical registry appropriate to improve patient counseling and to provide
a basis for the development of interventional clinical trials. In
the long-term, the data will help to improve therapy protocols
and thus conserve vision, reduce late term side effects, and
increase quality of life.
P-244 Histopathologic Risk Characteristics of
Retinoblastoma After Secondary Enucleation in
Patients Undergoing Organ-Saving Treatment
T. Ushakova1 , Y. Serov1 , O. Gorovtsova1 , N. Ivanova1 , I.
Trofimov2 , A. Yarovoy3 , V. Yarovaya3 , A. Pavlovskaya4 , B.
Dolgushin2 , V. Polyakov1
1 SR
Institute of pediatric oncology and heamatology N.N. Blokhin Russian
Cancer R, HEAD AND NECK TUMORS, Moscow, Russia; 2 SRI of clinical
and experimental radiology of N. N. Blokhin Cancer Research Center,
laboratory of interventional radiology, Moscow, Russia; 3 S.Fyodorov Eye
Microsurgery Complex, ocular oncology, Moscow, Russia; 4 SRI clinical
oncology of N. N. Blokhin Cancer Research Center, pathology, Moscow,
Russia
Background/Objectives: The development of metastasis in
retinoblastoma (RB) depends on histopathologic risk characteristics such as tumor invasion of the optic nerve with retrolaminar proliferation, massive invasion of choroid, sclera and
structures of anterior chamber. To demonstrate histopatholgic features of retinoblastoma eyes enucleated after organsaving treatment, including intra-arterial melphalan with special focus the type of tumor recurrence if present.
Design/Methods: From 01.2011 to 10.2016, 16 eyes (16
patients) were enucleated after prior combined organ-saving
treatment, including selective intra-arterial chemotherapy at
our institute.
Results: 10 of 16 eyes had insufficiency or minimum tumor
invasion choroid and/or prelaminar invasion of the optic nerve
and/or massive vitreous tumor spread. The adjuvant therapy
was not administrated for patients of this group. 4 of 16 eyes
S277 of S518
had massive tumor invasion choroid and/or including anterior
segment and/or a beginning optic nerve of the eye. The second
line of chemotherapy was administrated for patients of this
group. 2 of 16 eyes had a type IV regression. These eyes were
enucleated in connection with the development of secondary
complications as glaucoma, hemophthalmus and subatrophy
of eye. So far none of our patients developed metastatic
disease.
Conclusions: The most common reason for secondary enucleation of the eye was intraocular tumor progression, including anterior segment of the eye. Recurrent tumors in 4 cases
with massive tumor invasion choroid and/or including anterior segment and/or a beginning optic nerve of the eye had
the potential risk to develop metastatic disease.
P-245 Long Term Follow Up of Retinoblastoma
Survivors: Experience from India
R. Seth1 , A. Singh1 , V. Guru1 , B. Chawla2 , S. Pathy3 , S. Sapra1
1 ALl
India Institute of Medical Sciences, Pediatrics, Delhi, India; 2 ALl
India Institute of Medical Sciences, Ophthalmology, Delhi, India; 3 ALl
India Institute of Medical Sciences, Radiation Oncology, Delhi, India
Background/Objectives: Retinoblastoma (Rb) is the most
common primary intraocular tumor of infancy and childhood.
Survivors’ ocular and visual problems and increased risk for
subsequent malignancy are well documented but data on long
term health status of Rb survivors are limited: this being particularly true for India
Design/Methods: Children who had completed treatment for
retinoblastoma at least 2 years ago before and were under follow up at the after cancer treatment clinic were evaluated.
Results: In our series of 213 patients, the median age was
29 months, there was a male preponderance, and majority
had unilateral disease. Enucleation was done in almost three
fourth and 3% underwent bilateral enucleation. Majority of
the patients received chemotherapy, and few received radiation.. Growth was affected in about one third and majority
were those who had received radiation. Diminished vision was
noticed in about one-sixth. Orbital hypoplasia and contracted
socket was seen in 14.1% cases. 2.7% were hearing impaired.
About one-sixth had a global intelligence delay. Second
neoplasms were seen in 0.01%. No other abnormalities
seen.
Conclusions: Common late effects in our Rb survivors
include diminished vision in the salvage eye,Intellectual disability and contracted socket; there is a need for timely institution of prosthesis to avoid late effects like hypoplasia, contracted sockets and better cosmesis and enhanced self esteem.
Second neoplasm is a concern. Lifelong follow up and counseling of a healthy lifestyle is needed for Rb survivors.
SIOP ABSTRACTS
S278 of S518
P-246 Expression Pattern of Immune
Checkpoints PD-1 and PD-L1 in Retinoblastoma
and ITS Prognostic Significance
L. Singh1 , S. Kashyap2 , S. Sen2 , M.A. Rizvi3
1 Jamia
Millia Islamia and AIIMS, Ocular Pathology and Biosciences, New
Delhi, India; 2 All India Institute of Medical Sciences, Ocular Pathology,
New Delhi, India; 3 Jamia Millia Islamia, Biosciences, New Delhi, India
Background/Objectives: Retinoblastoma (RB), malignant
tumor of the sensory retina, is the most common eye cancer of
childhood due to the defect of RB gene. The immune system
plays an important role in controlling and eradicating cancer.
Recent studies suggest that programmed death-1/programmed
death ligand (PD-1/PD-L1) pathway in T-cell activation plays
a major role in tumor escape mechanism from host immunity.
Therefore, we investigated the expression of PD-1 and PD-L1
in human retinoblastoma cancer to define their clinical significance in patient's prognosis after surgery.
Design/Methods: PD-1 and PD-L1 protein expression was
evaluated in 60 prospective cases of primary enucleated
retinoblastoma specimens by immunohistochemistry and validated by western blotting. PD-1 and PD-L1 mRNA expression was investigated by quantitative real time PCR (qPCR).
Expression of PD-1 and PD-L1 were then correlated with clinical, histopathological parameters and patient survival.
Results: Immunohistochemistry showed cytoplasmic PD-1
expression in (9/60) 15 % cases, whereas PD-L1 showed
nuclear expression in (31/60) 51.6% cases. Western blotting confirmed the immunoreactivity results on representative
cases. The protein and the mRNA levels of determination by
IHC and real time qPCR were closely correlated. Expression
of PD-L1 showed significant correlation with poor tumour
differentiation and tumor invasion (p<0.05). There was a significant difference in the overall survival of patients with PDL1 expression.
Conclusions: These data suggest that PD-L1 expression may
be a new biomarker for patients with retinoblastoma in tumor
originating from sensory retinal cells. This study provides first
data for the role of immune checkpoints in retinoblastoma
patients. Further studies are necessary to confirm this observation and to evaluate the predictive value of PD-1 and PD-L1
in retinoblastoma in the context of PD-1 inhibition.
P-247 Correlation of p65/RelA Expression with
Tumour Invasion in Primary Retinoblastoma
M.K. Singh1 , S. Kashyap1 , S. Sen1 , N. Pushker2
1 All
2 All
India Institute of Medical Sciences, Ocular Pathology, Delhi, India;
India Institute of Medical Sciences, Ophthalmology, Delhi, India
Background/Objectives: Retinoblastoma (Rb) is a malignant
tumor of developing retina of children which occur before the
age of five years. Nuclear factor kappa B (NF�B) has been
shown to play a role in cell proliferation, apoptosis, cytokine
production, and oncogenesis. The nuclear factor-�B (NF-�B)
transcription factors family is thought to play an important
role in the development of certain cancers. Therefore, the aim
of this study was to investigate the localisation and expression
of p65/RelA protein in retinoblastoma.
Design/Methods: Prospective analysis of 55 primary
retinoblastoma cases over a period of one year. Expression
of RelA was analyzed by Immunohistochemistry (IHC)
in formalin fixed retinoblastoma specimens. Their mRNA
expressions were analyzed on 25 fresh primary enucleated
retinoblastoma tissues by real time polymerase chain reaction
(qPCR). Results were then correlated with clinical and
pathological parameters.
Results: Expression of p65/RelA proteins was found to be
30% in retinoblastoma cases but not in normal retina. This protein was more frequently detected in poorly-differentiated and
invasive tumours than in well-differentiated and non-invasive
tumours. Increased expression of p65/RelA was statistically
significant with choroidal invasion and invasive tumors (>1
HRFs). mRNA expressions of p65/RelA was found to be
upregulated in 35% of cases. mRNA expressions were correlated well with immunostaining.
Conclusions: This study demonstrated that expression of
p65/RelA protein represent a reliable prognostic marker of
retinoblastoma and might be related to retinoblastoma tumorigenesis and progression through a non-canonical pathway.
Targeting NF�B combined with other therapies may represent a novel approach to retinoblastoma.
P-248 Intra-Arterial Melphalan and Topotecan
Therapy for Retinoblastoma: Hacettepe Experience
A. Varan1 , H. Kiratli2 , I. Bajin1 , A. Akgoz3 , C. Akyuz1
1 Hacettepe
University- Institute of Oncology, Dept. of Pediatric Oncology,
ANKARA, Turkey; 2 Hacettepe University- Faculty of Medicine, Dept. of
Ocular Oncology, Ankara, Turkey; 3 Hacettepe University- Faculty of
Medicine, Dept. of Radiology, Ankara, Turkey
Background/Objectives: Retinoblastoma is the most
common intraocular malignancy in children. Here we
present our results of intra-arterial chemotherapy (IAC)
with melphalan and topotecan (IAC-MT) in the treatment
of newly diagnosed or relapsed-refractory retinoblastoma
patients.
Design/Methods: In this study we retrospectively analysed the clinical features and outcomes of the 37 patients
and 41 eyes treated with IAC-MT between October 2015
and February 2017. Tumor control and globe salvage
with IAC-MT were analyzed. Complete blood counts were
SIOP ABSTRACTS
S279 of S518
examined 7 and 15 days after the IACT for systemic
toxicity.
Results: The median age at diagnosis was 13 months (range
1-101 months). There were 18 girls and 19 boys. Intra-arterial
chemotherapy with melphalan and topotecan was the primary
treatment in 21 eyes and secondary in 20 eyes. The eyes
who received IAC-MT as a first-line therapy were classified
according to the International Classification of Retinoblastoma (ICRB) as group A (n = 2), B (n = 1), C (n =3), D
(n = 14), or E (n = 2). After IAC with a mean follow-up
of 6 months (range 2-16 months), complete regression was
achieved for tumor in 22 eyes (53%). Four of 41 eyes were enucleated (10%), 1 from 21 first-line treated group and 3 from
20 second-line treated group. Globe salvage was achieved in
95% of primary-treated cases and in 85% of secondary-treated
cases.The 1-year enucleation-free survival rate was 70%. The
further treatment requirements after IACT were as follows:
enucleation in 4 eyes, and local therapy in 11 eyes. No severe
systemic side effect observed.
Conclusions: Our preliminary results supported that globe
salvage and avoidance of toxicity related with systemic
chemotherapy may be achieved by IAC-MT. Given its safety
and high efficacy, it is expected that IAC-MT will replace conventional strategies.
P-249 Identification of RB1 Germline Mutations
and the Inheritance Pattern of Retinoblastoma in
Jordan
1
1
1
2
2
Y. Yousef , M. Mehyar , I. Nawaiseh , I. Sultan , R. Deebajah , A.
Tbakhi3
1 King
Hussein Cancer Center, Department of Surgery Ophthalmology,
Amman, Jordan; 2 King Hussein Cancer Center, Pediatric Oncology,
Amman, Jordan; 3 King Hussein Cancer Center, Cell Therapy and Applied
Genomics, Amman, Jordan
Background/Objectives: Retinoblastoma (RB) is a childhood cancer developing in the retina due to mutations in the
RB1 gene. Herein we are trying to identify the oncogenic
mutations in the RB1 gene and the inheritance pattern of RB
in the Jordanian RB patients.
Design/Methods: The peripheral blood of 50 Retinoblastoma patients was collected, and genomic DNA was
extracted. DNA sequencing was conducted by Next Generation Sequencing analysis, Sanger sequencing, Quantitative multiplex PCR (QM-PCR), and Allele-specific
PCR.
Results: In this cohort, 50 affected patients were studied.
Twenty (40%) patients had unilateral RB, and 30(60%) had
bilateral RB. Overall, 36(72%) patients had germline disease, 17(47%) of them had the same mutation detected in
one of the parents (inherited disease). In the bilateral group,
all (100%) patients had germline disease, and 13(43%) had
inherited mutation, and in the unilateral group, 6(30%) had
germline disease and 4(20%) had inherited mutation. Of interest, in the inherited cases, paternal mutation was seen in
88% of the affected patients. Only one (2%) of the patients
had mosaic mutation detected, and in one(2%) of the inherited cases the mother had mosaic mutation. Over the 17
inherited cases, 16(94%) of them had unaffected carrier
parent.
Conclusions: Even all bilateral RB patients in our cohort had
germline disease, 30% of unilateral disease were germline,
and 47% of patients with germline disease had inherited disease from affected(6%) or unaffected carrier(94%). Therefore
molecular screening is very important for the genetic counseling regarding the risk for inherited Retinoblastoma in both
unilateral and bilateral cases.
S O LID NO N BRAIN TUM O URS LIVER TUMOURS
P-250 Genomic Studies in Hepatoblastoma:
Insight into Somatic Mutations Using Array-CGH
Analysis and Whole-Exome Sequencing
T. Aguiar1 , T. Rodrigues2 , F.A. dos Santos3 , J. Sobral2 , S.S. da
Costa2 , C.M.L. da Costa3 , I.W. da Cunha4 , M. Cypriano5 , S.R.C. de
Toledo5 , J.E.S. de Souza6 , E. Valadares7 , R. Borges8 , V. Odone9 , I.
Tojal6 , D.M. Carraro6 , C. Rosenberg2 , A. Krepischi2
1 A.C.CAMARGO
CANCER CENTER, CIPE, são paulo, Brazil; 2 University
of Sao Paulo, Genetic, Sao Paulo, Brazil; 3 A.C.CAMARGO CANCER
CENTER, Pediatric Oncology, Sao Paulo, Brazil; 4 A.C.CAMARGO
CANCER CENTER, Pathology Department, Sao Paulo, Brazil; 5 GRAACC,
Pediatric Oncology, Sao Paulo, Brazil; 6 A.C.CAMARGO CANCER
CENTER, CIPE, Sao Paulo, Brazil; 7 Baleia's Hospital, Pediatric
Department, Belo Horizonte, Brazil; 8 Conceição Children's Hospital,
Pediatric Department, Xangri-Lá, Brazil; 9 ITACI, Pediatric Oncology, Sao
Paulo, Brazil
Background/Objectives: Hepatoblastoma is the most common primary liver tumor in children, accounting for over
1% of pediatric cancers. Although molecular data on HB
tumorigenesis is still scarce because of its rarity, recently new
insights have been gained into their molecular biology. The
main objective of this study was to investigate the mutational
burden of HBs.
Design/Methods: A whole-exome sequencing was performed
in a discovery cohort of 6 HBs and their matched non-tumoral
liver tissues (244K Agilent SureSelect Target Enrichment).
Bioinformatic analysis of exome data identified somatic variants in 69 genes which were chosen for validation using a target sequencing panel (SureSelectXT Target Enrichment System for Illumina Paired-End Sequencing Library). The gene
panel was composed of the detected 69 genes and other 48
SIOP ABSTRACTS
S280 of S518
genes related with HB or cancer, and it was used to investigated additional 13 HB samples as a validation group. To
complement the screening of somatic mutations, we performed an array-CGH analysis (Agilent 180K) in twelve HB
samples to screen for copy number alterations.
Results: A total of 71 somatic mutations were validated in
53 genes considering the entire HB group. The somatic analysis reveals pathogenic mutations in the CTNNB1 gene and
a recurrent missense mutation in the CX3CL1 gene; the role
of these mutations was explored by IHQ studies of their proteins as well as by gene expression analysis by RT-PCR.
Array-CGH analysis showed mainly whole-chromosome and
chromosome-arm aneuploidies, and a few focal aberrations
could be also mapped.
Conclusions: Our data highlighted a relatively stable tumoral
genome in this type of pediatric liver tumor, which present a
low mutational burden regarding potentially pathogenic mutations and copy number alterations.
Grants: FAPESP (2016/04785-0), FAPESP (2013/08028-1),
CNPq (141625/2016-3).
P-251 Investigations of Gankyrin as a Potential
Target for Liver Cancer
A. D'Souza1 , L. Valanejad Keifer2 , K. Lewis2 , A. Cast2 , M.
Wright2 , R. Karns3 , N. Timchenko2
1 Cincinnati
Children's Hospital Medical Center, Cancer and Blood Disease
Institute, 45229, USA; 2 Cincinnati Children's Hospital Medical Center,
Pediatric Surgery, Cincinnati, USA; 3 Cincinnati Children's Hospital
Medical Center, Gastroenterology, Cincinnati, USA
Background/Objectives: One of the critical steps in development of hepatoblastoma (HBL) is the loss of control of proliferation of hepatocytes. Our examination of a large bank of
HBL samples found that an oncogene Gankyrin is elevated
in all examined HBL patients with high rate of proliferation.
The goal of this project was to examine the role of Gankyrin
in activation of liver proliferation.
Design/Methods: To test the role of Gankyrin in liver proliferation, we generated liver-specific Gankyrin knockout mice
(Gank LKO) and examined liver proliferation using two models: proliferation after surgery and after liver injury. Liver proliferation was monitored using a combination of approaches
including measuring DNA replication, mitosis and expression
of cell cycle genes and oncogenes. Immunostaining, QRTPCR and Western blotting assays were used.
Results: Gank LKO mice had normal livers by gross examination and serum hepatic function testing. However, RNA-Seq
analyses showed that Gank LKO mice have reduced expression of genes that are involved in liver regeneration and liver
cancer. Consistent with these findings, we found that liver proliferation after partial hepatectomy (PH) is dramatically inhib-
ited in Gank LKO mice. Looking for underlying mechanisms,
we found that tumor suppressor proteins (TSPs) are reduced
by Gankyrin in control mice after PH, but are elevated in Gank
LKO mice. These elevated TSPs in Gank LKO mice inhibit
liver proliferation. Similar inhibition of liver proliferation was
observed in Gank LKO mice after liver injury mediated by
carbon tetrachloride.
Conclusions: Gankyrin is a powerful oncogene in HBL. Our
study demonstrates that deletion of Gankyrin is sufficient to
inhibit liver proliferation in animal models, which is an important mechanism behind carcinogenesis. These results strongly
suggest that inhibitors of Gankyrin should be investigated as
potential targeted therapy for HBL.
P-252
Liver Transplantation for Hepatoblastoma
B. Dembowska-Bagińska1 , E. Swieszkowska1 , H. Ismail2 , D.
Broniszczak2 , M. Markiewicz2 , J. Teisseyre2 , M. Drogosiewicz1 , A.
Brozyna1 , W. Grajkowska3 , M. Pyzlak3 , P. Kaliciński2
1 The
Children's Memorial Health Institute, Oncology, Warsaw, Poland;
Children's Memorial Health Institute, Pediatric Surgery and Organ
Transplantation, Warsaw, Poland; 3 The Children's Memorial Health
Institute, Patology, Warsaw, Poland
2 The
Background/Objectives: Liver transplantation (LTX) has its
established role in the treatment of children with hepatoblastoma.
Aim; presentation of treatment results and complications of
LTX for hepatoblastoma.
Design/Methods: Between 2002 and 2017, 22 children
underwent liver transplantation for unresectable hepatoblastoma. Age at transplantation ranged from 8/12 to 13 and 8/12
(median- 2 and 2/12 years). There were 10 patients with POSTEXT III, 9 with POSTEXT IV. Six patients were stage IV
disease, bilateral lung metastases. All patients received preoperative chemotherapy according to SIOPEL recommendations. All six patients had no evidence of metastatic disease
before LTX. Twenty children received grafts from related
donors, 2 cadaveric grafts. All patients received chemotherapy after transplantation (median 2 courses – cisplatin, vincristine, 5 FU).
Results: 18 out of 22 patients are alive with a median followup of 3 years. Patients survival is 100%, 81,6 %, 61,2 % at
1, 5 and 10 years. Four patients died; one 10 years from
LTX of bone marrow aplasia of unknown etiology, 3 patients
from relapses refractory to chemotherapy 4, 7, 11 months
from LTX. Relapses occurred in the lungs of 3 patients,
in 1 of them bone metastases were also observed. Posttransplantation chemotherapy was well tolerated. One patient
underwent 2 re-transplantations 2 years then 1 month from
primary and second LTX.
Conclusions: Our data confirm that LTX is a treatment option
for children with unresectable Hepatoblastoma.
SIOP ABSTRACTS
S281 of S518
P-253 Characteristics and Outcome of
Hepatoblastoma: Experience at the Instituto
Nacional De Enfermedades Neoplasicas (INEN) Peru
R. Diaz1 , E. Ruiz2 , S. Chavez1 , V. Caloretti1 , E. Maradiegue1 , A.
Wachtel3
1 Instituto Nacional de Enfermedades Neoplásicas, Pediatric Oncology,
Lima, Peru; 2 Instituto Nacional de Enfermedades Neoplásicas, Chief
Abdominal Surgical Department, Lima, Peru; 3 Instituto Nacional de
Enfermedades Neoplásicas, Pediatric Oncology, Lima, Peru
Background/Objectives: Hepatoblastoma (HB) represents
6% of solid pediatric malignancies at the INEN. The purpose
of this study was to evaluate the clinical features and outcome
of these patients between 1999 and 2014.
Design/Methods: This is a retrospective and descriptive
study. Between January 1999 and December 2014, 145
patients under 15 years of age were diagnosed having HB,
14 patients were excluded. Survival analysis was performed
using Kaplan-Meier method.
Results: The median age was 3.3 years (range 0.08 to 14
years), M/F ratio 2/1. Fifty patients (38.1%) had complete
remission, 22 had progressive disease (16.7%). 49 patients
recurred (37.4%) and 37 died (28.2%) Staging according
to PRETEXT was: I 10.6% (14), II 38.9 %( 51), III 35.8
%(47), IV 10.6 %( 14). Nineteen patients (14.5%) had pulmonary metastases at diagnosis. The 5 year overall survival
(OS) was 65.8% and Event Free Survival (EFS) 61%. OS
in the non-metastatic group was 71.9% and 42.8% in the
metastatic group. The OS for Pretext I 90.9%, II 66.9%, III
57.6%, IV 38.1% OS according to initial treatment neoadjuvant chemotherapy or surgery was SIOPEL 79%, carboplatin/doxorubicin 64.1%, VCR/5FU/cisplatin 35% and
67.1% for those with initial surgery. The EFS for these patients
was 60%, 56%, 25% and 62% respectively
Conclusions: HB is not a rare tumor at our Institution and
a multidisciplinary team approach is crucial for the improvement on survivorship. The lung metastases conditions a worse
prognosis and there has been improved survival since 2008
with SIOPEL treatment.
P-254 Epigenetic Mechanisms in Liver Tumors:
Gene Expression Analysis of the Epigenetic
Machinery in Hepatoblastomas
1
1
1
2
1
M.P. Rivas , E. Goulart , L. Caires , T. Aguiar , S.S. Costa , I.W.
da Cunha3 , C.M.L. Costa4 , M. Cypriano5 , S.R.C. de Toledo5 , M.
Maschietto6 , D.M. Carraro2 , C. Rosenberg1 , A. Krepischi1
1 Institute
of Biosciences - University of São Paulo, Genetics and
Evolutionary Biology, Sâo Paulo, Brazil; 2 AC Camargo Cancer Center,
International Research Center, São Paulo, Brazil; 3 AC Camargo Cancer
Center, Department of Pathology, São Paulo, Brazil; 4 AC Camargo Cancer
Center, Department of Pediatric Oncology, São Paulo, Brazil; 5 Pediatric
Oncology Institute GRAACC- Federal University of São Paulo, Department
of Pediatrics, São Paulo, Brazil; 6 National Center for Research in Energy
and Materials, CNPEM, Campinas, Brazil
Background/Objectives: Liver tumors in children account
for 1-4% of all pediatric solid tumors. While hepatocellular
carcinoma is predominant in adults, the most common liver
cancer in children is hepatoblastoma. Mechanisms underlying hepatoblastoma development are still poorly explored, and
prognosis in advanced tumor stages remains poor. It is suggested that this embryonal tumor is associated with a blockage in hepatocyte differentiation. These tumors carry a low
mutational burden, and the impairment of epigenetic mechanisms, which are the core of embryogenesis and development,
stands out as an alternative route for tumorigenesis. The main
objective of this study was to explore the role of genes associated with methylation and hydroxymethylation in hepatoblastomas.
Design/Methods: The cohort of tumors consisted of 29 hepatoblastomas and a control group of 8 non-tumoral liver tissues.The expression of genes of the epigenetic machinery
(DNMT1, DNMT3A, DNMT3L, UHRF1, TET1, TET2 and
TET3) was analyzed by qPCR (Taqman). A 5hmC quantification assay (Quest 5-hmCTM DNA ELISA Kit) was applied
to assess the level of 5hmC in tumors compared to controls.
Results: TET1 and TET2 genes were found to be up-regulated
in tumors. A significant increase in the 5hmC levels was also
evident in hepatoblastoma samples when compared to nontumoral tissues. These data suggested that hepatoblastomas
could present a pluripotency pattern of gene expression; to
address this issue, the expression levels of three genes associated with pluripotency (POU5F1, SOX2 and NANOG) were
evaluated, and no alteration was detected.
Conclusions: The upregulation of DNA methylation genes,
such as TETs, and an increased level of 5hmC, support the
hypothesis that hepatoblastomas exhibit an epigenetic signature of immature cells, suggesting a blockage during hepatic
cells differentiation in their genesis. However, the absence of
pluripotency markers showed commitment with the differentiation process. Our hypothesis is that hepatoblastomas are in
a transitional stage of hepatic differentiation, probably hepatoblasts.
Funding: FAPESP; CAPES
P-255 Development of Hepatoblastoma During
Growth Hormone Therapy
T. Oue1 , T. Sasaki1 , M. Zenitani1 , N. Tanaka1
1 Hyogo
College Of Medicine, Pediatric Surgery, Nishinomiya-shi- Hyogo,
Japan
Background/Objectives: Growth hormone (GH) is reported
to affect tumor growth and increases the risk of neoplasia such
SIOP ABSTRACTS
S282 of S518
as leukemia. However, the association between GH and hepatoblastoma (HB) has been rarely reported. Here we present
two cases of HB that developed during GH therapy.
Design/Methods: Patient medical records were collected and
retrospectively reviewed.
Results: Patient 1 was a 2-year-old boy and patient 2 was a
13-year-old boy. Both were administered with GH therapy for
growth retardation due to poor GH secretion, as shown by tolerance tests. Abdominal distention of the right upper quadrant
was observed 2 month and 2 years after GH therapy initiation in patients 1 and 2, respectively. Imaging studies including abdominal computed tomography (CT) revealed a huge
tumor in the left hepatic lobe, and serum alpha-fetoprotein
was markedly elevated in both cases. GH therapy was discontinued and tumor biopsy was immediately performed to confirm the diagnosis of HB. The tumor was completely resected
after several courses of chemotherapy using cisplatin and doxorubicin, according to the protocol of the Japan Pediatric
Liver Tumor Study Group. After additional chemotherapy,
the patients are alive without disease for 4 years and 1 year,
respectively. GH secretions normalized and catch-up growth
was observed in both cases after the treatment of HB.
Conclusions: In patient 1, as HB was noticed soon after
the initiation of GH therapy, GH may have accelerated the
growth of an already present HB. In patient 2, HB developed during the 2 years of GH therapy; therefore, GH may
have initiated HB tumorigenesis. In both cases, GH therapy
was immediately discontinued because GH likely accelerated
tumor growth. Normalized GH secretion after tumor resection
may indicate that HB tumors secrete a type of GH antagonist.
P-256 What is the Role of Aneuploidy in
Embryonal Tumors? Cytogenomic Analysis of
Hepatoblastomas
M. Rivas1 , J. Barros1 , T. Aguiar2 , S. Costa1 , C. Costa2 , I.
Werneck2 , D. Carraro2 , S. Toledo3 , M. Cypriano3 , C. Rosenberg1 ,
E. Novak4 , V. Odone-Filho4 , A. Krepischi1
1 Institute
of Biosciences - University of São Paulo, Genetics and
Evolutionary Biology, Sâo Paulo, Brazil; 2 AC Camargo Cancer Center,
Department of Pediatric Oncology, São Paulo, Brazil; 3 Pediatric Oncology
Institute GRAACC, Department of Pediatrics, São Paulo, Brazil; 4 Instituto
de Tratamento de Câncer Infantil ITACI, Pediatric Department at São Paulo
University Medical School, São Paulo, Brazil
Background/Objectives: Cytogenetic alterations leading to
changes in chromosome copy number (aneuploidy) are hallmarks of cancer cells. Hepatoblastoma (HB) is an uncommon
embryonal liver tumor accounting for approximately 80% of
childhood hepatic cancer and is mostly diagnosed in children
under the age of 18 months. Currently, there are no validated
prognostic or therapeutic biomarkers for HB patients. Most
HBs are sporadic cases, although its incidence is elevated in
certain genetic syndromes, including Beckwith–Wiedemann
and familial adenomatous polyposis. To explore the cytogenomic profile of HBs, we investigated a cohort of 10 hepatoblastomas by microarrays aiming to identify relevant chromosome regions and genes.
Design/Methods: An array-CGH 180K platform was performed, and we have characterized the copy number profile
of two different commercial HB cell lines as well as two hepatocellular carcinoma lineages.
Results: The array-CGH analysis revealed quite stable
genomes in this kind of embryonal tumor. Four HBs presented
with no detectable chromosomal imbalances, whereas four of
them exhibited mainly whole-chromosome and arm aneuploidies, with a prevalence of gains affecting 1q and the entire
chromosomes 2 and 8. Few focal alterations could be delimitated, including a 2q24.3 amplification in two tumors sharing a minimum common region of 5,3 Mb that harbors 20
genes; a complex rearrangement of non-contiguous deletions
at 3p26.1-p25.2; and a large 55 Mb segment deleted at 4q314q25. Two HBs presented a higher load of chromosomal rearrangements compared to the HB group.
Conclusions: The characterization of the liver tumor cell
lines highlighted the quiet chromosomal landscape of the
embryonal liver tumors compared to their adult counterpart,
hepatocellular carcinomas, which carry several cytogenetic
changes in a complex genome. Our data suggested that aneuploidy possibly plays a limited role in HB tumorigenesis,
rather linked to the process of acquisition of entire chromosomes than to the amplification of oncogenes and tumor
suppressors losses. Funding: CAPES (1671499); FAPESP
(2013/08028-1)
P-257 Contributions of Propranolol for the
Treatment of Infantile Hepatic
Hemangioendothelioma: The Mexico Experience at
the National Institute of Pediatrics
J. Palacios1 , S. Solórzano2 , J. Shalkow3 , R. Rodríguez4 , A. León5 ,
E. Cruz1 , D. Hernández1
1 National
Institute of Pediatrics, Surgical Oncology, Mexico, Mexico;
Institute of Pediatrics, Radiology, Mexico, Mexico; 3 Ministry Of
Health, Childhood Cancer, Mexico, Mexico; 4 National Institute of
Pediatrics, Pathology, Mexico, Mexico; 5 Ministry Of Health, Oncology,
Mexico, Mexico
2 National
Background/Objectives: Infantile hepatic hemangioendothelioma (IHEE) is the most common benign liver tumor
in infancy. Presenting symptoms may include abdominal distention, hepatomegaly, associated cutaneous hemangiomas,
congestive heart failure (CHF), anemia, and thrombocytopenia. Recently, propranolol has proven a good therapeutic
alternative.
SIOP ABSTRACTS
S283 of S518
Design/Methods: We retrospectively reviewed 10 cases of
IHEE treated with propranolol at the Surgical Oncology
Department of the National Institute of Pediatrics in Mexico
between 2007 and 2016. Demographic, clinical data and outcomes were collected.
Results: There were 7 girls and 3 boys. All were diagnosed
after birth, except one by prenatal ultrasound. All presented
with a palpable abdominal mass, 7 had CHF, 6 had associated
cutaneous hemangiomas and bi-lobar liver involvement. One
developed thrombocytopenia. No case presented hypothyroidism. Diagnosis was confirmed by Doppler US and angioCT-scan. All were treated first-line with propranolol at 2.5
mg/Kg/day after cardiac evaluation, with no adverse reactions
to treatment. Response was seen at 3 months. After radiographic response, propranolol was gradually waned. Nine
patients are alive without recurrence between 3 and 8 years
follow-up. Eight showed complete response, one did not
respond and required hepatic embolization. One patient died
due to severe coagulopathy (Kasabach-Merrit syndrome).
Conclusions: Propranolol offers an excellent therapeutic
alternative to IHEE, probably due to its anti-angiogenic properties (vasoconstriction, decreased expression of VEGF, and
apoptosis of capillary endothelial cells), with 90% survival
and no recurrence in this series. 80% of our patients had complete clinical and radiographic response without adverse reactions to treatment.
P-258 Aggressive Hepatoblastoma is Associated
with C/EBPA Mediated De-Differentiation of
Hepatocytes into Cells Expressing Stem Cell
Markers
1
1
1
1
2
N. Timchenko , A. Cast , L. Valanejad , M. Wright , A. Gupta , L.
Zhu3 , S. Shin1
1 Cincinnati
Children's Hospital Medical Center, Division of Pediatric
General and Thoracic Surgery, Cincinnati, USA; 2 Cincinnati Children's
Hospital Medical Center, Division of Pathology, Cincinnati, USA; 3 St. Jude
Children's Research Hospital, Department of Pharmaceutical Sciences,
Memphis, USA
Background/Objectives: Aggressive form of Hepatoblastoma, HBL, is associated with a poor prognosis. Tumor suppressor proteins (TSPs) are usually eliminated in HBL. While
examining a large cohort of HBL patients, we have identified a
group of aggressive HBL samples which express high levels
of TSPs. One of these TSPs, C/EBP�, is de-phosphorylated
at Ser190. The goal of this work was to determine the role
of post-translationally modified C/EBP� in aggressive liver
cancer and determine molecular mechanisms by which de-phC/EBP� causes development of liver cancer.
Design/Methods: To test the role of Ser190-de-ph C/EBP� in
liver cancer, we generated a mouse model, C/EBP�-S193A,
and investigated development of spontaneous liver cancer.
These mice were also treated with Diethylnitrosamine (DEN);
and liver cancer was examined by state-of-the-art approaches.
Liver cancer was also investigated in additional models of
aggressive liver cancer such as Pten/p53 DKO mice.
Results: We found that de-phosphorylation of C/EBP� converts this protein from a TSP into an oncogene. Using
C/EBP�-S193A mice and liver samples from patients (HBL
and HCC), we found that mouse and human C/EBP�, dephosphorylated at Ser193/Ser190 correspondingly, causes dedifferentiation of hepatocytes into cells which express markers of stem cells (tumor initiating hepatocytes, TIH). The
S193-de-ph-C/EBP�-dependent pathway of transformation of
hepatocytes into TIH includes increased hepatocyte proliferation, multi-nucleation of hepatocytes, and enlarged hepatocytes with intra-nuclear inclusions expressing DLK1 and containing glycogen. The molecular mechanisms of this transformation are associated with epigenetic alteration and formation
of high MW multi-protein complexes.
Conclusions: In patients with aggressive HBL, dephosphorylation of C/EBP� at Ser 190 converts this
tumor suppressor into protein with oncogenic activities. The
tumor promotion activity of oncogenic form of C/EBP�
includes the transformation of hepatocytes into tumor initiating cells that express markers of stem cells. These findings
provide molecular basis for development of a therapy to treat
aggressive liver cancer.
P-259 Role of Hepatic Artery Blockage in the
Treatment of High Risk Infantile Hepatic
Hemangioma
J. Wang1 , Q. Shu1 , M. Li1 , M. He1 , J. Cai1 , J. Mao1 , X. Chen1
1 Children's
Hospital - Zhejiang University School of Medicine, Department
of Surgical Oncology, Hangzhou, China
Background/Objectives: Infantile Hepatic hemangioma
(IHH) is the most common tumor of the liver during infancy.
Children with diffuse lesions are more likely to have a greater
risk of death, especially in cases with severe congestive heart
failure (CHF) and abdominal compartment syndrome (ACS).
Aggressive treatment is crucial to improve mortality. In this
study, the efficacy of hepatic artery blockage in the treatment
of high risk IHH was evaluated.
Design/Methods: Nineteen patients with diffuse IHH aged
from 12d to 37d admitted to our center between Jan. 2014 and
Sep. 2016 were included in this study. Clinical data were retrospectively analyzed. Glucocorticoid (methylprednisolone,
4mg/kg/day) plus propranolol (1mg/kg/day) were administrated as the first-line treatment. Symptoms including CHF
or ACS could not relieve or even deteriorated 48 hours after
drug administration in 8 patients (high risk group). Hepatic
artery blockage was suggested in high risk group. Five cases
SIOP ABSTRACTS
S284 of S518
underwent surgery (4 cases by hepatic artery ligation and
one case blocked by micro-coil embolization). Other 3 cases
refused hepatic artery blockage method kept glucocorticoid
plus propranolol treatment.
Results: In cases underwent hepatic artery blockage, CHF
and ACS relieved promptly after surgery in 4 cases (including
3 cases of hepatic artery ligation and 1 case of hepatic artery
embolization), 1 case had deteriorated heart failure and died
eventually. Other 3 cases in high risk group refused hepatic
artery blockage all died from deteriorated CHF and ACS.
Conclusions: Severe congestive heart failure and abdominal
compartment syndrome are high risk factors in children with
diffuse infantile hepatic hemangioma. Blockage blood flow of
hepatic artery is a simple method to relieve CHF and ACS.
Hepatic artery blockage combined with drug therapy may
improve mortality of high risk IHH.
P-260 Report of Childhood Hepatoblastoma: 74
Cases from a Single Center
T. Wang1 , C. Pan1 , J. Tang1 , Q. Ye1 , M. Zhou1 , Y. Gao1 , W. Hu1
1 Shanghai
children's medical center, Hematology/Oncology, Shanghai,
China
Background/Objectives: To investigate the efficacy of the
protocol for pediatric hepatoblastoma and the prognostic factors.
Design/Methods: All consecutive cases were divided into
either low risk group or high risk group according to grouping criteria. Complete remission was defined as both negative for imaging and � fetoprotein. Retrospective analysis was
performed for clinical features, short and long-term outcomes
and prognostic factors.
Results: 74 cases including 45 males and 29 females were
enrolled. The median age at diagnosis was 1.7 years old.
According to PRETEXT staging, 18 cases were in stage I-II
and 56 in stage III-IV. 19 of 74 cases existed distant metastasis at first presentation including 13 with lungs and/or pleura
metastasis. The median cycles of chemotherapy were 5 in low
risk group and 8 in high risk group. AFP was back to normal
after median 5 cycles of chemotherapy in total plus surgery
and 2 cycles post total tumor resection. Untill August 30,
2016, the median follow-up time was 24.17 months. 59 cases
achieved complete remission. 1 case did not reach remission, 3
progressed, another 5 relapsed, and total 6 cases already died.
The estimated five years EFS were 72.4% and OS were 90%.
The five years EFS and OS in low risk group were both 100%,
and those in high risk group were 68% and 87.6%, respectively. The five years OS rates were 75.3% and 94.9% respectively for with and without distant metastasis (P=0.016). After
3 cycles of chemotherapy post tumor resection, AFP returned
to normal in 43 and still high in 26 cases, with five years OS
rates were 100% and 80.9%, respectively (P = 0.011).
Conclusions: The result of this protocol is reasonable when
comparing with worldwide researchs. Besides staging, metastasis, pathological subtypes, postoperative AFP after 3 cycles
of chemotherapy back to normal or not is also a prognostic
factor.
S O LID NO N BRAIN TUM O URS GERM CELL TUMOURS
P-261 Experience of Low and Intermediate Risk
Malignant Extra-Cranial Pediatric Germ Cell
Tumors at CCHE
S. Ahmed1,2 , O. Arafah1,2 , G. Taha3 , N. elkinaai4 , M. Elwakeel5 , W.
Rashed6 , D. Elgalaly7 , M. Essam7
1 57357hospital,
Pediatric Oncology, Cairo, Egypt; 2 National Cancer
Institute. Cairo university, Pediatric Oncology, Cairo, Egypt;
3 57357hospital, Surgical Oncology, Cairo, Egypt; 4 57357hospital,
Pathology, Cairo, Egypt; 5 57357hospital, Radiodiagnosis, Cairo, Egypt;
6 57357hospital, Clinical trial unit, Cairo, Egypt; 7 57357hospital, Clinical
research, Cairo, Egypt
Background/Objectives: Survival rates for children with
malignant extra cranial germ cell tumors (MGCTs) have
increased significantly. Excellent outcomes are not distributed
uniformly across the heterogeneous distribution of stage, histologic features, and primary tumor site. Sustained favorable
outcome with therapy reduction in low and intermediate risk
encourages lesser toxic therapy to decrease long term side
effects.
Design/Methods: Out of 122 eligible patients with MGCTs,
a retrospective analysis was done for 47 cases, stratified and
treated at CCHE according to AGCT0132 protocol adopted
for low and intermediate risk MGCTs, from July 2007 till
end of December 2015. All cases were followed up until June
2016.
Results: For low and intermediate risk MGCTs, mean age was
4.3 years. Low risk (LR) patients were 23 (19 testicular and 4
ovarian). Yolk sac tumor predominates in male cases while
main histological types in female cases were Mixed GCT,
followed by Dysgerminoma. Intermediate risk (IR) were 24
cases with male to female ratio 1.7:1, with two extragonadal
cases (2 males with sacrococcygeal tumors) and 22 gonadal
cases (13 males and 9 females). Yolk sac tumor predominates
in male cases while main histological types in female cases
were Yolk sac tumors, Mixed GCT, and Dysgerminoma. Five
years OS were 100% and 95.7% for LR and IR respectively,
while five years EFS were 88 % and 91.3 % for LR and IR
respectively.
Conclusions: Reduction of therapy did not compromise the
favorable outcome in the low and intermediate risk groups
with excellent salvage potential. Long term survival raises
SIOP ABSTRACTS
concerns about late side effects encouraging more therapy
reduction.
P-262 Outcome of the Sacrococcygeal Teratoma:
A Single Institutional Study
T.T. Nguyen1
1 Dr
Nguyen Thanh Truc, Children Hospital N 2, HoChiMinh city, Vietnam
Background/Objectives: To report our initial experience
with Sacrococcygeal Tumors (SCT) treated at our hospital
over a 5 year period with reference to clinical presentations,
surgical attentions and short outcomes like: urinary and defecation functions, and tumor recurrence.
Background: statement of the problem e.g. incidence, difficulty with diagnosis, poor antenatal diagnosis, late referral or
difficulties with referral. The rarity of SCT indicates the need
for concentration in a specialist center and the need for long
term follow up.
Design/Methods: All infants with Sacrococcygeal tumors
who had surgery in our hospital from 1/2010 till 12/2015 were
selected. Details of gender, prenatal investigation, presentation,preoperative investigations, initial surgical outcome and
short term follow up were noted. Only patients with a follow
up greater than one year were included.
Results: Of 44 cases of Sacrococcygeal tumors 16 (36%)
were male and 28 (64%) were female. Chief complaint was
Sacrococcygeal mass. A prenatal diagnosis was established
in 23 (53), among these 21 cases had cesarean. The remaining
21 cases without prenatal diagnosis were delivered normally.
Most, 42 cases, were delivered at term. Preoperative investigation included Ultrasound (22) CT scan (20) and MRI in 12.
AFP and BHCG were done in 79.5%( and 77.3 %. The mean
age at diagnosis was 1.2 day and surgery was complete resection with coccycgectomy (35) or without coccycgectomy(9).
Mean length of stay was 18 days. Complications included:
wound infection (6 cases), wound dehiscence (3 cases), rectal
perforation in need of temporary stoma (2cases). In the short
term (1-5 year) constipation was noted in 5 patients, 1 local
benign and 2 malignant recurrences with an average time to
recurrence of 12 moths (benign and malignancy is defined as
AFP high associated recurrent institut tumor )
Conclusions: Sacrococcygeal tumor surgery in infants is a
relatively safe procedure not without potential complications.
P-263 Sacrococcygeal Teratoma: Analysis of
Surgical Outcome
N. Peters1 , J.K. Mahajan2
1 PGIMER2 PGIMER-
Chandigarh India, Pediatric Surgery, Chandigarh, India;
Chandigarh, Pediatric Surgery, Chandigarh, India
Background/Objectives: We reviewed our experience with
presentation and treatment of sacrococcygeal teratoma (SCT).
S285 of S518
Design/Methods: From July 2000 – May 2016, charts of 14
patients of SCT were retrospectively reviewed.
Results: There were 11 females and 3 males. Age at time
of surgery ranged from 1 day to 8 years (median 58 days).
Seven patients underwent surgery within 1st week of life and
4 were antenatally diagnosed. 6 patients underwent surgery
between 1.5 to 8 years, neoadjuvant chemotherapy (3) and non
resolving perianal abscess (1) being the reason for delayed
surgery. Ten patients were of Altman type I, 3 were type II
and 1 patient was of type III. Eight patients underwent CT
scan and 4 had preop ultrasound. Two patients had giant SCT
(>10cm). Serum AFP levels ranged from 4.36 – 48400 ng/ml.
Levels were raised for all cases of malignancy and 6 of the
8 others. Levels fell to normal within 1 year for all patients.
One patient with normal AFP and mature histology developed
recurrence after 1 year. Two patients, 1 each with giant benign
and malignant tumor developed neurogenic bowel and bladder. Ten patients had mature histology, 1 had immature and
remaining 3 had malignant histology. There was no postoperative mortality. One patient (mature histology and type III
morphology) died at 5 months post operative due to unrelated
causes. The median follow up was 3 years (range 1-17 years),
most recent being a telephonic follow up. All survivors are
disease free and had a good quality of life.
Conclusions: Surgical excision of SCT is associated with
good outcome. Serum AFP levels may take up to 1 year to
normalize. Recurrence can occur even with mature histology;
hence long term follow up is required. Neurogenic bladder and
bowel incontinence may be associated with large benign and
malignant tumors.
P-264 Profile of Paediatric Orbital and
Periorbital Tumors- A Report from a Tertiary Eye
Care Centre in India
N. Pushker1 , R. Meel1 , A. shashni1 , N. Gupta1 , S. Modaboyina1 , S.
Kashyap2 , S. Sen2 , M.S. Bajaj1
1 All
India Institute of Medical Sciences- New Delhi, ophthalmology, Ansari
Nagar- New Delhi, India; 2 All India Institute of Medical Sciences- New
Delhi, ocular pathology, Ansari Nagar- New Delhi, India
Background/Objectives: To assess the frequency of occurrence of orbital and periorbital tumors in paediatric age group
operated at our centre.
Design/Methods: This was a retrospective study in which all
the patients of age less than 16 years who were operated for
orbital and periorbital tumor at our centre from 2015 to 2016
were included.
Results: A total of 109 patients were included in this study.
The mean age of presentation was 7.82 ± 5.03 years. Among
these 57 % were male and 43 % were female. 44 cases
(40.4%) were dermoid. Other tumors were conjunctival nevus
(11%), capillary hemangioma (9%), neurofibromas (7%),
SIOP ABSTRACTS
S286 of S518
rhabdomyosarcoma(5.5%), inclusion cyst (4.5%), lymphangioma (3.6%), pyogenic granuloma(3.6%), sebaceous cyst
(2.7%), basal cell carcinoma(1.8%), pilomatrixoma (1.8%)
with 1 case each (0.9%) of neuroblastoma, reactive follicular lymphoma, squamous cell carcinoma, apocrine cyst,
inflammatory pseudotumor, lymphoblastic lymphoma, follicular conjunctival hyperplasia, chalazion.
Conclusions: In paediatric patients who were operated for
orbital and periorbital tumor at our centre, dermoid was found
to be the most common tumor requiring surgical intervention.
P-265 Dermoids in Paediatric Orbit- A
Retrospective Case Series
R. Meel1 , A. Shashni1 , N. Pushker1 , S. Modaboyina1 , N. Gupta1 , S.
Sen2 , S. Kashyap2 , M.S. Bajaj1
1 All
India Institute of Medical Sciences- New Delhi, ophthalmology, Ansari
Nagar- New Delhi, India; 2 All India Institute of Medical Sciences- New
Delhi, ocular pathology, Ansari Nagar- New Delhi, India
Background/Objectives: To study the clinical and radiological features of ocular and orbital dermoid in paediatric age
group
Design/Methods: A retrospective case series analysing the
clinical and radiological features of ocular and orbital dermoid in patients less than 16 years of age who were operated
at our centre were included in this study
Results: Total 33 patient were included in this study. The
mean age of the patient was 6.71 ± 5.53 years. Of all the
patients 70 % were male and 30% were female. 51.5% (17/33)
cases had limbal dermoid, 24.2% (8/33) cases had an internal angular dermoid (located at frontonasal suture line), 15%
(5/33) cases had an external angular dermoid (located at frontozygomatic suture line), 9% (3/33) cases had an epibulbar
dermoid (lipodermoid). 9% (3/33) cases of limbal dermoid
were bilateral. 24.2% (8/33) cases were associated with Goldenhar syndrome. Majority of the cases showed cystic lesion
with fat density on imaging (Ultrasound biomicroscopy and
Computed tomography). None of the patients had an intracranial extension
Conclusions: Dermoid is the most common benign tumor
of paediatric eye and orbit and may present as ocular surface mass or periocular tumor. Most cases can be successfully
managed with surgical excision.
P-266 Pediatric Testicular Tumors in Poland. A
Report from the Polish Pediatric Solid Tumors
Group (2008-2016)
J. Stefanowicz1 , M. Jezierska2 , E. Adamkiewicz-Drożynska2 , K.
Połczyńska2 , E. Iżycka-Świeszewska3 , M. Rąpała4 , K. Bilska5 , L.
Chełmecka-Wiktorczyk6 , R. Dębski7 , B. Dembowska-Bagińska8 ,
G. Karolczyk9 , I. Karpińska-Derda10 , B. Kazanowska11 , E.
Leszczyńska12 , M. Matysiak13 , A. Mizia-Malarz14 , J.
Nurzyńska-Flak15 , G. Sobol-Milejska16 , J. Peregud-Pogorzelski17 ,
K. Wachowiak-Szajdak18
1 Gdansk
Medical University, Department of Pediatrics- Hematology and
Oncology, Gdańsk, Poland; 2 Medical University of Gdansk, Department of
Paediatrics- Haematology and Oncology, Gdańsk, Poland; 3 Medical
University of Gdansk, Department of Pathology and Neuropathology,
Gdańsk, Poland; 4 Marciniak Hospital, Department of Pediatric Surgery,
Wrocław, Poland; 5 Institute of Mother and Child, Clinic of Oncological
Surgery of Children and Adolescents, Warsaw, Poland; 6 Children's
University Hospital, Department of Pediatric Hematology and Oncology-,
Cracow, Poland; 7 Nicolaus Copernicus University, Department of
Pediatrics- Hematology and Oncology, Bydgoszcz, Poland; 8 Children's
Memorial Health Institute, Department of Oncology, Warsaw, Poland;
9 Children Hospital, Division of Pediatric Hematology and Oncology,
Kielce, Poland; 10 Chorzow Pediatrics and Oncology Center, Department of
Pediatric Hematology and Oncology, Chorzów, Poland; 11 Wroclaw Medical
University-, Department and Clinic of Pediatric Oncology- Hematology and
Bone Marrow Transplantation, Wroclaw, Poland; 12 Medical University of
Bialystok, Department of Pediatric Oncology and Hematology, Bialystok,
Poland; 13 Medical University, Department of Pediatric Hematology and
Oncology, Warsaw, Poland; 14 Upper Silesia Children's Care Health
Centre- Medical University of Silesia, Department of Pediatric OncologyHaematology and Chemotherapy, Katowice, Poland; 15 Medical University
of Lublin-, Department of Pediatric Oncology and Hematology, Lublin,
Poland; 16 Medical University of Silesia, Department of Pediatric OncologyHematology and Chemotherapy, Katowice, Poland; 17 Pomeranian Medical
University in Szczecin, Department of Oncology and Hematology-,
Szczecin, Poland; 18 Medical University of Poznań, Department of Pediatric
Oncology- Hematology and Transplantology-, Poznań, Poland
Background/Objectives: The aim of the study was to evaluate the results of the treatment children and adolescents with
testicular tumors in Poland.
Design/Methods: A statistical analysis was performed on the
clinical data and the results of treatment of patients with testicular tumors reported to the database of extracranial germ
cell tumors of the Polish Pediatric Solid Tumours Group in
the years 2008-2016.
Results: The study included 138 patients aged 0 to 18 years
old who were treated according to TGM 95 protocol. The
mean age of respondents was 13.8 years, the median 16.3. For
the whole group, 5YOS was 95.6±2.2%, 5YEFS 88.1±3.3%.
Children over 10 yr formed the majority (84%), while 16%
were patients ≤10 yr. The results of treatment were comparable in both age groups (5-year OS in the group of children ≤10
yr. 100% vs. children >10 yr. 95.9±2.4%, p=0.419, 5-year
EFS 88.2±7.8% vs. 89.1±3.5%, p=0.794). Most of these were
secretory tumors (84%). It was found that the results of treatment did not differ in the groups of non-secretory and secretory tumors (5YOS 100% vs. 94.8±2.6%, p=0.461, 5YEFS
83.3±10.8% vs. 88.03±3.6%, p=0.54). The mean AFP concentration was 2670.7 ±4966, a median 792, range 11.0 – 30
000, IU/ml. The other prognostic factors were analysed: histological structure - mixed tumors 70%, yolk sack tumor 8%,
embryonal carcinoma 5%, other 17%; the stage of disease:
5YOS for stages I, II, III - 100%, for stage IV – 84.7±7.2%,
p=0.0173, and the risk group: in the high risk group 5YOS
was 90±4.8%, in the standard risk group 100%, p=0.0234.
SIOP ABSTRACTS
Conclusions: The results of treatment of patients in the developmental age with testicular tumors in Poland are very good.
The most significant prognostic factors are the stage and the
risk group.
SOLID NON B R A I N T U MO U R S RARE TUMOURS
P-267 Multiple Mutations in Genes Associated
with Colon Carcinoma: Analysis of Whole Exome
Sequencing and Array Comparative Genome
Hybridization (ACGH) Data in 15-Year-Old Patient
S. Cardellicchio1 , C. Cecchi1 , P. Scalini1 , S. Giglio1 , A. Tamburini1
1 Meyer
Children's Hospital, Oncology/Hematology Unit, Firenze, Italy
Background/Objectives: Colon carcinoma is a rare disease
in the pediatric population. A 15-year-old male, without a
strong family history of cancer, presented with metastatic
colon-adenocarcinoma, medium grade of differentiation,
methylation of MGMT gene, amplification of HER2 and MET
without ROS1, ALK, TRKA, BRAF genes’ rearrangements.
He died in 16 months after five treatment lines. Whole exome
sequencing was employed to identify single-nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient's and parent's germline.
Design/Methods: DNA was extracted from the patient's and
parent's blood. DNA libraries were constructed and sequenced
on Illumina HiSeq1000. aCGH was performed.
Results: Whole exome sequencing highlighted: in exon 1 of
BCL2A1 gene a variant inherited from both parents (c.245G>
A); in exon 33 of POLE gene a variant (c4187A> G) inherited
from his father and in exon 19 a variant (c.2083T > A) inherited from the mother; in exon 22 of the ATM gene a variant
(c3161C> G) inherited from both parents.
S287 of S518
The POLE gene variants identified in our patient, may correlate with an early onset and a more aggressive course, instead
it is hard to speculate on the role of the deletions found in
MARCH-1 and AUTS2 genes in absence of protein expression studies.
P-268 Long-Term Survivorship for Children and
Adolescents With HIV-Related Kaposi Sarcoma in
Lilongwe, Malawi
W. Kamiyango1 , J. Villiera1 , J. Kamwagha1 , P. Mehta2 , M.
Scheurer2 , P. Kazembe1 , N. El-Mallawany2
1 Baylor
College of Medicine Children's Foundation Malawi, Pediatrics,
Lilongwe, Malawi; 2 Texas Children's Hospital, Pediatrics, Houston, USA
Background/Objectives: Kaposi sarcoma (KS) is among the
most common childhood cancers in sub-Saharan Africa and
continues to occur at high numbers despite the increased availability of antiretroviral therapy (ART). Although one-two
year survival estimates for pediatric KS have been reported
throughout the region, longer-term outcomes have not been
described.
Design/Methods: We retrospectively reviewed the pediatric
KS database of HIV-infected children and adolescents diagnosed with KS at a pediatric HIV referral center in Lilongwe,
Malawi. Long-term survivorship was determined in patients
diagnosed between 2006-2013 that were still alive at last
follow-up. All but two survivors were treated with chemotherapy plus ART according to Malawian national guidelines;
the two exceptions received ART alone. Typically, patients
received 8 cycles of bleomycin and vincristine over 6 months.
Evaluating characteristics of survivors only, demographics,
duration of survival, time off of chemotherapy, and need for
2nd line chemotherapy or ART were described.
Conclusions: The mutation identified in homozygosity of
BCL2-A1 gene, involved in embryogenesis and tumorigenesis processes, is shown in Human Gene Mutation Database
as associated with an increased risk of colorectal carcinoma.
Results: There were 50 (31%) long-term survivors among 161
HIV-related cases of pediatric KS. The median age at time
of KS diagnosis among survivors was 8 years (interquartile
range [IQR] 4.6-13); there were 22 females (44%). Median
overall survival was 4.8 years (IQR 3.6-6.8), with the longest
survivor alive 10.5 years from date of KS diagnosis. Fourteen (28%) patients experienced relapse requiring additional
doses of chemotherapy and remained alive at time of data collection. The median time off of chemotherapy was 3.5 years
(IQR 2.1-5.3) with the longest duration reaching 10 years. In
total, 28 (56%) patients were still on 1st line ART, with 22
(44%) receiving 2nd line ART.
The variants of the POLE and ATM genes, expressed in heterozygous, present an uncertain pathogenic role; they are not
reported in the literature but in ClinVar (archive which shows
the correlations between clinically significant variations and
phenotypes) are related with increased susceptibility to colon
cancer.
Conclusions: Long-term survival is possible for HIVinfected children and adolescents with KS in Malawi despite
myriad limitations. The majority of patients were able to
achieve long-term disease control with up-front chemotherapy and life-long ART, with over half of children still on 1st
line ART regimens.
Using array CGH analysis we found: an interstitial deletion
of 4q32.3 MARCH-1 gene, inherited from the mother and an
interstitial deletion of 7q11.22 AUTS2 gene inherited from his
father.
SIOP ABSTRACTS
S288 of S518
P-269 Potential for Improved Survival Outcomes
after Treatment with Intensified Chemotherapy and
Antiretroviral Therapy in Children with Pulmonary
Kaposi Sarcoma Presenting with Severe Pleural
Effusions
J. Villiera1 , W. Kamiyango1 , P. Mehta2 , P. Kazembe1 , N.
El-Mallawany2
1 Baylor
College of Medicine Children's Foundation Malawi, Pediatrics,
Lilongwe, Malawi; 2 Texas Children's Hospital, Pediatrics, Houston, USA
Background/Objectives: In the initial eight years of the pediatric Kaposi sarcoma (KS) program in Lilongwe, Malawi,
there has never been a survivor of pulmonary KS (n>10)
after up-front treatment with bleomycin and vincristine. With
all but two patients dying within 6 months, and the longest
duration of survival being 9 months, a programmatic shift
was implemented to initiate patients with pulmonary KS on a
chemotherapy regimen intensified by adding doxorubicin. We
report a case series of pulmonary KS patients with improved
survival.
Design/Methods: We evaluated a series of HIV-infected
children presenting with pulmonary KS manifested by large
serosanguineous pleural effusions in addition to characteristic hyperpigmented KS skin lesions or woody edema. Patients
were treated with an intensified chemotherapy regimen of
doxorubicin, bleomycin, and vincristine (8 cycles total, given
every 3 weeks) plus protease-inhibitor based antiretroviral
therapy. Clinical characteristics and treatment response were
described.
Results: There were three patients (one female) with pulmonary KS that achieved disease control and prolonged survival. Patient ages at presentation were 7, 8, and 14 years.
All presented with large serosanguineous pleural effusions
and severe respiratory distress requiring supplemental oxygen
via nasal cannula (for duration ranging 2-5 weeks) and multiple thoracentesis procedures (range 2-15 taps), but ultimately
achieved resolution of hypoxia and effusions. One patient had
concurrent skin and lymph node KS lesions and the other two
both had characteristic woody edema. All had pleural fluid
cytology evaluation performed; as anticipated, none yielded
malignant KS cells. All three children are alive in partial
remission with stable disease achieving overall survival duration of 7, 10, and 22 months, off of chemotherapy for respective durations of 1, 4, and 16 months.
Conclusions: Improved survival may be achievable for pediatric pulmonary KS patients receiving intensified chemotherapy and antiretroviral therapy. Longer follow-up is required to
determine definitive long-term outcomes.
P-270 Secondary Malignancies After Chilhood
Cancers: A Single Center Experience
F. Akici1 , G. Aydogan1 , Z. Salcioglu1 , G. Ersoy1 , A. Akçay2 , D.
Tugcu3 , S. Sander4 , E. Darendeliler5
1 Kanuni
Sultan Suleyman Training and Research Hospital -, Pediatric
Hematology Oncology, Istanbul, Turkey; 2 Acibadem University Atakent
Hospital, Department of Pediatric Bone Marrow Transplantation, Istanbul,
Turkey; 3 Istanbul University School of Medicine, Pediatric Hematology
Oncology, Istanbul, Turkey; 4 Kanuni Sultan Suleyman Training and
Research Hospital -, Pediatric Surgery, Istanbul, Turkey; 5 Istanbul
University School of Medicine, Radiation Oncology, Istanbul, Turkey
Background/Objectives: The occurrence of second malignancies (SM) is an important late event following the treatment of childhood cancers. It is 3 folds greater thn the normal
population, the incidence is about 3% in the first 20 years after
pirmary diagnosis.
Design/Methods: The incidence of SMs is studied in a population of 1678 patients with minumum 3 years follow up after
cessation of chemoradiotherapy or radiotherapy for childhood
cancers between June 1990 and January 2017. The study
included the patients treated in inpatient and outpatient clinics
of Kanuni Sultan Süleyman Research and Training Hospital.
Results: SMs were found in 6 (0,5%) patients. The mean
time for the occurence of SM was 8 years (3-14 years). Case
1: A girl 9 years old with diagnosis of Nodular Sclerosing
Hodgkin Lymphoma stage 3 treated with both radiotherapy
and chemotherapy developed thyroid papillary carcinoma 7
years 3months after primary diagnosis. Case 2: A boy 8 years
old diagnosed as non- Hodgkin Lymhoma developed hepatocellular carcinoma 10 years after treatment. Case 3: B cell
non-Hodgkin lymphoma patient 3 years old was diagnosed as
epidermoid carcinoma of external ear 12 years after. Case 4: 8
years old male patient developed adrenal cortex carcinoma 7
years after treated successfully for Burkitt Lymphoma. Case 5:
A female patient was diagnosed as breast carcinoma after 14
years of acute lymphoblastic leukemia (ALL) treatment. Case
6: Mucoepidermoid Carcinoma of parotid gland was seen 3
years after completition of ALL chemotherapy at age of 8.
Conclusions: All of the SM s were solid neoplasms. One
patient has thyroid carcinoma which could depend on thyroid irradiation, the alkalyting agents could be the cause
of the other neoplasms. Continued follow-up is mandatory
after treatment for childhood cancers. Since the prognosis of
most SM is unfavorable, early recognition and prevention are
important.
P-271 Clinical Characterization of Malignant
Rhabdoid Tumors – The Sick Kids Experience
A. Fonseca1 , A. Gupta1 , R. Grant1 , A. Huang1
1 The
Hospital for Sick Children, Paediatric Haematology Oncology,
Toronto, Canada
Background/Objectives: Rhabdoid Tumors (RTs) are rare
cancers defined by bi-allelic loss of function alterations
SIOP ABSTRACTS
of SMARCB1, which encodes a critical component of the
SWI/SNF chromatin-remodeling complex. They can arise in
the brain where they are called Atypical Teratoid/Rhabdoid
Tumors (ATRTs) and in various extra-cranial locations where
they are called Malignant Rhabdoid Tumors (MRTs). Both
ATRTs and MRTs are frequently lethal diseases for which best
therapeutic approaches remains to be determined. Herein, we
describe the Sick Kids experience.
Design/Methods: Patients diagnosed with MRT at the hospital for Sick Children between 1996-2016 were identified and
charts reviewed. Demographic data, treatment details and survival information was collected.
S289 of S518
tion in Brazil. The prognostic, surgical and histopathologic
aspects were analyzed.
Design/Methods: From 1987 to 2017, a total of twenty five
patients with ages ranging from 10 months to 16 years old with
pathologically confirmed diagnosis of paratesticular RMS
treated at our institution.
Results: The median age at presentation was 12 years (range
10 months – 16 years). Sixteen patients were ≥10 years old
(76%). Eighteen patients had initial surgery at non-oncologic
hospital and seven needed a second surgery. One third of
patients who underwent initial surgery outside our institution required second surgery (three hemiscrotectomy and four
lymphadenectomy). Partial cystectomy was performed in one
patient due to vesical metastasis. The histopathological classification of RMS was: embryonal in 19, alveolar in four and not
classified RMS in two. The patients were treated following the
International Rhabdomyosarcoma Study Group from 1987 to
2008 (88%) and European Pediatric Soft Sarcoma Group protocol since 2009 (12%). All patients received chemotherapy
and only seven received radiotherapy. The 5-year overall survival (OS) was 76%, with follow up from 6 months to 20 years
(median 4 years). The mortality among patients ≥10 years of
age was 37,5%, while all patients < 10 years are alive.
Results: We identified twenty-five patients diagnosed with
MRTs between 1996 and 2016. Median age at diagnosis was
3.2 years (1 month -16.6 years), 64%(n=14) were female
and 36%(n=8) were male. Thirty-two percent of the tumors
were intra-abdominal (n=8), 24% (n=6) para-spinal, 16% in
extremities (n=4), 8% nasopharyngeal (n=2), 8% multifocal
(n=2), 4% Skull base (n=1), 4%Chest wall (n=1) and 4% neck
(n=1). Most of the patients, 56% presented with advanced disease (stage III and IV), 8% (n=2) of the patients presented
with multifocal disease and correspond to patients diagnosed
with rhabdoid tumor predisposition syndrome. The median
time to progression was 6 months (ranging from 1 month to 25
months). Most of the patients (n=20) were treated with multimodal therapy including chemotherapy in 18 patients, radiation therapy in 11 patients and surgery in 14 patients. Only
20% of patients are alive and free of disease, 64% of patients
succumbed to the disease.
Conclusions: The 5-year OS was worse in patients ≥10 years
old, confirming current data. The patients who underwent initial surgery at non-oncologic hospital needed second surgery
more frequently, including hemiscrotectomy. Continued effort
is required to educate providers on appropriate workup of
scrotal masses to avoid scrotal violation.
Conclusions: MRTs continues to be a disease with poor outcomes. Young patients and patients presenting with metastatic
disease have a dismal prognosis. Insights in the biology of this
entity are urgently needed to guide therapeutic approaches and
the development of clinical trials.
P-273 Our Experience with Primary Total
Thyroidectomy and Lymph Node Biopsy in
Papillary Thyroid Carcinoma
Z. Jenovari1 , P. Hauser2 , M. Garami2 , E. Varga2 , Z. Karady2 , A.
Sallai2 , E. Hosszu2 , T. Budi2 , T. Prokopp2
P-272 Paratestitular Rhabdomyosarcoma in
Children: Surgical Analysis
R. Vianna1 , E. Lopes1 , V. Nascimento1 , S. Coelho1 , F.N.
Gutierrez1 , J. Oliveira1 , F. Lima2 , S. Ferman3 , A. Ikeda3 , P. Faria4
1 Instituto
Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil;
Nacional de Câncer, Pediatric Research Nurse, Rio de Janeiro,
Brazil; 3 Instituto Nacional de Câncer, Pediatric Oncology, Rio de Janeiro,
Brazil; 4 Instituto Nacional de Câncer, Pathology, Rio de Janeiro, Brazil
2 Instituto
Background/Objectives: In children, about 7% of all cases
of genitourinary rhabdomyosarcoma are paratesticular in origin. Prognosis for paratesticular rhabdomyosarcoma (RMS) is
favorable; approximately 60% to 80% of patients have localized disease at diagnosis. The purpose of this study was to
report a retrospective review of paratesticular RMS in children
treated at the Pediatric Oncology Department at one institu-
1 Semmelweis
University, 2nd. Department of Pediatrics, Budapest,
Hungary; 2 Semmelweis University, 2nd Department of Pediatrics,
Budapest, Hungary
Background/Objectives: There are concerns about the optimal primer surgery in case of papillary thyroid carcinoma.
From 2006 we moved on the total thyroidectomy and regional
lymph node biopsy as the first attempted procedures in all
cases, to provide opportunity for postoperative iodine isotope
therapy. There are few evidences about the results of this procedure.
Design/Methods: We retrospectively analyzed the data of the
children underwent primary total thyroidectomy in our unit
from 2006-2016.
Results: 29 patients were found, the mean age 15.3 year
(7-20), M/F ratio 8/21. All had papillary thyroid carcinoma
SIOP ABSTRACTS
S290 of S518
proven by FNAB and histology postoperatively. US and
MRI were done for all. There was not pulmonary metastasis detected. 12 patients had regional lymph node enlargement on radiology. 13 patients underwent lymph node biopsy
of the intraoperatively suspected nodules, central neck lymph
node dissection done in 5 cases. Lateral neck dissection never
attempted as primer procedure. The recurrent laryngeal nerve
and the parathyroid glands (at least 1) were identified and preserved.
None of the patients had recurrent nerve lesion, or permanent
hypocalcemia, or residual thyroid tissue.
13 out of 29 patients received postoperative iodine isotope
therapy. Only 5 out of the 13 had pathologic lymph node
enlargement postoperatively (>1cm, positive scan or MRI). 4
out of this 5 patients had isotope treatment twice, one patient
3 times. Finally 4 out of 5 underwent extended regional lymph
node dissection.
The average follow up was 59 months (6-131 months).
Conclusions: The primary total thyroidectomy in papillary
thyroid carcinoma is effective and safe procedure, the complications, (recurrent nerve injury or hypocalcemia) can be
minimised by experienced surgeon. The postoperative iodine
isotope therapy seems less effective for pathologic enlarged
lymph nodes, in this cases the primer regional lymph node
dissection of the affected region should be prior to the isotope
therapy.
P-274 Immunotherapy of Metastatic Pediatric
Melanoma with Checkpoint Inhibitors
E. Kabickova1 , M. Kyncl2 , R. Kodet3 , M. Kalinova3 , L. Krskova3 ,
O. Belohlavek4 , D. Sumerauer1
1 2nd
Faculty of Medicine- Charles University and University Hospital
Motol, Pediatric Hematology and Oncology, Prague 5, Czech Republic;
2 2nd Faculty of Medicine- Charles University and University Hospital
Motol, radiology, Prague 5, Czech Republic; 3 2nd Faculty of MedicineCharles University and University Hospital Motol, Pathology and
Molecular Medicine, Prague 5, Czech Republic; 4 Na Homolce Hospital,
PET Centre, Prague 5, Czech Republic
Background/Objectives: Metastatic melanoma in children is
rare, fatal disease. The introduction of immune checkpoint
inhibitor antibodies has dramatically improved the clinical
outcomes for adult patients with advanced melanoma. Data
on checkpoint inhibitors treatment in children with melanoma
is limited.
Design/Methods: We present two cases of primary metastatic
melanoma in uncommon locations in children treated with
immune checkpoint inhibitors. Both patients were diagnosed
and treated at our centre within the last 2 years.
Results: The first patient was a 16-year-old girl with
metastatic melanoma of unknown primary site (MUP) with
multifocal visceral infiltrates. The second patient was an 8-
year-old boy with primary leptomeningeal melanoma in neurocutaneous melanosis. In both BRAF mutations were absent.
Due to the significant melanoma dissemination urgent control of the disease was required. Both patients started with
chemotherapy CVD (cisplatin, vinblastine, dacarbazine). The
girl with MUP reached partial response (PR) after 2 cycles of
CVD and continued with ipilimumab monotherapy (3 mg/kg
every 3 weeks for 4 doses) with prolonged stable disease
(SD). Five weeks after the last ipilimumab administration disease progression (DP) was documented. After further 4 CVD
cycles second PR was observed. One month after the last CVD
course pembrolizumab monotherapy (2 mg/kg) started. The
girl expired from rapidly progressive disease within 37 days
of the initial dose of pembrolizumab.
The boy with CNS melanoma had only SD after 3 courses
of CVD. That's why we decided to continue with palliative craniospinal irradiation (36 Gy). Monotherapy with pembrolizumab (2 mg/kg every 3 weeks) was started during radiotherapy. No objective response was observed after radiotherapy and during immunotherapy. He died 23 days after the 3rd
dose of pembrolizumab from CNS melanoma progression.
Conclusions: Immunotherapy with checkpoint inhibitors in
our patients was well tolerated, but did not change their disease course.
P-275 Inflammatory Myofibroblastic Tumor in
Children: Morphological and Molecular
Characterization
A. Suleymanova1 , E. Imyanitov2 , V. Roschin3 , T. Shamanskaya1 , Y.
Olshanskaya4 , A. Kazakova4 , S. Talypov5 , D. Konovalov3 , D.
Kachanov1 , N. Mitiushkina2 , S. Varfolomeeva1
1 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Clinical Oncology, Moscow, Russia; 2 N.N. Petrov Institute of
Oncology, Laboratory of Molecular Oncology, Saint-Petersburg, Russia;
3 Federal Research Center of Pediatric Hematology - Oncology Immunology, Pathology, Moscow, Russia; 4 Federal Research Center of
Pediatric Hematology - Oncology - Immunology, Cytogenetics, Moscow,
Russia; 5 Federal Research Center of Pediatric Hematology - Oncology Immunology, Surgery, Moscow, Russia
Background/Objectives: Inflammatory myofibroblastic
tumor (IMT) is a rare type of childhood malignancies with
intermediate biological behavior. The aim of the study was
to analyze clinical, morphological and molecular features of
IMT in a cohort of patients treated in Russian federal center.
Design/Methods: Nine patients with IMT during the period
from 01.2012 to 12.2016 were included in the analyses. The
diagnosis was established by histological examination. ALK
immunostaining was done with two different antibodies: ALK
(ultra) and ALK (D5F3). Rearrangement of the ALK gene was
detected by FISH. ALK, ROS1, PDGFRB fusion genes were
analyzed by PCR.
SIOP ABSTRACTS
Results: Median age at diagnosis was 61.9 months (range
5.9 - 102.5 months). In most cases the tumor was located
in the abdominal cavity - 4/9 (44.4%). The histological
type of the tumor was represented by a compact/spindle
cell variant in 5/9 (55.5%), myxoid/vascular in 2/9 (22.2%)
and hypocellular fibrous in 2/9 (22.2%). Expression of
ALK protein was observed in 6/9 (66.6%) cases, in 5/6
cases expression was detected by two antibodies. In 1
case, the expression of ALK antibody (D5F3) was positive, while the reaction with ALK antibody (ultra) was negative. In ALK-positive tumors the following translocations
were detected: TPM4ex7/ALKex20 in 2/6 (33.3%) cases,
TPM3ex6/ALKex20 in 1/6 (16.6%), CLTCex31/ALKex20 in
1/6 (16.6%). In 1/4 (25%) of ALK-negative tumors translocation TFGex4/ROS1ex35 was detected. In 4/9 (44.4%) tumors
translocations were not detected, of which 2/4 (50%) were
cases with positive expression of ALK protein. All patients
are alive. The median follow up was 24.3 months (range 15.234.6 months).
Conclusions: This work allowed to conduct an in-depth study
of the clinical, morphological and molecular-genetic characteristics of IMT in a cohort of children in Russia. It was shown
that in some cases expression of ALK protein does not correlate with the presence of gene rearrangements.
P-276 Childhood Lung Adenocarcinoma Treated
with Crizotinib
C. Akyüz1 , N. Kalkan2 , N. Kurucu1 , M. Haliloğlu3 , D. Orhan4 , A.
Üner5
1 Hacettepe
Univercity Oncology İnstitude, Pediatric Oncology, Ankara,
Turkey; 2 Hacettepe Univercity Medical Faculty, Pediatric Oncology,
Ankara, Turkey; 3 Hacettepe Univercity Medical Faculty, Radiology,
Ankara, Turkey; 4 Hacettepe Univercity Medical Faculty, Pediatric
Pathology, Ankara, Turkey; 5 Hacettepe Univercity Medical Faculty,
Pathology, Ankara, Turkey
Background/Objectives: Although lung cancer is the most
common invasive type of cancer worldwide, it is a rare in
children. Goal directed treatment besides chemotherapy has
become popular in the last decade. Crizotinib is a tyrosine
kinase inhibitor and has been shown to affect survival in
NSCLC patients with anaplastic lymphoma kinase (ALK) or
c-ros oncogene 1 (ROS-1) translocation.
Design/Methods: Here an adolescent case of adenocarcinoma with crizotinib treatment was reported.
Results: The patient had complaints of night fever, lymph
node enlargement and weight loss for six months of duration.
Chemotherapy was started after epithelial neoplasm thymoma
type B3 was diagnosed from supraclavicular lymph node
metastasis and biopsy from lung nodules. The patient was
referred to our hospital due to no- response to the treatment.
Histopathologic evaluation of the lymph node biopsy in our
S291 of S518
hospital revealed lung adenocarcinoma metastasis. A mass
of 4x5 cm in the right lung middle lobe, bilateral parenchymal, subpleural nodular lesions, focal areas of consolidation and signs of lymphangitis carcinomatosis was detected.
Two courses of docetaxel and gemcitabine was administered initially and crizotinib of 250 mg/dose bid started since
immunohistochemistry for ROS1 was positive. First assessment after the treatment showed excellent clinical and radiologic response. Although primary mass lesion regressed after
7 ½ month of crizotinib treatment, 36 Gy of cranial radiotherapy was administered due to brain metastasis. Subsequently,
cisplatin and pemetrexed treatments were started.
Conclusions: Lung cancer is a rare tumor of childhood and
constitutes 0.2% of all childhood cancers. This illustrative
case reminds adenocarcinoma when there is lack of clinical
and pathological correlation and emphasizes the assessment
for monoclonal antibody therapy by checking the presence of
oncogenes as ROS-1 and ALK. Although treatment is challenging in patients presented with advanced stage disease, currently survival rates were significantly improved with such
goal directed therapies.
P-277 Pediatric Nasopharyngeal Carcinoma: A
Single Institute Experience from Developing
Country
P. Khullar1 , A. Thakwani1 , K. Chufal1 , K. Medi1
1 Batra
Hospital And Medical Research Centre, Radiation Oncology, New
Delhi, India
Background/Objectives: Pediatric nasopharyngeal carcinomas (NPCs) accounts < 1% of all pediatric tumors. There is
limited data on clinical features, treatment results, prognostic factors, outcome and late toxicities of pediatric NPC from
India
Design/Methods: This analysis was carried out in consecutive 47 patients of pediatric NPCs, who were registered at
our center in between 1st May 2006 to 30th April 2016 ( 10
years). Patients’ records were retrospective reviewed and data
obtained from case records files. Patients were treated with
Neoadjuvant chemoradiotherapy (CTRT) with cisplatin and
followed by cisplatin and 5-fluorouracil (5-FU) or concurrent
CTRT with cisplatin.
Results: The median age was 15 years (range 10-18 years) and
male:female ratio was 1.5:1. The median duration of symptoms was 6 months (range 0.5-2 years). AJCC stage distribution was stage II- 15%, stage III- 40%, and stage IV- 45%.
Distant metastasis at presentation was seen in 5 patients. Complete response was seen in 65% and overall response was
observed in 90% of cases. With a median follow-up time
of 36 months, the 3-year overall survival (OS) rate, localregional control (LRC) rate and distant metastasis-free survival (DMFS) rate were 42%, 56% and 38% respectively. In
SIOP ABSTRACTS
S292 of S518
multivariate analysis, T4 (p = 0.01) and stage IV (p = 0.001)
were the independent adverse prognostic factors for OS. Significant reduction in trismus and xerostomia were observed in
patients treated by intense modulated radiotherapy ( IMRT).
Conclusions: Most of patients with pediatric NPC present
with advanced stage disease at our center. No difference in
response rate and outcomes were seen with the two schedules
of CTRT ( Neoadjuvant vs concurrent). Local control could be
achieved in majority of patients; however, distant metastasis
was the most common reason for relapse. Reducing late toxicities with IMRT might be the future direction for the management of pediatric NPC
P-278 Solid Pseudopapillary Tumor of the
Pancreas in a Patient with a Diagnosis of Tuberous
Sclerosis Complex
S.S. Kilic1 , M. Alkan1 , O. Ozden1
1 Cukurova
University Faculty Of Medicine, Pediatric Surgery, Adana,
Turkey
Background/Objectives: Tuberous Sclerosis Complex
(TSC) is a genetic disease that effects to cell development.
Epilepsy, mental retardation, development of hamartomas in
the different part of body could sign of the TSC. Renal, brain
basis tumors and neuroendocrine tumor of the pancreas could
develope in TSC patients. Solid Pseudopapillary Tumor of
The Pancrease (SPTP) is the low grade malign tumor of the
adolescent age.
Design/Methods: Cukurova University Medical Faculty Hospital record of a patient who was operated for pancreatic mass
investigated.
Results: In 2012, Abdominal Magnetic Resonance investigation has made to a 15 years old male TSC patient and a nodulary lesion, measuring 2,5 cm, has found in the tail of pancreas. Nodulary lesion was supposed as hamartoma of pancreas that developed secondary to TSC. Patient was followed
up. In 2016, a hypoechoic and sharp edges lesion, measuring 4 cm, was found with Ultrasound (US) investigation in
the tail of pancreas. Lesion has solid feature was found by
Computed Tomography. Cause of increase in lesion measurements, operation decision was maked. A solid lesion, measuring 5x5x4 cm, in the tail of pancreas has found during operation. Tail of pancreas was detached from side. Splenic artery
and vein was tried to detach from lesion, but it was not able.
Than, Distal pancreatectomy including lesion was made by
using surgical stapler with containing splenic artery and vein.
Spleen appeared normal and preserved. Pathology report of
lesion was SPTP with tumor free surgical board. One month
later an US was made and blood flow of spleen was found normal. There was not residual tumor tissue. Patient is following
with no treatment by pediatric oncology.
Conclusions: Pathologies of pancreas could develop in TSC
patients but SPTP is seen rarely. Lesions in the TSC patients
which followed as hamartoma in pancreas should remember
that it could be SPTP.
P-279 Head and Neck Hemangiomas of
Childhood: A Single Center Experience
D. Kizmazoglu1 , D. Ince1 , N. Agrali2 , E. Erkoc3 , M. Erdem1 , T.
Erdag3 , K. Mutafoglu1 , and N.Olgun1
1 Dokuz
Eylul University Institute of Oncology, Pediatric Oncology, İZMİR,
Turkey; 2 Dokuz Eylul University Faculty of Medicine, Pediatrics, İZMİR,
Turkey; 3 Dokuz Eylul University Faculty of Medicine, Dept. of
Otorhinolaryngology, İZMİR, Turkey
Background/Objectives: Aim of this study is to analize clinical characteristics and treatment responses of our patients
with head/neck hemangiomas.
Design/Methods: Medical records of 121 patients with
head/neck hemangiomas between 2006 to 2016 were evaluated retrospectively.
Results: The median age of diagnosis was 12mos (10days16yrs), F/M:2.0. The localization of lesions were only at head
and neck in 85(70.2%) patients, remaining patients have also
hemangiomas on other parts of body.Localization of hemangiomas were as follows; periorbital 35.5% (n=43), cheek
19.8%(n=24), cervical 14% (n=17), scalp 13.2% (n=16), periauricular 9.9% (n=12), mouth and lip 9.9% (n=12) forehead 8.2% (n=10), subglottic 7.4% (n=9), nasal 5%(n=6),
parotis 3.3% (n=4). Sixtysix patients (54.5%) have been followed up without medical treatment.Treatment indications
were local complications (haemorrhage, ulceration,infection)
(6.7%), life threating organ dysfunction (73.0%) and cosmetic (20.3%). The median follow-up period was 8 mos (0
mos-7yrs). Remaining 55 patients required medical treatment (propranolol in 45, corticosteroids in two cases, both of
them in 8 cases). Chemotherapeutics (vincristine, vinblastine
and cyclophosphamide) were used in one case. Majority of
our cases received propranolol, and there was no observed
propranolol related side effects. The median duration of
propranolol treatment was 10 mos (10 days – 35 mos).Twentyone patients have still receiving propranolol.Treatment cessation was done in 32 cases.Complete regression was achieved
in 13 patients,and partial regression was achieved in 19
cases with propranolol. The patients who had subglottic
hemangioma were the most problematic cases because of
respiratory and feeding difficulties.Two of them required
tracheostomy.Complete regression occured in all subglottic
hemangiomas with medical treatment.Ocular complications
(ambylopia, strabismus etc) occured in 15 patients with periorbital hemangioma despite medical treatment.
Conclusions: Although childhood hemangiomas can regress
spontaneously, head/neck hemangiomas are usually required
SIOP ABSTRACTS
medical treatment because the risk of ocular, feeding and respiratory complications. Novadays propranolol is a well tolerated, effective and safe drug option for treatment of childhood
hemangiomas.
P-280 Primary Peripheral Neuroectodermal
Tumor of Orbit- Case Series of a Rare Childhood
Malignancy
R. Meel1 , S. Kashyap2 , N. Pushker1 , S. Sen2 , M. Bajaj1 , S. Bakhshi3
1 All
India Institute of Medical Sciences, Dr Rajendra Prasad Centre for
Ophthalmic Sciences, New Delhi, India; 2 All India Institute of Medical
Sciences, Dept of Ocular Pathology- Dr Rajendra Prasad Centre for
Ophthalmic Sciences, New Delhi, India; 3 All India Institute of Medical
Sciences, Dept of Medical Oncology- Dr BRA IRCH, New Delhi, India
Background/Objectives: Peripheral primitive neuroectodermal tumor (pPNET) belongs to the Ewing sarcoma family of
tumors. Primary PNET constitutes 4% of all childhood soft
tissue tumors. Primary PNET of orbit is rare with only a handful of cases reported in literature.
Design/Methods: Retrospective review of clinical records,
imaging and histopathology of all primary orbital pPNET presenting in childhood that were treated at our center between
Jan 2004- Dec 2016 (13 years).
Results: Clinical, imaging and histopathology details of nine
pediatric patients with primary orbital pPNET were analyzed.
The median age of presentation was 6 years (age range 1.5 months – 13 years). One case presented with congenital
PNET of Orbit. 5/9(55.5%) were male and 4/9(44.4%) were
female children. Duration of symptoms ranged from 5 days – 8
months (median-1.75 months). The most common presenting
complaint was proptosis followed by eyelid swelling. Imaging
showed variable enhancing mass lesions with heterogeneous
attenuation in all, with calcific densities in 2 cases. Calcified
tumor matrix was seen as radiating spicules in one case. Bone
erosion and extra-orbital extension was seen in 8/9 (88.8%)
cases. Metastasis to foot was present in one case at presentation. Diagnosis was made on histopathological examination
of incision/ excision biopsy specimen in 7 cases, while 2 cases
were diagnosed on fine needle aspiration biopsy. All cases
showed positivity for MIC2 and S100 protein on immunohistochemistry, and were negative for PAS.
Conclusions: Primary PNET is a rare malignancy to occur in
pediatric orbit. Majority of the patients in our series presented
with large tumors that had extraorbital extension of disease at
the time of presentation.
P-281 Lipoblastoma and Lipoblastomatosis. 5
Years´ Experience in a Pediatric Institution
M.E. Nana1 , M. Garcia Lombardi1 , E. De Matteo2 , M. Medin2
S293 of S518
1 Hospital
de Niños R. Gutierrez, Oncology, Ciudad Autónoma de Buenos
Aire, Argentina; 2 Hospital de Niños Ricardo Gutierrez, Pathology, Buenos
Aires, Argentina
Background/Objectives: Lipoblastoma and lipoblastomatosis are rare benign mesenchymal tumors. They occur in
infancy and early childhood, generally in boys. The aim of
this study is to report clinical characteristics, diagnostic strategy, type of treatment and outcome of pediatric patients (p)
with lipoblastoma/lipoblastomatosis (LL). We will compare
our results with other published reports.
Design/Methods: Retrospective and descriptive study. We
reviewed the clinical reports of p with LL admitted at
the Oncology Unit of Hospital de Niños Ricardo Gutierrez
between January 2012 and January 2017.
Results: Six p with LL were admitted in 5 years. They represent 0.8% of all the p treated in this Unit. Boys 4/Girls2.
Age range: 5 - 24 months. Clinical presentation: fast growing and painless mass in all cases. Localization: paravertebral 3p, suprapubic 2p and gluteal 1p. Inicial diagnostic methods: ultrasound 5p, computed tomography 3p and magnetic
nuclear resonance 1p. Maximum tumor diameter range: 2 to
9 cm. In 4/6p a fine needle aspiration (FNA) was performed
with compatible cytology. Pathological diagnosis: lipoblastoma 5p and diffuse lipoblastomatosis 1p. Treatment: surgery
(complete resection all p and 1p without margins). Median
follow-up time: 20 months (R: 4 - 61 months). None p relapsed
and all remained alive.
Conclusions: LL represented a small percentage of all the
diagnosis in our Unit, All p were younger than 3 years and
most of them boys. We used ultrasound and FNA for inicial
diagnosis approach and biopsy for confirmation. Surgery was
the treatment strategy. No p relapsed. However, the followup time was short. Our results were similar to the published
reports. Although LL are rare tumors, they should be considered in infants and children with painless fast growing softtissue tumors.
P-282 Congenital Metastatic Ewing's Sarcoma /
Primitive Neuroectodermal Tumor Presenting as
“Blueberry Muffin”Cutaneous Lesions: A Case
Report
W.E. Oliveira Júnior1 , M.C. Angelini2 , G.T. Comes2 , D.R. Jozala2 ,
B.K. Takegawa2 , R.G. Marques2 , A.M. Rodrigues2 , R.C. Ribeiro1 ,
V. Kremer1 , P.L.T.A. Lourençao2 , E.V.P. Ortolan2
1 Barretos
Childrens Cancer Hospital, Pediatric Surgery Department,
Barretos, Brazil; 2 Botucatu Medical School, Surgery and Orthopedics
Department- Pediatric Surgery, Botucatu, Brazil
Background/Objectives: Ewing's Sarcoma/Primitive Neuroectodermal Tumors (EWS/PNET) are extremely rare in
newborns. Less than 20 newborns (28 days) with congenital
SIOP ABSTRACTS
S294 of S518
EWS/PNET of soft tissue have been reported in the English
literature. The prognosis generally is poor, and most of the
babies not survive more than 24 months of life.
describe the DICER1 mutation status and clinical characteristics of Chinese patients with PPB, which will add more evidence for further understanding of pathogenesis of PPB.
Design/Methods: To describe a 14-day-old newborn diagnosed with metastatic retroperitoneal EWS/PNET with
“blueberry-muffin”cutaneous lesions.
Design/Methods: Medical history and family history of 12
children with PPB were collected. Blood samples from children with PPB and their first degree relative were tested for
DICER1 mutations by Next-Gen sequencing. Whole genome
sequencing of peripheral blood of the proband, the proband's
parents and twin sister, and FFPE of the proband tumor tissue was performed. All participants’ parents signed a consent
form to genetic testing and medical history collection.
Results: A 14-day-old newborn female was admitted due
to multiple and progressive skin nodules, associated with
hemothorax and signs of central nervous system involvement.
She was a full-term cesarean neonate without a family history of genetic diseases. A physical examination revealed
multiple erythema-violaceous nodules, with firm constancy
characterized as “blueberry muffin” lesions, also were found
bilateral ocular proptosis and a posterior thoracic-abdominal
mass, hard, with poorly defined limits. Computed tomography (CT) detected a massive solid retroperitoneal mass,
measuring 6.2 cm x 5 cm, hypodense, with calcifications,
involving the Aorta at an angle higher than 180 degrees,
invading the superior mediastinum and left pleural cavity,
widening the posterior intercostal spaces to the left, encompassing the costal arches, extending to the posterior wall
invading left paravertebral musculature reaching the skin;
also hypodense solid nodules with contrast enhancement distributed in the liver, spleen, adrenal, and pancreas areas, compatible with hematogenous and lymphatic metastases. Since
the mass was unresectable, she was submitted to biopsy of
skin lesions and initiated empirical chemotherapy protocol
for Neuroblastoma. A pathologic examination found histological evidence of malignant, small round tumor cells. The
tumor cells were immunohistochemically positive for CD99
and CD56, compatible with Ewing's Sarcoma / Primitive Neuroectodermal Tumor. Given the aggressiveness of the disease,
two days after the diagnosis the newborn died.
Conclusions: Our report illustrates the extreme difficulties in managing a newborn with a congenital metastatic
EWS/PNET. Since these tumors are highly aggressive, prognosis is terrible, and treatment challenging.
Results: Twelve patients with pleuropulmonary blastoma (6
patients suffering from type II pleuropulmonary blastoma and
6 patients suffering from type III pleuropulmonary blastoma,
respectively) were evaluated for germline DICER1 mutations.
Seven patients were identified deleterious DICER1 mutation,
among which 6 mutations lead to premature protein truncation as a result of frameshift mutation or nonsense mutations.
Another one case carried a germline DICER1 mutation which
was suspected to deleteriously affect splice site. Case 02 have
a total of 135,109 somatic mutations, consisting of a nonsense mutation located within TDG and missense mutations
of DICER1. Two DICER1 mutation positive cases were found
to have lung cysts preceding the diagnosis of PPB. Furthermore, only one child was found a remarkable family history
of thyroid diseases.
Conclusions: Germline mutation frequency of Chinese
patients with PPB is similar with published studies. Routine
germline DICER1 test might be benefit to improve the accuracy and awareness of differential diagnosis type I PPB from
other diseases, especially lung cysts.
P-284 Granulosa Cell Tumors: A Study of Nine
Rare Cases Over a Period of Fifteen Years in a
Single Institute
Y. Saad-eldin Sadek1
P-283 Germline DICER1 Mutations in Twelve
Chinese Patients with Pleuropulmonary Blastoma
X. Peng1 , S. Cai2 , X. Ma3
1 Capital
Medical University, School of Public Health, Beijing, China;
Children's Hospital- Capital Medical University, Center for
Clinical Epidemiology and Evidence-based Medicine, Beijing, China;
3 Beijing Children's Hospital- Capital Medical University, Hematology
Oncology Center, Beijing, China
2 Beijing
Background/Objectives: A growing number of studies committed themselves to explore the role of DICER1 mutation in
development of PPB. However, the majority of reported cases
were Caucasian. Therefore, 12 consecutive cases of sporadic
PPB from Beijing Children's Hospital were tested in order to
1 Faculty
of Medicine-University of Alexandria, Pediatric Surgery,
Alexandria, Egypt
Background/Objectives: Ovarian tumors in children are
rare, comprising 1% of all childhood tumors.Juvenile granulosa cell tumors are rare subtypes the sex cord-stromal cell
tumors.
The study aimed at reporting and studying cases of juvenile
granulosa cell tumors over a period of 15 years
Design/Methods: All cases of juvenile granulosa cell tumors
treated over a period of 15 years in the Main University Hospital were reported.They were studied concerning: the age, the
ways of clinical presentation and the tumor markers: Alpha
Phetoprotein (AFP) and Human Chorionic Gonadotrophic
SIOP ABSTRACTS
Hormone (HCG),The imaging done for diagnosis, the treatment procedures and follow up were also reported.
Results: Nine cases of granulosa cell tumors were reported: 5
cases were retrospective and 4 cases were prospective. Eight
cases with an age range 4-6 years and only one case was 7
months old.
All cases presented with pseudo- precocious puberty in the
form of: breast hypertrophy with extensive suprapubic hair
in 6 cases,suprapubic hair with enlarged clitoris in one case,
suprapubic hair with huge intra-abdominal swelling in one
case and vaginal bleeding in one case.
Tumor markers: AFP and HCG were negative in all
cases.ultra-sonography revealed unilateral solid ovarian
tumors in 7 cases,huge ovarian swelling with mixed solid and
cystic elements in one case and a small ovarian cyst in one
case.
Cases were treated as follows: unilateral oophorectomy in 8
cases and partial oophorectomy in one case.The histopathological study revealed benign granulosa cell tumors in all
cases.Follow-up revealed regression of signs of pseudoprecocious puberty over a period ranged from 10 to 120 days.
Conclusions:
*Juvenile granulosa cell tumors should be considered in prepubertal girls with pseudo-precocious puberty and negative
tumor markers (AFP & HCG), and differentiated from functioning germ cell tumors including ovarian carcinoma.
*Unilateral oophorectomy is the curative treatment because
they are mostly benign.
P-285
Uveal Melanoma in Young Patients
S. Saakyan1
1 Moscow
Helmholtz Research Institute of Eye Disease, Ocular Oncology
and Radiology, Moscow, Russia
Background/Objectives: Purpose To analyze the clinical profile and survivability of young patients with uveal
melanoma.
Design/Methods: Retrospective case-control series. Out of
1224 patients with uveal melanoma treated in 2005-2015
there were 21 patients (1,7%) aged 20 and younger (15 male,
6 female). The mean age of those patients was 15,7±0,5
years. In all cases the tumor was unilateral. All patients
were examined with standard ophthalmological procedures,
and also ultrasound Color Doppler Imaging, OCT and Fluorescein angiography. The tumors were treated by ruthenium
plaque brachyterapy (11 cases), transpupillary thermotherapy
(2cases), proton beam therapy (2 cases) and enucleation (6
cases).
Results: All patients were divided into 2 groups: with organ
preservation treatment (71%) and without (29%). In the first
S295 of S518
group the mean tumor height was 4.8±0.4 mm. In the second
group 9.9±0.4 mm, enucleation was performed in all cases.
Case monitoring in the 1 group demonstrated the 100% 2-year
survivability and 90.9% 5-year survivability vs 100% 1-year
survivability and 83.3% 2-year survivability in the 2 group.
Conclusions: There was no increasing the incidence of uveal
melanoma at young patients during the last years and the most
common there were the medium and large tumor's sizes and
they demonstrated good results of the local treatment.
P-286 Overexpression of MIR-483-3P and
MIR-149-3P IS Associated with Clinical
Characteristics of Pediatric Adrenocortical Tumors
C.A.P. Corrêa1 , R.C.P. Lira1 , A.F. Andrade1 , J.A. Yunes2 , S.R.
Brandalise2 , M.J. Mastellaro2 , L.F. Leal1 , S.R.R. Antonini1 , L.G.
Tone1 , C.A. Scrideli1
1 Ribeirão
Preto School of Medicine - University of São Paulo, Pediatrics,
Ribeirão Preto, Brazil; 2 Boldrini Children Center, Pediatrics, Campinas,
Brazil
Background/Objectives: Although childhood adrenocortical
tumors (ACT) are rare neoplasms, its incidence in Brazil is
particularly higher. Currently, there are no reliable biomarkers, which predict diagnosis or prognosis of ACT in children.
Aiming to find potential biomarkers of ACT prognosis, we
validated the expression of two miRNAs that were found differentially expressed in a microarray-based miRNA profiling
conducted with 37 pediatric ACT samples
Design/Methods: The validation of miR-149-3p and miR483-3p expressions was evaluated by RT-qPCR in 47 ACT
pediatric tumors and 8 non-neoplastic adrenal pediatric samples. The comparison between miRNA profiles and clinical/biological features were performed by Mann-Whitney test
and Kaplan-Meier curves with log-rank test for Event-free
survival (EFS) analysis and relative risk (RR) and multivariate analysis by Cox Regression Model
Results: The miR-483-3p was overexpressed in tumor samples (P<0.0001), which also showed significant association with virilizing tumors (P=0.002) and TP53 mutation
p.R337H (P=0.042). The miR-149-3p expression was significantly higher in patients classified as Sandrini's stage
IV (P=0.008), relapse/metastasis (P=0.006) and unfavorable event (P=0.021). Patients with expression levels higher
than median of miR-149 showed a lower 5-years EFS
(66.5.7%±9.9% versus 91.3%±0.59%; P=0.028; RR: 4.7, 95%
IC: 1.028-21.489). Multivariate analysis showed that this
overexpression was an independent prognostic factor (P =
0.042) when analyzed in association with tumor size and
advanced stage. Moreover, miR-483 presented negative correlations with inhibitors of Wnt pathway: DKK3 (Rho=0.48; P=0.003) and SFRP1 (Rho=-0.033; P=0.05). Contrary
to this, miR-149 showed positive correlation with MYCC
SIOP ABSTRACTS
S296 of S518
(Rho=0.47; P=0.005), an important target-gene of Wnt pathway
Conclusions: We observed overexpression of miR-483-3p in
ACT when compared to non-neoplastic samples. The higher
expression of miR-149-3p in tumors seems to be related with
poor prognosis of pediatric ACTs. Interestingly, both miRNAs showed significant and opposite correlations with genes
of Wnt signaling, ptahway suggesting a possible relationship
of these miRNAs with an essential pathway for adrenal development
P-287 Aberrant PDGFR Signaling as a Target for
Treatment of the Infantile Myofibromatosis with
Sunitinib
R. Veselska1,2,3 , M. Sramek2,3,4 , J. Neradil2,3,4 , P. Macigova3,4 , P.
Mudry1,4 , K. Melicharkova1,2 , O. Slaby1,5 , J. Vanackova5 , J.
Sterba1,2,4
1 University
Hospital Brno, Department of Pediatric Oncology, Brno, Czech
Republic; 2 St. Anne's University Hospital, International Clinical Research
Center, Brno, Czech Republic; 3 Masaryk University- School of Sciences,
Department of Experimental Biology, Brno, Czech Republic; 4 Masaryk
University- School of Medicine, Department of Pediatric Oncology, Brno,
Czech Republic; 5 Masaryk University, CEITEC MU - Center of Molecular
Medicine, Brno, Czech Republic
Background/Objectives: Infantile myofibromatosis (IM)
belongs to the family of soft tissue tumors. Majority of them
shows a benign behavior but resistant and malignant forms
are also known. Although molecular mechanisms of the IM
pathogenesis are not completely explained, some studies suggest the association of mutations in platelet-derived growth
factor receptor beta (PDGFRb) gene and other related genes
with this disease.
Design/Methods: We analyzed in detail a primary IM cell
line as well as fresh frozen tumor tissues from two siblings suffering with IM. Human phospho-protein arrays were
employed for detection of the phosphorylation status of
49 receptor tyrosine kinases (RTKs) and of 24 mitogenactivated protein kinases (MAPKs) and other important
downstream signaling proteins. Expression and phosphorylation of selected candidate proteins involved in PDGFR signaling was determined using immunoblotting. The whole-exome
sequencing was used to uncover germinal and tumor-specific
mutations in the signaling-related genes.
Results: Tumor samples from both siblings showed a relatively highest phosphorylation level of PDGFRb and ERK1/2
implicated over-activation of the PDGFRbeta/MAPK signaling axis. Subsequent sequencing revealed germ-line heterozygous c.1681C>A missense mutation of PDGFRB gene. Furthermore, the same germinal mutation in PTPRJ gene, which
product specifically binds and dephosphorylates ERK1/2
kinases, were detected in both of siblings. Subsequent in
vitro experiments using primary tumor-derived cell line
were focused on testing of different low-molecular-weight
inhibitors to examine the cell viability and the responsiveness
of the PDGFRb/MAPK signaling axis. The results showed
that sunitinib, i.e. multi-targeted RTK inhibitor, was able to
inhibit PDGFRb but its effect on downstream MAPKs was a
marginal only.
Conclusions: According to the in vitro experiments, sunitinib
represents a suitable treatment of IM. Up-to-date, these results
were verified by positive therapeutic response to the administration of sunitinib in both siblings.
Acknowledgement: Study was supported by grants 1634083A and 16-33209A from AZV MZCR.
P-288 Efficacy of Combined Transperineal (TP)
and Transabdominal (TA) Ultrasonography in
Diagnosis and Follow-Up of Vaginal Malignancies
X. Yang1 , J. Ye1 , J. Yu1 , Q. Shu2 , J. Wang2
1 Children's
Hospital - Zhejiang University School of Medicine, Department
of Ultrasound, Hangzhou, China; 2 Children's Hospital - Zhejiang
University School of Medicine, Department of Surgical Oncology,
Hangzhou, China
Background/Objectives: This study investigated the sonographic features of vaginal malignancies in girls and the efficacy of transperineal(TP) in conjunction with transabdominal
(TA) ultrasonography in the diagnosis and follow-up of vaginal malignancies in girls.
Design/Methods: Imaging data of 16 cases of vaginal malignancies in our center from January 2000 to December 2016
were retrospectively analyzed. Characteristics of ultrasonography, CT and MR were summarized. All cases confirmed
by pathology. Patients aged form 3m7d to 6y. In this group,
10 cases were vaginal endodermal sinus tumors, 4 cases
were embryonal rhabdomyosarcomas, one was nephroblastoma and one was metastatic neuroblastoma. All patients
underwent transperineal(TP) in conjunction with transabdominal(TA) ultrasonography, some underwent CT and MR.
Results: The results of transperineal and transabdominal
ultrasonography. In the 16 cases, the pelvic hypoechoic
masses could be shown by transabdominal ultrasonography.
4 cases combined intrauterine hematocele. However, it could
be clearly display the size, border, blood flow of the vaginal hypoechoic occupancy, and the relationship of the occupancy and vagina by transperineal ultrasonography. There
were no obvious necrotic liquefaction and calcification in
the mass. During the follow-up process of 14 cases after
chemotherapy, the vaginal tumor could not be clearly shown
by transabdominal ultrasonography after the tumor shrinkage, while it still be clearly shown by transperineal ultrasonography. Ten cases underwent CT examination. Lesions
SIOP ABSTRACTS
appeared as similar-circular soft tissue masses with heterogeneous density, variable necrosis and cystic degeneration on
unenhanced CT. Twelve cases underwent MR examination.
Masses were uniformly isointense on T1-weighted images,
heterogeneously hyperintense on T2-weighted images. Heterogeneous enhancement especially peripherally was noted on
both CT and MRI contrast-enhanced images.
Conclusions: Vaginal malignancies often have characteristic
echo pattens. Transperineal in conjunction with transabdominal ultrasonography are helpful in diagnosing and following
up of vaginal malignancies.Therefore,ultrasound may be preferred as the initial investigation for cases of vaginal malignancy as it is a non-invasive,radiation-free,inexpensive technique.
S297 of S518
A total 42 were performed. All patients received 6 courses.
There were 7 admissions due to febrile neutropenia and 17
episodes of grade 3-4 haematological toxicity. Seven of seven
patients present no active disease (NAD) after median follow
up of 4,16 month (range 1.9 to 86.1 month).
Conclusions: In our experience the treatment with reduced
doses of cladribine +/- cytarabin for refractory or reactivated
LCH patients was usefull to obtain and sustain NAD, with
very tolerable toxicity.
P-290 Multifocal Histiocytic Sarcoma in A 2 Year
Old Child, Successfully Treated with Acute Myeloid
Leukaemia Based Chemotherapy
M. Madni1 , M. Velangi1 , I. Colmenero2 , R. Zbigniew3
1 Birmingham
SOLID NON B R A I N T U MO U R S H I ST I O C Y TOS I S
P-289 Reduced Doses of Cladribine Plus
Cytarabine for Refractory or Reactivated
Langerhans Cell Histiocytosis (LCH)
M.F. Gutierrez1 , M. Urbieta1 , M. Garcia Lombardi1 , R. Ramirez1 ,
S. Acosta1 , A. Oller1
1 Hospital
de Niños Ricardo Gutierrez, Pediatric Oncology, Capital federal,
Argentina
Background/Objectives: Treatment with Cladibrine (2CDA)
as single drug or with Cytarabine at higt doses (9 mg/m2/d and
1000 mg/m2/d for 5 days) has been effective in children with
refractory or reactivated LCH after 2 or 3 previous treatment
regimens
OBJECTIVES: To describe our experience in reduced doses
2CDA plus Cytarabine scheme in refractory or reactivated
patients(p) with LCH, follow up and acute toxicity.
Design/Methods: Retrospective analysis of patients records
treated between January 2008 and February 2017 with refractory o reactivated LCH after standard therapy. Patients
received 2cda (5 mg / M2 daily for 5 days) +/- cytarabine (100
mg / m2 / day for 4 days). Courses were repeated every 3-4
weeks.
Results: Fifty one patients with LCH were admitted during
the indicated period, 7p were treated with 2-CDA plus AraC, 1p with 2-CDA alone. The median age at diagnosis was
24.57 months (range 3 to 180 months). All patients had multisystemic LCH at diagnosis. Four patients had risk organ
involvement and 2 had SNC tumorous lesions. Median of previus chemotherapy schemes:2 (1-3). Seven of 8 patients were
evaluables. One patient was excluded because of severe liver
toxicity the first day of infusion (grade 3).
Children's Hospital, Hematology and Oncology,
Birmingham, United Kingdom; 2 Birmingham Children's Hospital,
Histopathology, Birmingham, United Kingdom; 3 Birmingham Heartlands
Hospital, histopathology, Birmingham, United Kingdom
Background/Objectives: Histiocytic and dendritic cell neoplasms are rare malignant disorders originating from tissue
macrophages/ histiocytes. The incidence is estimated as 0.05
per 100,000 per year in Europe. In the past, most of these disorders were misdiagnosed as lymphomas, especially diffuse
large B cell lymphoma or anaplastic large cell lymphoma.
However, after the WHO 2008 classification the diagnosis
has been simplified. Historically, histiocytic sarcoma (HS) is
associated with an unfavourable prognosis with no consensus
on treatment strategy and most of the literature is available
in the form of case reports with variable treatment protocols
used with variable success. In most of the cases these tumours
respond poorly to the treatment commonly used in Langerhan
cell histiocytosis.
Design/Methods: Case Report
Results: We describe a 2 years old patient with multifocal HS. She presented with multiple soft tissue and bony
lesions involving the maxilla and mandible with disease also
present in abdomen, tibia and femur. Initial impression on
histopathology favoured a myeloid malignancy and she was
commenced on treatment according to AML 15 protocol.
On-going Immunohistochemical investigation concluded the
diagnosis of HS on the basis of positivity of CD68, CD163,
and Lysozyme. After a good response to initial AML therapy and, in the knowledge that there is no optimum treatment
strategy for HS we continued the same chemotherapy regimen. She is currently 23 months off treatment and maintaining clinical and radiological remission.
Conclusions: We conclude that HS can be successfully treated with chemotherapy alone commonly
used for Acute Myeloid Leukaemia without significant
toxicity.
SIOP ABSTRACTS
S298 of S518
P-291 Spectrum of Presentation, Management
and Late–Effects of Langerhans Cell Histocytosis
Over A 10-Year Period, in a UK Tertiary Paediatric
Oncology Centre
P-292 Mortality Risk Factors of Children with
Hemophagocytic Lymphohistiocytosis: A
Prospective Study at Children's Hospital 1, HO
CHI MINH, Vietnam
A. Mitchell1 , U. Uparkar1 , R. Ramanujachar1 , G. Nicolin1 , A.
Cooke1 , J. Gray2
T. Nguyen1 , A. Phan1 , D. Tran1 , C. Cao1
1 Children's
Hospital 1, Hematology-Oncology, Ho Chi Minh, Vietnam
1 Department
of Paediatric Oncology, Southampton Children's Hospital,
Southampton, United Kingdom; 2 University of Southampton, Child Health,
Southampton, United Kingdom
Background/Objectives: Langerhans Cell Histiocytosis
(LCH) describes a clinical spectrum of disease caused
by clonal proliferation of pathological Langerhan's cells
infiltrating tissues. We aimed to characterise the disease
presentations in the South of England to the Southampton
Principal treatment centre (PTC) over the past 10 years
due to clinical concern regarding increased incidence
and complexity of clinical LCH presenting over recent
years.
Design/Methods: Retrospective data was collected on demographics, disease sites, treatment modalities at diagnosis/relapses, remission free periods and outcome at latest evaluation at follow-up.
Results: 1041 children were treated for cancer at Southampton PTC over the past 10 years (1/1/2006-31/12/2016).
46 cases of LCH were identified, median age of 2 yrs 6
months accounting for 4.3% of our patients. Male:female
ratio 1.2:1. 62% (28) presented with single-system disease and 38% (16) multi-system disease. 4 children were
identified as having diabetes insipidus 8.7%. 78% of cases
were biopsied. 2 cases of neuro-degenerative LCH were
identified.
Majority (88%, 23/26) of children with single system disease
had uncomplicated course, no further disease recurrence at
last follow up. Uni-focal bone disease was treated by curettage except one who was already resolving at time of review
and therefore observed. multi-system (34%, 16 cases) patients
had a more complicated course with 64% suffering a relapse
(10/16) and 2/16 patients had at least 4 relapses needing
salvage therapy. 15% of our overall cases had risk organ +
disease.
Conclusions: We present our centres experience with LCH
over the past 10 years. We witnessed a spike in incidence of
LCH in 2016 however further data is required to delineate a
clear trend of increasing incidence. Novel strategies to evaluate and monitor BRAF in blood and urine such as those being
employed in the latest international LCH IV trial offer the
opportunity to better understand the risk factors for disease
severity.
Background/Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Whether primary or secondary, prompt initiation of HLH
therapy is mandatory to prevent irreversible tissue damage.
We identify risk factors of mortality of Vietnamese children
with HLH who were treated by the HLH-2004 protocol.
Design/Methods: We conducted a prospective study between
Jan 2009 to Dec 2011. The diagnosis of HLH at the Children's
Hospital 1 in Ho Chi Minh city, Vietnam was compatible with
the diagnostic criteria of the HLH-2004 proposed by the HLH
Study Group of the Histiocyte Society, and patients who fulfilled at least five of the following signs or laboratory findings
were enrolled: fever (higher than 38◦ C for more than 7 days),
splenomegaly or hepatomegaly, cytopenia (affecting ≥2 of
three lineages in the peripheral blood: hemoglobin (<90 g/l),
leucopenia (<5x109 /l), neutropenia (<1x109 /l), thrombocytopenia (<100x109 /l), hypertriglyceridemia (≥3 mmol/l) or
hypofibrinogenemia (≤1 g/l), hyperferritinemia (≥500 mg/l)
and hemophagocytosis in bone marrow or lymph nodes.
Results: A total of 144 patients, median age 2.5 years (range
0.1-15 years) with a male:female ratio of 1.6:1 were enrolled
into the study. All patients were treated with the HLH-2004
protocol and had a median time from diagnosis to treatment
of 2 days (range 0-6days). The overall 5-years survival rate
was 70.1±5.3% with a median follow-up of 5.4 years. Of all
patients, 64 (44.4%) achieved complete resolution, 16 (11.1%)
had active disease, 21 (14.6%) developed reactivation and 43
(29.9%) died. Factors independently associated with mortality included persistent elevated ferritin levels (OR=5.5, 95%
CI=4.3-6.2), central nervous system involvement (OR=4.5,
95% CI=2.7-6.3), severe liver failure (OR=2.4, 95% CI=2.12.9), gastrointestinal bleeding (OR=4.1, 95% CI=3.7-4.6),
persistent fever > 1 week of induction therapy (OR=2.8, 95%
CI=2.2-3.4).
Conclusions: Early diagnosis and prompt management of
HLH in children with a close follow-up of mortality risks factors can improve patient survival.
P-293 Langerhans Cell Histiocytosis: A Single
Center Experience of 92 Cases
A. Raj1 , A. Batra1 , S. Bakhshi1 , B. Biswas1
SIOP ABSTRACTS
S299 of S518
Ward- Institute Rotary Cancer Hospital- AIIMS, Medical Onology
Department, New Delhi, India
been identified in 54 % of Erdheim-Chester disease (ECD)
but none in other non-LCH lesions.
Background/Objectives: Langerhans cell histiocytosis
(LCH) is a rare disease. Limited data has been published
from India regarding long-term outcomes.
Design/Methods: Retrospectively reviewed.
1 MRO
Design/Methods: We performed a retrospective analysis of
patients with LCH treated at Institute Rotary Cancer Hospital,
New Delhi from August 2002-January 2017.
Results: Ninety-two patients were registered during August
2002-January 2017. Median age was 3 years, with male:
female ratio of 7:3. Median time from symptoms to diagnosis was 6 months. Bony swellings (61.5%), fever (37.3%) and
skin rash (27.8%) were most common presenting complaints.
Bony lytic lesions, anemia, lung involvement, jaundice, bone
marrow involvement were seen in 84%, 52%, 11.2%, 8.9% and
6.7% of patients, respectively. Patients were divided into three
risk categories [A – multifocal/unifocal bone only (28.7%) B
– Soft tissue involvement with no organ dysfunction (42.5%),
C – Organ Dysfunction (28.8%)]. The patients were treated
with DALHX-83 protocol (prednisolone, vinblastine, etoposide, 6-Mercaptopurine). Response assessment was done at
12 week, end of treatment and suspected disease progression.
Eighty-nine of 92 patients received first-line treatment. Complete response (CR) was observed in 15.3%, partial response
or stable disease (PR/SD) 72.1%, whereas 12.6% had disease
progression at 12 weeks of therapy. Thirty-three patients progressed among whom 29 took second-line treatment. Prednisolone, vinblastine and etoposide or cladribine were used in
second-line treatment. The CR to 2nd line therapy was 23%.
Progression free survival (PFS) at 60 months was 59.1% [95%
CI: 0.46-0.70] and overall survival (OS) at 10 years was 92.8%
[95% CI: 0.8 –0.97]. On multivariate analysis, total bilirubin
>3 g/dl (p=0.03), 12 week response (p<0.001) and DALHX83 risk category (p=0.03) were significant predictors of PFS.
Conclusions: This is the largest Indian series of LCH with
outcome results comparable to western population with a 5year PFS of 59.1% and 10 year OS of 92.8%.
Results: Patient # 1 presented with headache and recurrent
vomiting. MRI of the brain revealed multiple intracranial
extra-axial masses. A biopsy of the right temporal lesion was
originally reported as JXG. The lesion was found to have a
BRAF mutation by BRAF immunohistochemistry, with subsequent confirmation by molecular methods.
Patient #2 developed intractable seizures at the time of diagnosis. A cerebellar lesion was identified and a biopsy of this
was originally diagnosed as Rosai-Dorfman disease (RDD)
on the basis of the immunohistochemical profile, although the
lesion did not show all the typical features of RDD.
Patient #3 was brought to medical attention due to bilateral
proptosis and multiple cranial lesions. A biopsy of the right
parietal bone lesion was reported as JXG.
Bone marrow study, bone scintigraphy and imaging of the
chest and abdomen were performed in all patients and there
was no evidence of extracranial disease involvement in any of
the patients.
Patients #2 and #3 received intuitional chemotherapy regimen
for LCH that consisted of vinblastine, prednisolone, cytarabine, 6-mercaptopurine and methotrexate for a total of 46
weeks. All three patients underwent radiotherapy to the primary affected site with varying doses of radiation. At the
median follow up time of 20 months, all patients are alive with
partial to complete disease response.
Conclusions: In our report, we detected BRAF V600E mutation in all 3 JXG patients with indolent presentation. Targeted
BRAF inhibitor may have a potential role in refractory JXG
cases with this mutation. Further study of BRAF status in a
lager series of JXG is warranted.
BRAIN TUMOURS
P-294 BRAF V600E Mutation in Pediatric
Cranial Juvenile Xanthogranuloma
P-295 Medulloblastoma, Treatment Outcome and
Prognostic Factors at National Cancer Institute,
Egypt “2008 – 2013”
P. Techavichit1 , D. Sosothikul1 , K. Chiengthong1 , C.
Teerapakpinyo2 , P. Thorner3 , S. Shuangshot2
A. Mustafa1,2 , N. Ali1,2 , R. Emad1 , E. Ebeid1
1 Chulalongkorn
University, Pediatrics, Bangkok, Thailand;
2 Chulalongkorn University, Pathology, Bangkok, Thailand; 3 Hospital for
Sick Children and University of Toronto, Laboratory Medicine, Toronto,
Canada
Background/Objectives: Juvenile xanthogranuloma (JXG)
is a rare primarily pediatric non-Langerhans cell histiocytosis
(non-LCH). BRAF V600E mutation is observed in approximately 60% of LCH. In addition, the mutation has recently
1 National
Cancer Institute, Pediatric Oncology, Cairo, Egypt; 2 Nci
-Children Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt
Background/Objectives: Medulloblastoma (MB) is the most
common malignant brain tumor of childhood. It occurs at
all ages, peaking in incidence between 4 and 7 years. Our
aim was to assess the outcome and prognostic factors among
MB pediatric patients at the National Cancer Institute, Cairo
University.
SIOP ABSTRACTS
S300 of S518
Design/Methods: This is a retrospective study included 53
eligible patients with established diagnosis of medulloblastoma during the period from January 2008 to December 2013.
high-dose chemotherapy (HDCT). Multivariate COX regression and survival analyses were performed to assess the efficacy of different treatment strategies.
Results: Among the 53 patients, 31 were males (58.5%).
Median age at diagnosis was 6 years (range 0.6-18 years).
Vomiting was the most frequent presenting symptom followed
by headache detected in 90.6% and 86.8% of patients, respectively. The majority of our patients were high risk 45 patients
(84.9%) (15% of them infantile ≤3 years), while 8 patients
(15.1%) were standard risk. Median follow up period was
38.6 months (range 13.3 to 81.9). The 5-year overall survival
(OS) and progression-free survival (PFS) rates were 54.6%
and 74.8%, respectively. The presence of postoperative residual, spinal seedling, M staging, and completing chemotherapy
protocol had a significant difference regarding survival rate
(p=0.045, p<0.001, p=0.021 & p<0.001, respectively). There
was no significant difference between patients presented at age
≤ 3 years versus >3 years old regarding survival rate (5-year
OS 50.0% versus 55.2%, respectively), also histopathological
sub-types had no impact on survival (p=0.099). At the end of
this study 29 patients (54.7%) were alive, 22 patients (41.5%)
were dead and 2 patients (3.8%) lost follow up. Two out of 53
patients relapsed after treatment.
Results: Of the patients analyzed, 66% received either focal
or whole brain and spine radiation. IT and HDCT was administered to only 35% and 34% of patients respectively. Most
reports collected were reported post 2004 (88%). Patients
were treated heterogeneously with different protocols that
resulted in different clinical outcomes. Multivariate COX
regression analyses reveal statistically significant differences
in various treatment strategies and chemotherapeutic agents
according to certain patient characteristics such as age and
tumour location.
Conclusions: The outcome of patients in this study is favorable and comparable to international trials. Patients with
advanced stages and incomplete surgical resection had a
poorer outcome. Most of mortalities were caused by infection
and sepsis, raising the importance of strict infection control
and strong supportive care measures.
Conclusions: Our results strongly indicate that patient's clinical demographics significantly influence treatment success,
and that some chemical classes of drugs may not benefit all
types of ATRT. A personalized approach taking into account
patient age, tumour location, and molecular subtype will be
required in order to tailor treatment strategies appropriately.
P-297 Treatment Efforts and Survival Benefits in
Pediatric Patients with Atypical Teratoid Rhabdoid
Tumors (ATRT) at King Faisal Specialist Hospital
and Research Centre, Riyadh, Saudi Arabia
A. Alkofide1 , E. Elshail2 , M. Hassonah3 , I. AlFawaz1 , A. Ali1 , M.
Ayas1 , A. Haq4 , A. Mousa5 , Y. Khafagh6 , A. Dababo7 , H.A. Hind
AlHindi8 , M. Foudaneel9 , K. Siddiqui1
1 King
P-296 Evaluation of Prognostic Factors for
Patients with Atypical Teratoid Rhabdoid Tumour
(ATRT): A Meta-Analysis
S. Al-Karmi1 , A. Fonseca1 , A. Huang1 , E. Bouffet1
1 The
Hospital for Sick Children, Neuro-oncology, Toronto, Canada
Background/Objectives: Atypical Teratoid Rhabdoid
Tumour (ATRT) are rare, highly lethal embryonal brain
tumours that occur in children predominantly younger than
three years old. Recent studies have led to advancements
in treatment stratification based on (epi)-genomic and transcriptional profiling, however, prognosis despite aggressive
chemotherapy remains poor for most patients.
Design/Methods: We performed a systematic meta-analysis
of the literature comparing treatment strategies of ATRT
patients diagnosed from 1990-2016. Treatment information
including chemotherapy, radiation and surgery, and clinical information such as age and tumour location was
curated for 409 patients. We sub classified chemotherapy
regimens by chemical class, and also evaluated the effect
of specific delivery methods such as intrathecal (IT) and
Faisal Specalist Hospital & Research Center, Pediatric Hematology
Oncology, Riyadh, Saudi Arabia; 2 King Faisal Specialist Hopsital &
Research Center, Neurosciences, Riyadh, Saudi Arabia; 3 King Faisal
Specalist Hospital & Research Center, Neurosciences, Riyadh, Saudi
Arabia; 4 King Faisal Specalist Hospital & Research Center, Neuroscience,
Riyadh, Saudi Arabia; 5 King Faisal Specalist Hospital & Research Center,
Raidation Oncology, Riyadh, Saudi Arabia; 6 King Faisal Specalist Hospital
& Research Center, Radiation Oncology, Riyadh, Saudi Arabia; 7 King
Faisal Specalist Hospital & Research Center, Dept of Path Lab Medicine,
Riyadh, Saudi Arabia; 8 King Faisal Specalist Hospital & Research Center,
Dept of Path & Lab Medicine, Riyadh, Saudi Arabia; 9 AlFaisal Unversity,
Medical College, Riyadh, Saudi Arabia
Background/Objectives: Atypical teratoid rhabdoid tumors
(ATRT) are rare aggressive tumors with poor prognosis
accounting for 1-2% of all childhood malignancies. Primarily occur in children under the age of three though they may
be seen in older age groups.
Design/Methods: Medical charts of pediatric patients diagnosed with ATRT between 1993-2013 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, were
reviewed and treatment profile and outcome data were analyzed.
Results: Forty three cases were evaluated. Median age at
diagnosis among males (n=23, 53.5%) was 1.8 years (0.0320.7) compared to 2.1 years (0.17-20.1) among females
SIOP ABSTRACTS
(n=20, 46.5%). All patients underwent surgery: 6 had biopsy
only; 23 subtotal resection (STR), and 14 gross total resection (GTR). VP-shunt was inserted in 9 patients prior to
surgery and in 17 after surgery. All but one tumor were
immunonegative for INI 1. Disease was localized in 65.1%
(28) and disseminated in 34.9% (15). Rhabdomyosarcomabased chemotherapy was given to 30 (68.9%) patients. Nineteen patients received radical dose of radiation therapy. Eight
patients received focal irradiation while 11 had whole craniospinal axis irradiation followed by localized boost to primary lesion. Patients treated with focal radiation only, had no
clinical, radiological or cytological evidence of spinal seeding. Total radiation dose for localized field ranged from 5050.4 Gy in 28-32 fractions, while the craniospinal axis radiation dose ranged from 30.6 Gy to 36 Gy. At last followup, 22(51.2%) patients were alive; 2(9.1%) in CR, 5(22.7%)
with SD and the remaining 15(68.2%) had disease progression (PD). Median follow-up of 25.1 months, the probability
of five year overall survival was 31%, having a median survival time of 19 months (95% CI: 5.6-32.4).
Conclusions: ATRT outcome remains unsatisfactory despite
multimodality treatment. Targetted strategies utilizing agents
mimicking effects of INI1/ h SNF5 may hold promise in future
studies for this aggressive tumor.
P-298 Excellent Neuro-Cognitive Outcomes in
Infant Patients with Medulloblastoma Treated with
Post-Operative Chemotherapy and Focal Radiation
P. Angelini1 , A. Michalski1 , K. Phipps2 , D. Gumley3
1 Great
Ormond Street Hospital, Paediatric Oncology, London, United
Kingdom; 2 Great Ormond Street Hospital, Neurosurgery, London, United
Kingdom; 3 Great Ormond Street Hospital, Neurosciences, London, United
Kingdom
Background/Objectives: Infant medulloblastoma patients
suffer severe cognitive sequelae from conventional treatment,
particularly from radiotherapy. We present the results of a protocol comprising dose-intense induction chemotherapy, focal
radiotherapy and consolidation chemotherapy, and the neurocognitive outcome of survivors.
Design/Methods: Twenty-six patients were treated between
11/1997 and 04/2011. All patients underwent an attempt
at surgical resection, followed by induction chemotherapy (cyclophosphamide, carboplatin, vincristine). Radiotherapy was administered based on initial staging and
tumour response. Post radiotherapy the patients received 4
cycles of consolidation chemotherapy (lomustine, cisplatin,
vincristine).
Results: Nineteen patients received radiotherapy, 14 focal, 5
craniospinal (CSI). OS was 56.8% ± 10.5%. EFS was 51.1%
±10.2%. Twelve patients relapsed, 13 died, 11 are long term
S301 of S518
survivors and two are lost to follow-up. Gross tumour resection, desmoplastic variant and radiotherapy (either focal or
CSI) correlated with better OS and EFS, while metastases,
gender and age at diagnosis had no impact. Twelve of 13
evaluable patients reported one or more long term sequelae
of their tumour or treatment. Fourteen patients, including all
long-term survivors, had a neuro-psychological or developmental assessment 2 to 10 years after the diagnosis. Six had
learning difficulties (42%), of whom three (female), had moderate learning difficulties, and three (boys) had severe learning disabilities. 2 children had language difficulties, one with
average cognition. Six patients had normal IQ between 89 and
113 and no other problems.
Conclusions: Our study confirms that 1: patients with desmoplastic medulloblastoma have a favourable prognosis and 2:
delaying radiotherapy and reducing the field of radiation
lead to normal neuro-cognitive outcome in 42%, and mild
deficits in 21% of survivors. However, the report of 4 second malignancies (28.6% of non-relapsed patients) is of concern and brings into question the whole approach with chemoradiotherapy for these tumours.
P-299 The Promote Study: Patient Reported
Outcome Measures Online to Enhance
Communication and Quality of Life after
Childhood Brain Tumour – Systematic Review
K. Bull1 , C. Kennedy1 , S. Hornsey2 , J. Shepherd3 , K. Welch3 , C.
Morris4
1 University
of Southampton, Clinical and Experimental Sciences,
Southampton, United Kingdom; 2 University of Southampton, School of
Psychology, Southampton, United Kingdom; 3 University of Southampton,
Southampton Health Technology Assessments Centre, Southampton, United
Kingdom; 4 University of Exeter, Medical School, Exeter, United Kingdom
Background/Objectives: Quality of life in children treated
for brain tumours is at risk of being significantly impaired
into adulthood including cognitive functioning, emotional,
behavioural, and social issues. However, typically there is no
systematic screening for such problems. Referral to appropriate services is often reactive rather than proactive. We are
testing the feasibility of individualised application of patientreported outcome measures (PROMs) to improve communication in outpatient consultations. We need to select appropriate PROMs based on available evidence of measurement
properties.
Design/Methods: We have conducted a systematic search of
MEDLINE, EMBASE, and PsycINFO to identify evidence
of studies evaluating measurement properties of English language versions of PROMs suitable for use with children who
have been treated for brain tumours. Two reviewers have independently screened all titles and abstracts from the search to
select those articles that are likely to yield relevant results.
SIOP ABSTRACTS
S302 of S518
Full texts are being extracted from this list and read by 3
reviewers to confirm their relevance and ascertain their contribution to the evidence base. The review team will then consider the evidence and decide on the extent to which each
PROM can be considered robust for measuring quality of life
in individual children treated for brain tumours.
Results: After duplicates had been removed, the systematic search identified 473 possible relevant studies in which
PROMs had been psychometrically evaluated for use with
children treated for brain tumours. To date 53 (21%) studies
from 250 titles and abstracts screened have been included for
the next stage in the review process.
Conclusions: We will present evidence from this review that
informs the selection of PROMs for use with children treated
for brain tumours in a subsequent stage of the research for
which decisions on the final selection of PROMs will be made
in consultation with families and clinicians.
P-300 In Human Glioblastoma Cell Lines,
Doxycycin Inhibits Tumorigenicity by Tumor Stem
Cells
C.F. Classen1
1 University
Childrens Hospital, Oncology Hematology, Rostock, Germany
Background/Objectives: Glioblastoma multiforme still is a
lethal diagnosis for most patients. Operation and radiotherapy are very effective to reduce the tumor burden, however, a
strong adjuvant therapy is lacking. Based on the cancer stem
cell hypothesis, we expected an increased tumorigenicity in
stem-like glioblastoma cells. Our objective was then to analyse how this might be influenced by different culture conditions in vitro in cell lines established from individual patients,
in order to identify therapeutic targets acting on epigenetic
regulation. Since continuous exposure to temozolomide is
part of standard treatment, its effect on stemness was analysed. Doxycycline is a polycyclic antibiotic, inhibiting protein
biosynthesis by binding to the small subunit (30S) of bacterial ribosomes. Since it acts similarly on the 28S subunit of
mitochondrial ribosomes, which could be a critical part in the
metabolism of stem-like cells it might also inhibit stem cell
formation.
Design/Methods: Patient derived cells were grown in classical cell culture (with 10% fetal calf serum) and cancer stem
cell culture (serum free, supplemented with growth factors),
both as adherent or spheroid culture. In these settings, we
analysed the effect of continuous treatment with the cytostatic
drug temozolomide (50�M), without and with doxycycline.
Results: As we found, cells cultivated upon stem cell culture conditions displayed an increased tumorigenicity in vitro,
as compared to their respective serum culture counterparts.
Cells cultivated as spheroids achieved a more stem-like
phenotype than adherent cells. Interestingly, similar effects
were observed after treatment with temozolomide (50�M).
Furrther, doxycylin was studied it in our temozolomideinduced tumorigenicity model. In fact, it reversed the effects
of temozolomide.
Conclusions: In summary, we found that by numerous modifications of growth conditions, the stem-like phenotype and
tumorigenicity of glioblastoma cells may be influenced, thus
opening new options for a targeted approach in glioblastoma
therapy.
P-301 Application of Visual-Motor Exerciser in
Children and Teenagers After Antitumor Therapy
of Central Nervous System Cancer
V. Anisimov1 , A. Dreneva1 , I. Borodina1 , V. Kasatkin1
1 Dmitry
Rogachev National Research Center of Pediatric HematologyOncology and Immunology, Clinical Rehabilitation Research Center for
patients in remission “Russkoye pole”, Moscow, Russia
Background/Objectives: The progress of treatment in children with brain tumors has led to a significant increase in
their survival. However, radiotherapy and chemotherapy produce dramatic impact on survivors’ health state. Hence, the
question of effective cognitive and motor rehabilitation of survivors is in a great interest. The aim of our research was to
study the applicability of a new method for motor and executive functions development and to evaluate its effectiveness in
relation to rehabilitation therapy in patients with brain tumors.
Design/Methods: The cohort included 46 children with
posterior fossa tumors: 27 males and 19 females (median
age=11). The diagnoses were: medulloblastoma (n=31), pilocytic astrocytoma (n=11), anaplastic ependymoma (n=1), diffuse brainstem glioma (n=1), neurinoma (n=1) and fibrillar meningioma (n=1). Depending on treatment protocol, 11
patients received surgery, 3 patients received surgery and
radiotherapy, 1 patient received surgery and chemotherapy,
and 31 patients received all three types of intervention. Remission period varied from 2 to 113 months (median=21).
All patients received occupational therapy consisted of 5-7
sessions at Dynavision D2 ®. This training device is designed
for the enhancement of visual-motor integration and attention
skills.
Results: Our findings revealed significant improvement of
reaction time in all patients (P<0.0126). Females showed better performance (P<0.0001) that can be explained by earlier psychomotor maturation in girls. The group of patients
who received only surgical intervention demonstrated better results comparing to others (P<0.0313). Performance
scores significantly correlated with ophthalmological diagnoses (P<0.00001). No significant age differences were
found.
SIOP ABSTRACTS
No negative feedback was received from patients during the
time they were working with the device.
Conclusions: The results suggest that Dynavision D2 ® can
be successfully applied to training of reaction time, visualmotor integration and hand-eye co-ordination in rehabilitation
of pediatric cancer survivors.
P-302 Executive Functions State in Childhood
Brain Tumor Survivors before and After Working
Memory and Attention Training
A. Ryabova1 , A. Dreneva1 , A. Aizenshtein1 , V. Kasatkin1
1 Dmitry
Rogachev National Research Center of Pediatric HematologyOncology and Immunology, Clinical Rehabilitation Research Center for
patients in remission “Russkoye pole”, Moscow, Russia
Background/Objectives: Childhood brain tumors and their
treatments are closely associated with cognitive impairment
that occurs in a substantial proportion of patients. The aim of
the investigation was to evaluate the impact of rehabilitation
therapy, which included executive functions training, on such
parameters as working memory, sustained attention and processing speed, in posterior fossa tumor survivors.
S303 of S518
1 National
Scientific and Practical Center of Pediatric HematologyOncology and I, Pediatric department for hematology and oncology,
Moscow, Russia; 2 National Scientific and Practical Center of Pediatric
Hematology- Oncology and I, Laboratory of Cytogenetics and Molecular
Genetics, Moscow, Russia; 3 National Scientific and Practical Center of
Pediatric Hematology- Oncology and I, Laboratory of molecular biology,
Moscow, Russia; 4 National Scientific and Practical Center of Pediatric
Hematology- Oncology and I, Department of pathological anatomy,
Moscow, Russia; 5 National Scientific and Practical Center of Pediatric
Hematology- Oncology and I, Department of pediatric surgery, Moscow,
Russia; 6 National Scientific and Practical Center of Pediatric HematologyOncology and I, Department of radiation therapy, Moscow, Russia;
7 National Scientific and Practical Center of Pediatric HematologyOncology and I, Department of medical rehabilitation, Moscow, Russia;
8 Regional Children's Hospital 1, Pediatric oncology ward, Yekaterinburg,
Russia; 9 City Clinical Hospital 31, Department of pediatric oncology, St.
Petersburg, Russia; 10 Chelyabinsk Regional Children's Hospital,
Department of pediatric oncology and hematology, Chelyabinsk, Russia;
11 Regional Children's Hospital, Department of pediatric oncology and
hematology, Orenburg, Russia; 12 Nizhnevartovsk Regional Chuldren's
Hospital, Department of pediatric oncology and hematology,
Nizhnevartovsk, Russia; 13 Altay Regional Children's Hospital, Department
of pediatric oncology and hematology, Barnaul, Russia; 14 National
Scientific and Practical Center of Pediatric Hematology- Oncology and I,
Department of neurooncology, Moscow, Russia; 15 National Scientific and
Practical Center of Pediatric Hematology- Oncology and I, Institute of
pediatric oncology- radiology and nuclear medicine, Moscow, Russia;
16 National Scientific and Practical Center of Pediatric HematologyOncology and I, Medical administration, Moscow, Russia
Design/Methods: Thirty-one children (20 boys, 11 girls,
median age=11) were included. The diagnoses were medulloblastoma (n=24), pilocytic astrocytoma (n=4), anaplastic
ependymoma (n=1), diffuse brainstem glioma (n=1), neurinoma (n=1) and fibrillar meningioma (n=1).
Background/Objectives: Medulloblastoma, the most common CNS malignancy of childhood, is known for a significant
clinical heterogeneity. 4 distinct molecular subgroups (WNT,
SHH, groups 3 and 4) with unequal outcome have been distinguished.
The executive functions training was performed in all patients
during three-week time period. The state of executive functions before and after the training was evaluated by Cambridge
Neuropsychological Test Automated Battery (CANTAB ®).
Design/Methods: In the pilot study aimed to investigate clinical significance of molecular grouping of medulloblastoma
in Russian cohort of patients we analyzed profile of 26 genes
expression (P. Northcott et al. 2012 with slight modifications)
in 33 FFPE tumor samples from patients 0-15 years of age
by Nanostring technology. All patients were treated according to HIT protocol. Median of follow-up time achieved 23.3
months.
Results: Most of patients demonstrated significant improvement in spatial working memory capacity (P<0.0087) and
delayed pattern recognition (P<0.0325). An increasing tendency was revealed for ability to manipulate visuospatial
information (P<0.0743) and for immediate pattern recognition (P<0.0839).
Conclusions: The results indicate the effectiveness of executive functions training in childhood brain tumor patients. They
also show that CANTAB ® is a sensitive method for neuropsychological assessment in pediatric cancer survivors.
P-303 Prognostic Significance of Molecular
Grouping in Russian Cohort of Medulloblastoma
Patients
L. Papusha1 , A. Druy2 , L. Yasko3 , Y. Olshanskaya2 , D. Konovalov4 ,
S. Ozerov5 , A. Samarin5 , A. Nechesnyuk6 , D. Kobyzeva6 , I.
Borodina7 , A. Zaychikov8 , M. Belogurova9 , S. Kovalenko10 , A.
Shapochnik11 , G. Sharapova12 , A. Rumyantsev13 , E. Kumirova14 ,
A. Karachunskiy15 , G. Novichkova16 , A. Rumyantsev16
Results: 8 patients had metastatic dissemination and 8 had
incomplete resection with residual disease larger then 1.5
cm2. Molecular group distribution was as follow: WNT- 2,
SHH- 9, group 3- 11, group 4- 11 patients. Classical histologic variant of medulloblastoma included all groups with the
exception of SHH, anaplastic – only group 3. Correspondence
of desmoplastic/nodular histology to SHH group was 7/8 in
infants; however in patients >3 years desmoplastic medulloblastoma belonged to group 3 and 4 (2 and 3 patients respectively). All 8 infants with desmoplastic variant were treated
only by chemotherapy (HIT SKK) and had excellent outcome,
even in cases with metastatic disease. Group 3 patients had
poor outcome: event-free survival (EFS) was 0.42±0.16. 3 out
of 11 patients did not respond to the first-line therapy and 3
had a relapse.
SIOP ABSTRACTS
S304 of S518
Group 4 and WNT patients in our series had excellent outcome. In the group 4 all patients with the exception of one
were above 3 years of age and received craniospinal irradiation. Differences in EFS between molecular subgroups were
significant, p-value for trend was 0.007.
Conclusions: Our study confirmed the prognostic significance of molecular grouping of medulloblastoma. Nanostring
is fast and reliable method for this purpose and could be
offered for routine clinical practice.
P-304 Experience of the Management of Central
Nervous System Tumors in Children Younger than
5 Years-Old in the Last 15 Years
M. Garcia-Ariza1 , R. Lopez-Almaraz1 , A. Echebarria Barona1 , R.
Adan Pedroso1 , I. Ojinaga Niño1 , A. Ricondo De Diego1 , N. Bilbao
Salcines1 , M.J. Martinez Gonzalez2 , A. Garcia Rives2 , I.
Valduvieco3 , L. Galbarriatu Gutierrez4 , E. Ruiz de Gopegui Ruiz4 ,
L. Zaldumbide Dueñas5 , I. Martin Guerrero6 , O. Aurtenetxe Saez6 ,
L. Collazos Zabala7 , A. Navajas Gutierrez1 , I. Astigarraga Aguirre1
1 Hospital
Universitario Cruces, Pediatric Hematology and Oncology Unit,
Cruces- Bilbao, Spain; 2 Hospital Universitario Cruces, Pediatric
Neurology Departament, Cruces- Bilbao, Spain; 3 Hospital Marques de
Valdecilla, Neurosurgery Departament, Santander, Spain; 4 Hospital
Universitario Cruces, Neurosurgery Departament, Cruces- Bilbao, Spain;
5 Hospital Universitario Cruces, Department of pathological anatomy,
Cruces- Bilbao, Spain; 6 Hospital Universitario Cruces, Biocruces Health
Research Institute, Cruces- Bilbao, Spain; 7 Hospital Universitario Cruces,
Pediatric oncological psychology. Pediatric Hematology and Oncology
Unit, Cruces- Bilbao, Spain
Background/Objectives: Treatment of young children with
central nervous system (CNS) tumors remains a challenge.
The objective of avoiding radiation therapy due to its long
term sequelae, and the controversy about the high-dose
chemotherapy (HDCT) difficult the management of these
patients. We present our experience in children with CNS
tumors less than five years.
Design/Methods: Review of the CNS tumors in children
under five years diagnosed from 2001 to 2016. Collected
and analyzed data were clinical, histological, treatment and
sequelae.
Results: Sixty-three infants were identified. Males 52%.
Mean age 2.7years(range 0-5years). Tumor sites were supratentorial 62%, infratentorial 34.5% and spinal-cord16%. Dissemination was 9.5% at diagnosis. Histologies were: lowgrade astrocytic tumor 43%, embryonal 22%, high-grade
gliomas 13%, ependymal 9.5%, neural and selar tumors 4.8%
and melanocytic and choroid plexus tumor 2%. Optic-pathway
was afected in 25.4% and hypothalamus/hypophysis in 17.5%.
Management included surgery 76% (complete resection 34%,
partial resection 24%, biopsy 13%, and subtotal resection 5%).
No biopsy in 15 cases, some optic-pathway gliomas, DIPG
and a hypophysis tumor. Chemotherapy was administered
in 56%, 23% beyond the first line, and HDCT 6%. Radio-
therapy, administered in 19 (30%), was focal 25% (ependymomas, medulloblastoma and PNET above 2 years-old) and
craneospinal 5% (medulloblastoma and ependymoma above
3.5 years-old). Observation without therapy in 7 cases, predominantly low-grade gliomas. Overall survival 63.5% with
median follow-up of 62 months (range30-109). Most frequent sequelae were neurological (70%) and ophthalmological (52%). Three cases presented no sequelae.
Conclusions: The management of children less than fiveyears with CNS tumors remains challenge. We should consider carefully age, histology and localization for therapeutic decisions. Chemotherapy was administered in most cases
(56%) and may contribute to the delay of RT in some patients.
The role of HDCT in young children needs to be analyzed in
larger studies. In survivors, the tumor and treatment sequelae
were frequent and important.
P-305 Congenital Giant Cell Astrocytomas - A
Comprehensive Clinical, Histopathological and
Molecular Evaluation
W. Grajkowska1 , K. Kotulska2 , J. Trubicka1 , M. Roszkowski3 , E.
Jurkiewicz4 , B. Dembowska-Bagińska5
1 The
Children's Memorial Health Institute, Pathology, Warsaw, Poland;
Children's Memorial Health Institute, Neurology and Epileptology,
Warsaw, Poland; 3 The Children's Memorial Health Institute, Neurosurgery,
Warsaw, Poland; 4 The Children's Memorial Health Institute, Radiology,
Warsaw, Poland; 5 The Children's Memorial Health Institute, Oncology,
Warsaw, Poland
2 The
Background/Objectives: Subependymal giant cell astrocytoma (SEGA) is a brain tumor associated with tuberous sclerosis complex (TSC). It usually grows in a second decade of
life, but may develop in the first months of life. The aim of this
work was to establish the incidence, clinical, histopathological and molecular features, as well as outcome of congenital
SEGA in TSC patients.
Design/Methods: Cohort of 510 TSC patients was reviewed
to identify cases with growing or hydrocephalus producing
SEGAs in the first three months of life. Clinical presentation,
size of the tumor, growth rate, histopahological and mutational analysis, treatment applied, as well as outcome were
evaluated.
Results: Twelve patients (2.4%) presented with SEGA in the
first three months of life. All of them had documented SEGA
growth and all developed hydrocephalus. In nine patients,
mutational analysis was done, and in all of them, TSC2 gene
mutations were identified. Mean maximum SEGA diameter at baseline was 50 mm. Seven patients underwent SEGA
surgery and surgery- related complications were observed in
57.1 % cases. Two patient received everolimus as a primary
treatment.
SIOP ABSTRACTS
S305 of S518
Conclusions: Congenital SEGA develops 2.4% of TSC
patients. Patients with TSC2 mutations, and especially with
TSC2/PKD1 mutations, are more prone to develop SEGA
earlier in childhood and should be screened for SEGA from
birth. In young infants with SEGA, both surgery and mTOR
inhibitor should be considered as a treatment option.
This work was supported by Internal Funding from The
Children's Memorial Health Institute, Warsaw, Poland
(08/ZG/2016, grant titled: “Identification of molecular
background of epilepsy in patients with tuberous sclerosis
complex”).
P-306 Demography and Treatment of
Craniopharyngioma in a Tertiary Centre in India
1
S. Gupta , H. K P
1 All
1
India Institute of Medical Sciences, Radiotherapy, New Delhi, India
Background/Objectives: Craniopharyngioma are rare
tumors of the sellar region. Data on demographic details,
symptomatology, treatment and response is limited from the
Indian sub-continent.
Design/Methods: Patients included in the retrospective analysis were those who presented to the neuro-oncology clinic
under radiation oncology department after surgery between
years 2003 and 2016. The treatment charts were reviewed.
This is an update of data from our institution.
Results: A total of 54 patients were treated. Age of presentation ranged from 2 to 45 years.The sex distribution was
Male:Female of 38:16. The presenting symptom was visual
symptoms in 34 patients, hormonal imbalance in 3, neurological deficit in 1 patient, seizures in 1 patient and raised
intracranial tension in 15 patients. Lesion size was< 4 cm for
32 patients and > 4 cm for 22 patients. Baseline TSH levels
were available for 34 patients (Raised – 1; Decreased – 3).
Baseline GH levels were available for 32 patients(Raised – 0;
Decreased – 3). Baseline prolactin levels were available for
29 patients (Raised – 3; Decreased – 1). Baseline ACTH levels were available for 32 patients (Raised – 1; Decreased – 6).
Radiation was delivered by 3 D- CRT in 41 patients. IMRT in
2 patients and SRT in 1 patient. Radiation dose was 50.4 Gray
in 28 fractions to 55 Gray over 5.5 to 6 weeks.36 patients had a
complete response, 5 patients a partial response. 2 stable disease and 1 progressive disease. 7 patients recurred at local site.
6 patients underwent surgery. 4 of those patients had progressive disease at last follow up. No grade 3 or 4 toxicity was
documented. Univariate analysis done on available data did
not detect any association of age, sex, hormonal perturbations
or lesion size with response to primary therapy or recurrence.
Conclusions: Craniopharyngioma have good response to
surgery with radiation
P-307 SFCE Metro 01 Four-Drug Metronomic
Regimen has Anti-Tumour Activity in Pediatric
Low-Grade Glioma
M.A. Heng-Maillard1 , N. André1 , P. Dory-Lautrec2 , R. Truillet3 , P.
Chastagner4 , P. Leblond5 , I. Aerts6 , N. Corradini7 , N. Entz-Werle8 ,
J.C. Gentet1 , S. Honoré9 , A. Verschuur1
1 La
Timone Children's Hospital, Department of Pediatric Oncology,
Marseille, France; 2 La Timone Children's Hospital, Department of
Neuroradiology, Marseille, France; 3 La Timone Children's Hospital,
CIC-CPCET, Marseille, France; 4 Children's Hospital, Department of
Pediatric Oncology, Nancy, France; 5 Oscar Lambret Centre, Pediatric
Oncology Unit, Lille, France; 6 Institut Curie, Pediatric Department, Paris,
France; 7 Centre Léon Bérard, Department of Paediatric Haematology and
Oncology, Lyon, France; 8 CHU Hautepierre, Pédiatrie Onco-Hématologie,
Strasbourg, France; 9 La Timone Children's Hospital, Department of
Clinical Pharmacy, Marseille, France
Background/Objectives: To investigate the anti-tumour
activity of a 4-drug metronomic regimen in relapsing/refractory pediatric brain tumours (BT) as defined
as progression-free survival (PFS) after 2 cycles (4 months)
of therapy.
Design/Methods: Patients of ≥4 to 25 years of age with progressing BT and adequate organ function. Treatment consisted of an 8-week cycle of oral celecoxib BID daily (D1D56), 100/200/400 mg according to BW, weekly IV vinblastine 3 mg/m2 , oral cyclophosphamide 30 mg/m2 /d qd for 3
weeks alternating with oral methotrexate 10 mg/m2 twice a
week for 3 weeks, with a 2-week rest period. Maximum treatment was 2 years. Kepner and Chang two-steps model was
used with 10 patients in the first stage. If primary objective
was reached in 2 or more patients, 8 additional patients were
recruited. This regimen was considered efficacious if PFS
after 2 cycles was over 34% (alpha 10%, beta 10%).
Results: 29 patients were included in 2 groups: ependymoma
(N=8) and other BT:3 medulloblastoma (MB), 5 high grade
glioma (HGG) (2 of which DPIG), 11 low grade glioma
(LGG), 2 other. One patient with HGG stabilized for 2 years
and one ependymoma stabilized 4 months. None of the other
HGG, ependymoma or MB stabilized. Of the patients with
LGG, median age was 9,5 years, median duration of illness
6,5 years and 10 patients received vinblastine previously. 1 PR
was observed, 8 SD, 1 PD, one non evaluable after 2 cycles.
Median number of cycles was 6 (range 1 to 12). Seven patients
received at least 1 year of therapy. Treatment was interrupted
temporarily in 5 patients for grade 3/4 toxicity.
Conclusions: This metronomic regimen is active in patients
with other BT, especially LGG, even if patients had received
vinblastine previously. (This study was supported by “Enfants
et Santé” Foundation and PHRC-grant).
P-308 Temozolomide Effect on Mitophagy in
Glioblastoma Chemoresistance Cell Lines
SIOP ABSTRACTS
S306 of S518
R. Javed1 , X. Liu2 , F. Akhter3 , J. Zhou2 , X. Liu2 , L. He1
1 Guang
Zhou Women and Children's Medical Center, Guangzhou Institute
of Pediatrics, Guangzhou, China; 2 Guangzhou Institute of Pediatrics,
Pediatrics Department, Guangzhou, China; 3 Higuchi Bioscience Center,
Department of Pharmacology and Toxicology, Kansas, USA
Background/Objectives: Despite aggressive therapies,
including combinations of surgery, radiotherapy and
chemotherapy, GBM remains a highly aggressive brain
cancer with the worst prognosis of any central nervous
system disease; the median post-diagnostic survival period
of GBM patient is approximately one year. Temozolomid
(TMZ) first line chemotherapy drug for GBM, commonly
use in the adjunctive treatment of gliomas and extends
median survival from 12.1 months to 14.6 months but
eventually chemotherapy becomes impaired by development
of chemoresistance. Mitophagy-The targeted degradation
of unneeded and dysfunctional mitochondria, deregulation
have been linked to human cancer. Mitophagy related stress
tolerance can enable cell survival by maintaining energy
production that can lead to tumor growth and therapeutic
resistance.
Background/Objectives: Medulloblastoma is an embryonal
tumor with aggressive behavior and is more commonly seen in
children than adults. The aim of this study was to determine
epidemiological and treatment patterns and implications for
survival in children with medulloblastoma.
Design/Methods: A total of 67 patients younger than 18 years
diagnosed with medulloblastoma from January 2002 to
December 2016 were evaluated in a retrospective cohort in
our institution. Prognostic Factors such as age, risk, surgery,
metastates, leptomeningeal dissemination, time to delay of
surgery, radiation and chemotherapy were analyzed.
Design/Methods: Glioblstoma resistance cell lines T98G,
U251 and U138 were treated with TMZ at different time intervals to induce mitophagy. Confocal Microscopy and Flow
Cytometery were used to monitor Mitophagy.
Results: The median follow-up time was 18.5 months (range
1-146 months). In patients with High-Risk disease, 2 and 5year overall survival (OS) rates were 71.5% and 58.5%, and
Disease Free Survival (DFS) were 53.7% and 33.5%, respectively. In patients with standard-risk disease, 2 and 5-year OS
and DFS rates were 50.5%, 34.4% and 36.3%, 19.9%, respectively. Median duration of symptoms was 31.5 days (range,
0-120). Seventy-one percent of patients presented in Stage 0
and had a localized tumor. Thirty-eight patients received radiation post-surgery (all of them had more than 3 years) by craniospinal irradiation up to 36 gray followed by boost up to 54
gray. Median time to radiation was 39 days (range, 22-120).
In multivariate analysis, group risk was an independent prognostic factor for OS along with metastatic disease, risk and
positive CSF. A delayed start of radiation therapy (>42 days)
was associated to inferior OS (p=0.0186).
Results: Membrane potential (𝚫� m ) results depicted that
U251 and U138 showed no loss of Δ� m at 12h but a significant loss of Δ� m were observed at 24h and 36h. T98G cell
line showed no loss of Δ� m at 24h but showed comparatively
higher loss of Δ� m at 36h and 48h.
Conclusions: In children older than 3 years, a delayed radiation start after surgery was significant factor for unfavorable
prognosis. Early treatment, in addition to a quickly diagnosis, is the key to management of medulloblastoma, which still
needs to be achieved.
Objectives: To investigate whether TMZ can induce
mitophagy in GBM cell lines.
ROS assay results depicted that U138 cells showed slightly
higher ROS positive cells in treated cells than control and similar results were observed in U251. In T98G a very significant
difference were observed at 36h in treated cells than control
compare to 24h and 48h.
Conclusions: This study presents that TMZ could induce
mitochondrial membrane potential decreased and ROS level
increase in GBM cell lines so on the basis of our results we
speculated that TMZ resistance may correlated to mitophagy.
Further study is needed to explore the mitophagy mechanism
in GBM TMZ resistance.
P-309 Childhood Medulloblastoma:
Single-Center Experience of 16 Years in Peru
L. Vasquez1 , C. Alvarez2 , E. leon1
1 Hospital
Nacional Edgardo Rebagliati, Pediatric Oncology, Lima, Peru;
Nacional Edgardo Rebagliati, Fellow of Pediatric Oncology,
Lima, Peru
2 Hospital
P-310 Expression of ERCC1, TOP2A, RFC1,
TUBB3 and MGMT Proteins as Markers of Drug
Resistance to MTX-OPEC and LIKE-SJMB03
Chemotherapy in Childhood Medulloblastoma
A. Levashov1 , D. Khochenkov2 , A. Stroganova3 , M. Ryzhova4 , S.
Babelyan1 , S. Gorelyshev5 , G. Mentkevich1 , N. Subbotina1 , V.
Daylidite1 , I. Dolgopolov1
1 Pediatric
Hematology and Oncology Institution FSBI «N.N. Blokhin
Russian Cancer Research Center», Pediatric Hematology and Oncology
Institution, Moscow, Russia; 2 Experimental Diagnostic and Treatment of
Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center»,
Experimental Diagnostic and Treatment of Tumor Institution, Moscow,
Russia; 3 Department of pathology- FSBI «N.N. Blokhin Russian Cancer
Research Center», Department of pathology, Moscow, Russia; 4 Department
of Neuropathology- N.N. Burdenko Neurosurgical Institute, Department of
Neuropathology, Moscow, Russia; 5 Department of Neurosurgery №1- N.N.
Burdenko Neurosurgical Institute, Department of Neurosurgery №1,
Moscow, Russia
SIOP ABSTRACTS
Background/Objectives: According to data of some international pediatric protocols there were revealed markers of unfavorable outcome (C-MYC/N-MYC gene amplification, iso17q
(Group3)), but expression of drug resistance proteins in tumor
specimens is unknown. The aim of this study was to estimate
ERCC1, TOP2a, RFC1, TUBB3 and MGMT proteins expression in medulloblastoma specimens.
Design/Methods: ERCC1, TOP2a, RFC1 and MGMT proteins expression was assessed by immunohistochemical
method using anti-ERCC1 (clone 8F1, Abcam), anti-TOP2a
(Ki-S1, Dako), anti-RFC1 (SCL19A1ab, Genetex), antiTUBB3 (TU-20, SantaCruz), anti-MGMT (MT3.1, Thermo).
ERCC1, TUBB3 and MGMT positive specimen was defined
as weak (+), moderate (++), strong (+++) colouring of the
tumor nuclei and cytoplasm (for ERCC1 and MGMT), nuclei
(for TUBB3) with number of positive tumor cells above 10%
(for both ERCC1 and TUBB3), 25% (for MGMT). TOP2a
and RFC1 positive specimen was defined as moderate (++),
strong (+++) colouring of the tumor nuclei and cytoplasm
(for TOP2a), membrane (for RFC1) with number of positive
tumor cells above 25%.
Results: ERCC1 positive samples were revealed in 18 out of
31 samples (58%; 66.7% for infants, 54.5% for children, p
= 0.535), TOP2a in 13 out of 31 (41.9%; 33.3% for infants,
45.5% for children, p = 0.535), RFC1 in 9 out of 33 (27.2%;
0% for infants, 37.5% for children, p = 0.031), TUBB3 in 18
out of 26 (69%) and MGMT in 23 out of 37 (62%, 44.4% for
infants, 67.8% for children, p = 0.208). There was also determined significant correlation between TOP2a positive specimen and molecular subgroups of medulloblastoma (33.3% for
SHH, 100% for Group 3 and 20% for Group 4, p = 0.025).
Conclusions: These data suggest that absence RFC1 expression in infant's medulloblastoma specimen could decrease
effectiveness of methotrexate in this group. Etoposide could
show more effectiveness against SHH and Group 3 medulloblastoma.
P-311 Expression of Cytokine-Associated
Proteins (VEGF, VEGFR1, VEGFR2, PDGFRA,
PDGFRB, GCSFR) and Transcription Factors
(C-MYC, P-STAT3TYR705) in Childhood
Medulloblastoma
A. Levashov1 , D. Khochenkov2 , A. Stroganova3 , M. Ryzhova4 , S.
Gorelyshev5 , G. Mentkevich1 , S. Babelyan1 , N. Subbotina1 , V.
Daylidite1 , I. Dolgopolov1
1 Pediatric
Hematology and Oncology Institution FSBI «N.N. Blokhin
Russian Cancer Research Center», Pediatric Hematology and Oncology
Institution, Moscow, Russia; 2 Experimental Diagnostic and Treatment of
Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center»,
Experimental Diagnostic and Treatment of Tumor Institution, Moscow,
Russia; 3 Department of pathology- FSBI «N.N. Blokhin Russian Cancer
Research Center», Department of pathology, Moscow, Russia; 4 Department
S307 of S518
of Neuropathology- N.N. Burdenko Neurosurgical Institute, Department of
Neuropathology, Moscow, Russia; 5 Department of Neurosurgery №1- N.N.
Burdenko Neurosurgical Institute, Department of Neurosurgery №1,
Moscow, Russia
Background/Objectives: The aim of this study was to
estimate expression of cytokine-associated proteins (VEGF,
VEGFR1, VEGFR2, PDGFRb, GCSFR) and transcription
factors (C-MYC, p-STAT3tyr705 ) in medulloblastoma specimens.
Design/Methods: These proteins expression was assessed by
immunohistochemical method using anti-VEGF (clone VG1,
Daco), anti-VEGFR1 (Polyclonal, Dako), anti-VEGFR2 (A3,
SantaCruz), anti-PDGFRb (P-20, SantaCruz), antu-CMYC
(EP121, CellMarque), anti-p-STAT3tyr705 (EP2147Y, Genetex), anti-GCSF3R (S2184, Genetex) antibodies. Positive
specimen was defined as: weak (+), moderate (++), strong
(+++) colouring of the tumor membrane and cytoplasm for
VEGF, VEGFR, PDGFR, GCSFR, cytoplasm and nuclei for
C-MYC, p-STAT3tyr705 with number of positive tumor cells
above 25%.
Results: There was no estimated VEGF positive specimens
within this group (0 out of 26). VEGFR1, VEGFR2 positive samples were revealed in 10 out of 26 samples (38.4%),
PDGFRb in 9 out of 27 (33.3%), GCSFR in 24 out of 37
(64.5%), p-STAT3tyr705 in 9 out of 39 (23%) and C-MYC in
2 (both with C-MYC amplification) out of 8 (25%, only in
Group 3). p-STAT3tyr705 positive specimens were presented
in patients with M0 status in 8 out of 26 (30.8%), with M1
in 1 out of 13 (7.7%), predominantly with SHH medulloblastoma in 5 out of 15 (33,3%). GCSFR positive specimens were
presented in patients with M0 status in 18 out of 25 (72%),
with M1 in 6 out of 12 (50%), predominantly with SHH (10
out of 15 – 66.7%) and Group 4 medulloblastoma (8 out of
11 – 72.7%). There was not determined significant correlation between positive specimens and age groups (infants and
children), C-MYC/N-MYC amplification, iso17q.
Conclusions: These data suggest that childhood medulloblastoma is characterized by low activity of autocrine mechanism stimulation VEGF/VEGFR and PDGFR-dependent signal pathway, decreased level of transcription factors (excluding variants with C-MYC amplification) and high activity of
GCSFR-dependent signal pathway.
P-312 A 40-Year Multi-Institutional Review of
Intracranial Germ Cell Tumours in Adolescents
and Young Adults
A. Lo1,2,3,4 , N. Laperriere3,4 , D. Hodgson3,4 , J. Dang4 , S.
Tyldesley1,2 , E. Bouffet5,6 , U. Bartels5,6 , S. Cheng7,8 , J. Hukin8,9 , P.
Bedard10,11 , K. Goddard1,2
1 British
Columbia Cancer Agency, Radiation Therapy, Vancouver, Canada;
of British Columbia, Surgery, Vancouver, Canada; 3 University
of Toronto, Radiation Oncology, Toronto, Canada; 4 Princess Margaret
2 University
SIOP ABSTRACTS
S308 of S518
Cancer Centre, Radiation Medicine Program, Toronto, Canada; 5 The
Hospital for Sick Children, Hematology/Oncology, Toronto, Canada;
6 University of Toronto, Paediatrics, Toronto, Canada; 7 British Columbia
Children's Hospital, Hematology/Oncology, Vancouver, Canada;
8 University of British Columbia, Pediatrics, Vancouver, Canada; 9 British
Columbia Children's Hospital, Neurology, Vancouver, Canada; 10 Princess
Margaret Cancer Centre, Hematology/Oncology, Toronto, Canada;
11 University of Toronto, Medicine, Toronto, Canada
Background/Objectives: The study aim was to determine the
outcomes and complications of intracranial germ cell tumours
(IGCT) in adolescents and young adults (AYA) according to
different therapeutic approaches.
Design/Methods: One-hundred ten patients with IGCT aged
15–39 were managed at either Princess Margaret Cancer
Centre or British Columbia Cancer Agency from 1975–
2015. The charts of these patients were retrospectively
reviewed. Kaplan-Meier analyses were performed to calculate outcomes and complication rates at 10 years after
treatment.
Results: Median duration of follow-up was 9.3 years. Ninety
patients had germinomas, and 20 had non-germinomatous
germ cell tumours (NGGCT). Thirteen patients (12%) presented with spinal metastatic disease. Progression-free survival (PFS) was 82% and overall survival (OS) was 87%. For
patients with germinoma, PFS was 91% after craniospinal
radiation therapy (CSRT) with chemotherapy (N=11), 100%
after whole ventricular RT (WVRT) or tumour bed RT
(TBRT) with chemotherapy (N=20), 91% after CSRT alone
(N=43), and 37% after WVRT, whole brain RT, or TBRT
alone (N=15) (P<0.0005); OS was 91%, 100%, 91%, and
70%, respectively (P=0.046). For patients with NGGCT, PFS
was 83% after CSRT with chemotherapy (N=6), 67% after
CSRT alone (N=3), and 58% after TBRT with chemotherapy
(N=8) (P=0.28); OS was 100%, 67%, and 58%, respectively
(P=0.17). Irradiation-induced complications included a 14%
rate of hypopituitarism, 5% seizure disorder, 2% second neoplasms, 1% cerebrovascular events, and 1% visual deterioration. Treatment-induced hearing loss or tinnitus was 10% after
RT alone, and 28% after both chemotherapy and RT. Neurocognitive impairment from either disease or treatment was
43% after CSRT or WBRT (N=69), 48% after WVRT (N=23),
and 17% after TBRT (N=18).
Conclusions: We demonstrate excellent overall outcomes
in the largest study of IGCT in AYA to our knowledge.
High relapse rates were observed after non-CSRT without chemotherapy in germinoma, and after TBRT with
chemotherapy in NGGCT.
Acknowledgements: Funded by Brain Tumour Foundation of
Canada
P-313 Outcomes for Pediatric Medulloblastoma –
A Single Institute Experience
T. Mehmood1
1 Shaukat
Khanum Memorial Cancer Hospital and Research Centre,
Radiation Oncology, Lahore, Pakistan
Background/Objectives: We retrospectively examined the
incidence, outcomes by treatment type, especially use of
radiotherapy of medulloblastoma patients from 2001 to 2010.
Design/Methods: The outcomes according to treatment, 5year groups (2001-2005, 2006-2010) M status, gender, age,
and use of radiotherapy in first line treatment are presented.
Results: 76 patients were treated over 10 years, 40 male and
36 female. 44 patients had M0 disease and 32 had metastatic
disease. There were 34 patients under age 5 with a greater proportion having M+ disease: 42% vs. 30% for those older. First
line therapy was chemotherapy only in 9.6% of patients, radiotherapy only in 11.4%, with a decrease from 16.4% in the first
group (2001-2005) to 6.8% in the second group (2006-2010),
and combined chemotherapy and radiotherapy in 60.8% of
patients. In the 2001-2005 period, high dose chemotherapy
was used alone in 8.7% and with radiotherapy in 23.1%. Survival at 5 years was 80% for patients receiving radiotherapy
and 40% for those not receiving radiotherapy (p= 0.0001).
Stage M0 vs. M+, and age under 5 years were also significantly related to survival (both p=0.038) in the COX Hazard
model. There was no difference in survival by gender or 5-year
periods.
Conclusions: There was no improvement in survival over the
study time period, and the use of radiotherapy as first line was
the most important prognostic factor. Younger children, under
5 years, presented with a worse stage. There was an independent effect of young age and stage on prognosis, but to a much
lower extent than the use of radiotherapy as first line therapy.
P-314 Clinical Management of Pediatric
Ependymoma in Iran: A Retrospective Single
Center-Based Study
M. Tashvighi1 , A. Mehrvar1 , A.A. Hedayati Asl1 , N. Mehrvar2 , A.
Naderi1 , M. Alebouyeh1 , I. Qaddoumi3 , M. Faranoush1
1 MAHAK
Pediatric Cancer Treatment and Research Center, Oncology,
Tehran, Iran; 2 Cancer Research Center, Shahid Beheshti University of
Medical Sciences, Tehran, Iran; 3 St. Jude Children's Research Hospital,
Oncology, Memphis, USA
Background/Objectives: The literature on treating pediatric
ependymoma in Iran is scarce. Thus, we designed this study
to review the clinical care, treatment regimens, and follow-up
of Iranian pediatric patients with ependymoma.
Design/Methods: Data were gathered from medical records
retrospectively based on definitive inclusion and exclusion
criteria. All of the patients were younger than 15 years and
had an approved histopathology report confirming the diagnosis of ependymoma. Patients were divided into two sub-
SIOP ABSTRACTS
groups based on their age at diagnosis (i.e., ≤3 years vs >3
years) and type of initial surgical procedure (i.e., surgery
vs. biopsy). Finally, parametric and nonparametric statistical
analyses were done SPSS software (ver 22).
Results: In total, 73 eligible patients were enrolled in the
study; 20 patients were categorized into the younger group
and 53 into the older group. The majority (91.8%, n=67) of
patients underwent initial gross-total or partial surgical resection, and six (8.2%) had a biopsy. Thirty patients delayed diagnosis more than 1 month after the onset of clinical signs or
symptoms, and 21 patients experienced ependymoma recurrence. The median duration of follow-up was 49 months. The
3-year overall survival and progression-free survival rate were
61% and 48.5%, respectively. At the time of this review, 27
patients had died of various causes.
Conclusions: We conclude that accurate disease staging and
histopathology reporting and standardized radiotherapy and
chemotherapy regimens need to be implemented in Iran to
improve the clinical care and follow-up of pediatric patients
with ependymoma.
Acknowledgement: We thank colleagues in the Medical
Records department at MPCTRC who provided the medical
documents for this review, Mr. Tim Hammond for assistance
with graphic design of the figures, and Dr. Angela McArthur
for editing the manuscript.
S309 of S518
NF1 gene status. All patients remain in follow-up except one,
who died from other cause.
Results: The age at diagnosis of optic pathway gliomas
ranged from 3 months-10 years. (Medium: 3 years). Group
I: The age ranged from 3 months-6 years (Median: 4 years).
Total visual loss after biopsy was noted in two cases. Group
II: The patients’ age ranged from 8 months-3 years (median:
2 years). They had progressively decrease visual activity at
diagnosis. They received chemotherapy. Significant improvement of the visual activity was noted. Group III: The patients’
age ranged from 3 years-10 years (Median: 3 years). They
received chemotherapy, but there was no improvement of the
visual activity.
Conclusions: 1) Children with Café au lait spots need a careful monitoring of the visual activity and imaging for optic
glioma. 2) Early diagnosis of tumor and detection of visual
impairment may help to improve the visual activity with
chemotherapy. 4) Chemotherapy is not effective in delay diagnosis of the optic pathway gliomas.
P-316 Oxytocin in Childhood-Onset
Craniopharygioma - First Experiences with
Neuropsychological Effects of Oxytocin
Administration
H.L. Müller1 , A. Daubenbüchel1 , A. Hoffmann1 , K. Tjaden1 , S.
Boekhoff1 , M. Warmuth-Metz2 , J. Özyurt3
P-315 Early Diagnosis of Optic Glioma in
Children with Neurofibromatosis Type 1 (NF1)
M. Moschovi1 , M. Nikolaou1 , A. Athanasiadou1 , I. Nikas2 , G.
Chrousos3
1 University of Athens Medical School, 1st Pediatric DeptHematology/Oncology Unit, Athens, Greece; 2 “Aghia Sofia” Children's
Hospital, Department of Imaging, Athens, Greece; 3 University of Athens
Medical School, 1st Pediatric Department, Athens, Greece
Background/Objectives: Children with neurofibromatosis
type-1 (NF1) develop optic pathway gliomas, which result
from impaired NF1 protein regulation of Ras activity. The
importance of early diagnosis of optic pathway gliomas in
children with Nf1, in order to eliminate the impairment of
visual activity.
Design/Methods: Twenty one children with optic pathway
gliomas who were diagnosed and treated in our unit were
enrolled in this study. Patients were divided in three groups.
Group 1: seven patients without café-au-lait spots who were
diagnosed because of symptoms caused by the tumor. Group
II: seven patients with café-au-lait spots who had a routine
follow-up with brain-MRI, from early age. Group III: seven
patients with café-au-lait spots without routine follow-up who
were diagnosed due to visual loss or heavy decrease of visual
activity. All patients received chemotherapy according to the
1 Klinikum
Oldenburg AöR- Medical Campus University Oldenburg,
Department of Pediatrics and Pediatric Hematology / Oncology,
Oldenburg, Germany; 2 University of Würzburg, Department of
Neuroradiology, Würzburg, Germany; 3 Carl von Ossietzky UniversityOldenburg, Department of Psychology, Oldenburg, Germany
Background/Objectives: Quality of survival after childhood
craniopharyngioma (CP) is frequently impaired by hypothalamic involvement (HI) and sequelae such as obesity and neuropsychological deficits. Oxytocin (OXY) is produced in the
hypothalamus, secreted by posterior pituitary gland, and plays
a major role in regulation of behavior and body composition.
Design/Methods: In a cross-sectional study, OXY saliva concentrations were analyzed in 34 CP and in 73 healthy controls. OXY was measured in saliva before and after standardized breakfast and associations with gender, body mass
index (BMI), HI, diabetes insipidus, and irradiation were analyzed. Furthermore, emotion recognition abilities were analyzed with regard to OXY concentrations in saliva and urine
before and after nasal administration of 24 IU OXY in 10
CP with hypothalamic lesions (4 grade I: limited to anterior hypothalamus; 6 grade II: involving mammillary bodies
and posterior hypothalamus). Perception and identification of
emotional expressions were tested using the Geneva Multimodal Emotion Portrayals (GEMEP) corpus. Mental state was
assessed by Multidimensional Mood Questionnaire.
SIOP ABSTRACTS
S310 of S518
Results: CP with preoperative HI showed similar OXY levels
compared to CP without HI and controls. However, CP with
grade I hypothalamic lesions presented with lower OXY levels (p=0.017) under fasting condition compared to CP with
grade II lesions and CP without hypothalamic lesions. CP
patients’ changes in OXY levels before and after breakfast correlated (p=0.02) with BMI. In a pilot trial, nasal administration of OXY was well tolerated and resulted in increased OXY
concentrations in saliva and urine. After OXY administration, CP with grade I hypothalamic lesions showed improvements in emotional identifications compared to CP with grade
2 lesions.
Conclusions: CP patients continue to secrete OXY, especially
when anterior hypothalamic areas are not involved, but OXY
shows less variation due to nutrition. OXY might have positive effects on emotion perception in CP with specific lesions
of anterior hypothalamic areas.
P-317 The Oncogenic Role of a Novel
KLC1-ROS1 Fusion Gene Identified in a Pediatric
Low-Grade Glioma
Y. Nakano1 , A. Tomiyama1 , K. Yamasaki1 , H. Fukushima2 , T.
Inoue2 , T. Kohno3 , A. Yoshida4 , K. Fukuoka1 , Y. Matsusaka5 , J.
Hara6 , H. Sakamoto5 , K. Ichimura1
1 National
Cancer Center Research Institute, Division of Brain Tumor
Translational Research, Tokyo, Japan; 2 Osaka City General Hospital,
Department of Pathology, Osaka, Japan; 3 National Cancer Center
Research Institute, Division of Genome Biology, Tokyo, Japan; 4 National
Cancer Center Hospital, Department of Pathology and Clinical
Laboratories, Tokyo, Japan; 5 Osaka City General Hospital, Department of
Pediatric Neurosurgery, Osaka, Japan; 6 Osaka City General Hospital,
Department of Pediatric Hematology/Oncology, Osaka, Japan
Background/Objectives: We investigated novel oncogenic
fusion genes identified in pediatric gliomas for their potential
as novel therapeutic targets.
Design/Methods: RNA sequencing was performed on three
pediatric low grade gliomas which did not harbor any of
the oncogenic driver mutations known in gliomas (BRAF,
FGFR1, IDH1, IDH2 and H3F3A) to discover novel oncogenic gene fusions. The presence of candidate fusion genes
in clinical samples was verified by fluorescence in-situ
hybridization and their expression by reverse transcription
polymerase chain reaction and immunohistochemical staining. Several oncogenic signal transduction pathways and
oncogenic phenotypes mediated by these candidates were
also analyzed by immunoblotting, focus forming assay, and
invasion assay using glioma cell lines overexpressing these
candidates.
Results: We identified a novel KLC1-ROS1 fusion gene in
a low-grade glioma from a three-years-old female patient.
Expression of this fusion RNA and protein in the clinical sample was confirmed. An immunoblot analysis of cell lysates
of glioma cell lines expressing the KLC1-ROS1 fusion gene
demonstrated an elevated activation of growth factor-related
signaling such as ERK1/2, Akt, or mTOR. Furthermore, the
glioma cell lines transfected with this fusion gene demonstrated enhanced formation of foci by focus forming assay and
elevated invasiveness by transwell invasion assay, all of which
were blocked by treatment with ROS1 inhibitor, Crizotinib.
Conclusions: The novel KLC1-ROS1 fusion gene which we
identified from a pediatric low grade glioma has an oncogenic
activity via ROS1 signaling and could potentially serve as a
novel therapeutic target against gliomas which possess this
fusion gene.
P-318 Molecular Characterization of NF1 Gene
in a Small Turkish Population with
Neurofibromatosis Type 1 and a Novel Mutation
F.G. Pinarli1 , F. Alpaslan Pinarli2 , H. Saat2 , C. Yildirimoglu2 , A.
Okur1 , C. Karadeniz1
1 Gazi
University Medical Faculty, Pediatric Oncology, Ankara, Turkey;
Yildirim Beyazit Research Hospital, Medical Genetics, Ankara,
Turkey
2 Diskapi
Background/Objectives: Neurofibromatosis type I (NF1)
is an autosomal dominant disorder caused by heterozygous
mutations in the neurofibromin gene (NF1; 613113) on chromosome 17q11. Here we describe the results of next generation sequencing (NGS) of 18 patients who presented with
the clinical features of NF-1 at Gazi University Department
of Pediatric Oncology.
Design/Methods: DNA was isolated from peripheral blood
using MagNA Pure LC DNA Isolation Kit. Ion Ampliseq Custom NF Panel has been designed and used for massively parallel sequencing for target regions (all Exons, UTRs, Splicing sites) of NF1 gene with IonS5. Mutation surveying has
been done by using Ion Reporter and Alamut Visual software
and different mutation databases and tools according to the
2016 ACMG Variant Classification and Interpretation Guideline. Detected mutations which have been linked with Clinical
data have been confirmed with DNA Sequencing by Capillary
electrophoresis by using 3130 (Applied Biosystems).
Results: The study included 10 male and 8 female patients
with a median age of 10.5 years. Sixteen patients were diagnosed as NF-1 according to clinical criteria. Two patients
had only multiple café-au-lait spots. The family history was
present in 7 patients (38.9%). Three patients had optic gliomas
(16.7%) and one patient was diagnosed as atypical meningioma after surgical excision. We detected a genetic variant in 12 patients (66.6%) via NGS. The types of these
mutations were as follows: likely benign (n=1), variants of
uncertain significance (VUS, n=2), likely pathogenic (n=3),
VUS + pathogenic (n=1), and pathogenic (n=5). One of the
SIOP ABSTRACTS
pathogenic variants is c.7023delC (p.Leu2342Cysfs*4) heterozygote at 47th exon, which was not previously described in
the NF-1 database, ithus ndicating a novel mutation.
Conclusions: We describe a novel NF-1 gene mutation in a
Turkish patient. The lack of mutation detection in 33,3% of
our patients indicate that other methods than NGS must be
used in NF-1 mutation screening.
P-319 Pediatric Medulloblastoma Experience in
Mexico
V. Salceda-rivera1 , F. Arreguin2 , R. Gonzalez3 , R. Bellido4 , I.
Tejocote5 , S. Anaya6 , R. Rivera-luna7 , E. Perez8 , E. Reyes9 , D.
Ortiz10 , R. Rivera11 , C. Leal12 , A. Garcia13 , N. Garcia14 , S.
Lagarda15 , T. Larios16 , D. Cortes17 , C. Simon18 , A. Lopez19 , J.
Finlay20
1 Onkokid,
Pediatric Oncology, Guadalajara, Mexico; 2 Centro Médico
Nacional 20 de Noviembre, Pediatric Oncology, Ciudad de Mexico, Mexico;
3 Centenario Hospital Miguel Hidalgo de Aguascalientes, Pediatric
Oncology, Aguascalientes, Mexico; 4 Hospital General Regional de León,
Pediatric Oncology, Leon, Mexico; 5 Hospital para el Niño IMIEM,
Pediatric Oncology, Toluca, Mexico; 6 Centro Médico Nacional La Raza,
Pediatric Oncology, Ciudad de Mexico, Mexico; 7 Instituto Nacional de
Pediatría, Pediatric Oncology, Ciudad de Mexico, Mexico; 8 Hospital
Infantil de Morelia Eva Samano de López Mateos, Pediatric Oncology,
Morelia, Mexico; 9 Hospital de Especialidades del Niño y la Mujer,
Pediatric Oncology, Queretaro, Mexico; 10 Hospital General de México
“Eduardo Liceaga”, Pediatric Oncology, Ciudad de Mexico, Mexico;
11 Hospital General de Tijuana, Pediatric Oncology, Tijuana, Mexico;
12 Hospital Universitario Dr. Jose E. González UNAL, Pediatric Oncology,
Monterrey, Mexico; 13 Hospital Infantil de Especialidades, Pediatric
Oncology, Chihuahua, Mexico; 14 Hospital del niño Dr. Federico Gómez
Santos, Pediatric Oncology, Coahuila, Mexico; 15 Instituto Estatal de
Cancerología de Colima, Pediatric Oncology, Colima, Mexico; 16 Hospital
Infantil e Integral de la mujer del Estado de Sonora, Pediatric Oncology,
Sonora, Mexico; 17 Hospital del Niño DIF del Estado de Hidalgo, Pediatric
Oncology, Pachuca, Mexico; 18 Hospital del Niño Dr. Rodolfo Nieto Padrón,
Pediatric Oncology, Tabasco, Mexico; 19 Hospital materno infantil de
ISSEMYM, Pediatric Oncology, Toluca, Mexico; 20 Nationwide Children's
Hospital, Pediatric Neuro-Oncology, Columbus, Mexico
Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. Data from developing
countries is limited. We describe our multi-institutional experience in pediatric medulloblastoma in Mexico.
Objectives: To describe the clinical features of Mexican children with medulloblastoma. Draw comparisons of the different chemotherapy regimens used, determine patient overall
(OS) and event-free survival (EFS). Determine clinical risk
factors for death or relapse.
Design/Methods: We conducted a retrospective multivariate
analysis of patients with medulloblastoma from 20 hospitals
around Mexico, between 1997-2017. Statistical methods used
were the Kaplan-Meier curve, the survival log-rank test, and
Cox-regression model. Patients were divided into two groups:
1)children >3-5 years of age with non-metastatic disease, and
post-surgical tumor <1.5cm2 , compromised the standard-risk
S311 of S518
group; 2)patients without the previously mentioned characteristics were classified as high-risk.
Results: A total of 255 patients were included with an
average age at diagnosis of 6.8 years (0.1-17yo), 17.6%
<3yo, 23.1% were standard-risk, and 76.9% were high-risk.
Histology: classic (53.3%), desmoplastic (14.5%), anaplastic/large cell (9.4%), not specified (22.7%). According to
Chang's classification: M0(53.3%), M1(15.7%), M2(11.8),
M3(11%), M4(2%). Chemotherapy regimens used were: ICE
(52.2%), cisplatin-based (22%), carboplatin-based (10.6%),
others (3.5%). The platinum-based regimens had better OS
compared to ICE (5y-EFS 71.1% vs. 64.1%; p=0.002). The
average radiation therapy dose was 29Gy (10-55Gy) craniospinal and 52.5Gy (24-56Gy) to the posterior fossa. The
hazard ratios calculated at p<0.05 were as follows: high-risk
3.55, residual tumor >1.5cm2 3.53, anaplastic 2.5, presence
of metastasis 1.76, ICE protocol 1.73. The 5y-OS was 61.1%
and the 5y-EFS 54.2%.
Conclusions: The most commonly used chemotherapy regimen was ICE and was related to a significantly lower OS.
Patients with residual tumor, anaplastic histology or metastasis were also associated with a lower OS. We need multiinstitutional prospective clinical trials to better define survival, risk factors and outcome in Mexico.
P-320 Medulloblastomas in Children Under Five
Years: Current Prognostic Factors and Treatment
Results
E. Salnikova1 , S. Ozerov1 , A. Samarin2 , A. Ektova3 , M. Ryzhova4 ,
A. Korshunov5 , O. Zheludkova6 , L. Papusha1 , I. Borodina7 , A.
Nechesnyuk8 , D. Kobyzeva8 , O. Shcherbenko9 , S. Gorbatykh10 , E.
Erega11 , A. Shapochnik12 , E. Inyushkina13 , A. Karelin14 , A.
Rumyantsev15 , E. Kumirova1
1 Dmitry
Rogachev National Research Center of Pediatric HematologyOncology and Immunology, Neurooncology, Moscow, Russia; 2 Dmitry
Rogachev National Research Center of Pediatric Hematology- Oncology
and Immunology, Surgery, Moscow, Russia; 3 Dmitry Rogachev National
Research Center of Pediatric Hematology- Oncology and Immunology,
Patomorfology, Moscow, Russia; 4 N. N. Burdenko Scientific Research
Neurosurgery Institute, Neuropatomorfology, Moscow, Russia; 5 The
German Cancer Research Center, Patomorfology, Heidelberg, Germany;
6 Federal State Budgetary Institution Russian Scientific Center of
Roentgenoradiology, Oncology, Moscow, Russia; 7 Dmitry Rogachev
National Research Center of Pediatric Hematology- Oncology and
Immunology, Polyclinic, Moscow, Russia; 8 Dmitry Rogachev National
Research Center of Pediatric Hematology- Oncology and Immunology,
Radiotherapy, Moscow, Russia; 9 Federal State Budgetary Institution
Russian Scientific Center of Roentgenoradiology, Radiology, Moscow,
Russia; 10 Morozovsky Children's City Hospital, Oncology, Moscow, Russia;
11 Children's regional clinical hospital, Oncogematology, Khabarovsk,
Russia; 12 Orenburg regional oncological clinic, Children's dep, Orenburg,
Russia; 13 Moscow regional oncological clinic, Children's dep, Balashiha,
Russia; 14 Dmitry Rogachev National Research Center of Pediatric
Hematology- Oncology and Immunology, Medical and rehabilitation
scientific center, Moscow, Russia; 15 Dmitry Rogachev National Research
Center of Pediatric Hematology- Oncology and Immunology, Director
General, Moscow, Russia
SIOP ABSTRACTS
S312 of S518
Background/Objectives: Current diagnostic capabilities will
enable to modify risk group and individualize treatment
patients with medulloblastoma. To evaluate treatment results
of 48 patients under 5 years (13-57m, median 42.5m) with
primarily diagnosed medulloblastoma (MB) depending on the
current risk factors.
Design/Methods: We retrospectively analyzed the data of
48 patients, who are observed in Rogachev's Center from
September 2002 till February 2017. Molecular genetic testing
was perfomed in all cases (DKFZ, Germany): Gr3 was diagnosed in 21 cases (44%), Gr4 - 12 (25%), SHH - 14 (29%),
WNT in 1. MYC/MYCN amplification/17q gain/17q loss/6q
loss were in 3/2/17/11/1 cases. HIT 2000/2008 treatment regimen used in 25 patients. Gr3: M0/M+ 9/12, R0/R+/Rx 6/14/1,
classic/anapl/desmo 15/4/2, without regional MTX/with
intraventricular/intrathecal MTX 14/6/1, with/without RT
20/1, PD in 11 cases (52.4%), are alive 14 (66.7%). Gr4:
M0/M+ 5/7, R0/R+ 5/7, classic/anapl/desmo 8/3/1, without
regional MTX/with intraventricular/intrathecal MTX 10/1/1,
with/without RT 11/1, PD in 2 cases (16.7%), are alive
10 (83.3%). SHH: M0/M+ 7/7, R0/R+/Rx 6/6/2, classic/anapl/desmo 2/1/11, without regional MTX/with intraventricular/intrathecal MTX 7/6/1, with/without RT 10/4, PD in
3 cases (21.4%), are alive 12 (85.7%).
Results: OS in Gr3/Gr4/SHH/WNT 0.63/0.77/0.86/1.00
(р=0.15). PFS in Gr3/Gr4/SHH/WNT 0.47/0.83/0.79/1.00
(р=0.06). PFS with/without MYC/MYCN-amplification
0.4/0.69 (p=0.16). Gr3 PFS: 12-36m/36-60m 0.33/0.5
(p=0.56); R+/R0 0.44/0.5 (p=0.59); М0/М+ 0.56/0.42
(р=0.57);
classic/anapl/desmo
0.53/0.5/0
(р=0.73);
with/without regional MTX 0.5 (p=0.82); with RT 0.5±0.11.
Gr4 PFS: 36-60m 0.81±0.12, single patient 12-36m is alive,
without PD; R+/R0 0.72/1.00 (p=0.24); М0/М+ 0.8/0.86
(р=0.90); classic/anapl 0.73/1.00 (р=0.33); without/with
local MTX 0.79/1.00; with/without RT 0.81/1.00. SHH PFS:
12-36m/36-60m 0.72/0.86 (p=0.53); R0 0.67, R+patients
are alive, without PD; М0/М+ 0.72/0.86 (р=0.53); desmo
0.73±0.08; with intraventrMTX 0.5±0.15, patients without
regional MTX are alive, without PD; with/without RT
0.8/0.75 (p=0.84).
Conclusions: The worst prognosis in Group 3 patients under
3 years, with R+, M+. For further strategy treatment verification additional studies are needed.
1 Amrita
Institute of Medical Sciences, Department of Medical Oncology,
Ernakulam, India; 2 Amrita Institute of Medical Sciences, Department of
Radiation Oncology, Ernakulam, India
Background/Objectives: Treatment outcomes for medulloblastoma with optimal therapy (surgery, radiation and
chemotherapy) have led to 5-year overall survival (OS) rates
in developed countries of 80% and 60% for standard and high
risk disease, respectively. In resource limited settings, similar outcomes are possible and new challenges include followup of treatment related side effects. This study assessed the
outcomes of medulloblastoma in a tertiary care setting and
follow-up of these patients.
Design/Methods: A total of 36 cases of medulloblastoma
below 18 years were treated on POG9031 or CCG9921
between January 2005 and January 2015. Patients were classified as standard risk or high risk disease based on modified
Chang criteria. The prognostic value of age, sex, risk category,
histopathological variants was assessed by univariate analysis
using the log-rank test. Nonparametric OS curves were computed using the Kaplan-Meier estimates, and the log-rank test
was used to compare survival according to histologic subtype.
Results: A total of 27 cases were eligible for analysis. The
median age of diagnosis was 8 years and median follow-up
was 24 months. The 5-year OS and 95% confidence interval was 90% (95% CI: 47-99%) and 60% (95% CI:13-88%)
for standard risk and high-risk disease, respectively. 17 (63%)
cases had regular follow-up with a medical provider post completion of therapy, 8 (33%) cases were documented to have
mild cognitive decline, though no formal testing had been
done.10 cases (40%) were regularly followed for endocrine
sequelae, of which 2 cases (7%) had a diagnosed growth hormone deficiency.
Conclusions: Based on our institutional data, we found that
our medulloblastoma outcomes were similar to what has been
reported in developed countries.
However new challenges exist in the follow-up and management of treatment related side effects in these patients. This
underlies the current need for multi-disciplinary follow-up
and care of this ever-growing population of cancer survivors.
P-322 Evaluation of Gaze Stability by Eye
Tracking Method in Patients with Medulloblastoma
M. Shurupova1 , V. Anisimov1 , A. Drenyova1 , A. Latanov2 , V.
Kasatkin1
P-321 The Changing Paradigm of Pediatric
Medulloblastoma in Kerala; Improved Outcomes
with New Challenges
1
1
1
1
2
S. Kotne , A. Philip , R. Pillai , W. Jose , D. Menon , K.
Pavithran1 , H. Sankaran1
1 Dmitry
Rogachev National Research Center, Clinical Rehabilitation
Research Center for patients in remission “Russkoye pole”, Moscow,
Russia; 2 Lomonosov State University, Faculcity of Biology, Moscow, Russia
Background/Objectives: Cerebellum plays a crucial role in
motor control and planning. The lesions of the cerebellum
lead to oculomotor impairments. Medulloblastoma is a severe
SIOP ABSTRACTS
disease and is localized mostly in the area of vermis and hemispheres of cerebellum. Presence of a malignant growth and
therapy's toxicity lead to stable invalidism.
Design/Methods: We assessed the feasibility of a test of
gaze stabilization on a target in patients with medulloblastoma. Patients underwent a standard course of rehabilitation
in Rehab Centre “Russian Field” (Chekhov, Russian Federation). Five patients (three girls and two boys, aged 13.4-17.9
years) and eight normal subjects (three girls and five boys,
aged 10.6-15.2 years) participated in the study. Eye movements were recorded by Arrington Research 60 Hz eye tracker.
In experiments the participants performed the gaze stabilization test (GST) involved the focusing on the four targets (left
and right, up and down at ±19◦ and ±11◦ of eccentricities,
respectively). Two GST sessions were carried out during first
and second rehabilitation courses separated by 3.2-9.2 months
interval.
Results: The gaze dispersion in patients were higher compared with that in normal subjects (p<0.0001). Such instability relates foremost to oculomotor control disorders in
patients which manifest in macrosaccadic oscillations, nystagmus, intrusive saccades, and square wave jerks. A decrease of
gaze dispersion in four patients (p<0.0001 for each) occurred
in the second GST session, presumably caused by reduction
of intrusive saccades frequency and context inappropriate saccades both representing higher efficacy of voluntary attention
control.
Conclusions: Patients with medulloblastoma demonstrated
poor gaze stability compared to normal subjects. The positive dynamics of gaze stability in patients has been achieved
by rehabilitation courses. Eye movement patterns could be
considered as objective indicators of specific oculomotor disorders. Eye tracking method represents additional diagnostic
tool in rehabilitation practice.
S313 of S518
prognosis. We report on our single institution experience in
seven consecutive patients.
Design/Methods: Between 2006 and 2016, seven patients
were diagnosed with an ETMR. Diagnosis was established prospectively by characteristic histopathologic features, LIN28 immunostaining and amplification of the locus
19q13.42 in five patients and retrospectively confirmed in 2
additional patients originally diagnosed as CNS PNET (central nervous system primitive neuroectodermal tumor).Tumor
location was supratentorial in all patients. Median age at diagnosis was 25 months (range 6-38). Male to female ratio was
1:6.
Results: All patients had a GTR or near total resection and
the first five patients were treated according to high risk PNET
or ATRT (atypical teratoid rhabdoid tumor) protocols including high-dose chemotherapy in three patients. All five patients
recurred after a median of 6 months (range 2-11) and all
except one patient who died after high dose chemotherapy
succumbed to their disease after a median of 13 months (range
7-28). Following a case report by Mozes et. al., (1) the last
two patients were treated with primary focal radiotherapy,
intrathecal therapy and concomitant temozolomide followed
by 12 courses of temozolomide 150-200mg/m2. Both patients
are in CR 18 and 12 months after diagnosis.
Conclusions: Complete surgical removal followed by early
focal radiotherapy and temozolomide seems to be superior to intensive conventional therapy including high-dose
chemotherapy.
(1) Mozes P., Hauser P., Hortobagyl T. et al., Evaluation of
the good tumor response of embryonal tumor with abundant
neuropil and true rosettes (ETANTR). J Neurooncol (2016)
126:99-105
P-324 Application of VMAT Technology in the
Treatment of Anaplastic Ependymoma
P-323 Focal Radiotherapy and Temozolomide
Following Complete Resection are Superior to
Intensive Chemotherapy in Children with
Embryonal Tumors with Multilayered Rosettes
(ETMR)
I. Slavc1 , A. Peyrl1 , A.A. Azizi1 , J. Gojo1 , D. Reisinger1 , L. Mayr1 ,
T. Czech2 , K. Dieckmann3 , C. Haberler4
1 Medical
University of Vienna, Pediatrics, Vienna, Austria; 2 Medical
University of Vienna, Neurosurgery, Vienna, Austria; 3 Medical University
of Vienna, Radiotherapy, Vienna, Austria; 4 Medical University of Vienna,
Institute of Neurology, Vienna, Austria
Background/Objectives: Embryonal tumor with multilayered rosettes (ETMR) is a rare new entity characterized by
LIN28A expression and alterations in the C19MC locus at
19q13.42. ETMR occurs in young children and has a dismal
E. Slobina1 , F. Antonenko1 , O. Zheludkova1 , N. Zelinskaya1
1 Russian
Scientific Center of RoentgenoRadiology, Radiotherapy of
Children Diseases, Moscow, Russia
Background/Objectives: Demonstrate the possibility of clinical application of modern methods of radiation therapy of
anaplastic ependymoma.
Design/Methods: From January 2016 to February 2017,
five patients (median age 3 years) for anaplastic ependymoma received complex treatment according to the protocol HIT2014, consisting of courses of weekly vincristinecontaining chemotherapy and external beam irradiation in the
volume of craniospinal irradiation (CSR) (dose per fraction
1,6Gr, total dose 24Gr (35.2 Gy), followed by local irradiation of the postoperative bed of the removed tumor, dose per
fraction 1.8Gr up to total dose 55Gr was carried out. Prelimi-
SIOP ABSTRACTS
S314 of S518
nary radiotherapy planning was performed using the 3D conformal radiotherapy with optimization (IMRT) for all patients.
After analyzing the received dose-volume histograms (DVH),
VMAT was used in the CSR in 2 patients, and in 3 patients
in the local irradiation. In 4 patients, treatment was performed
using 1-2 coplanar treatment arches, in 1 patient - using 2 nonplanar therapeutic arches. Radiotherapy using VMAT technology was performed using the Eclipse planning system on
the Truebeam linear accelerator.
found radiological response and rapid clinical improvement.
No toxicities were seen except self-limiting itchy macular
rash in older boy lasting for two weeks only, immediately at
the beginning of the treatment. Two other patients (4.5 year
old boy with OPG, 17 year old girl with NF-1 and posterior
fossa/brainstem glioma) with BRAF fusion, were treated with
trametinib at a dose 0.025 mg/kg/day. Both patient obtained
disease stabilization while on treatment, but the girl repeatedly experienced grade 2 papulopustular rash.
Results: When comparing the results of the preliminary planning of IMRT and VMAT, the total treatment time was
reduced from 10-15 minutes with IMRT up to 2-4 minutes
at VMAT. The number of monitoring units (MU) decreased
2.3 times on average with VMAT, while the coverage of the
planned treatment volume with 95% treatment isodose did not
significantly differ: 97.6% (IMRT) and 94.8% (VMAT) with a
significant reduction in the radiation load on the dose-limiting
organs. The early and late side effects of radiation therapy
(RTOG scale) were minimal.
Conclusions: Dabrafenib is active and well tolerated among
patients with BRAF V600 mutation-positive pediatric recurrent low-grade glioma, trametinib at least stabilizes tumors
with BRAF fusion, again with minimal toxicity
Conclusions: The use of VMAT opens new possibilities in
the treatment of oncological diseases in children, because
due to the above described properties, the risk of developing induced secondary tumors will decrease, and the time of
finding the child on the treatment unit will be significantly
reduced.
P-325 Targeted Therapy in Patients with
Progressive Low Grade Gliomas
D. Sumerauer1 , S. Cyprova1 , M. Kyncl2 , J. Zamecnik3 , L.
Krskova3 , E. Kabickova1
1 Faculty
Hospital Motol, Department of Pediatric Hematology and
Oncology, Prague 5, Czech Republic; 2 Faculty Hospital Motol, Department
of Imaging Methods, Prague 5, Czech Republic; 3 Charles University,
Department of Pathology and Molecular Medicine, Prague 5, Czech
Republic
Background/Objectives: Pediatric low-grade gliomas are
the most common brain tumors in children. They are characterized by alterations of the Ras/MAPK pathway. Although
frequently cured with complete resection, patients with unresectable lesions experience multiple progressions and are at
increased risk for long-term neurological sequelae.
Design/Methods: We present our experience with targeted
therapy in 4 patients with recurrent low grade glioma,
treated at the time of progression with either BRAF inhibitor
(dabrafenib) or MEK-inhibitor (trametinib) according to the
molecular alteration detected in the tumor tissue.
Results: Two patients, 8.5 year old boy with recurrent thalamic PXA and 6-month old boy with rapidly progressing
optic pathway glioma started dabrafenib treatment at a dose
5.25 mg/kg/day upon BRAF V600E activating mutation was
detected in the recurrent tumor. Both boys experienced pro-
P-326 Clinicopathological Review of Paediatric
Meningioma from A Single Centre
E. Tan1 , K. Phipps2 , S. Yasin3 , J. Pickles3 , M. Jorgensen4 , K.
Aquilina2 , T.S. Jacques3 , D. Hargrave4
1 KK
Women's and Children's Hospital, Paediatric Haematology &
Oncology, Singapore, Singapore; 2 Great Ormond Street Hospital,
Department of Neurosurgery, London, United Kingdom; 3 UCL Great
Ormond Street Institute of Child Health, Developmental Biology & Cancer
Programme, London, United Kingdom; 4 Great Ormond Street Hospital,
Department of Haematology & Oncology, London, United Kingdom
Background/Objectives: Paediatric meningiomas constitute
∼2% of paediatric CNS tumours, and differ from adult
meningiomas in certain aspects. Current management recommendations include complete resection, careful pathological
review and multidisciplinary discussions regarding postoperative treatment.
Design/Methods: Retrospective analysis of 37 children with
meningioma diagnosed between 1990 to 2016 was conducted.
Data on patient demographics, tumour characteristics, treatment and outcomes was obtained from hospital records.
Histopathological specimens were reviewed to align the subtype and grade with the WHO 2016 classification.
Results: Median age of diagnosis was 10.01 years (range:
1.03 – 16.03). Male: female ratio was 1.4:1. Nine patients
had neurofibromatosis type-2 (NF-2) (24.3%), one had neurofibromatosis type-1 (NF-1) and two had previous cranial
radiotherapy. Histopathology review confirmed the majority
of meningiomas to be low grade (WHO Grade I or II). Two
had rhabdoid meningioma (WHO Grade III) – one died within
5 months despite complete resection (CR) and radiotherapy,
whereas the other patient is still alive 6 years after CR. Three
had multiple meningiomas in both intracranial and spinal
compartments. About one third of patients had meningiomas
at skull base (n=12). Other tumour locations were intraventricular (n=6), convexity (n=6), spinal (n=5), extracranial
(two involving optic nerve sheath, one occurring in maxillary sinus antrum) and sylvian fissure (n=2).2 patients had
SIOP ABSTRACTS
biopsies, 13 had incomplete resection and 22 achieved complete resection (5 achieved with more than 1 operative procedures). 7 patients had adjuvant radiotherapy as part of primary
treatment.Median follow-up was 5.18 years (range: 0.15 –
21.75). Relapse occurred in 2/22 (9.1%) with complete resection and in 6/10 (60%) with incomplete resection and no adjuvant radiotherapy.
Conclusions: The strong association with NF2 reinforces recommendations for genetics referral to look for associated syndromes. Age, extent of resection and histological grade are
factors for consideration in postoperative treatment. Relapse
was higher without complete resection.
P-327 Investigation of RBM24 as a Potential
Regulator of Cellular Proliferation, Apoptosis and
Chemoresistance in Medulloblastoma
G. Alencastro Veiga Cruzeiro1 , M. Baroni2 , K. Bezerra Salomão2 ,
R.C. Peixoto Lira2 , L. Geron2 , A.F. Andrade3 , C. Alves Corrêa2 , D.
Antunes Moreno2 , V. Silva Silveira4 , C.A. Scrideli2 , L. Gonzaga
Tone2
S315 of S518
decrease in proliferation of 95% when compared to untreated
control and 45% compared to treated control. For apoptosis, 80% of KO cells went for early apoptosis and 20% for
late apoptosis. We also detected an increase in protein levels
of P53 phosphorylation, P63-alpha, P73 and P21 in KO cell
lines.
Conclusions: This data suggests a new role of RBM24 as
a negative regulator of P53 family members and a potential
oncogene suppressor of apoptosis, driver of proliferation and
promoter of chemoresistance.
Finantial Support by FAPESP Process Num.2013/12006-3
P-328 Differential Expression of MST2 and
MST4 Among the Molecular Subgroups of
Medulloblastoma
M. Baroni1 , A.F. Andrade1 , G.A.V. Cruzeiro1 , C.A.P. Correa1 , C.G.
Carlotti2 , S. Aguiar3 , J.A. Nunes3 , S.R. Brandalise3 , C.A. Scrideli4 ,
L.G. Tone1
1 Ribeirão
1 Ribeirao
Preto Medical School - USP, Genetics, Ribeirão Preto, Brazil;
Preto Medical School - USP, Surgery, Ribeirão Preto, Brazil;
3 Centro Infantil Boldrini, Pediatrics, Campinas - SP, Brazil; 4 Ribeirão
Preto Medical School - USP, Pediatrics, Ribeirão Preto, Brazil
Background/Objectives: Medulloblastoma (MB) is the most
common malignant brain tumor in children and is classified
in subgroup Wnt, Shh, Group 3 and Group 4. Despite the current therapy displayed good outcomes, patients with MB SHH
TP53 mutant have poor prognosis due to primary resistance
to chemotherapy and progressive metastasis. Our study identified a RNA Binding protein named RBM24 overexpressed
in MB SHH TP53 mutant cell lines and in TP53 allele Loss in
patients. We performed Knockout in RBM24 gene on mutant
TP53 cell lines in prior to investigate its roles in Apoptosis
and proliferation.
Background/Objectives: Medulloblastoma (MB) is the most
common tumor of central nervous system in childhood. The
MB molecular classification was based on several studies
dividing in four molecular subgroups: WNT, SHH, Group
3 and Group 4, facilitating diagnosis and treatment. In the
search for potential targets, we found MST2 and MST4, members of MST kinases family (Mammalian Sterile Twenty
Like). Several studies have shown the involvement of MSTs
in carcinogenesis of different tumor types, and some studies
show the relationship with developmental pathways associated with MB. Therefore, the aim of this study was to analyze
the expression of MST kinases in MB samples, and investigated the difference of MST expression among molecular subgroups.
Preto Medical School - University of Sao Paulo, Pediatrics,
Ribeirao Preto, Brazil; 2 FMRP USP, Pediatrics, Ribeirão Preto, Brazil;
3 Institut de Recherche en Cancérologie de Montpellier IRCM- France,
Cancérologie, Montpellier, France; 4 FMRP USP, Genetics, Ribeirão Preto,
Brazil
Design/Methods: To assess mRNA levels of RBM24 in MB
cell lines and patients with MB. It was performed Real Time
PCR using TaqMan probes for RBM24 (Hs00290607_m).
The platform Methylation array Illumina 450k was used to
asses copy number profile of TP53 in patients with MB.
Trough lentiviral transduction and flow sorting of GFPexpressing cells, it was generated UW473 CRISPR RBM24KO (KO) Mutant TP53 MB cell line. It was performed in vitro
Proliferation assay using CKK8 cell counting and AnnexinV (FITC) kit for apoptosis assay. All experiments were performed thrice. One-way ANOVA was performed for Statistical analysis.
Results: Our study identified reduction of cellular proliferation and increase of apoptosis levels in KO cell lines. Moreover, when treated with Doxorubicin for 48h, we identified a
2 Ribeirão
Design/Methods: We analyzed the expression of MST2 and
MST4 in 48 samples of MB, 4 cell lines of MB and 5 nonneoplastic human cerebellum controls by qRT-PCR. For this
analysis, it was used Taqman gene probes and the endogenous
controls were GUS and HPRT. Comparisons of MST expression in tumor samples versus cerebellum non-neoplastic and
molecular subgroups was performed using Mann-Whitney
test.
Results: MST2 is upregulated in tumors (p=0,015) and cell
lines (p=0,032) when compared to non-neoplastic cerebellum, and the expression of MST4 have no difference comparing tumor and cell lines with controls. Analysis of gene
expression among molecular subgroups showed difference of
MST2 expression comparing Group Shh/Wnt and Group 3/4,
MST2 is upregulated in the Group Shh/Wnt (p=0,033). MST4
SIOP ABSTRACTS
S316 of S518
expression is also different between the molecular subgroups.
Group Wnt has MST4 downregulated compared with others
groups: Wnt x Shh (p=0,001), Wnt x Group 3 (p=0,027) and
Wnt x Group 4 (p=0,006).
Conclusions: The MST2 and MST4 expression shows relationship to molecular subgroups of MB and may be related
with molecular pathways like Wnt and Shh. Studies and novel
assays are being conducted to understand better these findings.
P-329 The Germline Variants in DNA Repair
Genes and Life-Threatening Toxicity During
Chemotherapy in Children with Medulloblastoma
suffered from rare life-threatening AE more frequently than in
control group (p=0.0005).
Conclusions: Our results, based on the largest systematic
study of medulloblastoma, provide preliminary evidence for
a link between defects in DNA repair genes and treatment
related toxicity. We suggest, that for patients with presence of
DNA repair genes variants, the special vigilance during and
after currently applied therapeutic regiments is required. Also,
the potential revision of the mode of treatment should be considered for those patients in the future.
This work was supported by National Science Centre (6917/B/
P01/2011/40,N N407 691740; 2016/21/B/NZ2/01785) and by
Funding from the CMHI (S124/2012 and 233/15).
J. Trubicka1 , T. Żemojtel2 , J. Hecht3 , R. Płoski4 , D. PiekutowskaAbramczuk5 , M. Perek-Polnik6 , M. Drogosiewicz6 , W.
Grajkowska1 , K. Chrzanowska5 , B. Dembowska-Bagińska6 , M.
Łastowska1
P-330 Primary Intracranial Tumors Diagnosed in
the First Year of Life: A Retrospective Study of
Belgian Cases Between 2001 and 2014
1 The
J. Derême1 , S. Jacobs2 , E. Sariban3 , S. Schifflers4 , L. Willems5 , J.
Verlooy6 , N. Van Damme7 , B. Depreitere8 , M.C. Nassogne9 , B.
Brichard1 , A. Van Damme1
Children's Memorial Health Institute, Pathology, Warsaw, Poland;
Universitätsmedizin Berlin, Institute for Medical Genetics and
Human Genetics, Berlin, Germany; 3 Charité Universitätsmedizin Berlin,
Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany;
4 Warsaw Medical University, Department of Medical Genetics, Warsaw,
Poland; 5 The Children's Memorial Health Institute, Department of Medical
Genetics, Warsaw, Poland; 6 The Children's Memorial Health Institute,
Department of Oncology, Warsaw, Poland
2 Charité
Background/Objectives: Agents which interfere with DNA
repair mechanisms are employed as therapeutic compounds in
pediatric oncology. Furthermore, alterations in DNA repair
genes in patients may affect repair efficiency and response
to therapy. The purpose of this study was to establish relationship between presence of abnormalities in selected DNA
repair genes and life-threatening toxicity during chemotherapy in children with medulloblastoma.
Design/Methods: The coding sequences of MSH2 and
RAD50 genes were investigated using targeted gene sequencing, and NBN pathogenic variants (p.I171V and p.K219fs*19)
by Sanger sequencing in altogether >100 patients. In three
patients with presence of rare life-threatening adverse events
(AE) and no detected variants in the analyzed genes, whole
exome sequencing was performed. Presence of identified
variants was correlated with the occurrence of rare lifethreatening AE, other clinical features and molecular group
of tumour.
Results: Potentially pathogenic variants in DNA repair
genes were identified in eight out of fifteen patients who
suffered from life-threatening toxicity during chemotherapy. The altered genes included: MSH2 (variants: p.A733T
and p.V606I), RAD50 (variant p.R1093*), FANCM (variant p.L694*), ERCC2 (variant p.R695C) and EXO1 (variant p.V738L), in addition to two known NBN gene variants.
Patients with defects in either of MSH2, RAD50 or NBN genes
1 Cliniques
Universitaires Saint Luc, Pediatric Hematology and Oncology,
Woluwe Saint Lambert, Belgium; 2 Universitaire Ziekenhuizen Leuven,
Pediatric Hematology and Oncology, Leuven, Belgium; 3 Hôpital des
Enfants Reine Fabiola, Pediatric Hematology/Oncology, Brussels, Belgium;
4 CHC Liège, Pediatric Hematology/Oncology, Liège, Belgium; 5 University
Hospital Ghent, Pediatric Hematology/Oncology, Ghent, Belgium;
6 University Hospital Antwerpen, Pediatric Hematology/Oncology, Antwerp,
Belgium; 7 Belgian Cancer Registry, Belgian Cancer Registry, Brussels,
Belgium; 8 University Hospital Leuven, Neurosurgery, Leuven, Belgium;
9 Cliniques Universitaires Saint Luc, Pediatric Neurology, Woluwe Saint
Lambert, Belgium
Background/Objectives: Brain tumours represent 15% of
cancers in children younger than one year. Studies describing
brain tumours in this age group are limited and some revealed
differences compared to the older paediatric population. We
aimed to describe brain tumours in children under one year
of age in Belgium and to define how they differ from older
children.
Design/Methods: Retrospective analysis of records of
patients diagnosed with primary intracranial neoplasms in the
first year of life in Belgium between 2001 and 2014. Eligible patients were retrieved from hospital databases of Belgian Paediatric Oncology Departments and the Belgian Cancer Registry. Brain metastases, vascular malformations, spinal
tumours and hamartomas were excluded. Various parameters
such as clinical presentation, intracranial localisation, histologic subtype, late morbidity and outcome, were recorded.
Results: Sixty patients met the inclusion criteria. Median
age at diagnosis was 7 months. Fifteen percent of tumors
were metastatic at diagnosis. The median follow-up time was
86.19 months. The median pre-diagnosis interval was 28
days. The most frequent tumour type was pilocytic astrocy-
SIOP ABSTRACTS
toma (25%), atypical teratoid/rhabdoid tumour (11.6%) and
glioblastoma (8.3%). Signs of intracranial hypertension were
present in 64.3% of cases. The most common signs were vomiting (43.3%) and bulging fontanelles (26.7%). Hydrocephalus
was present in 41.7%. Clinical presentation correlated with
anatomical localisation. Five-year overall survival was 66.6%.
Survival varied significantly with histologic type, grade and
completeness of surgical resection. However, age, localisation, age at diagnosis, prediagnosis symptom interval and primary dissemination did not correlate with overall survival.
Conclusions: Most infants with brain tumours present with
signs of intracranial hypertension. Outcome is determined by
histology and completeness of resection. Outcomes compare
favourably with series from the literature, possibly due to a
higher proportion of low grade lesions. This series describes
clinical characteristics, treatment and outcome of infant brain
tumours in infants before the era of molecular diagnostics and
therapeutics.
P-331 The Link Between Neurocognitive
Functioning and Health-Related Quality of Life in
Pediatric Brain Tumors
L. Van den Wyngaert1 , G. Vercruysse1 , K. Vandenabeele1 , M.
Haers1 , C. Sleurs1 , A. Uyttebroeck1 , S. Jacobs1 , J. Lemiere1
1 University
Hospital Leuven, Pediatric Hematology-Oncology, Leuven,
Belgium
Background/Objectives: Thanks to medical advances during
the last decades, children with a brain tumor reach adulthood
more often. Measurements of health-related quality of life
(HRQOL) and neuropsychological functioning have therefore
become increasingly important. Our study aimed to examine the impact of neurocognitive functioning on HRQOL in
patients, both immediately after diagnosis and in follow-up.
Design/Methods: Children diagnosed with a brain tumor at
the University Hospitals Leuven, were followed with neuropsychological assessments. In total, 49 patients (mean age
at diagnosis 8.91 ± 4.18 years) were included, diagnosed
with pilocytic astrocytoma (n=25), medulloblastoma (n=9),
ependymoma (n=3), craniopharyngioma (n=3) and atypical
brain tumors (n=9). Neuropsychological assessments were
acquired within maximum six months after diagnosis, as well
as after two years. Assessments included objective measurements of cognition (intelligence, memory, visual-motor functioning, attention and executive functioning) and subjective
measurements of HRQOL (PedsQLTM Brain Tumor Module). Paired T-tests and pearson correlations were used to
assess relationships between the neurocognitive variables and
HRQOL in this population.
Results: Based on paired T-tests, attention (t(48)=-3.39,
p=0.001) and executive functioning (t(48)=-2.27, p=0.03)
S317 of S518
declined over time. Consistent with literature, we found
few significant correlations between the neurocognitive variables and the general measure of HRQOL. At diagnosis, a significant association between memory and patientreported HRQOL was found (r=0.453, p<0.05). Interestingly, the follow-up measurement showed different correlations. More specifically, parent-reported HRQOL was correlated with both performance intelligence and executive functioning (r=0.410, p<0.01;r =-0.323, p<0.05). Correlations
between subscales of HRQOL showed at diagnosis an association between verbal intelligence and parent-reported cognition (r=0.427, p<0.05) and at follow-up between attention
and parent-reported cognition (r=-0.356, p<0.05).
Conclusions: Newly arising correlations after two years suggest a stronger link between attention and executive functioning, most strongly declining neurocognitive functions in our
population, and subjective measurements of HRQOL. Possibly, parents’ expectations of daily life functioning also change
throughout time.
P-332
Central Nervous System Tumors
B. Yilmaz1 , N. Eker1 , G. Tokuc1 , O. Dogru1 , E. Senay1 , B. Berk1
1 Marmara
University Pendik Training and Research Hospital, Pediatric
Hematology and Oncology, Istanbul, Turkey
Background/Objectives: Central nervous system (CNS)
tumors are the most common solid tumors in childhood. Our
instution is the one of the major referral center for pediatric
brain tumors in Turkey. We aimed to analyzed children with
brain tumors who were diagnosed and treated at our center in
this study.
Design/Methods: This is a retrospective study of 96 pediatric patients with brain tumors treated in between 2009 to
2017. Sixteen patients were lost to follow-up and 80 patients
were included in the analysis. Demographic informations, histologic subtypes, stage at diagnosis, treatment modalities and
outcomes were evaluated, retrospectively.
Results: Of the 80 patients, 42 (52.5%) were males, 38.5
(47.5%) were females. The mean age was 6.8 ± 4.6 years
(ranging from 0.17 years to 15.5 years). The mean duration
of follow up was 30 months. Mean survival time was 71.4
months (95% CI: 61.8 - 80.9). The most common localization was the infratentorial area (38.8%). Among all of the
patients, gliomas are the most common histologic form (54
%) and 51,3% had grade IV stage for WHO. Five-year overall
survival (OS) is 68 %. The most important factor for OS was
tumor total resectabity. Total resectable patients OS was 81%
vs gross total resection (GTR) was 49.5% vs partial resection
was only 28% within 5 years. The children with diffuse infiltrative pontine glioma (DIPG) and atypical teratoid/rhabdoid
SIOP ABSTRACTS
S318 of S518
tumor (AT/RT) had the worst prognosis and these patients
died in the first year of their treatment.
Conclusions: In developing countries, as the use of molecular studies could not be routinely performed in clinical practice. Brain tumors are relatively common cancers among children.usually the first and the most important step in therapy.
Patients with the most complete resection have significantly
longer survival despite all of the technological advances.
P-333 Comparative Analysis of miRNA
Expression in Pediatric Neuronal and Mixed
Neuronal-Glial Tumors
M. Zakrzewska1 , W. Fendler2 , K. Stawiski2 , R. Gruszka1 , K.
Zakrzewski3 , P.P. Liberski1
1 Medical
University of Lodz, Department of Molecular Pathology and
Neuropathology, Lodz, Poland; 2 Medical University of Lodz, Department of
Biostatistics and Translational Medicine, Lodz, Poland; 3 Polish Mother
Memorial Hospital Research Institute, Department of Neurosurgery, Lodz,
Poland
Background/Objectives: The current knowledge concerning
the molecular biology of pediatric low-grade brain tumors is
still unsatisfactory. Moreover the data concerning the biology
of CNS neuronal and mixed neuronal-glial tumors continue to
be enigmatic due to their rare occurrence.Those tumors show
considerable genomic heterogeneity even in case of the same
histological features. The aim of the study was to evaluate
the microRNA profiles of pilocytic astrocytoma (PA), ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor
(DNT).
Design/Methods: A total group of 60 cases in equal proportion of histological types was incorporated into this study. The
material for molecular analyses was obtained during standard
neurosurgical procedures. Total RNA was extracted according to the standard procedures. Microarray testing was performed with the using of the miRCURY LNATM microRNA
Array technology. After filtration 782 miRNAs were eligible
for analysis. Obtained data was compared using the analysis of
variance (ANOVA) with the Benjamini-Hochberg procedure
used to estimate false discovery rates (FDR). MicroRNAs that
were significant in ANOVA were considered eligible for further post-hoc pairwise comparisons using the t-test.
Results: The pattern of expression changes differed considerably among the miRNAs between analysed subgroups of
tumors with: miR-4754, miR-4350, miR-4777 and miR-628
having the highest expression in DNTs, miR-155 being elevated in GGs and miR-3660 showing elevated expression levels in the PAs. Conversely, miR-PlusA-1086, let-7b, miR891a and miR-4758 were downregulated in DNTs tumors in
comparison to the other groups.
Conclusions: Current study provides information regarding
the miRNA alterations related to the pediatric low grade brain
tumors especially to the relatively rare neuronal and mixed
neuronal-glial tumors. Each tumor type showed characteristic
miRNA expression profile. It could be interesting particularly
in case of PA which could be the component of the most DNT
as well as the main manifestation of its plausible recurrence.
Work supported by
2014/15/B/NZ4/00744
the
Polish
NCN
Grant
No.
P-334 Use of Bevacisumab as a Single or in
Adjunct with Single Agent Carboplatin or
Vinblastin or Vincristine/Carboplatin Regimens in
Children with Unresectable or Progressive PLGG
N. Zhukova1 , R. Rajagopal2 , A. Lam4 , L. Coleman4 , P. Shipman3 ,
T. Walwyn2 , M. Campbell1 , M. Sullivan1 , K. Bhatia1 , N. Gottardo2 ,
J.R. Hansford1
1 Children's
Cancer Centre, The royal Children's Hospital, Melbourne, VIC;
of Paediatric and Adolescent Clinical Haematology and
Oncology, Princess Margaret Hospital for Children, Perth, WA;
3 Department of Radiology, Princess Margaret Hospital for Children, Perth,
WA; 4 Department of Radiology, The royal Children's Hospital, Melbourne,
VIC
2 Department
Background/Objectives: Low grade gliomas (LGG) are difficult to treat due to variable degree of chemosensitivity and
common proximity to vital brain structures which makes them
not amenable to surgical resection, as a result many children experience multiple progressions of their disease and
require several lines of therapy during their life. Historically
being a mainstream therapy, radiation is now deferred as a
last resort due to numerous significant side effects especially
in young children and multiple chemotherapy regiments are
employed with encouraging outcomes. Single agents Vinblastine and Carboplatin, Vincristine/Carboplatin combination have demonstrated progression free survival (PFS) of 3953% at 5 years with variable toxicity profile, which remains
suboptimal to irradiated tumours with PFS of 60-80%. Vascular Endothelial Growth Factor (VEGF) is important for
tumour neovascularisation and is increased in gliomas. Bevacizumab, a humanized monoclonal antibody to VEGF has
shown antineoplastic effects in multiple malignancies in adult
and paediatric population.
Design/Methods: Addition of Bevacizumab to the treatment regimens of progressive LGG will result in durable
stabilisation of disease, clinical and radiological improvement, and decrease tumour-related morbidity. Bevacizumab
was added to the 2nd to 4th line of therapy for progressive
PLGG between 06/2014-02/2016. Combinations of single
agent Carboplatin or Vinblastine and Vincristine/Carboplatin
with Bevacizumab. Bevacizumab was administered as a single IV dose of 10mg/kg once biweekly or once monthly as
per discretion of treating physician. Clinical and radiological
responses were assessed.
SIOP ABSTRACTS
S319 of S518
Results: We present the treatment outcomes of 15
patients with progressive PLGG with optic pathway/midline/thalamic/spinal location and disseminated
disease treated with the above approach. Patients were
given between 3 and 18 doses of Bevacizumab. Responses
were variable with the majority of patients having a partial response. Toxicity was acceptable, the tumour related
morbidity was prevented in all cases.
Conclusions: To sum, we demonstrate that a mass
spectrometry-based proteomic approach allows to distinguish molecular signatures linked to medulloblastoma
subgroups.
The study was supported by Ministry of Health of the Czech
Republic grant AZV 15-30657A and the project MEYS-NPS
I – LO1413.
Conclusions: Avastin can be used in treatment of PLGG.
T R E AT M E N T A N D CA R E - SU RG E RY
(IPSO)
P-335 Subgroup-Specific Quantitative Proteomic
Profiling in Medulloblastoma
1
1
2
1
L. Hernychova , M. Nekulova , M. Kyr , P. Dvorakova , L.
Capkova1 , O. Slaby3 , Z. Pavelka2 , M. Jezova4 , B. Vojtesek1 , J.
Sterba2 , K. Zitterbart2
1 Masaryk
Memorial Cancer Institute, Regional Centre for Applied
Molecular Oncology, Brno, Czech Republic; 2 University Hospital Brno and
Faculty of Medicine- Masaryk University, Department of Pediatric
Oncology, Brno, Czech Republic; 3 Central European Institute of
Technology, Molecular Oncology II, Brno, Czech Republic; 4 University
Hospital Brno and Faculty of Medicine- Masaryk University, Department of
Pathology, Brno, Czech Republic
Background/Objectives: Medulloblastoma, an embryonal
neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. Molecular genetic
studies led to the consensus defining four main subgroups of
medulloblastoma (WNT, SHH, Group 3 and Group 4) based
on transcriptional profiling. Recently, quantitative proteomics
developed as a robust approach additional to genomics to
identify prognostic markers and drugable targets in human
cancer. Here, we employed a shotgun proteomic method to
identify main pro-oncogenic signaling components in different molecular and clinical subgroups of medulloblastoma.
Design/Methods: Briefly, medulloblastoma tissues (n=28)
were lysed using urea buffer, stored at -80◦ C overnight and
centrifuged for 30 minutes and the protein concentration was
determined using BCA protein assay kit. One hundred micrograms of protein was digested using filter aided sample preparation. Peptides were labeled using 10plex isobaric mass tags
and mixed together. Finally, the samples were analyzed using
Orbitrap Elite coupled with UltiMate 3000 RSLCnano chromatograph and the acquired data processed with Proteome
Discoverer 1.4.
Results: A list of quantified proteins from tumor proteome
was obtained and subjected to bioinformatical and statistical evaluation. The clustering revealed that proteomic analyses recapitulate transcription-based subgroup assignment in
medulloblastoma and identified subgroup-specific proteins,
which were further classified by gene-annotation enrichment
analysis and pathway mapping.
P-336 Use of 3D Printing and Augmented Reality
for Preoperative Planning of Complex Central
Abdominal Tumors
S. Abdessalam1 , L. Wong2 , G. Linke1 , T. vonAhlefeld1
1 Children's
2 Children's
Hospital and Medical Center, Pediatric Surgery, Omaha, USA;
Hospital and Medical Center, Pediatric Radiology, Omaha,
USA
Background/Objectives: Neuroblastoma is the most common solid extracranial tumor in the pediatric population. One
of the most difficult locations to remove these tumors is within
the central abdomen where encasement/abutment of major
vascular structures makes removal very challenging and is
accompanied by high morbidity and potential mortality. CT
scans and MRI are used as the primary modalities in preoperative planning. At the forefront of technological growth in
the world of medicine are 3D printing and Augmented Reality
(AR). We are the first to use these technologies to help with
the preoperative planning and intraoperative management of
patients with central neuroblastomas.
Design/Methods: CT scanning is done with 1 mm cuts of a
prospective patient with a central neuroblastoma. The scans
are reviewed between the surgeon and the radiologist to determine which structures are to be modeled. A 3D technologist
works closely with the radiologist to accurately render a digital 3D model in medical segmentation software suite. The
computer generated model is then reviewed with the surgeon
for final approval using Augmented Reality glasses. Finally
the model is printed in a piecemeal fashion for ease of manipulating the structures.
Results: For our last three patients with a central neuroblastoma, we implemented the above technologies with excellent results. All three patients had successful removal of the
entire tumor and associated lymphadenopathy with no major
or minor intraoperative complications.
Conclusions: 3D printing and Augmented Reality are very
useful technological tools that go beyond the two dimensional
world of CT. The ability to physically look at and touch the
SIOP ABSTRACTS
S320 of S518
3D print gives the surgeon insight into the precise anatomic
detail of the complex vascular structures providing for safer
operations. Also worth noting, patient/family satisfaction and
understanding were heightened as a result of the physical
model in comparison to showing images from the CT's.
P-337 CTNNB1 Gene-Encoding B -Catenin
Deletions or Mutations in Hepatoblastoma in India
S. Agarwala1 , A. Varshney1 , A. Chopra2 , R. Kumar2 , S. Bakhshi3 ,
V.K. Iyer4 , V. Bhatnagar1
1 All
India Institute of Medical Sciences, Pediatric Surgery, Delhi, India;
All India Institute of Medical Sciences, Laboratory Oncology,
Delhi, India; 3 BRAIRCH- All India Institute of Medical Sciences, Medical
Oncology, Delhi, India; 4 All India Institute of Medical Sciences, Pathology,
Delhi, India
2 BRAIRCH-
Background/Objectives: The incidence of Hepatoblastoma(HB) is significantly elevated in patients with familial
adenomatous polyposis who carry germ-line mutations in the
APC tumor suppressor gene suggesting a role of over activation of the Wnt signaling pathway in tumor pathogenesis.
Mutation or deletion of exon 3 in CTNNB1 gene-encoding �catenin has been frequently detected in hepatoblastoma cases
worldwide. Mutation presence has been correlated with better response to neoadjuvant chemotherapy and better overall
survival.
Design/Methods: Analyses of oncogenic mutations(missense
mutations and interstitial deletions in exon 3) were performed
by focusing on exon 3 of CTNNB1 in 26 HBL tumor samples,
using standard PCR followed by subsequent DNA sequencing. Mutation identification was confirmed with at least 2
amplification reactions from the original DNA.
Results: Samples from 23 patients in and age range 6-132
months were included. There were 9 standard risk(SR) and
14 High risk(HR) patients. All patients received neo-adjuvant
chemotherapy (Cisplatin monotherapy for SRHB or PLADO
for HRHB). Poor response to neoadjuvant chemotherapy
was seen in 5/23(22%). Two older patients (108 and 132
months) could not be resected while the remaining 21 underwent resection. Five of the 23 (22%) patients died while
2 who could not be resected discontinued therapy. Of the
21 resected patients there were 7 (33.3%) recurrences, of
whom 3 are alive after salvage therapy, 1 died and 3 discontinued therapy with progressive disease. Exon 3 �-catenin
gene deletion was detected only in a single patient who
was a 11-month old PRETEXT-3 SRHB patient with good
response to neoadjuvant chemotherapy and is in CR after
resection. No missense mutations in CTNNB1 gene were
detected. No correlation was found between presence of mutation and response to neoadjuvant chemotherapy or ultimate
outcome.
Conclusions: Beta catenin gene deletion or mutation seems to
be rare in hepatoblastoma in India and may not be important
in pathogenesis of hepatoblastoma.
P-338 Is Antibiotic Prophylaxis Beneficial: A
Comparative Study in Totally Implantable Venous
Access Devices
S.A. Akbar1 , Z.F. Qudsia2 , N. Ashraf3 , M.A. Tarar1 , A.Q. Qazi1
1 Shaukat
Khanum Cancer Hospital and Research Center, Surgical
Oncology, Lahore, Pakistan; 2 Prince Philips hospital, Breast Surgery,
Llanelli Carmarthenshire, United Kingdom; 3 Aga Khan University, Medical
College, Karachi, Pakistan
Background/Objectives: Totally implantable venous access
devices (TIVADs) play an important role in administering
chemotherapeutic agents in children with oncological disorders. This study aimed to analyze the efficacy of prophylactic antibiotic at the time of insertion of TIVADs in preventing early central line associated blood stream infection
(CLABSI).
Design/Methods: Consecutive patients with TIVAD insertion between January 2005 and June 2016 were reviewed retrospectively. There was a natural division of the patients into
two groups due to change of surgeons in 2013 with a different
surgical practice: Group A (n = 351) who received a single
dose co-amoxiclav before September 2013 and Group B (n
= 279) did not receive it. CLABSI was defined as per CDC
guidelines.
Results: Both groups were comparable in terms of gender ratio, type of malignancy and neutrophil count with
no major confounding factors. Mean age was significantly
higher in the group that received antibiotic (68.7 versus 51.1
months, p-value 0.038). The rate of CLABSI was slightly
lower in the group that received antibiotic (11.6 versus
12.9%) but the difference was statistically insignificant (pvalue 0.365). The device was removed in first month in 17
cases (10/41 in group A and 7/36 in group B). Tip culture
was positive in 10% in the group that received antibiotic as
compared to 57% in the other group but the p-value was
insignificant (0.06), although the numbers were very small to
assess.
Conclusions: In our study there is no advantage of using prophylactic antibiotic at the time of TI-VAD insertion in preventing early postoperative CLABSI. To establish this a prospective RCT is recommended.
P-339 Advanced Hepatoblastoma with Tumoral
Thrombi in Right Atrium and Inferior Vena Cava:
Which is the Best Management?
SIOP ABSTRACTS
R. Angelico1 , A. Passariello2 , M. Pilato3 , T. Cozzolino2 , M.
Piazza3 , R. Miraglia4 , D. Paolo5 , C. Grimaldi1 , M.C. Saffioti1 , D.
Alberti6 , M. Spada1
1 Pediatric
Hospital Bambino Gesu’, Abdominal Transplant and
hepatopancreaticbiliary surgery, Roma, Italy; 2 University of Naples
“Federico II”- Naples- Italy, Department of Translational Medical Science,
Naples, Italy; 3 IRCCS - ISMETT Mediterranean Institute for
Transplantation and Advanced Specialized Therapies, 4Cardiac Surgery
and Heart Transplantation Unit- Department for the Treatment and Study of
Cardiothoracic Diseases and Cardiothoracic Transplantation, Palermo,
Italy; 4 IRCCS - ISMETT Mediterranean Institute for Transplantation and
Advanced Specialized Therapies, Radiology service, Palermo, Italy;
5 “Giovanni Di Cristina” Children's Hospital, Palermo, Italy; 6 Spedali
Civili” Children's Hospital, Pediatric surgery, Brescia, Italy
Background/Objectives: Advanced hepatoblastoma (HBL)
with tumour thrombi extending into major vessels needs
multimodal treatment approaches combining chemotherapy
and surgery. Surgical recommendations for pretreatment
extent disease (PRETEXT) staging III-IV strongly advocate primary liver transplantation (LT). However, when
tumour thrombi infiltrate the inferior vena cava (IVC) and
the right atrium, LT might be technically challenging and
it is associated with unfavourable survival rates for local
recurrence HBL. Therefore, the best surgical approach is
not clear and transplant surgeons are exploring technical
alternatives.
Design/Methods: A 11-months-old boy with serum alphafetoprotein(AFP) of 50.795.200IU/mL and computed tomography showing a right hepatic lobe mass(90x78mm) suspicious of HBL, with tumour thrombi extending from the right
hepatic vein into the IVC up to the right atrium, and bilateral lung lesions (PRETEXT III) was referred. After 8 months
of chemotherapy (SIOPEL 2004-high risk Protocol), HBL
decreased to 61x64mm and lung lesions disappeared, but the
tumour thrombi was still present. The child underwent ante
situm liver resection: en bloc resection of the extended-right
hepatic lobe, retro/suprahepatic IVC, tumoral trombi extended
into the right atrium. The IVC was replaced with fresh aortic
graft from blood-group compatible cadaveric donor. During
the resection, the remnant liver (SII-III) was perfused through
the portal vein with Celsior at 4◦ C, cooled with ice, and reimplanted by end-to-side anastomosis of the left hepatic vein to
the neo-IVC.
Results: The post-operative course was uneventful and
after 10 months of follow-up the child is in good clinical condition with normal liver function test, AFP of
1.1UI/mL, free of disease recurrence and with patent aortic
graft.
Conclusions: This is the first case of ante situm liver resection combined with hypothermic CPB and IVC replacement for HBL, which is a realistic option to avoid LT for
skilled transplant surgeons thanks to the improvement of LT
technique.
S321 of S518
P-340 Comparative Cost Analysis of Treatment of
Pediatric Solid Tumors in Semi-Governmental
Hospital in India
S. Bhatnagar1
1 B.J.Wadia
Hospital for Children- Bombay Hospital, Pediatric Surgery,
Mumbai, India
Background/Objectives: The rate structuring in hospitals
in India show a huge fluctuation ranging from completely
free of cost public hospitals (Government), charitable institutes with subsidized rates, semi-government to autonomous,
corporate/private hospitals/nursing homes with varying rate
structures. The cost of treatment of pediatric solid tumors
varies widely from one facility to another even within the
same city. The parents concerns regarding the cost of therapy
when child is diagnosed with tumor becomes very difficult
to satisfy for multiple reasons, the foremost of which is lack
of hospital based cost analysis data. Hence, study of comparative cost analysis with different modalities of treatment of
solid tumors in children has been undertaken.
Design/Methods: From the time the child is clinically
detected to have solid tumor, the cost study has been performed by including cost of hospitalization (bed charges), cost
of diagnostic studies, cost of chemotherapy stage wise, cost of
surgery and related costs, cost of intensive care monitoring,
cost of consumables, cost of radiotherapy, cost of supportive
therapy, cost of immunization during treatment. The ancillary
costs like accommodation, food and travel, loss of wages for
parents, etc. have not been studied. The study has been undertaken taking into account most recent expenses at tertiary care
semi-government/charitable institute in Mumbai, India.
Results: Of the overall expenditure for treatment, cost analysis for a stage 3 tumor showed the various costs as: Diagnosis 7%, Chemotherapy - 43%, Consumables - 14%, Surgery - 7%,
Intensive care - 3%, Radiotherapy -8.5%, Supportive treatment - 14%. Cost analysis tumor wise and stage wise revealed
that with advanced disease, the cost of chemotherapy, intensive care and supportive care increased drastically.
Conclusions: Costing is a crucial tool in counseling and stratifying the financial status of the parents, thus creating pathways to achieve completion of therapy even with the poor
socio-economic section of society.
P-341 Outcomes of Pediatric Chest Wall
Reconstruction Using a Bio-Prosthetic Absorbable
Material
M. Collin1 , M. Mutch1 , J. Karpelowsky2,3
1 The
Children's Hospital at Westmead, Paediatric Surgery, Westmead,
Australia; 2 The Children's Hospital at Westmead, Paediatric Oncology and
Thoracic Surgery, Westmead, Australia; 3 University of Sydney, Children's
Cancer Research Unit, Sydney, Australia
SIOP ABSTRACTS
S322 of S518
Background/Objectives: Reconstruction in large chest wall
tumours aims to create an airtight cavity, rigidity to protect
thoracic contents, stability to permit respiration and long-term
aesthetically acceptable results. Described techniques (using
non-absorbable prosthetics) have limitations, especially in
pre-pubertal children in which growth deformity may result.
We aim to review medium-term outcomes when using bioprosthetic absorbable materials.
Design/Methods: This retrospective series includes prepubertal children that have undergone chest wall reconstruction at our centre. Poly-L-lactide struts (to replace cartilage/bone structures) and a porcine dermal collagen patch
with muscle flaps where available (to provide soft-tissue
replacement) were used as a matrix for native-tissue ingrowth
and allow complete implant resorption. Complications, functional and cosmetic results were obtained with review of photography and axial imaging.
Results: Five patients were included; 4 males and 1 female,
median age 4 years (range 0-10), median follow-up 3 years
(range 1-4). Pathology included 2 Ewing sarcomas, 1 osteochondroma, 1 chondromesenchymal hamartoma and 1 highgrade spindle-cell sarcoma. A median of 3 ribs were resected
(range 1-4). The single-rib reconstruction (for osteochondroma) was required for significant adjacent rib displacement
with a subsequent large thoracic defect. Four patients remain
disease free while 1 patient suffered metastatic Ewing relapse
(with local control persisting). Complications included a
seroma at 2 months in one patient and a sterile collection at
8 months in another (both drained and resolved). The reconstruction provided good initial thoracic integrity enabling
early extubation. Long-term cosmetic and functional results
are satisfactory, with good chest wall shape and function.
There were no post-operative restrictions on daily activities,
including sport in patients old enough (4/5). Pitfalls include
the low-level PET avidity of the prosthesis (when considering relapse surveillance) and the presence of mild scoliosis
noted on imaging.
Conclusions: The technique of a bio-prosthetic absorbable
chest wall reconstruction in the pediatric population has had
good functional and cosmetic results.
P-342 Outcomes of Brachytherapy in Pediatric
Non-Rhabdomyosarcoma Pelvic Sarcomas
M. Collin1 , J. Chard2 , V. Ahern2 , E. Flower3 , J. Karpelowsky4,5
1 The
Children's Hospital at Westmead, Paediatric Surgery, Westmead,
Australia; 2 The Children's Hospital at Westmead, Radiation Oncology,
Westmead, Australia; 3 University of Sydney, Institute of Medical Physics,
Camperdown, Australia; 4 The Children's Hospital at Westmead, Paediatric
Oncology and Thoracic Surgery, Westmead, Australia; 5 University of
Sydney, Children's Cancer Research Unit, Sydney, Australia
Background/Objectives: Pelvic brachytherapy is well
described in association with surgery for obtaining local
control for rhabdomyosarcoma of the pelvis. Its primary
benefits are as an organ sparing technique, whilst delivering
high doses to the target volume. We describe our use of
brachytherapy in the setting of non-rhabdomyosarcoma of
the pelvis in the paediatric population.
Design/Methods:
Selected
patients
with
nonrhabdomyosarcoma of the pelvis were treated at our
institute with brachytherapy. Cases were identified from
theatre databases and the data was collated as a retrospective
audit to report the technique of brachytherapy, associated
surgical procedure and outcomes including overall mortality,
and morbidity including bladder and bowel function
Results: Three female patients (age range 11-18 months)
have been treated with pelvic brachytherapy for nonrhabdomyosarcomas at our institute. Two cases involved preoperative brachytherapy to the tumour volume with transperineal catheters placed under image guidance. The third case
involved post-surgical resection placement of a modified
Frieburg flap applicator into the pelvis and sciatic notch. All
3 patients received high dose rate brachytherapy with excellent dose coverage of the target volume and organ at risk doses
within set constraints. Two of the 3 patients have survived to 2
and 4 years post intervention with no evidence of relapse. The
oldest child has maintained good bladder and bowel function
despite some initial concerns of urinary incontinence, with
ultrasound demonstrating good bladder capacity and voiding (managed well with timed and double voiding and subsequently continent). The second case remains too young to
assess continence. There was one mortality in the remaining
case who unexpectedly developed brainstem metastases six
weeks post treatment.
Conclusions: Our initial short to medium term follow ups
indicate that the use of pelvic brachytherapy may be extended
to non-rhabdomyosarcoma sarcomas of the pelvis in highly
selected young children as an organ sparing technique.
P-343 Biopsy and Excision of Pulmonary
Metastasis in Children with Extra-Cranial Solid
Tumors: Current Practice at Stand-Alone
Children's Hospitals
K. Corkum1 , G. Ares1 , E. Rowell1 , J. Reichek2 , T. Lautz1
1 Ann
and Robert H. Lurie Children's Hospital of Chicago, Surgery,
Chicago, USA; 2 Ann and Robert H. Lurie Children's Hospital of Chicago,
Oncology, Chicago, USA
Background/Objectives: Pulmonary metastases occur frequently in children with extra-cranial solid tumors, yet the
optimal approach for evaluating and treating suspicious nodules remains unresolved. Lung biopsy and nodule excision
SIOP ABSTRACTS
may be indicated to stage disease, guide therapy, or achieve
cure. The objective was to evaluate current national practices for addressing pulmonary nodules in patients with extracranial solid tumors.
Design/Methods: The Pediatric Health Information System
(PHIS) database was queried from 2010-2015 for patients
with extra-cranial solid tumors and associated pulmonary procedures. The approach and maximal extent of surgery were
stratified by primary tumor location.
Results: During the 6-year period, 15,640 patients were hospitalized, of which 19.6% had pulmonary metastatic disease, and 8.1% underwent a pulmonary procedure. Most common primary tumors were bone (20.3%), soft tissue (14.6%),
kidney (14.5%), adrenal (13.0%) and liver (7.5%). Biopsy
occurred in 6.4% of patients and only 12.2% required further
intervention with thoracoscopy/thoracotomy. Thoracoscopy
was the first-line approach in 51.0% of patients, with only
12.2% of those patients requiring subsequent thoracotomy.
Thoracotomy was the initial approach in 42.6% of patients, for
which bone tumors accounted for half of the cases. Patients
with bone tumors were also more likely to undergo multiple procedures than other solid tumors. Bone as a primary tumor site (OR 2.22), documented pulmonary metastasis (OR 2.80), high-volume center (OR 1.95), and anticipated
lobectomy (OR 11.34) were predictive of thoracotomy. ICU
utilization, mechanical ventilation, and post-procedural complications were more common in open cases compared to thoracoscopic or percutaneous approaches (p<0.001).
Conclusions: At least eight percent of children with extracranial solid tumors currently undergo lung biopsy or resection. The approach and extent of resection varies by patient
and hospital factors, including primary tumor site. Further
effort is required to define the optimal workup and treatment
algorithm for these patients to maximize diagnostic and therapeutic yield while minimizing complications.
P-344 The Clinical Characters of
Non-Rhabdmyosarcoma Soft Tissue Sarcomas—A
Retrospective Study in a Single Institution in 11
Years
K. Dong1 , W. Tang1 , X. Xiao1
1 Children's
Hospital of Fudan University, surgery, Shanghai, China
Background/Objectives: Non-rhabdmyosarcoma soft tissue
sarcomas (NRSTS) is a heterogenous group of tumors and
encompass many histology types, but they are less frequently
encountered and account for 3-5% of all childhood malignancies.The purpose of the study is to summarize our experience
in diagnosis and treatment on the non-rhabdomyosarcoma soft
tissue sarcomas.
S323 of S518
Design/Methods: We performed a retrospective analysis of
all the data of non-rhabdomyosarcoma soft tissue sarcomas in
our hospital in 2003-2014.
Results: 56 cases were found in this period. Pathology
study shows there were 8 types: synovical sarcoma, fibrosarcoma, PNET, hyalocyte sarcoma, acinous soft tissue sarcoma, embryonal sarcoma, malignant small cell sarcoma and
extraosseous Ewing's sarcoma. The case load of these 8 types
were 15(26.8%), 15(26.8%), 10(17.9%), 5(8.9%), 4(7.1%),
3(5.4%), 3(5.4%) and 1(1.8%), respectively. There was a
difference about tumor location among sarcomas (P<0.01).
There was no difference about the therapeutic protocols.
(P>0.05) But radical operation and radical operation plus
chemotherapy were the popular therapeutic protocols. There
was a difference about the use of chemotherapy(P<0.01).The
utilization of chemotherapy in PNET, malignant small cell
sarcoma, acinous soft tissue sarcoma and embryonal sarcoma
were 100%, while the utilization of chemotherapy were 42.7%
in other four sarcomas. The 2-year survival rate and 5-year
survival rate was 35.7%(20/56) and 8.9%(5/56), respectively.
The case fatality rate within 2 years was 26.8%(15/56).
Conclusions: Pediatric NRSTS had many histological subtypes. Although prognosis was not very good, radical operation plus chemotherapy have the effect of improving the survival rate in non-rhabdomyosarcoma soft tissue sarcomas.
P-345 Curative Surgical Treatment for
Hepatoblastomas by Live Donor Liver
Transplantation Combined with ICG Navigation
Y. Fuchimoto1 , Y. Yamada1 , K. Hoshino1 , N. Takahashi1 , K.
Matsubara2 , T. Hibi2 , Y. Abe2 , H. Yagi2 , N. Shimojima1 , M.
Shinoda2 , M. Kitago2 , H. Obara2 , Y. Kitagawa2 , T. Kuroda1
1 Keio
2 Keio
University School of Medicine, Pediatric Surgery, tokyo, Japan;
University School of Medicine, Surgery, tokyo, Japan
Background/Objectives: The prognosis of hepatoblastomas
depends greatly on curative treatment by surgical resection.
We performed the world's first re-liver transplantation using
ICG navigation technology in a case of recurrent hepatoblastomas after liver transplantation.
Design/Methods: The patient was a 15-year-old boy, had
undergone 2 hepatectomies after an explosion of hepatoblastomas when aged 8 years. At age 11 years he had a rescue
living body liver transplantation for recurrence of the tumors,
with his mother acting as the donor. His AFP level increased
gradually in the 4 years after transplantation and a partial
hepatectomy was performed because of tumor recurrence in
the transplanted liver. We found a peritoneal dissemination at
this operation and simultaneously resected the dissemination
lesion, diagnosed pathologically as stump-positive. Because
the AFP level increased post-operatively and a metastatic
SIOP ABSTRACTS
S324 of S518
lesion was detected in the liver we resected the dissemination
and intrahepatic metastatic lesion using ICG navigation technology. ICG was administered 3 days before the abdominal
operation using Photodynamic Eye (PDER, Hamamatsu Photonics). The nodules of liver and peritoneum revealed pathologically well-differentiated fetal type hepatoblastoma.
to be the most pragmatic option. Frozen sections showed dysplasia of the rete testis and epididymis, confirmed by standard
histology with no malignant changes.
Results: Transplant intrahepatic multiple recurrences had
occurred, thereafter we performed an exploratory laparotomy
using ICG navigation for the purpose of considering the
need for re-transplantation. This showed that the dissemination lesion was controlled and confirmed that recurrence was
localized to the liver. After the approval of the Ethical Review
Board, we performed a re-liver transplantation using ICG navigation, with the donor being the father. Pathology showed the
tumor was localized in the liver with normal changes in AFP
level.
Conclusions: Frozen sections may accurately diagnose testicular and paratesticular masses. Though orchidectomy could be
avoided only in case 1 and 3, frozen sections may aid surgical
decision making with regards to sparing the testis in selected
paediatric cases. Pathologists must endeavour to make themselves familiar with the potential advantages and limitations
of frozen sections and the role of intraoperative frozen sections warrants further multidisciplinary evaluation.
Conclusions: ICG navigation was useful in the detection
of micro lesions not detected by imaging or the naked eye
such as peritoneal dissemination and intrahepatic metastases.
Liver transplantation combined with ICG navigation provided
curative treatment for hepatoblastomas, indicating this was a
potential new surgical treatment for these tumors.
P-347 Laparoscopic Adrenalectomy in Children
with Adrenal Tumors
P-346 Diagnostic Utility of Frozen Section in
Paediatric Testicular and Paratesticular Lesions
H. Gabra1
1 Great
North Children Hospital, Paedaitric Surgery, Newcastle Upon Tyne,
United Kingdom
Background/Objectives: Frozen sections are used routinely
to assess suspected tumours in adults and aid surgical decision
making. Similar application in paediatric tumours remains
limited, especially in the evaluation of paediatric paratesticular lesions where diagnosis is reliant on clinical and imaging findings. Many benign paratesticular lesions in infancy
and childhood may be difficult to distinguish from malignant
lesions and result in unnecessary orchidectomy.
Design/Methods: Retrospective of a series of 3 patients who
underwent frozen section at the time of surgery for suspected
testicular/ paratesticular lesions were reviewed. Clinical information including age, histological diagnosis were recorded.
Results: Case 1: 11-month old infant with a firm paratesticular mass not involving the testis. Rhabdomyosarcoma
was suspected clinically and on imaging which was atypical.
Intra-operative frozen section diagnosis confirmed a benign
lesion (fibrous hamartoma of infancy). The mass was excised
and the testis left in situ.
Case 2: 14 year old boy who presented with a large complex paratesticular mass closely abutting the entire testis. Even
though radiologically it was suspected to be benign, the clinical features were suspicious and orchidectomy was thought
Case 3: 9 year old with presented with chronic testicular pain,
USS was suspicious of polar testicular lesion. Frozen sections
showed normal histology and testis was spared.
P. Kerimov1 , A. Kazancev1 , D. Rybakova1
1 Russian
Cancer Research Center. NN Blokhina, Surgical separation of
tumors of thoracoabdominal localization, Moscow, Russia
Background/Objectives: laparoscopic adrenalectomy was
introduced relatively recently and took the leading position
in choosing the volume of surgery for adrenal neoplasm in
children.
Design/Methods: We present the results of treatment of 91
patients with various adrenal tumors in children aged 1 to 18
years who underwent 91 laparoscopic operations in the volume from 2007 to 2017: laparoscopic adrenalectomy (LA) on
the right - 50, LA on the left - 41. Male were 50 patients,
41 female. The most common neuroblastoma was diagnosed
in 71 cases, the ganglioneuroma was diagnosed in 9 cases,
the following diseases were observed in single observations:
adrenocortical adenoma 2, adrenal cortex cancer 2, pheochromocytoma 2, gangloneuroblastoma 2, adrenocortical cancer
1, neurinoma - 1, fibroma - 1.
Results: The duration of operations ranged from 40 to 90 min.
The average blood loss was 20 ml. The drainage tube was
installed to the entire patient and was removed on the first
day after the operation. The stay in the intensive care ward
was 1 day. There were no lethal outcomes, cases of access
conversion, serious intraoperative complications. We have not
been diagnosed with any cases of recurrence of the disease or
implantation metastases in malignant tumors of the adrenal
gland. The median follow-up was 82 months.
Conclusions: Laparoscopic adrenalectomy in children with
adrenal tumor pathology is an effective and safe method that
is accompanied by minimal surgical trauma and excellent cosmetic results, shortens the duration of the postoperative period
and does not worsen the oncological prognosis. Laparoscopic
adrenalectomy in children can be considered as the preferred
SIOP ABSTRACTS
S325 of S518
surgery regardless of the age and body weight of the patient
with both benign and malignant organ tumors.
plinary tumor treatment facilities with public-private partnership are the need of hour.
P-348 Epidemiology of Paediatric Solid Tumors
and Treatment Challenges at a Tertiary Care
Hospital in a Developing Country
P-349 Preoperative Blood Count Parameters and
Prophylactic Antibiotics and their Effects on Early
Catheter-Related Bloodstream Infections in
Pediatric Cancer Patients Undergoing Port-A-Cath
Insertion
V. Khanna1 , R. Muffazzal1 , S. Roy Choudhury1 , P. Singh Yadav1 ,
A. Puri1 , R. Chadha1
1 Lady
Hardinge Medical College & Associated Kalawati Saran Children's
Hospital, Paediatric Surgery, New Delhi, India
Background/Objectives: A study on epidemiology, treatment challenges and logistic difficulties in managing paediatric solid tumors.
Design/Methods: Prospective observational study from
February/2014 till January/2017 including all paediatric solid
tumors.
Results: A total of 101 patients (58males,43females)
were included. Primary diagnosis was Wilms tumor(WT)
22(21.7%); Neuroblastoma(NB) 21(20.8%); Germ cell
tumors(GCT) 15(14.8%); Sacrococcygeal teratoma(SCT)
14(13.8%); Hepatoblastoma(HB) 5(4.9%), PNET 6(5.9%),
Rhabdomyosarcoma(RMS) 4(3.9%) and miscellaneous
14(13.8%). Out of 14 patients with WT requiring DD4A
chemotherapy+Radiotherapy (COG protocol), 11(78.5%)
could not receive radiotherapy due to lack of necessary
infrastructure at our hospital, financial constraints and
already overburdening of centres giving radiotherapy. Two
patients, 1 with Clear cell sarcoma of kidney(CCSK) and
other with Rhabdoid tumor of kidney(RTK) were given
WT chemotherapy as they were reported as Wilms in initial
histopathology reports. CCSK patient is alive with disease
while RTK patient expired 2 months post-surgery. Out of 21
NB patients, 13(62%) were high risk. Low awareness and
diagnostic delays rendered presentation to our hospital at a
very advanced stage. Eleven(52.3%) NB patients died and
8(38%) are alive with disease. The salvage rate remains low
due to limited access to myeloablative treatments with bone
marrow rescue and biologic therapy. Two (14.2%) patients
with SCT had recurrence which were detected late due to
logistic difficulty in getting alphafetoprotein levels(AFP)
done. Both these patients died due to febrile neutropenia in
addition to their poor nutritional status on initiation of salvage
chemotherapy. All five patients with HB, 3 standard risk(SR)
and 2 high risk(HR) received PLADO. Three underwent
surgery and are alive and disease free.
Conclusions: Lack of education, poor government support
system and referral facilities decrease survival in cancer
patients in developing nations. The cancer treatment protocols are institutionalized depending on the availability of
resources, technology and research at disposal. Multidisci-
R. Wang1 , V. Lee1 , S.M. Cheah2 , Y.T. Lee3 , C.B. Tan4 , S.E.
Saffari7 , J.C.M. Lam5 , C.Y. Chong6 , A.H.P. Loh3
1 National
University of Singapore, Yong Loo Lin School of Medicine,
Singapore, Singapore; 2 KK Women's and Children's Hospital, Department
of Paediatric Medicine, Singapore, Singapore; 3 KK Women's and
Children's Hospital, Department of Paediatric Surgery, Singapore,
Singapore; 4 KK Women's and Children's Hospital, Division of Nursing,
Singapore, Singapore; 5 KK Women's and Children's Hospital, Department
of Paediatric Subspecialties Haematology Oncology Service, Singapore,
Singapore; 6 KK Women's and Children's Hospital, Department of
Paediatric Subspecialties Infectious Diseases Service, Singapore,
Singapore; 7 Centre for Quantitative Medicine, Duke-NUS Medical School,
Singapore
Background/Objectives: Prior to port-a-cath insertions in
pediatric cancer patients, preoperative antibiotic prophylaxis
has been employed either routinely or based on blood count
parameters, but the basis of this practice is not well studied. We aimed to analyse preoperative risk factors associated
with early catheter-related bloodstream infections (CRBSIs)
in port-a-cath insertions.
Design/Methods: We retrospectively reviewed the clinical
charts of pediatric cancer patients who had port-a-caths
placed between January 2009 and December 2015. Standardized skin preparation, implants, and technique were used on
all patients, though preoperative antibiotic use varied. Demographics, disease factors, intra-operative factors, and preoperative blood count parameters were correlated with occurrence
of early CRBSI within the first 30 postoperative days.
Results: In total 279 central venous catheters were placed
during the study period, of which 250 were port-a-caths.
Among these, 159 (64%) had acute lymphoblastic leukemia
(ALL) and 15 (6%) had acute myleogenous leukemia (AML);
160 (65%) patients had preoperative antibiotics administered.
Median preoperative absolute neutrophil count (ANC) was
1.18 (range: 0.27–15.5) x 109 /L. Fifteen CRBSIs occurred
at median 14 (range: 8–28) postoperative days. Only cancer type was significantly associated with early CRBSIs
(P=0.004); these were encountered in 8, 3, 2, and 2 patients
with ALL, AML, other leukemias, and solid tumours, respectively. Notably, preoperative ANC <1 x 109 /L and use of prophylactic preoperative antibiotics were not associated with
occurrence of early CRBSIs (P=0.816 and P=0.996, respectively). Surgeon and operative factors were also not associated
with early CRBSI. However, early CRBSI was significantly
SIOP ABSTRACTS
S326 of S518
associated with early port removal within 30 days of insertion
(P=0.009).
Conclusions: Preoperative ANCs of 1 x 109 /L, and use of
preoperative antibiotic prophylaxis were not found to be associated with a lower incidence of early CRBSIs within the first
30 postoperative days.
P-350 Testicular Transposition in Children
Undergoing Brachytherapy for Bladder-Prostate
Rhadomyosarcoma
G. De Lambert1 , F. Guérin1 , C. Chargari2 , C. Haie-Meder2 , V.
Minard-Colin3 , H. Martelli1
1 Bicetre
hospital APHP, Paediatric Surgery, Le Kremlin Bicetre, France;
Roussy Cancer Campus, Brachytherapy, Villejuif, France;
3 Gustave Roussy Cancer Campus, Paediatric Oncology, Villejuif, France
2 Gustave
Background/Objectives: Fertility preservation is a major
goal in children ’s cancer. Spermatogonias are affected by a
dose of 0.15 Gy and dose more than 4 Gy may lead to definitive sterility. Leydig cells are more resistant and endocrine
function can be maintained after exposure to dose up to 20
Gy in prepubescent males.
To describe a new technique of testicular transposition in
patients treated with pulse-dose-rate brachytherapy for bladder neck and/or prostate rhabdomyosarcoma (BP RMS).
Design/Methods: Medical records of consecutive patients
treated between september 2016 and february 2017 were studied. These patients underwent a testicular transposition performed during BP surgery by the same suprapubic incision.
The external oblique aponeurosis was not incised. The spermatic cord was mobilized up to the external inguinal ring and
the gubernaculum attachments were delivered from the scrotum. The testis was then flipped over with care taken to avoid
injury of the vessels or the vas, wrapped in a silicone material and sutured under the abdominal skin with a transfixing
stitch facing the anterior superior iliac spine. At the end of
brachytherapy, the testis was relocated in the scrotum during
general anesthesia for removal of tubes and stents.
Surgical outcome and dosimetric parameters were examined.
Results: Five patients were identified.
Median age was 25 months (range 22 – 80 months). All had
embryonal BP RMS and received chemotherapy according
to RMS 2005 protocol prior to local treatment. All patients
underwent conservative surgery followed by brachytherapy
(60 Gy) and could have testicular transposition of one testis.
None of the patients had intraoperative or postoperative complication.
Median radiation dose to the transposed testis was 3 Gy
(range: 2 - 4.8) and 9 Gy (range: 6.6 - 11) to the testis left
in place.
Conclusions: Testicular transposition is feasible in order to
potentially preserve fertility and future quality of life in children undergoing brachytherapy for BP RMS.
P-351 Recurrent Inflammatory Myofibroblastic
Tumor of the abdomen treated with Surgery and
ALK Inhibitors in a Child
S. Mishra1 , S. Jain2 , S. Singh3 , G. Kapoor2
1 Rajiv
Gandhi Cancer Institute and Research Hospital- Sector 5- Rohini-,
Pediatric Surgical Oncology, Delhi, India; 2 Rajiv Gandhi Cancer Institute
and Research Hospital- Sector 5- Rohini-, Pediatric Hematology Oncology,
Delhi, India; 3 Rajiv Gandhi Cancer Institute and Research Hospital- Sector
5- Rohini-, Surgical Oncology, Delhi, India
Background/Objectives: Extrapulmonary Inflammatory
myofibroblastic tumor (IMT), also known as inflammatory
pseudotumor is a rare in children. IMT is known for its
fibroinflammatory and pseusosarcomatous appearance on
histopathology (HPE). Immunohistochemistry (IHC) is
a useful tool in confirming the diagnosis. Surgery is the
mainstay of treatment and local recurrences are common.
We wish to share our experience with one case of recurrent
IMT of the abdomen successfully treated with surgery and
Anaplastic Lymphoma Kinase (ALK) inhibitors.
Design/Methods: Retrospective review of hospital records.
Results: Eleven years old boy presented with loss of appetite
and vomiting for 3 months. He had a palpable left lower
abdominal mass of size 8 x8 cms. Imaging confirmed a nonmetastatic mesenteric mass suggestive of a low-grade spindle cell tumor on FNAC. He underwent en bloc excision of
mass with segmental colectomy. HPE was suggestive of IMT.
He was kept on close follow-up during which he developed a
local relapse in the right abdomen after 7 months. Review of
previous HPE revealed the IMT to be ALK positive on IHC
in addition to SMA (diffuse +) and Desmin (weak +). He
was started on Crizotinib and was closely followed-up. There
was partial response with 50% reduction in size which became
static. After 9 months of Crizotinib he underwent laparotomy
and resection of residual calcified mass in ileocolic mesentery without bowel resection. HPE confirmed residual viable
IMT. Postoperatively he was continued on Crizotinib for 6
months and is disease free at 6 months follow-up after last
surgery.
Conclusions: ALK positivity in abdomino-pelvic IMT is
considered a favorable prognostic marker. In the absence of
definitive adjuvant therapy for locally recurrent IMT, ALK
inhibitors are a feasible option for targeted therapy of these
rare tumors as evidenced by this case report. However there
are no guidelines available for the duration of recommended
treatment.
SIOP ABSTRACTS
S327 of S518
1 Barretos
P-352 Anterior Mediastinal Mass in ChildrenPathway for Safe Diagnosis
Childrens Cancer Hospital, Pediatric Surgery Department,
Barretos, Brazil
R. Malik1 , D. Mullassery2 , A. Atra1 , B. Okoye2
Background/Objectives: Central vein catheterization is a
challenge in infants even in experienced hands. US guidance
has become the gold standard for central vein catheterization in the last two decades. US-guided internal jugular vein
(IJV) catheterization is generally the route recommended for
children. Most of the studies concerning infants are on internal jugular vein or subclavian vein (SCV) catheterization in
which technical success rates are lower than in adults and
complications are frequent. Recent studies shows the use of
the technique of ultrasound-guided supraclavicular brachiocephalic vein (BCV) catheterization in infants as a favorable
approach providing high technical success and less complications. This study proposes to assess the degree of difficulty
of vein catheterization by comparing the facility of guidewire
progression in the ultrasound-guided brachiocephalic vein
and internal jugular vein puncture.
1 St
George's Hospital NHS TRust, Department of paediatric oncology,
London, United Kingdom; 2 St George's Hospital NHS Trust, Department of
Paediatric Surgery, London, United Kingdom
Background/Objectives: Anterior mediastinal masses pose
a diagnostic challenge due to the cardiorespiratory risks associated with the mass which are exaggerated during a general
anaesthetic for biopsy. We reviewed our institutional practice
to assess the safety of our approach.
Design/Methods: Retrospective case record review of all
patients with an anterior mediastinal mass for diagnosis at our
tertiary paediatric oncology and surgery centre. All patients
admitted between January 2013 and December 2016 were
assessed for co-morbidities, clinical presentation, method of
tissue diagnosis and complications.
Results: There were 34 patients (median age 11.5 years, range
1 to 17 years, 21 male) admitted for diagnosis of AMM during the study period. Fifteen patients presented with respiratory symptoms. Eleven children had evidence of tracheobronchial compression on imaging. Histological diagnoses
included Hodgkin's lymphoma (11), Non Hodgkin's lymphoma (10), leukaemia (8), lipoblastoma (1), teratoma (1),
PNET (1), rhabdomyosarcoma (1) and mediastinal metastasis from nasopharyngeal carcinoma (1). Sixteen patients had
a lymph node biopsy. Alternative tissues (pleural fluid- 4,
peripheral blood film- 3) were used for diagnosis in 7 patients.
Eight patients had image guided core biopsy of the mediastinal mass and one patient had mediastinoscopic biopsy of paratracheal node. Ketamine sedation was used in 15 patients and
10 patients had a general anaesthetic.
There were no anaesthetic complications. Four patients
needed admission to PICU for tumour lysis syndrome. Two
patients needed a repeat node biopsy ( 1 post steroid and one
inadequate sample).
Conclusions: Safe tissue diagnosis of anterior mediastinal
masses can be obtained by a personalised multidisciplinary
approach. Alternative tissue and local anaesthetic must be
used when appropriate. Ketamine sedation is a good alternative for some high risk cases as it obviates the need for a full
general anaesthetic.
P-353 Ultrasound-Guided Brachiocephalic Vein
Catheterization Compared to Internal Jugular in
Infants with Cancer at a Developing Country
Setting
R.C. Ribeiro1 , W.E. Oliveira Júnior1 , V. Kremer1
Design/Methods: Children who underwent BCV or IJV
catheterization by the Pediatric Surgery Department at our
Pediatric Oncology Hospital from December 2014 to March
2017 were retrospectively analyzed. Demographic features,
disease, chooses vein, vein side, guidewire progression and
complications were obtained. Guidewire progression were
classified as easy or difficult.
Results: A hundred-fifty -five procedures were performed, 68
on IVJ and 87 on BCV. Were evaluated eighty-seven male
patients (68 female), 108 with solid tumors (47 hematologic
malignancies) with a median of 66 months of age and 21
kilograms. From IVJ patients, 21 had guidewire progression
classified as difficult compared to 10 difficult progressions
in the other group, showing statistic significance of BCV
vein catheterization (p-value: 0,0027). No major complications occurred in the BCV group.
Conclusions: Ultrasound-guided brachiocephalic vein
catheterization by supraclavicular is a easier way when
compared to internal jugular approach in children. A possible
explanation is because this technique enables visualization
of the needle and the BCV in the longitudinal axis while
preventing the vein from compression by the US.
P-354 Association of Large Vessel Compression
and Contralateral Extension with Operational
Risks in the Resection of Wilms Tumors
T. Oue1 , A. Yoneda2 , M. Zenitani1 , N. Tanaka1 , T. Sasaki1 , N.
Usui3 , H. Okuyama4
1 Hyogo
College Of Medicine, Pediatric Surgery, Nishinomiya-shi- Hyogo,
Japan; 2 Osaka City General Hospital, Pediatric Surgery, Osaka, Japan;
3 Osaka Medical Center and Research Institute for Maternal and Child
Health, Pediatric Surgery, Izumi, Japan; 4 Osaka Univerity Graduate School
of medicine, Pediatric Surgery, Suita, Japan
SIOP ABSTRACTS
S328 of S518
Background/Objectives: In the USA and Japan, the standard
treatment for Wilms tumor (WT) is primary resection followed by chemotherapy. However, in cases with large tumors,
hemorrhage and tumor spillage due to rupture or its extension
beyond the tumor capsule increase the surgical risk to patients.
In such cases, chemotherapy should be administered prior to
tumor resection. In the present study, we performed preoperative image analyses to identify factors associated with these
surgical risks.
Design/Methods: Twenty-nine patients with WT treated
between 2000 and 2015 were enrolled in this study. Patient
clinical records and image results, including computed
tomography (CT) scans, were collected and retrospectively
analyzed. Image factors, such as tumor size, tumor volume,
relationship among large vessels, and contralateral extension
of the tumor, were evaluated, and their relationship with surgical factors including operating time, hemorrhage, tumor
spillage, and unresectability were analyzed.
Results: Operating time and hemorrhage per body weight
were significantly related with tumor size, area, and volume.
Operating time was significantly longer and hemorrhages
were significantly more in cases with compression of abdominal aorta and/or vena cava by the tumor (p = 0.0156, p =
0.0161, respectively) and extension of the tumor beyond the
center of the vertebral body (p = 0.0124, p = 0.0323, respectively). Three patients had unresectable tumors and four had
tumor spillage; tumors of these patients were more frequently
associated with large vessel compression and contralateral
extension.
Conclusions: Besides the tumor size, large vessel compression and contralateral extension were significantly correlated
with surgical risks. These factors are easily determined using
CT images and are therefore useful in predicting the surgical
risks and unresectability of tumors and deciding whether to
use preoperative chemotherapy as a primary treatment strategy for large localized WT.
Design/Methods: Retrospective data analysis of all patients
undergoing an abdominal surgery for malignancy between
2005 and 2015 in a tertiary pediatric hospital. Data collection included demographics, tumor characteristics, details of
operative procedure, details of adjunct treatments (chemotherapy and radiotherapy), incidence of bowel obstruction and
details regarding its management. Patients with obstruction
were statistically compared to those without obstruction using
chi –square and students’ t-test with significance reported for
p<0,05.
Results: The analysis included 130 patients with a median
follow-up of 3,5 years (mean 4y). A majority of patients were
female (58%) with a median age at time of surgery for the
entire cohort of 3,8 years. The most frequent diagnosis was
Wilm's tumor (37%) followed by neuroblastoma (28%), hepatoblastoma (10%) and germ cells tumor (6%). The surgical
approach was an open procedure in 95% of cases. Fifteen
patients had a postoperative occlusion (11,5%): 13 cases of
adhesions, 1 internal hernia and 1 SB volvulus. The mean
operative time (396 min Vs. 311min, p=0,05) and mean blood
loss (875ml Vs. 262 ml, p<0,01) was significantly higher for
patients with bowel obstruction. Conservative management
was attempted for all cases of obstruction with a success rate
of 47% after a mean of 3 days. For 8 patients requiring surgical intervention, minimally invasive approach was successful
for two patients.
Conclusions: Bowel obstruction is a significant complication
after abdominal surgery for cancer in children. Conservative
management is frequently successful. For patients requiring
surgical treatment, laparoscopy can be a valuable option.
P-356 Solid Pseudopapillary Neoplasm of the
Pancreas in Children: An Experience in Developing
Country
R. Ribeiro1 , V. kremer1 , R. Balceiro2 , W. Oliveira Jr1 , L. Lopes2
1 Barretos
2 Barretos
P-355 Bowel Obstruction After Abdominal
Surgery for Cancer in Children
N. Piché1 , J. Côté2 , L. Krauel Gimenez Salinas3 , J. Trebichavsky1
1 CHU
Sainte-Justine, Surgery, Montreal, Canada; 2 Université de Montréal,
Faculty of medicine, Montreal, Canada; 3 Hospital Sant Joan de Déu,
Pediatric surgery, Barcelone, Spain
Background/Objectives: Pediatric cancer frequently affects
intra-abdominal organs and surgery is indicated for most
cases. Few publications have addressed the complication of
post operative bowel obstruction in that context. We analysed
our data over a 10 year period to determine the frequency, etiology and treatment options of this complication.
Children Cancer Hospital, Pediatric Surgery, Barretos, Brazil;
Children Cancer Hospital, Pediatric Oncology, Barretos, Brazil
Background/Objectives: Pancreatic tumors are very rare
entity in children. We reviewed the clinical and pathologic
features of pediatric patients with pancreatic solid pseudopapillary neoplasm (PSPPN), also called as Frantz tumor, at a single institution.
Design/Methods: We conducted a retrospective analysis of
the demographic data, clinical features, surgical approach, and
long-term outcomes of all patients diagnosed with PSPPN
between 2010 and 2016.
Results: There were six patients during the study period with
solid pseudopapillary neoplasm. All patients were female.
The median age at presentation was 15 years (range: 11 to
18 years). Abdominal pain was the most presenting symptom shown in 4 girls. Preoperative imaging studies included
SIOP ABSTRACTS
computed tomography (all cases) and magnetic resonance
imaging (3 cases). The median maximum diameter of the
tumor was 56 mm with a range of 36 to 120 mm. None
of the patients had evidence of metastasis at presentation.
Regarding the pancreatic location, three patients had a pancreatic head tumor, two underwent pancreaticoduodenectomy
and one nodulectomy; two girls the tumor was in tail and
underwent distal pancreatectomy with splenectomy, one of
those laparoscopic; and one patient had a pancreatic body
tumor and underwent a distal pancreatectomy. We had only
one late complication, related to a pancreatic pseudocysts
treated with drainage and octreotide. On immunohistochemistry, chromogranin was negative in 4 cases of 5 analyzed,
whereas vimentin were positive in all analyzed cases. Enolase
was positive in three cases analyzed.No adjuvant therapy was
done. All patients are alive and without evidence of disease
on a median follow up of 28 months (3 to 71 months).
Conclusions: We present our experience and long-term follow up data on children with PSPPN. In agreement with multiple clinical series, we believe that despite PSPPN generally
has a benign behavior; complete resection with clear margins
is mandatory to achieve the best long-term outcomes
P-357 Surgery Options and Results of Treatment
of Children with Solid Pseudopapillary Tumors of
the Pancreas
D. Rybakova1 , P. Kerimov1 , A. Kazancev1
1 Federal
State Budgetary Institution “Russian Cancer Research Center. NN
Blokhin ”of the Ministry of Health of Russia, children oncology, Moscow,
Russia
Background/Objectives: Development rational surgery for
solid pseudopapillary tumor (SPT) of the pancreas and implementation of Endosurgery.
Design/Methods: 15 children with SPT were operated since
2004 to November 2016. We analyzed clinical data, operation
options and results of treatment.
Results: All patients were girls age from 9 to 15 years (median
13y.o.). Localization tumors in pancreas: in the tail – 5, in the
body - 6 and in the head - 4. The size: 8.7 – 1.5 sm (M 4.6
sm). 5 children underwent laparoscopic distal pancreatectomy
with splenic preservation, 1 - laparoscopic central resection;
3 - gastropancreatoduodenal resection, 3 – central resection
of pancreas; 1 - distal subtotal resection with resection of the
superior mesenteric vein and 1 - Uncinate process of pancreas
resection with resection of duodenal wall. Time of operations:
95 – 290 min. Bleeding: Complications occurred in 5 patients:
in 3 cases – pancreatitis with pancreatic fistula, 1 - bleeding
from the pancreatic branch of the splenic artery after Whipple operation and 1 - pneumonia. There were 2 reoperation
for complications. The observation period of the patients was
S329 of S518
from 1 month to 8 years. All patients are alive without evidence of disease recurrence
Conclusions: The main method of treatment is surgery, however there is a moderate risk of complications because of
tumor localization. Great attention should be paid to the prevention of postoperative pancreatitis. A promising method
is endosurgery providing early rehabilitation and cosmetic
effects.
P-358 Water Jet Dissection Technique for Liver
Resections in Pediatric Oncology Surgery
T. Sharoev1 , A. Prityko2 , M. Rokhoev1 , A. Kotlovsky3
1 St
Luka's Clinical Research Centre for Children- Moscow- Russia,
Oncology, Moscow, Russia; 2 St Luka's Clinical Research Centre for
Children- Moscow- Russia, Administration, Moscow, Russia; 3 St Luka's
Clinical Research Centre for Children- Moscow- Russia, paediatric surgery,
Moscow, Russia
Background/Objectives: The water jet dissection technology
(WJDT) is particularly advantageous in liver surgery for isolating major blood vessels adjacent to the tumor and also for
sparing the surrounding hepatic parenchyma. In Russia we
have pioneered the WJDT in pediatric oncology surgery. The
objective of this review is to estimate the effectiveness of the
WJDT for liver resections in children with hepatic tumors in
our single-centre practice.
Design/Methods: From 2010 to 2017, liver resections of various anatomical types using the WJDT were performed in 25
children with hepatic tumors. Technologically, the ERBEJET
in the ERBE VIO system was utilized. The patient data was
prospectively collected and then analyzed, in particular considering tumor characterization and details of the surgical procedures.
Results: The mean patient age was 4.3 years (from 2 weeks
to 17 years). Malignant tumors were diagnosed in 22 cases.
The following types of liver resections were carried out: hemihepatectomy (n=11), trisegmentectomy (n=5), bisegmentectomy (n=8), segmentectomy (n=1). All procedures were completed successfully. Blood transfusions were required in 15
cases (60%). Postoperatively bile leak occurred in one patient
(4%). No other complications related to the technique used
were noted. The complete tumor clearance with negative surgical margins was histologically evident in all cases while the
mean volume of the tumors removed was 413 cm3 and the
maximum size - 24 cm (in the largest dimension).
Conclusions: In our experience the WJDT is a technically
straightforward, safe and effective technique for liver resections of various anatomical types in children with hepatic
tumors, in particular, in infants aged under 1 year. This technique allows provision of the reliable hemostasis while maximally sparing the hepatic parenchyma. We therefore believe
SIOP ABSTRACTS
S330 of S518
that application of the WJDT should be widespread for liver
resections in pediatric oncology practice.
Women's and Children's Hospital, Department of Paediatric Surgery,
singapore, Singapore; 2 KK Women's and Children's Hospital, Department
of Diagnostic and interventional Imaging, singapore, Singapore
P-359 The Navigation Surgery Using Indocyanine
Green Fluorescent Imaging for a Hepatoblastoma
Patient
Background/Objectives: Congenital vascular anomalies of
the abdominal great vessels are uncommon but can potentially impact surgical procedures and affect outcomes negatively, yet their incidence and clinical impact is poorly studied. We sought to assess the incidence of vascular anomalies of the abdominal great vessels in patients with retroperitoneal embryonal tumors, and study their impact on surgical
and oncologic outcomes.
R. Souzaki1 , Y. Kinoshita1 , N. Kawakubo1 , Y. Koga2 , J.
Takemoto3 , K. Kohashi3 , Y. Oda3 , S. Ohga2 , T. Taguchi1
1 Kyushu
university, Department of Pediatric Surgery, FUKUOKA, Japan;
university, Department of Pediatrics, FUKUOKA, Japan; 3 Kyushu
university, Department of Anatomic Pathology, FUKUOKA, Japan
2 Kyushu
Background/Objectives: Navigation surgery using indocyanine green (ICG) fluorescent imaging for metastasectomy of
lung and hepatectomy in hepatoblastoma (HB) patients has
been reported. However, the usefulness of this surgery for
HB has not been fully clarified. Furthermore, no cases using
this surgical navigation during video-assisted thoracoscopic
surgery (VATS) for metastasectomy of the lung have been
reported. We herein report experiences with surgical navigation for metastasectomy of the bilateral lung including a VATS
procedure and hepatectomy in an HB patient.
Design/Methods: In a PRETEXT III HB patient with bilateral lung metastasis following chemotherapy, a primary tumor
and lung metastatic lesions were intraoperatively examined
using a 10-mm infrared fluorescence imaging scope after the
administration of ICG preoperatively.
Results: Navigation surgery using ICG fluorescent imaging
was performed for an HB patient. The metastatic lesions were
recognized by computed tomography (CT) in both lungs. The
lesion in the left lung was 1.5 cm in diameter, so thoracotomy
was performed for the left lung. For the right lung, VATS
was performed. No lesions expect for those detected by CT
were palpable in the left lung. Although only one lesion not
detected by CT exhibited intense fluorescence in the right
lung, all lesions detected by CT exhibited intense fluorescence. All of these fluorescence-positive lesions except for the
one lesion of the right lung not detected by CT were pathologically proven to be made up of HB cells. None of the resection
stumps for the metastectomies showed fluorescence, and all
of the tumors were found to have been completely resected
on a pathological examination. Although the liver tumor was
strongly attached to the diaphragm, no fluorescence-positive
lesions were seen at the diaphragm after resection.
1 KK
Design/Methods: We retrospectively analyzed imaging, surgical, treatment and survival data of all pediatric patients
with retroperitoneal tumors who underwent resection in KK
Women's and Children's Hospital between January 2007 and
October 2016. Preoperative scans were compared with corresponding intraoperative observations. Disease and treatment
parameters, and survival outcomes, were compared using Chisquare test and Kaplan-Meier method, respectively.
Results: Among 66 children studied, primary tumors arose
from the kidney in 26 (39%), adrenal gland in 22 (33.3%)
and paravertebral in 18 (27.3%) patients. Mean age at diagnosis was 3.7 years (S.D., 2.9). Vascular anomalies were found
in 6 (9%) cases, namely renal (n=5) and adrenal (n=1) vessels. Interestingly, vascular anomalies were only associated
with right-sided tumors (22.2%) and not left-sided tumors
(P=0.023). Intraoperative complications were more common
in patients with vascular anomalies (67%) than those without (15%, P=0.013). Complete tumor resection was achieved
in 5 of 6 (83.3%) cases with vascular anomalies and 46
of 60 (76.7%) cases without. Relapse was more frequent
in patients with vascular anomalies (n=2 (33%)) than those
without (n=11 (18.3%)), but was not statistically significant
(P=0.317). The presence of vascular anomalies, extent of
resection, and intraoperative complications were not associated with overall and event-free survival, but relapse was associated with overall and event-free survival (P<0.001).
Conclusions: Vascular anomalies of abdominal great vessels
occurred in 9% of our patients with retroperitoneal tumors.
Vascular anomalies were associated with higher rates of intraoperative complications and disease relapse but did not impact
survival outcomes.
Conclusions: Navigation surgery using ICG for a patient with
HB was useful for identifying metastatic lesions and confirming complete resection, even with VATS.
T R E AT M E N T A N D CA R E RADIAT ION ONCOLOGY (PROS)
P-360 Retroperitoneal Tumors and Congenital
Vascular Anomalies of Abdominal Great Vessels
P-361 Radiation Necrosis in Pediatric Patients
with Brain Tumors Treated with Pencil Beam
Scanning Proton Therapy
S.W.M. TIP1 , Y.T. LEE1 , P.H. TANG2 , A.H.P. LOH1
SIOP ABSTRACTS
B. Bojaxhiu1 , F. Ahlhelm2 , M. Walser3 , L. Placidi3 , U. Kliebsch3 ,
L. Mikroutsikos3 , P. Morach3 , A. Bolsi3 , L. Tony3 , R. Schneider3 ,
D.C. Weber3
1 Inselspital,
Radiation Oncology, Bern, Switzerland; 2 Kantonsspital Baden,
Radiology, Baden, Switzerland; 3 Paul Scherrer Institute, Center for Proton
Therapy, Villigen PSI West, Switzerland
Background/Objectives: To assess the rate of radiationinduced radiation necrosis (RN) and white matter lesions
(WML) and related neurologic symptoms in pediatric patients
with primary brain tumors treated with Pencil Beam Scanning (PBS) proton therapy (PT) with or without concomitant
chemotherapy at the Paul Scherrer Institute, Switzerland.
Design/Methods: One hundred and seventy-one pediatric
patients (<18 years) with brain tumors were treated with PBS
PT between 1999 and 2015. Median age at diagnosis was 3.3
years (range, 0.3-17.0). Post PT brain parenchymal alterations
(WML and RN) were defined as a new area of abnormal signal intensity on T2-weighted images or increased signal intensity on T2-weighted images, and contrast enhancement on T1
occurring in the brain parenchyma included in the radiation
treatment field, which did not demonstrate any abnormality
before PT. The median follow-up period for the surviving
patients was 49.8 months (range, 5.9-194.7).
Results: One hundred and twenty-four patients (72%) did not
develop any parenchymal brain alteration after PT. Twentynine (17%) patients developed RN at a median time of 5
months (range, 1-26), most of them (n=17; 59%) being
asymptomatic (grade 1). Grade 2, 4 and 5 toxicities occurred
in 8, 2 and 2 patients, respectively. Eighteen (11%) patients
developed WML at a median time of 14.5 months (range, 262), most of them (n=13; 72%) being asymptomatic (grade
1). Grade 2 and 3 toxicities occurred in 4 and 1 patients,
respectively. The 5-year RN-free survival was 83% and the
WML-free survival was 87%. In univariate analysis, neoadjuvant chemotherapy (P=0.025), hydrocephalus before PT
(P=0.035), and ependymoma (P=0.026) were significant predictors of RN.
Conclusions: Children treated with PT demonstrated a low
prevalence of symptomatic radiation necrosis (7%) or white
matter lesion (3%). Chemotherapy administration before proton therapy, ependymoma, and hydrocephalus as an initial
symptom were significant risk factors associated with radiation necrosis in these children with brain tumors.
P-362 Role of Radiotherapy to
Primary/Metastatic Sites in Pediatric Patients with
Metastatic Rhabdomyosarcoma in the Bernie Study
A. Cameron1 , J. Chisholm2 , M. Elze3 , M. Casanova4 , B. Geoerger5 ,
M. Gaze6 , O. Oberlin5 , J. Bachir7 , S. Fürst-Recktenwald7 , J.H.M.
Merks8
S331 of S518
1 University
Hospitals Bristol NHS Foundation Trust, Bristol Haematology
and Oncology Centre, Bristol, United Kingdom; 2 The Royal Marsden NHS
Foundation Trust, Children and Young People's Unit, Sutton, United
Kingdom; 3 F. Hoffmann-La Roche Ltd, Innovative Pediatric Oncology Drug
Development, Basel, Switzerland; 4 Fondazione IRCCS Istituto Nazionale
dei Tumori, Pediatric Oncology Unit, Milan, Italy; 5 Gustave Roussy,
Department of Pediatric and Adolescent Oncology, Villejuif, France;
6 University College London Hospitals NHS Foundation Trust, Department
of Oncology, London, United Kingdom; 7 F. Hoffmann-La Roche Ltd,
Pediatric Oncology, Basel, Switzerland; 8 Emma Children's
Hospital-Academic Medical Center EKZ-AMC, Department of Pediatric
Oncology, Amsterdam, The Netherlands
Background/Objectives: Local control is a key part of treatment of local/locoregional rhabdomyosarcoma (RMS) and
often involves radiotherapy with/without surgery. The role of
radiotherapy in metastatic RMS is uncertain, with little published evidence to guide clinicians. We analyzed data from the
BERNIE trial to assess the benefit of radiotherapy for patients
with metastatic RMS.
Design/Methods: In BERNIE (NCT00643565), patients
aged ≥6 months to <18 years with metastatic RMS were randomized to receive chemotherapy with/without bevacizumab,
surgery and/or radiotherapy (at cycle 6–9) then maintenance
chemotherapy. Radiotherapy was recommended for all sites
of metastases if feasible (investigator discretion allowed,
resulting in variability in actual radiotherapy given). Patients
were categorized into those receiving radiotherapy for all
sites of disease, partial radiotherapy, and no radiotherapy.
Event-free survival (EFS) and overall survival (OS) were
calculated using Cox proportional hazards models and a
landmark approach: only patients who were event free at
day 221 (i.e. end of cycle 9 +1 month) were included
(EFS, n=85; OS, n=97). Variables adjusted for treatment (as
randomized), disease type (alveolar/embryonal/other), risk
group, age >10yrs, and metastatic lesion count (1, 2–3,
4+). The analysis was non-randomized, exploratory, and post
hoc.
Results: Of 102 patients with RMS, 22 received no radiotherapy, 49 partial radiotherapy, and 31 radiotherapy to all
sites. Baseline characteristics were mostly balanced; comparable proportions of patients received bevacizumab. Significantly longer OS (hazard ratio [HR]=0.249; 95% confidence interval [CI]: 0.119–0.524; p=0.00025) and a nonsignificant EFS improvement (HR=0.520; 95% CI: 0.267–
1.011; p=0.05405) were observed in the radiotherapy-treated
group versus no radiotherapy. The 3-year EFS and OS, respectively, were 9% and 23% (no radiotherapy), 42% and 53%
(partial radiotherapy), and 58% and 84% (radiotherapy to all
sites).
Conclusions: Radiotherapy in metastatic RMS was associated with significant OS benefits, albeit in small patient numbers. This should be confirmed in a prospective randomized
trial.
SIOP ABSTRACTS
S332 of S518
P-363 Paediatric Radiation Therapy Across
Europe – A European Questionnaire Survey
Supported by the SIOPE, ESTRO, PROS and
Several National Paediatric Hematology-Oncology
Societies (NAPHOS)
C. Demoor-Goldschmidt1 , C. carrie2 , G. whitfield3 , P. meijinders4 ,
K. dieckmann5 , P. banovic6 , M. solak mekic7 , Y. lassen8 , K.
alexopoulou9 , J. giralt10 , J. vizkeleti11 , L. jarusevicius12 , B.
ondrova13 , P. daly14 , P. brandal15 , G. Janssens16 , U. ricardi17 , R.
dieter-kortmann18
1 Inserm,
U1018, Villejuif, France; 2 centre léon berard, Radiotherapy, Lyon,
France; 3 The Christie, Radiotherapy, Manchester, United Kingdom;
4 Iridium Cancer Network Antwerp-GZA- University of Antwerp, Radiation
oncology, Antwerp, Belgium; 5 university of vienna, radiotherapy, Vienna,
Austria; 6 IMC Banja Luka - Member of the Affidea Group, Radiotherapy,
Banja Luka, Bosnia - Herzegovina; 7 Clinical Hospital Center “Sestre
milosrdnice”-University Hospital for Tumors, radiotherapy, zagreb,
Croatia; 8 Aarhus University Hospital, radiotherapy, Aarhus, Denmark;
9 Athens General Hospital for Children & Adolescents, radiotherapy, athen,
Greece; 10 Hospital Universitari Valld'Hebron, radiotherapy, barcelone,
Spain; 11 national institute of oncology, radiotherapy, budapest, Hungary;
12 The Hospital of Lithuanian University of Health Sciences LSMU Kauno
klinikos, radiotherapy, kaunas, Lithuania; 13 Proton therapy center Czech,
radiotherapy, prague, Czech Republic; 14 St Lukes Radiation Oncology
centre, radiation oncology, dublin, Ireland; 15 Norwegian Radium Hospital,
oncology, oslo, Norway; 16 University Medical Center Utrecht – Princess
Maxima Center for Pediatric Oncology, radiotherapy, utrecht, The
Netherlands; 17 univeristy or turin, radiotherapy, turin, Italy; 18 univeristy of
Leipzig, radiotherapy, leipzig, Germany
Background/Objectives: Increased focus has been made to
improve the quality of care and access to European trials in
paediatric oncology. Information about paediatric radiotherapy (Ped-RT) through Europe is not widely available. The aim
of this study was to provide an overview of resources and organization for Ped-RT.
Design/Methods: Experts in Ped-RT oncology were invited
by email to complete a 21-points questionnaire.
Results: Sixty-eight answers from 24 countries (7 centres
with proton) were collected and 16 centres were visited. A
minority of radiation oncologists (11.74%) treat only children,
which is in contrast with paediatric oncologists (93.44%) or
surgeons (71.67%) who are more often dedicated. In 5 countries, ped-RT is centralized in one centre. Access to ped-RT
formations in unequal through Europe even if everyone agree
with the fact that specific knowledges are needed.
Regarding the techniques, 12% use sometimes, meaning for
some patients, 2D- conventional radiotherapy, 4% still use
Cobalt and 15% never or rarely use IMRT (Intensity Modulated Radiotherapy), 64% use hypofractionated treatments,
defined as at least 3Gy per fraction and 32% when considering 5 Gy or more. Eighty-four percent have access to paediatric devices for personalized immobilization. Radiation treatments can be easily delivered under anaesthesia in 75% of the
centres if necessary, or under hypnosis in 9% of centres (2
countries).
The environment is mostly adapted to children, with dedicated
dedicated waiting area (47%), patient information (83%), gifts
(98%), the possibility to listen to music or songs (93%) or
watch cartoons (12%).
Conclusions: This survey provides quantitative data demonstrating the current healthcare inequalities for children and
adolescents who need radiotherapy in Europe. Nevertheless,
an effort to guarantee a treatment of quality with the local
environment has been pointed out.
Acknowledgments: We thank European NaPHOS and paediatricians who contributed to disseminate the survey in their
countries as well as every respondent.
P-364 A French Multicenter Treatment Planning
in Silico Inter-Comparison: A Skull Base
Rhabdomyosarcoma Radiotherapy Case
A. Ducassou1 , G. Hangard2 , C. Lanaspeze2 , V. Bernier3 , S. Bolle4 ,
F. Goudjil5 , S. Helfre6 , C. Kerr7 , J. Leseur8 , X. Muracciole9 , L.
Padovani9 , H. Potet10 , S. Supiot11 , G. Truc12 , C. Vigneron13 , A.
Laprie1
1 Institut
Claudius regaud -Institut Universitaire du Cancer - Toulouse
Oncopole, Radiation oncology, Toulouse, France; 2 Institut Claudius regaud
-Institut Universitaire du Cancer - Toulouse Oncopole, Departement of
physics, Toulouse, France; 3 Centre Alexis Vautrin, Radiation oncology,
Nancy, France; 4 Institut Gustave Roussy, Radiation Oncology, Villejuif,
France; 5 Institut Curie, Department of physics, Paris, France; 6 Institut
Curie, Radiation oncology, Paris, France; 7 Institut du Cancer de
Montpellier, Radiation Oncology, Montpellier, France; 8 Centre Eugène
Marquis, Radiation Oncology, Rennes, France; 9 CHU La Timone,
Radiation Oncology, Marseille, France; 10 Institut Jean Godinot-, Radiation
Oncology, Reims, France; 11 Centre René Gauducheau, Radiation
Oncology, Nantes, France; 12 Centre Georges-François Leclerc, Radiation
Oncology, Dijon, France; 13 Centre Paul Strauss, Radiation Oncology,
Strasbourg, France
Background/Objectives: To compare 13 radiotherapy plans
of a parameningeal alveolar rhabdomyosarcoma of the skull
base in a 5-year-girl, optimized in ten centers with IMRT,
VMAT, Tomotherapy or Proton therapy, and identify possible dose distribution differences.
Design/Methods: Dose prescription was 50.4 Gy in 28 fractions on PTV1 (involved volume before chemotherapy) with a
sequential boost of 5.4 Gy in 3 fractions in a reducted volume
(PTV2 ).
Six Tomotherapy, 4 VMAT, 1 IMRT step and shoot and 1 passive scattering Proton therapy plans were completed and compared. We also evaluated a commercially available treatment
planning system (TPS) for a PT plan in Pencil Beam Scattering (RayStation provided by RaySearch Laboratories®).
Comparisons were performed on the artiview system (Aquilab
®).
Results: All institutions achieved the planning objectives,
with CTV and PTV1 and 2 V95 of 95% whatever the modality chosen. Mean conformity index (CI) for PTV1 and PTV2
SIOP ABSTRACTS
were respectively 1.11 and 2.45 with VMAT, 1.24 and 2.78
with Tomotherapy and 1.31 and 2.95 with Proton therapy.
Mean standard deviations (STD) for CTV and PTV low risk
were respectively 1.57 and 0.71 with VMAT, 1.43 and 0.59
with Tomotherapy and 1.8 and 0.4 with Proton therapy.
No significant correlations between chosen modality and
DVH for targets and organs at risk (OARs) were observed.
The optimization strategies selected by the planners played a
key role in the delivered dose to the OARs. The cohort was too
small to enhance a significant sparing of critical structures.
Conclusions: In this complex pediatric tumor, the human factor and the constraints imposed to the target volumes and
OARs have a greater dosimetric impact than treatment planning and radiation delivery technology.
P-365 The Impact of Particle Therapy in
Pediatric Tumors with Emphasis on Clinical
Toxicity
J.L. Habrand1 , D. Stefan1 , S. Bolle2 , D. Lecomte1 , J. Datchary1 , S.
Helfre3 , C. Alapetite3
1 Centre
François Baclesse, Radiation oncology, Caen, France; 2 Gustave
Roussy Cancer Campus, Radiation oncology, Villejuif, France; 3 Institut
Curie, Radiation oncology, Paris, France
Background/Objectives: Assessing the impact of particle
radiation therapy (PT) on toxicity and sequelae in pediatric
and adolescent patients (pts) populations, through literature in
the context of modern technologies, with emphasis on comparative clinical studies.
Design/Methods: We performed an extensive review of published articles (pub), from 01/2005 through 12/2015 through
MEDLINE, according to following key-words: Radiotherapy,
English, Toxicity (acute & late sequelae), Novel technologies,
excluding case reports, editorials, letters, inexploitable data.
Our review concentrated on comparative studies between PT
and photon therapy (XRT), with emphasis on clinical evaluations.
Results: 128 pub were selected. Clinical studies represented
71/128 (55%), ranging from small (<20pts:19), to medium
(<50pts:22), large (<100pts:13), very large (<500pts:15), and
extra-large (≥500pts:2) cohorts, totalizing >7,000 pts. 18%
addressed inter-comparisons between XRT and XRT technologies (1276 pts, one pub), or PT vs XRT (1,151 pts,
13 pub). 12/13 pub concerned protons (P), and 1/13 carbon ions (C). Main types of toxicity per #pts/#pub investigated: Lung: 303/1, CNS/Quality of life (QOL): 244/4,
Second cancers (K2): 161/2, Endocrine: 160/3, acute toxicity: 150/3, Salivary/Head-Neck (HN): 133/1, respectively.
According to impact on technique: IM>3D-XRT:1 pub (pS),
PT>XRT:8 pub (pS:6), XRT>PT:3 pub (pS:2), PT=XRT:2
pub. According to impact on toxicity: Lung: XRT>PT
S333 of S518
(pS); CNS/QOL: PT>XRT: 2 pub (pS:1); XRT>PT: 1 pub
(pS); K2: PT>XRT: 2 (pS:1); Endocrine: PT>XRT: 3 pub
(pS:2); Acute: PT>XRT: 2 pub (pS). HN: XRT>PT:1 (pS);
C=PT+XRT: 1 pub
Conclusions: Few clinical comparative studies between PT
and XRT were performed, and none randomized. Most PT
were related with P, and only one with C. Impact on toxicity
is still controversial although acute, endocrine and CNS/QOL
tend to benefit most from PT. This early evaluation needs to
be strengthened by further literature.
P-366 Data Completeness is Directly Correlated
with Funding Support in the Pediatric Proton
Consortium Registry (PPCR)
C. Hess1 , D. Indelicato2 , A. Paulino3 , W. Hartsell4 , C. Hill-Kayser5 ,
S. Perkins6 , N. Laack7 , R. Ermoian8 , A. Chang9 , O. Cahlon10 , V.
Mangona11 , A. Mahajan7 , S. Gallotto1 , E. Weyman1 , D. Gaudet1 ,
N. Bedos12 , L. Raeke12 , S. Baedorf-Kassis1 , B. Yeap1 , T. Yock1
1 Massachusetts
General Hospital, Radiation Oncology, Boston- MA, USA;
of Florida, Radiation Oncology, Jacksonville- FL, USA; 3 MD
Anderson Cancer Center, Radiation Oncology, Houston- TX, USA;
4 Northwestern Medicine and Radiation Oncology Specialists, Radiation
Oncology, Chicago- IL, USA; 5 University of Pennsylvania, Radiation
Oncology, Philadelphia- PA, USA; 6 Washington University, Radiation
Oncology, St. Louis- MO, USA; 7 Mayo Clinic, Radiation Oncology,
Rochester- MN, USA; 8 University of Washington, Radiation Oncology,
Seattle- WA, USA; 9 ProCure- Oklahoma City, Radiation Oncology,
Oklahoma City- OK, USA; 10 ProCure New Jersey and Memorial Sloan
Kettering Cancer Center, Radiation Oncology, Somerset- NJ, USA; 11 Texas
Center for Proton Therapy, Radiation Oncology, Irving- TX, USA;
12 Massachusetts General Hospital, Program for the Coordination and
Oversight of Research Protocols PCORP, Boston- MA, USA
2 University
Background/Objectives: The Pediatric Proton Consortium
Registry (PPCR) was established to expedite research on PRT
and to better define its role in pediatric cancers by collecting
important late effects outcomes.
Design/Methods: The PPCR is a consented registry residing on the NIH-supported REDCap platform that comprehensively integrates baseline demographics, insurance status,
disease/health information, treatment details, proton radiation plan, follow-up vital status, late toxicity, and surveillance
imaging. All participating sites offer enrollment to pediatric
patients <22 years old. Sites were paid on a per capita basis
until 6-30-2015 when per capita funding ceased. We report
patient numbers by diagnoses and how data field completeness varied by budget era.
Results: By 3-20-17, 1,634 patients were enrolled across
12 sites. The most common CNS (63%) and non-CNS
(37%) diagnoses are: medulloblastoma/PNET (242),
ependymoma (205), gliomas (177), craniopharyngiomas
(146), GCT (94); and rhabdomyosarcoma (172), bone
sarcomas(114), Hodgkin lymphoma(60), chordoma/
chondrosarcoma (51) and neuroblastoma (45). Eleven
SIOP ABSTRACTS
S334 of S518
key registry fields including consent date, DOB, gender,
race, referring MD, surgery, chemotherapy, RT-related start
date, site, field description, and total dose were examined.
Missing data ranged from 0-1.4% per field before per capita
funding ceased and 0-53% thereafter. Notably, demographic
and diagnosis field completeness were unaffected by budget
cuts, but treatment details were missing 30-53% of the time.
Follow-up data and vital status were missing 23% and 34%
of the time before and after budget cuts. The relatively
high rate (23%) of missing follow-up data prior to funding
cuts, highlights the challenges of obtaining follow-up when
patients are not locally followed at the proton center.
Design/Methods: This cross-sectional multicenter study
included 35 children treated for head and rhabdomyosarcoma
(average treatment age:6years, range:1-14years) with EBRT
or brachytherapy for whom the original radiotherapy planning and facial growth deformity data (mean follow-up of 10
years) based on 3D stereophotograph analysis were available.
All bony structures within the field of view of the (reconstructed) planning CT scans were delineated, resulting in 712
delineated facial structures. For each delineated bony structure, the planned mean and maximum dose were analysed
with regard to the growth deformity quantified for the corresponding facial part on the 3D stereophotograph.
Conclusions: The PPCR has now accrued significant disease
specific patient cohorts that can answer important research
questions. PPCR Site PIs remain engaged despite lack of
resources prompting innovation of new data collection techniques. Innovative solutions for data collection efficiency
include selective review of shared electronic medical records
by centralized researchers aided by patient reported outcomes
(PROs).
Results: Growth deformities were more severe in patients
treated at a younger age than in patients treated when they
were older. A correlation between growth deformities and
dose indices was not found. However, overall more severe
growth deformities were observed when the dose exceeded
24Gy. Some bony structures were more susceptible to growth
disruption than others, for example the mandibular condyle
and lacrimal bone exhibited more growth deformities after
receiving the same mean and maximum dose than the frontaltemporal bone complex (both p<0.05).
P-367 Facial Growth Deformation Following
Pediatric Head and Neck Sarcoma: Should Dose
Constraints Regarding Specific Bony Structures Be
Considered?
Conclusions: We found significant differences for the susceptibility to growth deformity between different facial bony
structures. In the future, dose constraints for specific bony
structures of the face might therefore be beneficial in pediatric radiotherapy to limit facial deformities. Further research
based on a larger data set is needed to derive appropriate dose
constraints for each facial bone.
M.L. Hol1,2 , B. Pieters3 , J. Wiersma3 , A. Bel3 , N. Freling4 , B.
Balgobind3 , R. Davilla Fajardo5 , T. Maal6 , P. Saeed7 , J. Chisholm8 ,
O. Slater9 , T. Alderliesten3 , A. Becking10 , H. Mandeville11 , M.
Gaze12 , J. Merks1 , L. Smeele2
1 Academic
Medical Center, Department of Pediatric Oncology, Amsterdam,
The Netherlands; 2 Academic Medical Center, Department of Maxillofacial
Surgery and Head and Neck Surgery, Amsterdam, The Netherlands;
3 Academic Medical Center, Department of Radiation Oncology,
Amsterdam, The Netherlands; 4 Academic Medical Center, Department of
Radiology, Amsterdam, The Netherlands; 5 Princess Máxima Center for
Pediatric Oncology / University Medical Center Utrecht, Department of
Radiation Oncology, Utrecht, The Netherlands; 6 RadboudUMC,
Department of Maxillofacial Surgery- 3D lab, Nijmegen, The Netherlands;
7 Academic Medical Center, Department of Orbital Surgery, Amsterdam,
The Netherlands; 8 Royal Marsden Hospital, Department of Pediatric
Oncology, Sutton, United Kingdom; 9 Great Ormond Street Hospital,
Department of Pediatric Oncology, London, United Kingdom; 10 Academic
Medical Center, Department of Maxillofacial Surgery, Amsterdam, The
Netherlands; 11 Royal Marsden Hospital, Department of Radiation
Oncology, Sutton, United Kingdom; 12 University College London,
Department of Radiation Oncology, London, United Kingdom
Background/Objectives: During radiotherapy planning in
patients with pediatric head and neck cancer, multiple organs
at risk are taken into account and corresponding dose constraints are considered. However, dose constrains related to
facial bony growth have never been verified for specific facial
bones. The purpose of this study was to investigate the relation between dose to facial bony structures and facial growth
deformations.
P-368 High Dose Rate (HDR) Brachytherapy in
Childhood Rhabdomyosarcomas: Experience of a
Single Center
S. Kamer1 , A. Celik2 , A. Avanoglu2 , O. Ergun2 , M. Palamar3 , A.
Yagci3 , B. Kadioglu4 , N. Cetingul5 , M. Kantar5 , T. Turhan6 , Y.
Anacak7
1 Ege
University Faculty of Medicine, Radiation Oncology, IZMIR, Turkey;
University Faculty of Medicine, Department of Pediatric Surgery,
izmir, Turkey; 3 Ege University Faculty of Medicine, Department of
Ophthalmology, IZMIR, Turkey; 4 Behcet Uz Children's Hospital,
Department of Pediatric Oncology, IZMIR, Turkey; 5 Ege University Faculty
of Medicine, Department of Pediatric Oncology, IZMIR, Turkey; 6 Ege
University Faculty of Medicine, Department of Neurosurgery, IZMIR,
Turkey; 7 Ege University Faculty of Medicine, Department of Radiation
Oncology, IZMIR, Turkey
2 Ege
Background/Objectives: Radiotherapy (RT) is an important
component of the treatment in childhood rhabdomyosarcomas (RMS). Brachytherapy is a special irradiation technique
which gives a possibility to protect surrounding healthy tissues and organs from unnecessary irradiation. The use of
brachytherapy is favorable over external RT in particular sites
SIOP ABSTRACTS
S335 of S518
of childhood RMS. In this study we present the results of the
Ege University Hospital.
Design/Methods: From January 2008 to October 2016, HDR
brachytherapy was used as part of the treatment in 18 cases
with RMS in Ege University Hospital. Median age was 6
(range: 3-17) and Male/Female ratio was 1.5/1. Localization
of the tumors were vagina in 1 case, bladder in 8 cases, nonparamenengial head and neck in 3 cases, orbita in 4 cases,
pelvic wall in 1 case and biliary tractus in 1 case. IRS III
or IV chemotherapy regimens were used before RT. RT dose
was 24-36 Gy and a combined external and brachytherapy was
used in 2 cases.
Results: From January 2008 to October 2016, HDR
brachytherapy was used as part of the treatment in 18 cases
with RMS in Ege University Hospital. Median age was 6
(range: 3-17) and Male/Female ratio was 1.5/1. Localization
of the tumors were vagina in 1 case, bladder in 8 cases, nonparamenengial head and neck in 3 cases, orbita in 4 cases,
pelvic wall in 1 case and biliary tractus in 1 case. IRS III
or IV chemotherapy regimens were used before RT. RT dose
was 24-36 Gy and a combined external and brachytherapy was
used in 2 cases.
Conclusions: Brachytherapy is effective in the local–regional
control of childhood RMS. Careful planning of RT is
extremely important for maximum benefit. Late effects need
to be monitored for long term.
P-369 Nasopharyngeal Carcinoma in Children: A
Ten Year Experience with IMRT
S. Laskar1 , A. Bindal1 , N. Khanna1 , S. Chaudhari2 , G.
Chinnaswami3 , T. Vora3 , S. Kembhavi4 , S. Shah5 , M. Ramadwar6 ,
S. Qureshi7 , M.A. Muckaden8 , P. Kurkure3
1 Tata
2 Tata
Memorial Hospital, Radiation Oncology, Mumbai, India;
Memorial Hospital, Medical Physics, Mumbai, India; 3 Tata Memorial
Hospital, Paediatric Oncology, Mumbai, India; 4 Tata Memorial Hospital,
Radiodiagnosis, Mumbai, India; 5 Tata Memorial Hospital, Bio Imaging,
Mumbai, India; 6 Tata Memorial Hospital, Pathology, Mumbai, India; 7 Tata
Memorial Hospital, Surgical Oncology, Mumbai, India; 8 Tata Memorial
Hospital, Palliative Medicine, Mumbai, India
Gy/33 fr) included nodal regions adjacent to the involved
nodes and low risk CTV (54.8 Gy/33 fr) included uninvolved
nodal levels beyond intermediate risk CTV. CTh consisted of
Bleomycin, Methotrexate and Cisplatin.
Results: The loco-regional control, disease-free survival and
overall survival for the cohort were 85%, 60% and 65%,
respectively. At a median follow up of 33 mths (4-148 mths),
53 (56%) patients remained alive & disease free. Three
patients (3.2%) with regional recurrence alone were salvaged
with reirradiation, surgery and CTh, and remain disease free.
All patients with regional recurrence and distant metastases
(11.6%) died of progressive disease. Twenty four (25.3%)
developed distant metastasis only. Of them 4/24 (16.6%) with
oligometastases were salvaged with RT and CTh and are disease free, while 2/24 (8.3%) remain alive with metastatic
disease and 18/24 (75%) died of metastases. Four (4.2%)
patients died of CTh related complications. Xerostomia (16%
Gr II),clinical hypothyroidism (23%), autotoxicity (20% Gr
III), visual field defects (6.3%), and dental carries (20%) were
the major toxicities.
Conclusions: Combined treatment with IMRT and CTh
resulted in acceptable disease control & toxicities. Distant
metastasis remains a major cause of death in these children.
P-370 Impact of Postoperative Abdominal
Irradiation on Local Recurrence in Unilateral
Intermediate and High-Risk Wilms Tumour
(SIOP-2001/GPOH)
P. Melchior1 , Y. Dzierma1 , G. Mogeniene1 , R. Furtwängler2 , N.
Graf2 , C. Rübe1
1 Saarland
University Hospital, Radiation Oncology, Homburg-Saar,
Germany; 2 Saarland University Hospital, Pediatric Hematology and
Oncology, Homburg-Saar, Germany
Background/Objectives: To report the clinical outcome of
children with Wilms tumour (WT) after multimodality treatment following the SIOP-2001/GPOH protocol with special
regard to radiotherapy.
Background/Objectives: To evaluate the disease outcome in
children with Nasopharyngeal Carcinoma (NPC) treated with
Intensity Modulated Radiotherapy (IMRT) at the Tata Memorial Hospital.
Design/Methods: Analysis of 175 patients with unilateral
WT eligible for abdominal irradiation according to histological subtype and postoperative SIOP-stage, treated between
2001 and 2015.
Design/Methods: Between 2005 and 2015, 95 children with
NPC were treated at our Institute. The median age was 14
years [8-18 years]. Majority (92%) of patients had either T3T4 or N2-N3 disease at presentation. They received neoadjuvant Chemotherapy (CTh) followed by IMRT and adjuvant
CTh. Three clinical target volumes (CTV) were defined for
IMRT. High Risk CTV (70.2 Gy/33 fr) included nasopharyngeal region and involved nodes, intermediate risk CTV (59.4
Results: According to the SIOP-2001 protocol 175 of 967
children (18.1%) were eligible for postoperative abdominal
radiotherapy (PORT). The median follow up was 4.8 years.
Median age at diagnosis was 3.4 years. There were 132 children with intermediate risk histology (IR) (stage III) and 43
children with high risk histology (HR) (diffuse anaplastic
(stage II and III) and blastemal type (stage III)). 40 of 175
eligible patients were not irradiated.
SIOP ABSTRACTS
S336 of S518
There were 18 abdominal relapses (10.3%) in the whole
cohort. There were 6 local failures in 40 non-irradiated (15%)
vs. 12 in 135 irradiated children (8.9%). In 4 patients, local
relapse was the only site of failure. Most local recurrences
(14 of 18) were combined with distant metastasis. Mean time
to the first event was 0.98 years. Local recurrence occurred in
IR in 3 of 30 (10%) nonirradiated vs. 5 of 102 (4.9%) irradiated patients, in HR in 3 of 10 (30%) nonirradiated vs. 7 of 33
(21.2%) irradiated patients. Twelve of 18 local relapses were
localised in the flank, 8 infield failures and only 4 relapses
outside the radiation field.
The 5-year local control was 91.6% in the irradiated vs. 84.3%
in the nonirradiated group (p=0.29); 75.3% in HR vs. 94.5%
in IR patients with PORT.
Conclusions: Children with WT treated with a PORT have an
excellent local control, especially for IR. Most local relapses
occurred inside the radiation field and were combined with
distant metastases. Further prospective analyses are necessary
to evaluate new highly conformal radiation techniques.
P-371 Radiation Dose and Let Distributions in
Pediatric Craniopharyngioma Patients with and
Without Radiation-Induced Cerebral
Vasculopathies
A. Pica1 , D.G. Correia1 , L. Placidi1 , A. Bolsi1 , D.C. Weber1
1 Paul
Scherrer Institut, ProtonTherapy Center CPT, Villigen, Switzerland
Background/Objectives: The study aims are: a) to report two
cases of radiation-induced vasculopathies (RIV) after pencil
beam scanning (PBS) proton therapy (PT) for pediatric craniopharyngioma patients and b) to evaluate local dose and linear energy transfer (LET) distributions for these RIVs.
Design/Methods: We reviewed a series of 16 patients treated
at Paul Scherrer Institute (median dose 54 GyRBE). Two
(13%) out of 16 patient showed RIVs (one stenosis of right
ICA and one progressive multifocal RIV in the region of the
circle of Willis, 14 and 24 months after irradiation, respectively). A control group (no RIV) was selected based on the
same fields’ arrangement and the tumour size. CTs and MRIs
pre and post PT were used to contour organs at risks (OARs;
bilateral ICAs and circle of Willis). DVH parameters and dose
distributions were analysed. Dose weighted LET distributions
(Gy * keV/mm) and LET distributions were analysed.
Results: Dose distributions for patient in the control group
and presenting with RIV did not show any significant difference in terms of target coverage and OARs sparing, while RIV
structures have a lower Dmean,without significant difference
in the Dmax and in the D2%. Both patients presenting with
RIV toxicities were treated with ipsilateral fields, thus resulting in marked asymmetric LET distributions. Despite high
LET areas at the distal edge of the PTV, no significant differences were found in the maximum and mean LET values for
the RIV between patients with toxicities and control patients.
Conclusions: Quantitative analysis was not able to show significant correlations between delivered dose, LET and RIV.
Ipsilateral planning approach seems to have an impact in the
presence VT toxicity. This approach is generally less dosimetrically robust than the other one and it results in asymmetric
LET distributions, with high LET values at the contralateral
distal edge of the PTV.
P-372 Optimizing Technique and Technology and
Cost of Radiotherapy for Management of Childhood
Cancer: Experience from Regional Cancer Centre
in India (A Low- and Middle-Income Country)
V.K. Ramaiah1
1 Kidwai
Cancer Institute, Radiation Oncology, Bangalore, India
Background/Objectives:
Cobalt-based
conventional
technique (CCT) to linear accelerator based conformal
radiotherapy (3-D CRT) / particle therapy with or without
incorporating adoptive technology for regular position verification are the different modalities that may be available with
unpredictable variability for radio-therapeutic management
of childhood cancers in developing countries. Radiation
portals or tumor targets can be delineated by conventional
un-calibrated x-ray, x-ray / fluoroscope with simulator
scale or any of 3-D imaging. In-expensive soldering lead
wire placed on the border of radiation portal and over the
every centimeter mark on adhesive tape can be utilized to
customized radiation field. Need for sedation / anesthesia is
mostly patient-dependent rather than the technology itself.
Advanced radiotherapy techniques and technology have
reduced long-term side-effects due to dosimetric improvement without alteration the tumor control. We do not have
large long-term outcome results of resource-intensive novel
radiotherapy technology and techniques. In such scenario,
affordability and waiting time are the two main factors
determining the type of radiation technology utilization in
particular patients in low-resource setting.
Design/Methods: Retrospective analysis of radiation registers of pediatric patients with cancer treated between 2012 and
2016 at Kidwai Cancer Institute, Bangalore
Results: 8% (85) of all patients undergoing radiotherapy was
pediatric patients in our center. >1/2 (45) of all pediatric
patients were diagnosed with acute lymphoblastic leukemia
(ALL) and had undergone prophylactic cranial irradiation. 59
(69%) and 22 (25%) were treated by CCT and 3-D CRT.Cost
of radiotherapy of children with cancer for the same period
was Indian National Rupee 962500 i.e. 5.3% of total money
spent on radiotherapy for all patients.
SIOP ABSTRACTS
Conclusions: CCT still appears to be provide in-expensive
treatment for large number of pediatric patients with cancer. 3-D CRT has benefit of sparing normal tissue in intracranial, intra-thoracic and intra-abdominal tumors and for
dose-escalation to boost local tumors.
S337 of S518
P-374 Radiotherapy Under Anaesthesia of
Children with Cancer in Developing Countries:
Simulation and Treatment Under Dissimilar
Conditions is the Source of Geometric Tumor Miss
V.K. Ramaiah1 , S. Bhasker2
1 Kidwai
Cancer Institute, Radiation Oncology, Bangalore, India; 2 All India
Institute of Medical Scieces, Radiotherapy, New Delhi, India
P-373 Customized Technique for Radiotherapy
Simulation of Children with Cancer to Improvise
Radiation Delivery in Severely
Resource-Constrained Setting
V.K. Ramaiah1 , L. Vishwanath1
1 Kidwai
Cancer Institute, Radiation Oncology, Bangalore, India
Background/Objectives: Radiotherapy simulation is a
process where treatment is simulated but not really given.
Radiation portals are defined during simulation after patient
positioning and defining target area / region for subsequent
irradiation. Simulation can be achieved by done by conventional simulator or 3-dimensional computed imaging.
However, in severely resource-constrained setting, Co-60
tele-therapy equipment may be the only available radiation
equipment for management of patients. Surface anatomical
marking are the only landmark utilized for radiation portal
placement. Conventional X-ray without scale may be of
little help without optical distance indicator and cross hair
scale to account for magnification. There is a need to improvise radiation simulation with the available technology in
resource-constrained developing countries. To this effect,
we simulated children with cancer by utilizing customized
soldering lead wire scale, portal lead marker and conventional
x-ray.
Design/Methods: Hemi-length of adhesive porous plastic
surgical tape was stuck on to scale and small bits of soldering lead wire was placed at a distance of 1 centimeter.
Radiation portal was marked manually by utilizing anatomic
surface landmark and lead markers placed on all the borders of this portal with the help of same adhesive tape. The
customized scale was stuck on to the body within field of
view of X-ray. Patients were subjected to x-ray and radiation
portal was redefined based on the images of scale on x-ray
film.
Background/Objectives: Children with cancer needing
radiotherapy as part of multi-modality therapy are sometimes
not cooperative for radiotherapy immobilization, simulation
and / or treatment. Counselling, sedation, general anesthesia
or combination of these are generally prescribed to prevent
movement of children during radiotherapy immobilization,
simulation and treatment. Sometimes, patients are cooperative
/ non-cooperative to one or more steps of radiotherapy process. Such situation creates dissimilar condition between steps
of radiotherapy planning and treatment that in turn manifest
as non-overlap between the simulation position and treatment
position. Muscle relaxation after anaesthesia is the main reason for such positional mismatch between two different steps
of radiotherapy process. Our paper discuss of this mismatch
between various steps of radiotherapy and devised methods to
minimize such mismatch for radiotherapy planning and delivery using thermoplastic immobilization device.
Design/Methods: Patients are immobilized in hospital area
without anaesthesia after appropriate counselling of patients
that is different from the area of simulation and treatment in
resource-constrained. Patients were immobilized by immobilization device during the whole process of radiotherapy and
assessed for snugness of fit of immobilization device.
Results: Anaesthesia induced muscle relaxation is responsible for loosening of immobilization and subsequent geographical tumor miss.
Conclusions: Whole radiotherapy process of children with
cancer has to be carried-out under similar circumstances .i.e.
all process to be done under anaesthesia or all process to be
carried-out without anaesthesia to avoid geometric miss of
tumor during radiotherapy
P-375 Ripetitive Pediatric Anesthesia in a
Hospital Based Proton Center
Results: In the absence of any kind of simulator, we were able
to plan almost all children with cancer presenting to our centre. Positional and rotational movements and other errors of
maginification may be taken care of by corresponding the xray defined portal with surface anatomic landmarks.
1 Trento
Conclusions: Our is one of the first study to report successful radiotherapy simulation of children with cancer by customized simulation technique in acutely resource-constrained
developing countries
Background/Objectives: Repetitive sedation/anesthesia
(S/A) for children receiving fractionated proton beam
B. Rombi1 , S. Vennarini1 , D. Pedrotti2 , M. Detassis2 , P. Betonte2 ,
L. Meneghello3 , C. Bonazza3 , L. Gazzola3 , A. Petrone3 , L. Valle2 ,
A. Di Palma3 , M. Geat2 , M. Amichetti1
Hospital, Oncology Department - Proton Therapy Center, Trento,
Italy; 2 S. Chiara Hospital, Anaesthesiology Department, Trento, Italy; 3 S.
Chiara Hospital, Paediatric Department, Trento, Italy
SIOP ABSTRACTS
S338 of S518
radiotherapy (PBT) requires well-organized daily setting of
a multidisciplinary team with high degree of competence
during the induction and recovery phases for several weeks.
Typical cases for PBT due to setup and treatment complexity usually require longer S/A comparing photon based sessions. Our preliminary experience with A/S by age and
gender in children receiving daily PBT is reported.
Design/Methods: Records of 42 pediatric patients (≤18
years) were reviewed between June 2015 and March 2017 at
Proton Therapy Center - APSS, Trento (Italy) of whom 17
received PBT under A/S. All patients were treated for CNS
tumors.
Results: Fourteen (83%) children aged ≤ 6 years and three
(17%) patients aged 7–9 years received daily A/S for a median
number of 30 fractions. Seven (41%) patients with median age
7 years received cranio-spinal irradiation (CSI) under sedation while the following local primary boost was performed
without anesthesia after a week of dedicated training. Total
time under anesthesia ranged from 30 to 90 minutes for more
complex cases (i.e. CSI) with the use of Propofol. There were
no deaths. No cardiopulmonary resuscitation or aspiration
was required. Less serious events were more common with
O(2) desaturation below 90% for more than 30 s and central
apnea or airway obstruction occurred in 0.5% of the 568 sedation/anesthesia administrations. No stridor, laryngospasm or
vomiting was reported and excessive secretions occurred in
0.2% of cases. No unexpected admissions were required
Conclusions: The occurrence of undesired effects of A/S in
our experience was very low. A strong emphasis on teamwork
may have contributed to this favorable event rate. A/S can be
safely implemented in a technically and clinically complex
PBT context.
P-376 Potential Reduction of Acute
Hematological Toxicity in Dual-Phase Craniospinal
Proton Therapy for Pediatric Medulloblastoma
S. Vennarini1 , B. Rombi1 , P. Farace1 , S. Lorentini1 , G.S. Colafati2 ,
A. Carai3 , A. Cacchione4 , A. Mastronuzzi4 , M. Amichetti1
1 Trento
Hospital, Oncology Departement-Proton Therapy Center, Trento,
Italy; 2 IRCCS Bambino Gesù Children's Hospital, Neuroradiology UnitImaging Department, Rome, Italy; 3 IRCCS Bambino Gesù Children's
Hospital, Neurosurgery Unit-Department of Neuroscience and
Neurorehabilitation, Rome, Italy; 4 IRCCS Bambino Gesù Children's
Hospital, Department of Pediatric Hematology and Oncology, Rome, Italy
received the last CHT cycle with carboplatin at 550 mg/m2
one month before irradiation. All patients completed PT at a
total dose of 36GyRBE in two phases without interruption:
a first phase (20GyRBE) including the whole vertebral body
and a second phase (16GyRBE) to spinal cord excluding the
vertebral body. Two patients were administered oral temozolomide at 75 mg/m2/day during the treatment. White blood
cells (WBC), hemoglobin, platelets and absolute neutrophil
(ANC) were counted pre-CSI, at the end of the first phase
(middle-CSI) and at the end of the second phase (end-CSI).
Paired T-test was applied to statistically compare (p<0.05)
values at the different phases.
Results: WBC significantly decreased from pre-CSI (median
2.81×10^9 /L, range 1.4-7.4) to middle-CSI (1.39, 1.1-2.1) and
then significantly increased at end-CSI (2.34, 1.4-4.4) to values not significantly different form pre-CSI. Hemoglobin did
not significantly change from pre-CSI (median 10.59mg/dL,
range 9.1-10.4), to middle-CSI (10.39, 9.2-11.1) and end-CSI
(10.41, 9.3-11.8). Platelets significantly decreased from preCSI (median 266.9×10^9 /L, range 128-409) to middle-CSI
(144, 99-185), and then significantly increased at end-CSI
(183.2, 137-214) but to values still significantly lower than
pre-CSI. ANC decreased from pre-CSI (median 1.37×10^9 /L,
range 0.3-3.9) to middle-CSI (0.85, 0.5-1.3), and then significantly increased at end-CSI (1.49, 0.6-3.2,) to values not significantly different form pre-CSI.
Conclusions: Due to the distal fall-off, PT can effectively
deliver dual-phase CSI, with only limited dose to the vertebral
body (around 20GyRBE) that can reduce acute hematological
toxicity during treatment. It could be useful in reducing also
long-term growth impairment.
P-377 Pre-Operative Intensity-Modulated
Radiotherapy Compared to Three-Dimensional
Conformal Radiotherapy for High Grade Extremity
Sarcomas in Children: Analysis of Childrens
Oncology Group (COG) Study ARST0332
A. Rao1 , Q. Chen1 , L. Million2 , S. Spunt3 , T. FitzGerald4 , F.
Laurie5 , S. Kessel5 , K. Morano5 , S. Terezakis1
1 Johns
Hopkins University School of Medicine, Radiation Oncology and
Molecular Radiation Sciences, Baltimore, USA; 2 Stanford University
School of Medicine, Radiation Oncology, Palo Alto, USA; 3 Stanford
University School of Medicine, Department of Pediatrics, Palo Alto, USA;
4 University of Massachusetts Medical School, Radiation Oncology,
Worcester, USA; 5 IROC Rhode Island, UMASS - QARC, Lincoln, USA
Background/Objectives: To evaluate acute hematological
toxicity during craniospinal irradiation (CSI) with proton
therapy (PT) for children with high-risk (HR) medulloblastoma after intensive myeloablative chemotherapy (CHT).
Background/Objectives: We assessed tumor coverage and
dose to bone and skin in pediatric patients treated with IMRT
vs. 3D-CRT on ARST0332.
Design/Methods: We evaluated haematological toxicity in
ten pediatric patients (average age 7, range 4-9), who underwent CSI from February to December 2016. All patients
Design/Methods: Of the 551 eligible patients, 200 were
enrolled in Arm D of ARST0332 in which patients age<30
years received neoadjuvant ifosfamide/doxorubicin and 45
SIOP ABSTRACTS
S339 of S518
Gy, surgery, and an RT boost based on margins. 121 RT plans
were available for remote review through the Imaging and
Radiation Oncology Core (IROC) Rhode Island database. Of
these, 56 patients had extremity STS and 54 were in proximity to a long bone (humerus/femur/tibia). The dose delivered
to the clinical target volume (CTV), skin (contoured from the
surface to depth of 5 mm), and in-field bone was analyzed.
Results: Thirty-eight patients (65%) received 3D-CRT and 18
(32%) received IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT
to upper arm STS. There was no difference in CTV volume
between patients treated with IMRT or 3D-CRT (p=0.920);
however, IMRT resulted in significantly improved CTV coverage with 100% of the prescription dose compared 3D-CRT
(median CTV coverage, 95% vs. 87%, p=0.011). In patients
without skin bolus, skin V45Gy was significantly lower in
patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, p=0.039). IMRT resulted in
higher in-field bone V10Gy (mean 89.8% vs. 68.7%, p=0.001)
and V20Gy (mean 85.4% vs. 63.8%, p=0.014) compared to
3D-CRT. There was no difference in higher doses to bone
(V30/V40/V45) between radiation techniques.
Conclusions: Pre-operative IMRT compared to 3D-CRT may
result in improved RT target coverage with reduced dose to the
skin, but with increased low dose exposure to in-field bone.
Future studies should assess if these dosimetric findings translate into differences in clinical and toxicity outcomes.
P-378 Feasibility and Toxicity of Simultaneously
Administrated Chemotherapy and Proton Therapy
in Children and Adolescents
1
1
1
1
1
E. Schürmann , S. Tippelt , N. Siegler , R. Mikasch , S. Borkens ,
C. Plass2 , S. Peters2 , B. Timmermann2 , D. Reinhardt1 , G.
Fleischhack1
1 University
Hospital Essen, Pediatric Oncology and Hematology, Essen,
Germany; 2 University Hospital Essen, West German Proton Therapy
Centre in Essen WPE, Essen, Germany
Background/Objectives: Proton therapy (PT) is a promising
alternative in radiotherapy of solid tumors in eloquent regions.
While most recent studies deal with the outcome or long term
side effects of PT, the aim of this study is the investigation of
feasibility and acute toxicity of the simultaneous chemotherapy (CT) and PT.
Design/Methods: This retrospective study enrolled all consecutive patients at age <18 years treated at the West German
Proton Therapy Center in Essen, Germany, between September 2013 and December 2016. Based on the PT Registry and
the patients’ records data about patient's characteristics, pretreatment, recent treatment and acute adverse events (AE)
were collected and analyzed.
Results: Two-hundred-ninety-three children (169 male, 124
female, median age 6.3 years) suffering from CNS tumors
(n=166, 56.6%), sarcomas (n=92, 31.4%) or other tumor
entities (n=35, 11.9%) received in total 294 PT cycles. PT
was performed in 202 patients (68.7%) at primary treatment and in 92 (31.3%) at recurrence. 131 (44.6%) patients
received a simultaneous CT. Severe AE (SAE, CTCAE◦ 3/◦ 4)
were observed in 130 (44.2%) PT cycles, and were mostly
hematotoxicity (n=105; 80.8%) and infections (n=28; 21.5%).
Seventy-three hospitalizations due to an unexpected event
(mostly infections, mucositis, electrolyte imbalance) were
necessary in 54 out of 294 PT cycles. In the group with simultaneous CT 53 patients (40.5%) could not receive the recommended CT dose or time schedule. The frequency of SAE was
significant higher in the group with simultaneous CT than in
the group without (71.8% vs. 22.1%, � 2 test, p<0.001).
Conclusions: With regard to the increasing number of children in the PT centers in Western Europe, our data demonstrate the requirement of a well experienced interdisciplinary
team and an adequate infrastructure for management of complex patients regarding infectious, neurological, endocrinological problems and especially the individual adjustment of
a simultaneous chemotherapy.
Supported by German Children's Cancer Foundation
P-379 Proton Beam Therapy for Childhood
Cancers: A Case Series of Shizuoka Cancer Center
and Children's Hospital Collaboration
K. Watanabe1 , Y. Ishida2 , S. Yurikusa1 , H. Kitazawa1 , H. Kato2 , K.
Kawaguchi1 , I. Takahashi1 , T. Ogura1 , Y. Horikoshi1 , T. Wataya3 ,
N. Urushihara4 , S. Murayama5
1 Shizuoka
Children's Hospital, Department of Hematology and Oncology,
Shizuoka, Japan; 2 Shizuoka Cancer Center Hospital, Division of Pediatrics,
Nagaizumi, Japan; 3 Shizuoka Children's Hospital, Department of
Neurosurgery, Shizuoka, Japan; 4 Shizuoka, Japan; 5 Shizuoka Cancer
Center Hospital, Division of Proton Therapy, Nagaizumi, Japan
Background/Objectives: Proton beam therapy (PBT) offers
more precise targeting than conventional photon radiation
therapy and may limit radiation exposure to normal tissue.
Therefore, PBT has been increasingly applied for treatment
of childhood cancers in an attempt to reduce treatment-related
long-term toxicities such as second malignancy. Cooperation
of a pediatric oncology team with a PBT facility is crucial to
include PBT in a context of multimodal management of children with cancer. We have applied proton therapy for childhood cancers in close collaboration between a cancer center and children's hospital in Shizuoka prefecture in Japan for
more than 10 years.
Design/Methods: From April 2005 to February 2016, 35 children with cancer in Shizuoka Children's Hospital referred to
Shizuoka Cancer Center to receive PBT. We reviewed their
SIOP ABSTRACTS
S340 of S518
medical records and retrospectively analyzed clinical data and
outcome.
Results: The median age at the time of receiving PBT is 5
years old (range:1-16). Ten patients were female. Twentyseven patients (77%) had central nervous system tumor
(medulloblastoma, 6; atypical teratoid/rhabdoid tumor, 3;
choroid plexus carcinoma, 1; brainstem glioma, 6; intracranial
germ cell tumor, 4; ependymoma, 5; malignant meningioma,
1; undifferentiated sarcoma, 1), and the other patients (n=8,
23%) had non-CNS solid tumors (neuroblastoma, 4; Ewing
sarcoma, 1; PNET, 1; undifferentiated sarcoma, 1; hemangioma, 1). All patients with medulloblastoma and one with
choroid plexus carcinoma received proton beam CSI. The
irradiation dose ranged from 19.6 to 67.2 GyE (mostly in
1.8GyE/fr). Twenty-seven patients (77%) were alive at the
median follow up of 63 months (range: 4-134). There were
no severe acute toxicities.
Conclusions: PBT may be applied effectively and safely to
treatment of various childhood cancers under close collaboration between a regional cancer center and children's hospital.
Further study is needed to elucidate long-term complications
of PBT in patients with childhood cancer.
T R E AT M E N T A N D CA R E - N E W
D RUGS /EXPER I ME N TA L
THERAPEUTICS
Design/Methods: We used human osteosarcoma and fibrosarcoma cell lines (HOS and HT1080). These cells were treated
with cisplatin combined with or without anhydrous caffeine,
citric acid, and caffeine citrate. Cell survival ability, cell
proliferation, and mitochondrial membrane potential were
assessed by WST-8 cell proliferation assay, thymidine analog
thymidine analog 5-ethynyl-2′ -deoxyuridine (EdU) assay, and
tetramethylrhodamine ethyl ester (TMRE) assay, respectively.
Moreover, combination index (CI) of caffeine citrate was calculated as a combination of anhydrous caffeine and citric acid,
and the synergy was evaluated (CI<1.0).
Results: In all assays, cisplatin combined with caffeine citrate
significantly reinforced the anticancer effect compared with
cisplatin alone, combination of cisplatin and anhydrous caffeine, and combination of cisplatin and citric acid (P<0.01).
Moreover, CI was <0.1 in all conditions. The anticancer agent
reinforcement effect of caffeine citrate was synergy of anhydrous caffeine and citric acid. These results were observed in
both cell lines. Based on these results, we have filed a patent
application.
Conclusions: This is the first report that cisplatin combined with caffeine citrate showed a significant greater effect.
Although further analysis is mandatory, this novel treatment expects to ameliorate the prognosis of the patients with
sarcoma.
P-381 FDA Written Requests: Identified Trends
in Timelines and Drug Types
A. Barone1 , D. Casey1 , G. Reaman1
1 FDA,
P-380 Caffeine Citrate is a Novel Candidate
Enhancing Platinum-Based Chemotherapy for
Sarcoma
K. Abe1 , N. Yamamoto1 , K. Hayashi1 , A. Takeuchi1 , T. Higuchi1 ,
Y. Taniguchi1 , H. Aiba1 , Y. Araki1 , H. Tsuchiya1
1 Kanazawa
University, Orthopaedic Surgery, Kanazawa, Japan
Background/Objectives: The prognosis in patients with
sarcoma has been dramatically improved by multi-agent
chemotherapy. However, the chemotherapeutics have hardly
changed for 30 years. We developed caffeine-potentiated
chemotherapy for musculoskeletal sarcoma in 1989 and have
reported the excellent response and oncological outcome.
Even with this excellent result, it was difficult to conduct
an initiated clinical trial without patent. Citric acid was also
reported that it could enhance the cytocidal effect of cisplatin
in gastric cancer. So, the purpose of this study was to evaluate
the cytocidal effect of cisplatin combined with caffeine citrate compared to cisplatin combined with or without caffeine
and citric acid. Caffeine citrate is a newly emerged candidate
enhancing anticancer agents.
Office of Oncology and Hematology Products, Silver Spring, USA
Background/Objectives: The Best Pharmaceuticals for Children Act authorizes the Food and Drug Administration (FDA)
to request pediatric studies of a drug in approved or unapproved indications via a Written Request (WR). Fulfillment
of the WR provides a company with a six-month marketing
exclusivity for the entire drug moiety. Historically, WRs were
issued following approval for an adult indication. Our objective was to identify trends associated with WRs issued by
FDA for oncology products with regard to time of issue within
the drug development program, time to completion, and drug
class types.
Design/Methods: A review of FDA's Document Archiving,
Reporting &Regulatory Tracking System was performed to
identify WRs issued for oncology drugs. WRs were reviewed
for milestone dates, amendments, and status with regard to
exclusivity determination.
Results: Between 2000 and 2016, 58 WRs were issued for
oncology products and 45 were accepted. Overall, the proportion of WRs issued prior to the marketing approval of a drug
was 24% compared to 43% in 2016. Seventeen oncology prod-
SIOP ABSTRACTS
ucts were granted exclusivity upon completion of the studies
outlined in the WR. The average time from issuance of a WR
to exclusivity determination was 4.5 years. WRs were issued
for cytotoxic (N=22), immune-oncology (N=7), and targeted
(N=16) therapies. Between 2011 and 2016, the proportion
of WRs issued for targeted and immune-oncology therapies
combined (84.4%) was greater than that for cytotoxic drugs
(15.5%)
Conclusions: The WR is a powerful tool that can expedite
early evaluation of the safety and effectiveness of relevant
drugs for pediatric cancers. A modest increase was observed
in the proportion of WRs issued prior to marketing approval of
a drug in recent years. The increased investigation of targeted
and immune-oncology therapies reflects the changing landscape of cancer treatment in pediatric patients. FDA encourages parallel drug development programs when appropriate
for adult and pediatric cancer indications.
S341 of S518
in the treatment group were discharged from the hospital 2
mean days earlier than the control group (7.54±5.66 days vs
9.66±8.58 days), but it did not reach statistical significance
(P=0.133). The drug was well tolerated and no adverse effect
was reported.
Conclusions: Allium may effectively reduce ANC recovery
time leading to earlier discharge from hospital. The drug is
safe with no serious adverse effect reported. Larger multicenter studies are required to confirm its efficacy and safety.
P-383 Implementation of a Precision Medicine
Program in Pediatric Oncology: Prospective
Feasibility Study at Relapse/Progression in Spain
P. Berlanga1 , L. Pedrola2 , I. Calabria2 , M.J. Aparisi2 , M. Llavador3 ,
Á. Zuñiga4 , S. Dolz5 , A. Marco6 , P. Gargallo1 , C. Esquembre7 , P.
Escobar8 , J. Cervera4 , J. Font de Mora5 , V. Castel1 , A. Cañete1
1 Hospital
P-382 The Efficacy and Safety of Allium Porrum
in Reducing Neutrophil Recovery Time in
Childhood Cancer with Febrile Neutropenia
M. Bordbar1 , M. Vahidifar2 , M. Shahryari1 , S. Zareifar1 , O.
Zekavat1 , M. Karimi1
1 Shiraz
University of Medical Sciences - School of Medicine, Pediatric
Hematolgy-Oncology, shiraz, Iran; 2 Shiraz University of Medical Sciences School of Medicine, Pediatrics, shiraz, Iran
Background/Objectives: Febrile neutropenia is frequently
observed in cancer patients following chemotherapy. Experimental animal studies have shown the potential benefits of
the herbal agent “Allium Porrum” in boosting the immune
system. However, such findings have not been confirmed in
human subjects. The aim of this study was to evaluate the
efficacy of allium extract on bone marrow recovery time in
children with cancer suffering from febrile neutropenia.
La Fe, Pediatric Oncology Unit, Valencia, Spain; 2 La Fe Hospital
Research Institute, Genomic Unit, Valencia, Spain; 3 Hospital La Fe,
Department of Pathology, Valencia, Spain; 4 Hospital La Fe, Genetics Unit,
Valencia, Spain; 5 La Fe Hospital Research Institute, Laboratory of Cellular
and Molecular Biology- Center of Translational Medicine, Valencia, Spain;
6 Hospital La Fe, Pediatric Surgery Department, Valencia, Spain; 7 Hospital
General Alicante, Pediatric Oncology Unit, Alicante, Spain; 8 Hospital La
Fe, Department of Pharmacy, Valencia, Spain
Background/Objectives: To evaluate the integration of
advanced genomic sequencing technologies in the clinical
management of pediatric/adolescent patients with progressive/relapsed cancer in Spain.
Design/Methods: In this randomized double-blind clinical
trial, 107 children with different kinds of cancers in the
age range of 2-18 years who were admitted due to fever
and neutropenia were enrolled. All the patients were given
supportive care including broad-spectrum antibiotics, and
granulocyte-colony-stimulating-factor (GCSF). Those in the
treatment group were treated with 500 mg Allium extract in
the form of capsule twice daily for 7 days. The patients in the
control group were treated similarly with placebo capsules.
Total white blood cell (WBC) and absolute neutrophil counts
(ANC) were checked on a daily basis and bone marrow recovery time in both groups were compared.
Design/Methods: Consecutive case series of all patients ≤
18 years with recurrent solid tumors included in a precision medicine research project were analyzed. This project
was developed in our institution and open for recruitment
of patients from other centers. New tumor sampling at progression/relapse was recommended. Tumor profiling was perfomed using two commercial Next Generation Sequencing
(NGS) cancer panels: Ion AmpliseqTM Cancer Hotspot Panel
v2 (before December 2015; only for tumor samples) and
Human Comprehensive Cancer GeneRead DNAseq Targeted
Panel (since January 2016; for paired blood and tumor samples). Tumor material was mainly fresh frozen (57%). Tumor
samples were mainly obtained at the time of last relapse (55%)
or previous relapses (12%). For sixteen (33%) patients with
no available tumor sample at recurrence, the profiling was
performed on the tumor sample at diagnosis. Genomic profiling results were reviewed following a target prioritization
algorithm by a multi-disciplinary tumor board with basic and
translational researchers, molecular biologists, pathologists,
geneticists and pediatric oncologists.
Results: WBC and ANC were not significantly different in the
2 groups. Patients in the treatment group experienced shorter
neutrophil recovery compared to the control group (4.02 ±
2.32 days vs 6.38 ± 2.80 days respectively, P˂0.001). Patients
Results: From December 2014 to February 2017, 49 patients
from nine different hospitals were included. Main diagnosis was neuroblastoma (37%), followed by CNS tumors
(22%). All patients, except three, had suffered at least
SIOP ABSTRACTS
S342 of S518
one relapse/progression. In twenty patients (41%), at least
one somatic pathogenic mutation was detected, and eleven
patients (22%) had at least one actionable target alteration. In
three patients (6%), we identified germline pathogenic mutations, two of them without family history of cancer.
Conclusions: These results show that precision medicine
applied to pediatric and adolescent tumors using NGS technology is feasible in our country. Commercial cancer panels could identify actionable target alterations in 20% of the
patients. Target prioritization algorithm and interdisciplinary
tumor board discussion is of foremost importance.
P-384 SFCE Metro-01 Four-Drug Metronomic
Regimen Phase II Trial for Pediatric Extra-Cranial
Tumour
1
1
2
2
M.A. Heng-Maillard , A. Verschuur , A. Aschero , P. Petit , E.
Jouve3 , P. Chastagner4 , P. Leblond5 , I. Aerts6 , N. Corradini7 , N.
Entz-werle8 , J.C. Gentet1 , B. Deluca9 , N. André1
1 La
Timone Children's Hospital, Department of Pediatric Oncology,
Marseille, France; 2 La Timone Children's Hospital, Department of
Radiology, Marseille, France; 3 La Timone Children's Hospital,
CIC-CPCET, Marseille, France; 4 Children's Hospital, Department of
Pediatric Oncology, Nancy, France; 5 Oscar Lambret Centre, Pediatric
Oncology Unit, Lille, France; 6 Institut Curie, Pediatric Department, Paris,
France; 7 Centre Léon Berard, Department of Paediatric Haematology and
Oncology, Lyon, France; 8 CHU Hautepierre, Pédiatrie Onco-Hématologie,
Strasbourg, France; 9 La Timone Children's Hospital, Department of
Clinical Pharmacy, Marseille, France
Background/Objectives: To investigate the anti-tumour
activity of a 4-drug metronomic therapy (MT) in relapsing/progressing pediatric extracranial solid tumours (EST).
Primary objective was no progression after 2 cycles of
therapy.
Design/Methods: Patients of ≥4 to 25 years of age with progressing EST and adequate organ function. Treatment consisted of an 8-week cycle of oral celecoxib BID, weekly vinblastine 3 mg/m2, oral cyclophosphamide 30 mg/m2/d qd for
3 weeks alternating with oral methotrexate 10 mg/m2 twice
a week for 3 weeks, with a 2-week rest. Maximum treatment
was 2 years. Kepner- Chang two steps model was used with
10 patients in first stage. If primary objective was reached
in 2 or more patients, 8 additional patients were included
according to 4 groups: Neuroblastoma (NBL), Soft-tissue sarcoma (STS), Bone sarcoma (BS), Miscellaneous (Misc). IRB
approval was obtained.
Results: 47 patients were evaluable: 8 STS with 1 SD after 2
cycles: 1 patient with metastatic hemangioendothelioma stabilized and was treated during 24 months; 11 Misc with one
patient stabilized for one year; 10 BS (8 osteosarcoma and 2
Ewing) all progressed; 18 NBL with 3 patient stabilized. Of
the patients with SD, 1 stopped MT after 4 cycles being stable (physician's choice) and 2 patients remained stable for 1
year. 16 patients progressed before cycle 3. Median number
of cycles was 2 (range 0.5-6). Grade 3/4 toxicity occured in
13 patients.
Conclusions: This MT has no activity in BS and Misc and
limited though interesting activity in NBL and STS with some
patients being stable for > 1 year. (This study was supported
by “Enfants et Santé” Foundation and PHRC-grant).
P-385 Ex Vivo Expanded Multi-Antigen Specific
Lymphocytes for the Treatment of
Refractory/Relapsed Solid Tumors
A. Houghtelin1 , C.R. Cruz1 , L. McLaughlin1 , J. Hoover1 , F. Hoq1 ,
C. Barese1 , P. Hanley1 , C. Bollard1 , H. Meany1
1 Children's
National Health System, Hematology/Oncology, Washington-
DC, USA
Background/Objectives: Patients with solid tumors refractory to standard therapies have poor prognoses, and most
salvage therapies are toxic and ineffective. T cell therapies, which have been successful in hematologic malignancies, offer a promising alternative for targeted therapy. We
hypothesize that patient-derived tumor-associated antigenspecific T cells (TAA-T) targeting WT1, PRAME, and survivin expressed by many pediatric solid tumors can be safely
administered to treat relapsed/refractory disease. The objective of this phase I clinical trial is to determine the safety
of administering TAA-T to patients with refractory/relapsed
solid tumors. Secondary objectives include determination of
disease response and immune reconstitution post-infusion.
Design/Methods: T cells expanded from patient peripheral
blood are stimulated weekly with antigen presenting cells
expressing an overlapping peptide library spanning the tumor
antigens WT1, PRAME, and survivin in the presence of
cytokines. Following release testing (cytotoxicity assay, culture, flow cytometry), patients are infused with TAA-T every
4 weeks on a dose escalation study ranging from a dose of 1
× 107 /m2 (level 1) to a maximum dose of 4 × 107 /m2 (level
3). Clinical and immune reconstitution studies are performed
post-infusion to monitor for adverse effects and assess disease
and immune responses.
Results: We have generated TAA-T products from 5 patients
enrolled with relapsed/refractory solid tumors (neuroblastoma, osteosarcoma, Wilms tumor, Ewing sarcoma), all passing release criteria. We have safely infused 2 patients with no
product-related adverse events post-infusion. To date Patient
1 had partial response initially but later progressed; Patient 2
had progressive disease 6 weeks post-infusion and came off
study. We are currently enrolling additional patients and characterizing the persistence and anti-tumor effects of TAA-T in
vivo.
SIOP ABSTRACTS
Conclusions: To date, the infusion of TAA-T products has
been shown to be safe. Response has been mixed thus far. We
continue to evaluate, as outlined above, product and patient
samples for functionality, specificity, and persistence.
P-386 Omegachild - An Early Clinical Study
Aiming at a Novel Approach to Treat Neural
Tumors and Prevent Long-Term Side Effects
S343 of S518
vides robust evidence to calculate appropriate dosages for
future trials with the goal of promoting improved relapse-free
survival with less long-term side effects.
P-387 Long-Term Growth and Development in
Bevacizumab-Treated Pediatric and Adolescent
Patients: An Integrated Analysis
L. Ljungblad1 , M. Wickström1 , N. Eissler1 , J. Pickova2 , J.I.
Johnsen1 , K. Tedroff1 , B. Strandvik1 , H. Gleissman1 , P. Kogner1
H.L. Müller1 , J.H.M. Merks2 , B. Geoerger3 , J. Grill3 , D. Hargrave4 ,
J. Glade Bender5 , S. Gururangan6 , F. Navid7 , M. Johnston8 , J.
Bachir9 , M. Hilton9 , S. Fürst-Recktenwald9
1 Karolinska
1 Klinikum
Institutet, Department of Women's and Children's Health,
Stockholm, Sweden; 2 Swedish University of Agricultural Sciences,
Department of Food Science, Stockholm, Sweden
Background/Objectives: The long chain polyunsaturated
omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have anticancer properties that have
been implicated in cancer prevention. Additionally, tumor
growth has been inhibited in vitro and in vivo and the effect of
cytostatic drugs enhanced. DHA is abundant in the brain and
has been implicated in neuroprotection. In addition, omega3 supplementation has positive effects on children with neurodevelopmental disorders.
Altogether, these results suggest that omega-3 exhibits beneficial properties both as an adjuvant in the treatment of childhood cancer and as a dietary supplement for prevention of
relapses and reducing long term side effects in childhood cancer survivors.
Design/Methods: This dose escalating, dose-finding study
was designed to find the phase-2 omega-3 dose that increases
the omega-3 index to an optimum level >8% without sideeffects.
Secondary objectives were to evaluate omega-3 supplementation effects on platelet clotting ability, body weight and composition, immuneprofile, inflammatory parameters, lipid peroxidation, and perception/cognition/neuropsychiatric symptoms. We included forty children aged 2-18 (median 9.5)
in remission after completed cancer treatment; eight in each
dose-level: 400, 800, 1200, 2400 and 3000 mg/m2 omega3 fatty acids in 200 mL fruit juice daily for 90 days. Food
frequency questionnaire was performed at start. Blood and
urine sampling, body measurements and behavior questionnaires were performed before, during and after the study.
Results: Thirty-three out of forty completed the study
with compliance 83%-100%, seven withdrew voluntarily. No
severe adverse events were registered. Daily intake of omega3 enriched fruit juice significantly increased omega-3 index
>8% already at 800 mg/m2.
Conclusions: Daily intake of omega-3 increases omega-3
index significantly without severe adverse events and is feasible with high compliance. The dose-escalation strategy pro-
Oldenburg AöR- Medical Campus University Oldenburg,
Department of Pediatrics and Pediatric Hematology / Oncology,
Oldenburg, Germany; 2 Emma Children's Hospital-Academic Medical
Center EKZ-AMC, Department of Pediatric Oncology, Amsterdam, The
Netherlands; 3 Gustave Roussy, Department of Pediatric and Adolescent
Oncology, Villejuif, France; 4 Great Ormond Street Hospital, Department of
Haematology and Oncology, London, United Kingdom; 5 Columbia
University Medical Centre, Department of Pediatrics, New York, USA;
6 McKnight Brain Institute- University of Florida, Preston Wells Center for
Brain Tumor Therapy, Gainesville, USA; 7 Children's Hospital Los AngelesKeck School of Medicine- University of Southern California, Children's
Center for Cancer and Blood Diseases, Los Angeles, USA; 8 Genentech,
Safety Science, San Francisco, USA; 9 F. Hoffmann-La Roche Ltd, Pediatric
Oncology, Basel, Switzerland
Background/Objectives: Bevacizumab has an established
safety profile in adults, but long-term data in children are limited. This analysis examined the effects of BEV on growth and
development in pediatric and adolescent patients.
Design/Methods: Data (height, weight, body mass index
[BMI], bone age data) were pooled from five trials:
NCT00643565 (Phase II, soft tissue sarcoma); NCT01390948
(Phase II, high-grade glioma); NCT00085111 (Phase I,
refractory solid tumors); NCT00667342 (Phase II, osteosarcoma); and NCT00381797 (Phase II, glioma, medulloblastoma, ependymoma). Patients were aged <18 years and
received ≥1 dose of bevacizumab and chemotherapy (n=268)
or chemotherapy alone (n=135). Analyses were exploratory
and descriptive. Reference growth data were taken from WHO
(<2 years) and Centres for Disease Control (≥2 years).
Results: Across the trials, the mean number of bevacizumab
administrations per patient ranged from 5.6 to 19.9 (dose 5–
15mg/kg, every 2 or 3 weeks). Median follow-up time for
bevacizumab plus chemotherapy was 37.9 months (range 2.4–
64.2); for chemotherapy only, this was 22.9 months (range
2.8–69.2). At baseline, median height, weight, and BMI were
close to that of the reference population (mean standard deviation scores [SDS] close to 0). Over 60 months, a slight decline
was observed in the mean SDS for height and weight in
both arms in this cohort of patients with different tumors and
treatments, but remained within the normal range of healthy
children. Trends were similar for BMI. No delay in growth
velocity or bone age in bevacizumab-treated patients versus
chemotherapy only was observed over a 3-year follow-up,
SIOP ABSTRACTS
S344 of S518
regardless of age or gender. A subgroup analysis of patients in
the growth hormone-dependent development phase was consistent with the overall results.
Conclusions: In this analysis, bevacizumab inclusion in the
treatment regimen did not have a negative impact on pediatric
growth and development beyond that of chemotherapy alone.
P-388 A Pediatric Phase 1 Study of Larotrectinib,
A Highly Selective Inhibitor of the Tropomyosin
Receptor Kinase (TRK) Family
R. Nagasubramanian1 , K. Albert2 , N. Federman3 , B. Turpin4 , L.
Mascarenhas5 , A.S. Pappo6 , D.S. Hawkins2 , B. Tupper7 , S. Smith8 ,
S. Cruickshank8 , M.C. Cox8 , S.G. DuBois9 , T.W. Laetsch10
1 Nemours
Children's Hospital, Oncology, Orlando, USA; 2 Seattle
Children's Hospital- University of Washington- Fred Hutchinson Cancer
Research Center, Oncology, Seattle, USA; 3 University of California- Los
Angeles, Pediatric Oncology, Los Angeles, USA; 4 Cincinnati Children's
Hospital Medical Center-, Oncology, Cincinnati, USA; 5 Children's Hospital
Los Angeles- Keck School of Medicine- University of Southern California,
Oncology, Los Angeles, USA; 6 St Jude Children's Research Hospital,
Oncology, Memphis, USA; 7 Loxo Oncology, Clinical Development,
Stamford, USA; 8 Loxo Oncology, Clinical Development, South San
Francisco, USA; 9 Dana-Farber/Boston Children's Cancer and Blood
Disorders Center, Oncology, Boston, USA; 10 University of Texas
Southwestern Medical Center/Children's Health, Oncology, Dallas, USA
Background/Objectives: Larotrectinib is the first selective
small-molecule inhibitor of TRKA/B/C in clinical development. The adult phase 1 trial demonstrated prolonged
responses in patients (pts) with TRK fusions and a favorable
tolerability profile.
Design/Methods: This multicenter phase 1 study enrolled pts
with refractory solid tumors aged ≥ 1 month – 21 years. Pts
were dosed orally BID on a continuous 28-day schedule either
by capsule or solution. Pharmacokinetic (PK)-directed intrasubject dose escalation was permitted, with exposures targeting the adult recommended Phase 2 dose (RP2D) of 100mg
BID. The primary objective was to define the MTD / RP2D;
secondary objectives included PK and efficacy using RECIST
v1.1.
Results: As of December 31, 2016, 17 pts (12 with TRK
fusions, 5 without TRK fusions) with a median age of 5.2
years (0.4 – 18.3) were enrolled to 3 dose levels. Pts were
enrolled with fusions of all 3 NTRK genes in heterogeneous
tumor diagnoses: infantile fibrosarcoma (IFS) (n=6), other
sarcoma (n=4), and papillary thyroid cancer (n=2). Most
common AEs regardless of attribution were vomiting, diarrhea, and fatigue. While 8 (47%) pts experienced grade 34 AEs, none were attributed to larotrectinib. No DLTs were
observed and an MTD was not established. 12 pts (10 with
TRK fusions, 2 without TRK fusions) remain on treatment
with median follow-up of 2.8 months (0.7 – 8.4). Among TRK
fusion pts, the vast majority have achieved confirmed RECIST
responses regardless of tumor diagnoses. No responses were
seen in pts without TRK fusions (n=4). 5 pts discontinued
therapy, including 2 with TRK fusions: 1 pt with IFS had sufficient response to allow tumor resection, and 1 pt with IFS
progressed with a documented acquired resistance mutation.
Conclusions: Larotrectinib has demonstrated a favorable tolerability profile and histology- independent efficacy in pediatric pts harboring TRK fusions. Updated safety and efficacy
data will be presented.
P-389 Drug Development and Market Challenge:
Charity Stakeholder Perspective
S. Richards1 , L. Knox1 , N. Bird1 , J. Rogers1 , D. Ludwinski2
1 Solving
Kids’ Cancer Europe, Research Advocacy, London, United
Kingdom; 2 Solving Kids’ Cancer, Research Advocacy, New York, USA
Background/Objectives: Drug development and marketing
explicitly for paediatric cancers presents formidable challenges. A case study of dinutuximab, an anti-GD2 antibody
proven to be effective against high-risk neuroblastoma in a
pivotal US trial, gained US Food and Drug Administration
approval, but was rejected by National Institute for Health
and Care Excellence (NICE) for reimbursement in the UK
National Health Service (NHS) because of cost.
Design/Methods: A charity based in the US and UK has
proven to play a vital role challenging the NICE appraisal process, which is not suitable for evaluating the cost effectiveness
of paediatric rare disease drugs. Relying on patient representative input, media engagement, parent community awareness,
pro bono legal assistance, and emotive but expert arguments
were submitted as a challenge to the NICE decision to reject
the drug in the UK.
Results: In the first appeal of a NICE decision by a charity,
the challenge was successfully upheld despite lack of input
or engagement from the pharmaceutical company. The drug
company subsequently withdrew submission for NICE reappraisal when demand exceeded available drug supply, and
drug will no longer be provided for marketing outside of North
America in the foreseeable future.
Conclusions: Charities have been proven to play a vital role
in advocating for policies and regulatory issues affecting children with cancer.
P-390 Indisulam Inhibits Carbonic Anhydrases
Expression and Modulates Apoptotic Factors in
Pediatric Glioblastoma Cell Line
C.C.D. Monção1 , S.A. Teixeira1 , A.F. Andrade2 , P.V. De Andrade3 ,
R.G.P. Queiroz1 , C.G. Carlotti4 , L.G. Tone1 , C.A. Scrideli1
1 Faculdade
de Medicina De Ribeirão Preto-USP, Pediatrics, Ribierão
Preto, Brazil; 2 Université de Montpellier, Institut de Recherche en
Cancérologie de Montpellier, Montpellier, France; 3 Faculdade de Medicina
SIOP ABSTRACTS
De Ribeirão Preto-USP, Genetics, Ribierão Preto, Brazil; 4 Faculdade de
Medicina De Ribeirão Preto-USP, Surgery and Anatomy, Ribierão Preto,
Brazil
Background/Objectives: The treatment of glioblastoma
(GB) remains a major challenge since this tumor is highly
resistant to radio- and chemotherapy, and recurrence is
extremely common. The poor prognosis of patients with GB
is due to the intratumoral heterogeneity, invasive behavior,
resistance to apoptosis and the hypoxic tumoral microenvironment. The hypoxic condition of GB cells upregulates the
expression of membrane-bound carbonic anhydrases (CAs)
9 and 12 that have been shown to act on acidification of
the tumor microenvironment. In our previously study, it was
found antitumor effects when CA9 and CA12 was downregulated in pediatric glioblastoma cell lines, hence the aim of
this study was to validate and evaluate the effects of Indisulam (IS) on the CAs 9 and 12, and the apoptotic factors BAX
and BCL-2 expression in pediatric GB cell line.
Design/Methods: The pediatric GB cell line SF188 was pretreated with Cobalt Chloride (50�M) to mimic hypoxia for 24
hours. After, cells were treated with IS (IC50) and incubated
for 48 hours. Gene and protein expression of CA9, CA12,
BAX and BCL-2 were assessed using qRT-PCR and western
blotting, respectively.
Results: Indisulam significantly decreased gene expression
of CA9 (P<0.05) and upregulated CA12 (P>0.05). A similar
pattern to the CA9 and CA12 gene expression was observed
in the protein expression. A downregulation in protein expression were also found in BAX (P<0.05) and BCL-2 (P<0.001),
with a greater reduction of BCL-2 factor.
Conclusions: This study suggest that IS may have an antitumoral effect, evidenced by inhibition of CA9 gene and protein
expression and modulation of apoptotic factors. Thus, CAs
could be particularly relevant to understand the mechanisms
of glioma cell propagation and resistance to treatment and
Indisulam may be an interesting candidate for the development of antitumor therapies based on the inhibition of tumorassociated carbonic anhydrase.
P-391 Combination Therapy of Primary Tumor
Resection and Immune Checkpoint Inhibitors for
Metastases of Osteosarcoma: A Promising
Therapeutic Strategy
T. Shimizu1 , Y. Fuchimoto1 , K. Fukuda2 , H. Okita3 , Y. Kitagawa2 ,
T. Kuroda1
1 Keio
University School of Medicine, Pediatric Surgery, Shinjuku-ku,
Japan; 2 Keio University School of Medicine, General and Gastrointestinal
Surgery, Shinjuku-ku, Japan; 3 Keio University School of Medicine,
Pathology, Shinjuku-ku, Japan
S345 of S518
Background/Objectives: Immune checkpoint inhibitors have
been used as innovative immunotherapies for cancer. Metastases are thought to be the most important prognostic factor in pediatric solid tumors. The efficacy of immune checkpoint inhibitors for lung metastases of osteosarcoma has been
reported in several murine models. In this study, combination therapy with immune checkpoint inhibitors and primary
tumor resection was evaluated by using a murine model of
spontaneous lung metastasis.
Design/Methods: In C3H mice, 5 × 106 LM8 (osteosarcoma
originating from C3H mouse) cells were transplanted subcutaneously (primary tumor lesion). Thereafter, the mice were
divided into 4 groups as follows: the control group received
no intervention (CG, n = 5); the primary tumor resection
group, primary tumor resection 11 days after transplantation
(PTRG, n = 10); the triple antibody therapy group, 200 �g
of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86)
intraperitoneally on post-transplantation days 11, 14, 18, and
21 (ATG, n = 10); and the combination therapy group, primary tumor resection on day 11 and 200 �g of the three antibodies on days 11, 14, 18, and 21 (CMBG, n = 10). Survival
curves were plotted by using the Kaplan-Meier method and
compared with that plotted with the log-rank test. Then, the
lungs of the mice in the 4 groups were pathologically evaluated.
Results: The CMBG showed significantly longer survival
than the other three groups (p = 0.001–0.03). Six mice in the
CMBG survived more than 10 weeks after tumor transplantation. Pathological study revealed multiple lung metastases
4 weeks after tumor transplantation in all the groups but no
lung metastasis 16 weeks after tumor transplantation in the
CMBG.
Conclusions: The results of this study suggest that the combination therapy of primary tumor resection and immune checkpoint inhibitors could be a curative treatment for metastasis of
pediatric solid tumors.
P-392 Indisulam Affects Pediatric and Adult
Glioblastoma by Reducing Cell Proliferation and
Migration, Promoting Radio-Sensitization and
Prolonging Survival in Mouse Models
S. Teixeira1,2 , M. Sebastian Viapiano2 , A. Faria Andrade3 , N.
Mohan Sobhanna2 , C. Monção Damasceno1 , V. Kill Suazo1 , C.
Gilberto Carlotti4 , L. Gonzaga Tone1,3 , C. Alberto Scrideli1
1 Ribeirão
Preto Medical School- University of São Paulo, Department of
Pediatrics, Ribeirão Preto, Brazil; 2 Brigham and Women's Hospital &
Harvard Medical School, Neurosurgery, Boston, USA; 3 Ribeirão Preto
Medical School- University of São Paulo, Department of Genetics, Ribeirão
Preto, Brazil; 4 Ribeirão Preto Medical School- University of São Paulo,
Department of Surgery and Anatomy, Ribeirão Preto, Brazil
S346 of S518
Background/Objectives: Carbonic anhydrases (CA), tumorassociated enzymes highly expressed under hypoxic conditions, have been considered as potential biomarkers of tumor
cells and a promising target for specific therapies. In hypoxia,
there are genetic alterations that lead to the expression of
membrane-bound extracellular facing CA9 and CA12. In
glioblastoma (GBM), the most aggressive form of brain cancer with a dismal prognosis in children and adults, CAs has
been linked to aggressive and invasive behavior of cells and
resistance to therapy. Indisulam (IS) is a potent sulfonamide
inhibitor of CAs that has been used as an anti-cancer drug.
Then, the aim of this study was to evaluate the effects of inhibition of the CA9 and CA12 by IS in vitro and in vivo models.
Design/Methods: The pediatric (KNS42 and SF188) and
adult (U87 and U251) GBM cells lines were cultured in
hypoxia 1% and treated with IS (8-256�M). The effect of IS
on cell proliferation, migration, clonogenic capacity, apoptosis and radio-sensitizing was measured in vitro. The in vivo
antitumor and chemo-sensitizing effects of IS were assessed in
athymic nude mice (n=6) inoculated with the U87-GFP. The
mice were and treated (IP) with IS (25 or 50mg/kg). Tumor
growth and potential treatment toxicity were monitored until
survival endpoint.
Results: IS significantly reduced cell proliferation (dosetime-dependent), inhibited clonogenic capacity (P<0.05) and
increased apoptosis (P<0.05) of pediatric and adult GBM
cells. IS also reduces cell migration and potentiated the effect
of radiotherapy (P<0.01) in vitro. The pediatric cell line
KNS42 was the most sensible to IS treatment. Our results, in
intracranial mouse xenograft models, indicated that IS crossed
BBB and significantly increased animal survival (P=0.001).
Conclusions: This study provides evidence of the therapeutic potential of IS as a radio-chemo-sensitizing agent in drugresistant tumor cells and represent an attractive strategy to
improve adjuvant therapy for GBM.
Financial Support: FAPESP 2011/05957-6, 2011/07488-1,
2014/08899-5
P-393 A Phase I/II Study of Atezolizumab in
Pediatric and Young Adult Patients with
Refractory/Relapsed Solid Tumors
(Imatrix-Atezolizumab)
T. Trippett1 , G. Rossato2 , A.M. Langevin3 , J. Michon4 , D.
Frappaz5 , F. Locatelli6 , M. Kowgier7 , M. Tagen8 , A. Kwan9 , M.
Das Thakur10 , B. Geoerger11
1 Memorial
Sloan Kettering Cancer Center, Pediatric Developmental
Therapeutics, New York, USA; 2 F. Hoffmann-La Roche Ltd, Pediatric
Oncology, Basel, Switzerland; 3 University of Texas Health Science Center,
Pediatric Hematology/Oncology, San Antonio, USA; 4 Insitut Curie,
Department of Pediatrics, Paris, France; 5 Institut d'Hématologie et
d'Oncologie Pédiatrique, Pediatric and Adult Neuro-oncology, Lyon,
France; 6 Ospedale Pediatrico Bambino Gesù- University of Pavia,
SIOP ABSTRACTS
Department of Pediatric Hematology and Oncology, Rome, Italy; 7 F.
Hoffmann-La Roche Ltd, Pediatric Oncology, Mississauga, Canada;
8 Genentech, Pediatric Oncology, San Francisco, USA; 9 Genentech, Safety
Science, San Francisco, USA; 10 Genentech, Oncology Biomarker
Development, San Francisco, USA; 11 Gustave Roussy, Department of
Pediatric and Adolescent Oncology, Villejuif, France
Background/Objectives: Atezolizumab targets programmed
death-ligand 1 (PD-L1), leading to enhanced anti-cancer
T-cell response. The iMATRIX-Atezolizumab study (phase
I/II, multi-center, open-label; NCT02541604) assessed safety,
pharmacokinetics, and preliminary efficacy of atezolizumab
in pediatric/young adult patients with refractory/relapsed
solid tumors.
Design/Methods: Patients aged <30 years with refractory/relapsed non-central nervous system solid tumors
received atezolizumab every 3 weeks until loss of clinical benefit (<18 years old, 15mg/kg [maximum dose 1200mg]; ≥18
years old, 1200mg). Safety/pharmacokinetics were assessed
across tumor types, and initial response was assessed by
tumor-type cohorts after approximately ten patients in each
cohort had been treated.
Results: As of February 1, 2017, 85 patients (median age
14 years; range 2–29) were enrolled: osteosarcoma, n=12;
Ewing sarcoma, n=11; neuroblastoma, n=11; rhabdomyosarcoma, n=10; non-rhabdomyosarcoma soft tissue sarcoma,
n=10; Wilms tumor, n=10; Hodgkin lymphoma (HL), n=9;
non-HL, n=3; and other tumor types, n=9. Pharmacokinetic data (n=62) were similar to that reported in adults.
Most tumors had score 0 (<1%) tumor cell (TC) or tumorinfiltrating immune cell (IC) PD-L1 expression. TC- and ICpositive expression rates (score 1–3) were seen in 7% and 10%
of patients, respectively. HL had higher TC and IC PD-L1
expression (≥5% [score 2–3]) compared with other tumors.
81/82 of the safety evaluable population who received atezolizumab (median cycles 2.5; range 1–16) had ≥1 adverse
event (AE); 21 patients (26%) had treatment-related grade 3–4
AEs. Two patients had AEs that led to study drug discontinuation. Common AEs were pyrexia (45%), constipation (34%),
and fatigue (33%). 2/9 patients with HL and one patient with
a rhabdoid tumor (RT) had a partial response.
Conclusions: The pharmacokinetic/safety profile of atezolizumab in pediatric/young adult patients is similar to that
in adults. Preliminary anti-tumor activity was seen in HL and
RT. Atypical teratoid RT and RT cohorts have been opened to
explore this signal.
P-394 Supra-Regional Study Sites to Improve the
Pediatric Oncologic Patient Care and Recruitment
into Early-Phase Clinical Trials: A German Model
K. Waack1 , B. Wulff2 , K. Roellecke1 , D. Schneider3 , M. Paulussen4 ,
T. Zuzak5 , A. Laengler5 , T. Niehues6 , N. Brauer6 , I. Feddersen7 , U.
SIOP ABSTRACTS
Kontny8 , G. Calaminus9 , D. Dilloo9 , M. Irnich10 , A. Prokop11 , N.
Graf12 , B. Hero13 , M. Fischer13 , T. Simon13 , D. Reinhardt2
1 Center
for Research Acceleration in Pediatrics, AML-BFM Trial Center,
Essen, Germany; 2 University Hospital of Essen, Pediatric Oncology and
Hematology- Pediatrics III, Essen, Germany; 3 Municipal Hospital
Dortmund, Clinic of Pediatrics, Dortmund, Germany; 4 Witten/Herdecke
University, Vestische Kinder- und Jugendklinik, Datteln, Germany;
5 Gemeinschaftskrankenhaus Herdecke, Department of Integrative Pediatric
and Adolescent Medicine, Herdecke, Germany; 6 HELIOS Klinikum Krefeld,
Childrens Hospital, Krefeld, Germany; 7 Klinikum Mutterhaus der
Borromäerinnen, Pediatric Oncology and Hematology, Trier, Germany;
8 University Medical Center, Division of Pediatric Hematology- Oncology
and Stem Cell Transplantation, Aachen, Germany; 9 University of Bonn
Medical Center, Department of Pediatric Hematology and OncologyCenter for Pediatrics, Bonn, Germany; 10 Asklepios Hospital, Department of
Pediatrics- Division of Haematology and Oncology, St. Augustin, Germany;
11 Municipal Clinics of Cologne, Department of Pediatrics- Division of
Pediatric Oncology and Hematology, Cologne, Germany; 12 University of
Saarland, Department of Pediatric Hematology and Oncology, Homburg,
Germany; 13 University of Cologne, Department of Pediatric Hematology
and Oncology, Cologne, Germany
Background/Objectives: Early-phase clinical trials could be
a potential therapeutic possibility to patients without any other
treatment options in regular patient care. Trial recruitment
is hampered by the unevenly geographic distribution of only
three to five study sites for whole Germany, that limited the
recruitment radius just to a few kilometers otherwise patients
must be willing to travel to the center for each visit or must
be transferred to trial centers even in a pre-terminal situation.
A defined supra-regional virtual study site could solve this
challenging situation and simultaneously meet patients´ and
stakeholders’ requirements.
Design/Methods: Therefore, pediatric oncology centers
(n=12) committed to form a network covering one geographic
area (Northrhine-Westphalia). It is organized by one supraregional study site/central working study office (University of
Essen) that acts as a coordinating site for merging the associated sites. A periodically updated (every 6 to 12 months)
resource data and training plan for equipment and staff will
be analyzed and strengths and weaknesses can be balanced
between all participating centers. Whatever cannot be done
decentral the coordinating study office will cover the task centrally. All activities will be performed according to Good Clinical Practice. The structure and its activities are supervised by
a scientific leading group.
Results: Patients can enter early-phase clinical trials near the
patient's home. It improves the patient access and compliance
to experimental treatment options as well as the recruitmentrate early-phase clinical trials. The supra-regional site acts as
one single site to sponsors, ethic committees (EC) and competent authorities (CA). In spring 2017, one industry-sponsored
and one academic study apply that model to EC and CA.
Conclusions: The supra-regional study site presents an attractive structure model addressing the specific requirements in
recruiting pediatric oncology patients to early clinical trials
in unevenly populated area states like Germany.
S347 of S518
T R E AT M E N T A N D CA R E S UP P O RT IVE CARE
P-395 Cancer-Related Fatigue in Egyptian
Children
E.R. Abdel Khalek1 , L.M. Sherif2 , M. Almalky3 , N. Fawzy3
1 Faculty
of medicine- Zagazig University, Pediatrics, Cairo, Egypt;
of Medicine- Zagazig University, Peditarics, Zagazig, Egypt;
3 Faculty of Medicine- Zagazig University, Pediatrics, Zagazig, Egypt
2 Faculty
Background/Objectives: Cancer-Related Fatigue (CRF) is
one of the most frequent and stressful symptoms in children
with cancer that has a profound effect on Quality of Life
(QOL).
Aim: The purpose of this study is to find out the prevalence
and patterns of (CRF) in children during cancer treatment
Design/Methods: A prospective longitudinal descriptive
study was conducted on 60 children with cancer, aged 5–
15 years, who were receiving inpatient chemotherapy in the
pediatric oncology department of Zagazig University. The
“PedQL Multidimensional Fatigue scale” and a sociodemographic data form were given to the patients and their parents as well as 60 healthy control children. Participants were
enrolled in this study just before the start of a new round of
chemotherapy (CTX) and then following them for 10 days
and before the next cycle. Hemoglobin level and blood indices
were recorded with each fatigue measures.
Results: There is a statistically significant increase in fatigue
scores and all domains during treatment. There is the tendency
of overestimating the fatigue by the parents for sleep and cognitive domains. A peak in fatigue occurs on the day 6 after
starting CTX and then become better towards the beginning
of the next cycle. No significant variation in total fatigue score
and all its domains according to the gender and age at presentation, However, exist regarding the diagnosis; solid tumors
are associated with better fatigue scores than lymphoma and
leukemia. Low hemoglobin level was associated with high
fatigue score and all its domains. (p<0.05)
Conclusions: Patients have more problems with fatigue in the
first few days after the start of a cycle of CTX. An assessment
of fatigue should be done for every patient undergoing CTX
and repeated at different times to apply a timely and tailored
intervention to prevent fatigue.
P-396 Challenges in Managing Chemotherapy
Induced Febrile Neutropenia in Paediatric
Oncology in Developing Countries: The Children's
Hospital Lahore Pakistan Experience
A. Ahmad1
1 The
Children's Hospital and the Institute of Child Health Lahore,
Paediatric Haematology/Oncology, Lahore, Pakistan
SIOP ABSTRACTS
S348 of S518
Background/Objectives: The Oncology Department Of The
Children's Hospital Lahore is a 60 bedded unit providing
free treatment to over 1000 new childhood cancer cases each
year.The aim of this prospective study was to analyze the burden of chemotherapy induced FN and to assess the leading
risk factors.
Design/Methods: After obtaining an Institutional Review
Board (IRB) approval, we used our departmental database,
the Pediatric Oncology Network Database (POND) to identify patients who were registered between June 2010 and July
2013. We combined data from the POND registry and data
collected by chart review in one excel database.
Design/Methods: Prospective review of 100 patients with FN
admitted in July to August 2016 was done. Data regarding
their clinical features, baseline CBC, course of therapy, hospital stay and understanding of caregivers regarding FN analyzed.
Results: We identified 843 patients who were registered
in POND over the 3-year studied period. Median follow up was 9months(range, 0 to 37). Patients were diagnosed with leukemia(N=191, 23%), lymphoma(N=103,12%),
solid tumors(N=371,44%), central nervous system (CNS)
tumors(N=143,17%) and others(N=35,4.2%). There were
3561 CT scans ordered in our center for 560 patients(out
of 843 registered patients,66%). Median number of scans
per patient were 5(range, 1-43). A total of 557 surveillance
scans were ordered for 131 patients (median=4). Surveillance scans were ordered after a median of 6 days following the onset of neutropenia (range 0-47 days). The
majority of surveillance scans were done for patients with
leukemia/lymphoma(N=480) vs. solid/CNS tumors(N=77).
The most commonly scanned sites were chest(N=272),
sinus(N=211) and abdomen(N=44). Positive predictive value
(PPV) for possible fungal infection was 26% for all scans. PPV
per site were 25% for sinus scans, 21% for chest and 10% for
abdomen. There was no difference in PPV of patients with
leukemia/lymphoma vs. Solid/CNS tumors (P=0.62).
Results: Total 100 patients with age ranging from< 1 to 15
years (67% <5 yrs) were included. 72% of cases had ALL and
28% with solid tumors. 28% had last chemotherapy received in
72 hours, 30% in last week and rest in more than a week time
36% had respiratory tract infections, 18% gastrointestinal
infections, 20% mucositis, 10% no focus found and rest 16%
had other manifestations Only 2 % presented in <one hour
of start of symptoms, 27% <24 Hours, 61% in <5 Days and
10% >5 days duration of symptoms. 45% had Hb <8 gm%,
33% had platelets <50000, and 54% had WBC <1000 and
63% had ANC <100.(p-Value=0.003-Hospital Stay). 29%
presented with first episode while 51 % had 3 or more FN
episodes.28% cases stayed 1 hour distance from CHL while
72% had to travel >1-5 hrs. 17% had no treatment before
reached PTC. Only19% caregivers had adequate awareness
regarding FN, 72% had some understanding while 9% had no
knowledge about FN (p-value=0.000). 40% had social issues,
41% were unaware while 13% showed negligence in seeking
treatment (p-Value=0.005)
Conclusions: Health education of caregivers and health professionals is of utmost importance to prevent and manage FN
effectively. Need of capacity building in pediatric oncology
in low income countries is essential for provision of standard
childhood cancer care.
P-397 Yield of Surveillance Imaging for Invasive
Fungal Infection: Solid Tumors VS. Hematologic
Malignancies
A. Al- Nassan1 , M. Sabha2 , M. Mustafa Ali3 , I. Sultan1
1 King
Hussien Cancer Center, Pediatric, Amman, Jordan; 2 University of
Tolido, Internal medicine, Tolido, USA; 3 Cleveland Clinic, Internal
Medicine, Cleveland, USA
Background/Objectives: According to most recent guidelines for the management of febrile neutropenia in children
with cancer, CT imaging to rule out fungal infection remains
an essential tool that is commonly utilized despite risk of radiation exposure and uncertain yield in different disease categories.
Conclusions: Surveillance for fungal infections were commonly ordered for our patients according to our clinical practice guidelines with leukemia/lymphoma patients most commonly scanned. When patients with solid/CNS tumors were
scanned, the chance of having fungal infection was similar to
those with leukemia/lymphoma.
P-398 Timely Administration of Antibiotics in
Pediatric Hematology/Oncology Patients with
Febrile Neutropenia: A Retrospective Study in a
Tertiary Care Center
T. Bauters1 , P. Schelstraete2 , G. Laureys1 , A. Mannaerts1 , N.
Herman1 , C. Dhooge1
1 Ghent
University Hospital, Pediatric Hematology- Oncology and Stem Cell
Transplantation, Ghent, Belgium; 2 Ghent University Hospital, Pediatric
Pulmonology and Infectious Diseases, Ghent, Belgium
Background/Objectives: Febrile neutropenia (FN) is a common complication in pediatric hematology/oncology (PHO).
Current guidelines advocate timely administration of empirical broad-spectrum antibiotics. Antibiotic delivery to patients
with FN in < 60 min is an increasingly important quality
measure associated with improved outcomes. The aim of this
study was to measure the time to antibiotic administration
(TAA) for inpatients and outpatients in our department, targeting a TAA of < 60 minutes.
SIOP ABSTRACTS
Design/Methods: A retrospective study was performed, in
which TAA was defined as time between prescription and
administration of antibiotics (inpatients) and time between
admission to hospital and antibiotic administration (outpatients).
Results: The study population involved 42 patients (59.5%
males), mean age 6.7 years (range 2 months-16 years), representing 61 FN-episodes from which 25/61 inpatient (41.0%)
and 36/61 outpatient (59.0%) episodes. For inpatients, mean
TAA was 82 minutes (range 0-269); for outpatients 114 minutes (range 0-420). A total of 44.3% FN-episodes (27/61) were
within the targeted TAA of < 60 minutes, from which 13
(13/61; 21.3%) even within 30 minutes. In 18 FN-episodes
(18/61; 29.5%) TAA was between 1 and 2 hours. TAA for outpatients with FN was more than 2 hours in 16/61 (26.2%) of
episodes (range 121-420 minutes).
Conclusions: Results indicate a TAA of < 60 minutes for
44.3% of FN-episodes, which is a higher percentage than in
literature data, indicating 16-20% of FN episodes with TAA
of < 60 minutes. The TAA for outpatients is higher than for
inpatients. A possible explanation lies in time involvement of
anamnesis, clinical examinations upon arrival in hospital and
waiting time for laboratory results. This study confirms that all
efforts are performed to keep the TAA, proposed as a qualityof-care indicator in our department, as low as possible both
for inpatients and outpatients.
P-399 Spectrum of Respiratory Viral Infections
in Children with Cancers: Experience from a
Tertiary Cancer Centre in Eastern India
A. Bhattacharyya1 , A. Das1 , G. Goel2 , S. Bhattacharya2
1 Tata
Medical Center, Paediatric Oncology, Kolkata, India; 2 Tata Medical
Center, Microbiology, Kolkata, India
Background/Objectives: Pattern of respiratory viral infections (RVI) in children with cancers is not well characterized in India. We conducted this study to determine the spectrum, incidence of fever-neutropenia, need for hospital admission, economic burden, and outcome (concomitant bacterial/fungal infections, need for ICU care, and death) of RVI
in our pediatric-oncology unit.
Design/Methods: Data was prospectively collected over 19
months (July 2015-February 2017). All children under treatment for cancer presenting with cough and coryza underwent
multiplex PCR for respiratory viruses from nose and throat
swab.
Results: Positive results were obtained in 222/421 (52.73%)
cases, of which data was incomplete in 8 cases. Final analysis was done on 214 cases. Fever was present in 81%. Median
age was 5.35 years (range 0.5-17.8 years). Sixty percent were
receiving intensive chemotherapy and 85% had a haema-
S349 of S518
tolymphoid malignancy. Commonest viruses isolated were
Influenza A and B (46%), Respiratory Syncytial Virus (RSV
25%) and Human Metapneumovirus (14%). Peak months of
incidence were July to September which is the rainy season. Fifty percent (106) patients needed admission, while
73/106 had ANC<500 during the episode. Concomitant bacterial/fungal infection was seen in 11.2% cases. Median duration of admission was 5 days (range 1-35 days), and median
cost was USD 258 (range: 33-1939). Fifteen patients needed
ICU admission of which 11 had concomitant bacterial/fungal
infection (p=0.0001). Ventilation (invasive or non-invasive)
was required in 8/15 patients of which 4 had RSV. Two deaths
were recorded, both in patients with RSV and concomitant
bacteremia.
Conclusions: RVI adds significantly to the burden of admissions and expenses. Influenza vaccination given universally
may prevent a significant number of such illnesses and admissions. Such a programme has been initiated at our center, and data is being prospectively collected to measure its
impact. Concomitant bacterial/fungal infections add to morbidity/mortality.
Acknowledgements: Manashpratim Gogoi (data collection)
R Bhalachandra (sample collection)
Anusha Harishankar (PCR processing)
P-400 Profile, Reason and Disclosure of Pediatric
Oncohematologic Patients Admitted in a Pediatric
Intensive Care Unit in a General Brazilian Hospital
G. Bomfim1 , C. Cintra1 , S. Brandi1 , E. Santos1
1 hospital
Israelita Albert Einstein, Pediatria, São Paulo, Brazil
Background/Objectives: Our intensive care unit is a general
unit with 15 beds and a media of 1000 admissions/year; it
attends clinical and surgical patients whose reason of admission may be elective, urgency or emergency. OBJECTIVE: to
know the profile, causes of admission and disclosures of pediatric oncohematologic patients in the pediatric intensive care
(PICU) of a general hospital.
Design/Methods: METHOD: retrospective analyze of oncohematologic patients admitted in the PICU in 2016.
Results: RESULTS in 1073 admissions, 1.8% were oncohematologic patients. The indications were: elective (25%),
urgency (65%) and emergency (10%); 60% percent was female
and 40% male; 25% was under 1 year old, 35% between 1
and 5 years, 10% between 5 and 10 years and 30% older
than 10 years old. The rapid response team attended 20% of
these patients, 80% were evaluated by the local staff and sent
to the PICU. The origin was emergency room (20%), oncology and bone transplantation unit (35%), pediatric unit (15%)
and surgery rooms (30%); and the causes for admissions were
SIOP ABSTRACTS
S350 of S518
post-operatory care (25%), hemodynamic monitoring/sepsis
(45%), respiratory failure (25%). Many of these patients were
submitted to invasive procedures: 30% had a central venous
catheter, 25% invasive arterial pressure, 20% enteral feeding,
and 30% bladder catheter. None of the patients had complications as infection or pressure ulcer. Eighty percent was discharged for the origin unit, 15% to home and just one patient
died.
Conclusions: The oncohematologic pediatric patients admitted in the PICU require specialized intensive care and most
of them were admitted in emergency and urgency situations.
They are discharged back to the origin unit and then to home.
Other information can be added to the already collected in the
PICU, and a historical series allow this data to be accompanied and compared to other institutions.
vided superior cover compared to piperacillin/tazobactam
monotherapy.
Conclusions: The number needed to treat to improve our coverage based on this data would be 17. This needs to be balanced against the known adverse effects of empirical aminoglycoside when deciding appropriate local antimicrobial policies.
P-402 Can We Identify Chemotherapy-Related
Toxicity in Children with Cancer Through
Automatized Integration of Healthcare Information
Systems?
P. Berlanga1 , M.J. Herrero2 , A. Tórtola3 , M. Correcher3 , P.
Gargallo4 , A. Marco4 , V. Castel4 , B. Valdivieso5 , A. Cañete4
1 Hospital
P-401 The Aetiology of Fever in Children with
Cancer in the North of Scotland
T. Lawes1 , J. Calley1 , L. Adam1 , N. Abdelrazig1 , H. Bishop1 , N.
Ahmad1
1 Royal
Aberdeen Children's Hospital, Department of Paediatric Oncology,
Aberdeen, United Kingdom
Background/Objectives: Outcomes in children with cancer
continue to improve but febrile neutropenia (FN) remains a
major cause of mortality. Mortality from FN episodes is 2-3%
and 5 year mortality in acute lymphoblastic leukaemia due to
infection is 2.4%. Rapid antibiotic delivery (< 60 minutes)
is associated with improved outcomes. Guidance is available from the National Institute for Health and Care Excellence (NICE) and the Managed Service Network (MSN) for
Children & Young People with Cancer in Scotland regarding empiric antibiotic prescribing. Our centre is currently
unique in Scotland in practicing single agent first line empirical antibiotic therapy with piperacillin/tazobactam. Our aims
were to assess the aetiology of febrile episodes in children
with cancer in the North of Scotland and evaluate the adequacy of our empiric antibiotic policy in light of our local
antibacterial resistance patterns.
Design/Methods: Positive microbiological data for all paediatric oncology patients treated in the years 2013-2015 was
provided by our local laboratory for analysis. Isolates and
resistance patterns were compared with data from 2006-2012.
Results: Microbiological isolates demonstrate secular trends
of increased non-fermenting and environmental gram negatives and a reduction in Staph. aureus. There were
non-significant increases in resistance to key antimicrobials in both gram positive and gram negative organisms.
Between 2013-2015 there were 10 of an estimated total
of 166 febrile episodes where initial dual therapy with
piperacillin/tazobactam and gentamicin would have pro-
Universitario la Fe, Pediatric Oncology Unit, Valencia, Spain;
Fe Hospital Research Institute, Pharmacogenetics Unit, Valencia,
Spain; 3 Hospital La Fe, Systems Department, Valencia, Spain; 4 Hospital La
Fe, Pediatric Oncology Unit, Valencia, Spain; 5 Hospital La Fe, Planning
Department, Valencia, Spain
2 La
Background/Objectives: Integration of seamless healthcare data from multiple hospital data sources to identify
chemotherapy-related toxicity in pediatric patients.
Design/Methods: Integration into a DASHBOARD, using
Excel 2013 dynamic tables and Powerpivot, of all healthcare
data from the following hospital sources: Farmis_Oncofarm®
(chemotherapy), GestLab (clinical laboratory analysis), Delphin (blood bank), Philips ICCA(Intensive Care Unit), IRIS
(HIS Hospital LaFe) y Orion Clinic (electronic medical
record). Extract, Transform, Load (ETL) data integration process to acquire a data store (DATAMART) with the automatic
integration of all prior information, as well as laboratory toxicity grading according to CTCAE 4.0 criteria and identification of chemotherapy delays/dose reductions and unplanned
hospitalizations. Manual data extraction from patients’ medical records (solid tumors) treated in our pediatric oncology
unit and comparison of automatized data extraction reliability.
Results: The fine tunning of the information tool was carried
out following the next steps: A) Information tool design, B)
Information tool testing 1 (manual data extraction of toxicity related to 65 chemotherapy courses and comparison), C)
Information tool testing 2 (manual data extraction of toxicity related to 145 chemotherapy courses and comparison).
Automatized data extraction was superior to manual data
extraction with regards to identification of laboratory toxicity and chemotherapy dose reductions. A final test with more
than 800 chemotherapy courses is currently ongoing.
Conclusions: Automatized data extraction and integration of
healthcare data from different hospital data sources is superior
to manual data extraction. This information tool can simplify
SIOP ABSTRACTS
S351 of S518
data extraction, allow early identification of chemotherapyrelated toxicities and improve quality of care. Acknowledgments: this work has been funded by “Ayudas Investigación
Fundación Mutua Madrileña 2016”
P-404 Implementation of a Program Based on
Adapted Physical Activity and Recommendations
for Second Cancers Prevention for Adolescents and
Young Adults with Cancer
P-403 Impact of Removing Mucosal Barrier
Injury Laboratory-Confirmed Bloodstream
Infections on Central Line-Associated Bloodstream
Infection Rates in Pediatrics Cancer Centers in
Latin America
1 Centre
J. Carretier1 , A. Lion1 , B. Fervers1 , H. Boyle2 , P. Marec-Bérard2
M. Gonzalez1 , H. Forrest1 , M. Homsi1 , J. Kirby1 , M. Caniza1
1 St
Jude Children's Research Hospital, Global Pediatric Medicine,
Memphis, USA
Background/Objectives: Bloodstream infections may result
from translocation of gut microorganism into the bloodstream of immunocompromised patients. In January 2013,
the National Healthcare Safety Network (NHSN) released
the mucosal barrier injury laboratory-confirmed bloodstream
infection (MBI-LCBI) to identify the subset of central lineassociated bloodstream infections (CLABSIs) most likely
associated with mucosal barrier injury. Infectious Diseases
(ID) – Global Pediatric Medicine initiative mentored Infection Care and Prevention (ICP) teams in pediatric cancer centers (PCCs) in Latin America to separately track MBI and
non-MBI events using the NHSN/MBI-LCBI protocol. Here,
we describe MBI-LCBIs reported and determine impact of
removing MBI-LCBIs from CLABSI rates.
Design/Methods: Data were collected prospectively by our
ICP teams in Honduras, Ecuador, México, and Argentina. For
this report, we reviewed the collected ID-IO standardized HAI
surveillance monthly report data between January 2014 and
December 2016. CLABSI rates per 1000 central-line days
were calculated with and without the inclusion of MBI-LCBIs
to determine rate differences.
Results: From four PCCs with an average device utilization
ratio of 0.32 (range 0.12-0.94), 129 CLABSIs were reported;
41(32%) met the MBI-LCBI 1 criteria. The overall CLABSI
rate was 6 (range 3-14) per 1000 CL-days. When removing
MBI-LCBIs, the CLABSI rate decreased to 4 (range 2-10) per
1000 CL-days. In general, the percent change in the CLABSI
rate was 32% (ranges 16-43%). Among these PCCs, removing
MBI-LCBI from the CLABSI rate determination produced
the greatest CLABSI rate decrease (43%) in Mexico (3 vs. 2
per 1000 CL-days). The most common pathogens were Klebsiella pneumonia (34%), Escherichia coli (22%), and Serratia
marcescens (10%).
Conclusions: Our results support separate monitoring and
reporting of MBI and non-MBI–-LCBIs in low- to middleincome countries to allow accurate detection and tracking of
preventable (non-MBI) bloodstream infections.
Léon Bérard, Cancer Environment, Lyon, France; 2 Centre Léon
Bérard, Adolescents and Young Adults with cancer Department, Lyon,
France
Background/Objectives: Around 700 adolescents and young
adults (AYAs; 15 to 25 years) are diagnosed each year with
cancer in the French Auvergne-Rhône-Alpes region. While
long term survival is about 80%, they are six times more
likely to develop a second primary cancer (SPC) compared
to their peers. This risk is multifactorial and depends on the
type of first cancer, the treatment received and the prevalence
of risk factors (smoking, overweight, sedentary lifestyle, environmental exposures...).
This project aims to implement a clinical program based on
adapted physical activity and cancer prevention recommendations for AYAs with cancer.
Design/Methods: Patients attended adapted physical activity sessions during the active treatment period (4-6 months).
They were given questionnaires about physical activity
(IPAQ) and quality of life (EORTC QLQ-C30) at baseline
(T1) and at the end of treatment (T2). They participated to
individual information meetings on SPC risk prevention (T3),
and responded to a final QoL questionnaire by phone 1 year
after T1 (T4).
Results: So far, 57 AYAs (63% boys, 37% girls; median
age=18 [15-25]) have been included and completed T1. On
average, they participated in 4 sessions [2-12] at the hospital and 15 [4-42] at home. Currently, 41 AYAs (72%) have
completed the T2 assessment. Preliminary results indicate an
increase in the level of physical activity between T1 (680
MET-min/week [0-3666]) and T2 (1377 MET-min/week [02259]). Sedentary time seems to decrease on average from 51
h/week [10-70] at T1 to 42 h/week [7-90] at T2. At T3, 36
AYAs (63%) were highly satisfied with the program.
Conclusions: This study responds to AYAs’ needs for support
and information regarding physical activity and SPC prevention. To improve the quality of the program and its implementation, a gym room will be built at the hospital, and a
therapeutic education program dedicated to AYAs will be
developed.
P-405 Neck Circumference: An Indicator for
Assessment of Nutritional Status in Children and
Adolescents with Malignant Neoplasms at the Time
of Diagnosis?
SIOP ABSTRACTS
S352 of S518
R.L. Ferretti1 , P.S. Maia-Lemos1 , K.J.T. Guedes1 , E.M.M. Caran1
1 Pediatric
Oncology Institute - IOP/GRAACC/UNIFESP, Pediatric, Sao
Paulo, Brazil
Background/Objectives: Malignant neoplasms in children
and adolescents will trigger malnutrition, which may be
underestimated in the diagnosis of the disease, when considering General Adiposity Indexes, such as the Body Mass Index
(BMI). Anthropometric indicators may be able to detect early
malnutrition, especially at the time of diagnosis of the disease. However, it is necessary that these indicators present
good correlation with those that are consecrated to predict
the muscular mass of the patient, such as the Arm Muscular Area (AMA). Neck circumference (NC) is a simple,
low cost and easy to apply in clinical practice. The main
objective of this study was to verify if there is a correlation
between NC measurement and AMA of children and adolescents with malignant neoplasms in the diagnosis of the
disease.
Design/Methods: A cross-sectional study that evaluated
children and adolescents aged 0 to 20 years with malignant neoplasms at a Pediatric Oncology Specialized Institute from December 2015 to June 2016. Measurements of
NC were evaluated and, for AMA calculation, arm circumference and skinfolds triceps were evaluated, all performed
by trained evaluators, following standardized anthropometric
techniques. The correlation between NC and AMA was performed through the Pearson correlation.
Results: Among 40 new cases patients, 50% (20) were male.
The median age was 12.03 (± 4.75) for the female sex and
13.43 (± 6.99) for the male sex.The correlation between NC
and AMA was linear positive and very strong for both sexes,
female (r=0.94) and male (r=0.93).
Conclusions: It is concluded that there is a strong correlation between NC and AMA for boys and girls, and it
can be a promising indicator in clinical practice, because of
its practicality in the measurement, low cost, early detection of changes in the nutritional status of these individuals,
allowing rapid Intervention and implementation of nutritional
therapy.
Index is considered due to the various metabolic changes,
hydration status, and the side effects caused by the therapy
antineoplastic. Anthropometric measures are able of early
detection of malnutrition, specifically muscle mass depletion,
such as calf circumference (CC). The main objective of this
study is to verify if there is a correlation between the measurement CC and Arm Muscle Area (AMA), Triceps skinfold
(TSF), and Body Mass Index (BMI).
Design/Methods: A cross-sectional study evaluated children
and adolescents from 0 to 20 years of age with malignant neoplasms at a Pediatric Oncology Specialized Institute between
October 2015 and June 2016. Measurements of CC were evaluated and, for AMA calculation, arm circumference (AC) and
TSF were evaluated. The values of weight and length /
height were obtained for the calculation of BMI. All measurements were performed by trained evaluators. Correlation
between CC and other variables (AMA, BMI and TSF) was
performed through the Pearson correlation.
Results: Among 1232 patients, 43,59% (537) were female.
The mean age for males was 10.0 (± 7.19) and for females,
9.84 (± 7.16). When analyzing the correlation between CC
and the other independent variables, there were linear and positive correlations between CC and AMA (r=0.87), CC and
BMI (r=0.79) and CC and TSF (r=0.64).
Conclusions: It is concluded that there is a strong correlation between Calf Circumference and the independent variables analyzed (AMA, BMI and TSF). This result is greater
between CC and AMA, strengthening CC, besides being an
easy and low cost measure to be used in clinical practice, has
a strong correlation with AMA, which also reflects muscle
mass stores, being a good indicator for monitoring the nutritional status of children and adolescents with malignant neoplasms.
P-407 Outcomes of Paediatric Oncology
Admissions to the Paediatric Intensive Care Unit A Single Tertiary Centre Experience
S. Dillon1 , J. Weitz1
1 Oxford
University Hospitals NHS Foundation Trust, Paediatric Critical
Care, Oxford, United Kingdom
P-406 Calf Circumference: A Good Indicator of
Muscle Mass Depletion in Children and Adolescents
with Malignant Neoplasms?
R.L. Ferretti1 , P.S. Maia-Lemos1 , K.J.T. Guedes1 , E.M.M. Caran1
1 Pediatric
Oncology Institute - IOP/GRAACC/UNIFESP, Pediatric, Sao
Paulo, Brazil
Background/Objectives: Children and adolescents with
malignant neoplasms may present early malnutrition, but this
finding may be underestimated when only the Body Mass
Background/Objectives: Paediatric cancer remains a leading
cause of death in children, but continued advances in treatment and supportive care have helped to improve survival.
Paediatric oncology patients make up a significant proportion
of admissions to paediatric intensive care units (PICU). The
aim of this study was to assess the outcomes of children with
cancer that were admitted to PICU within a tertiary hospital.
Design/Methods: A retrospective analysis of the PICU
database system (Carevue, Phillips) in a tertiary paediatric
hospital was performed. All patients aged between 0 to 18
SIOP ABSTRACTS
years with an Oncological diagnosis, that were admitted
between June 2014 and March 2017 were included.
Results: A total of 111 patients were admitted to PICU on
139 occasions. Sixty-eight admissions (48.9%) had a diagnosis of CNS malignancy, 50 (35.9%) were haematological and
20 (14.4%) were solid tumour. The median length of stay was
2.2 days, with the longest stay being 40.9 days. Ninety-one of
these admissions were for post-operative care and 47 for medical care. Forty-three of the admissions required ventilator support (26 post-operative and 17 medical patients). Three of the
ventilated admissions also required inotropic support (2 postoperative and 1 medical patient). Two admissions required
continuous venonegativenous haemofiltration (CVVH). One
hundred and seven (96.4%) of the patients survived to discharge home. Three patients died on PICU (2 post-operative
and 1 medical patient). One patient was discharged from PICU
but did not survive to discharge from the hospital.
Conclusions: A large proportion of oncology patients admitted to PICU requiring intervention survived to discharge to
continue their treatment regimes. Several factors affected the
duration of stay for these patients, including the reason for
admission, underlying diagnosis, and the number of interventions required. Compared with data from previous studies our
results suggest that PICU outcomes for oncology patients have
greatly improved in terms of survival.
P-408 Aromatherapy with Citrus Oils for
Chemotherapy-Related Nausea and Vomiting
W. Dirksen1 , M. Torbecke1
1 University
Hospital Münster, Pediatric hematology and oncology, Münster,
Germany
Background/Objectives: At the pediatric cancer center of
University Children´s Hospital Muenster, 120 to 140 children and adolescents with newly diagnosed cancer are admitted per year and receive treatment with intensive chemotherapies. Nausea and vomiting are among the most frequent and
at the same time most distressing side effects of chemotherapy. In support of antiemetic drug therapy, complementary
nursing procedures can be applied. In this observational study,
we evaluated the use of aromatherapy with citrus oils in our
patient population.
Design/Methods: Aromatherapy is based on the local application of 100% natural etheric oils on intact skin. The oils act
against nausea via the olfactory system and by penetrating the
skin surface. In the professional nursing care of patients with
nausea and vomiting, especially citrus oils have shown efficacy. These include lemon, orange, tangerine, and grapefruit
essential oils. Two to three drops of the etheric citrus oil are
added to a clean cotton pad and locally applied at least twice
daily on intact skin of the chest or close to the head.
S353 of S518
Results: Most patients with chemotherapy-related nausea and
vomiting report to benefit from the smell of citrus oils which
overlay nausa-enhancing smells. The symptoms are often mitigated and in some instances, occurrence of symptoms can be
avoided.
Conclusions: Aromatherapy with citrus oils can suppport
drug-based antiemetic therapy. Individual preferences for
smells, often shaped by personal memories and emotions, are
highly relevant for therapeutic success and therefore should be
considered for the choice of the smell. In combination with the
medical standard of care, this and other complementary nursing procedures have an added value in the control of the agonizing side effects of chemotherapy and can thereby enhance
the patients compliance with the subsequent therapy.
P-409 Relationship Between State and
Nutritional Risk Assessed by Instrument for
Screening Children and Adolescents with Cancer
K.N. DA SILVA1 , R.V. PATIN1 , C.F. MARÇON2 , P.D.S.
MAIA-LEMOS2
1 UNIP,
Nutrition, São Paulo, Brazil; 2 IOP/GRAACC/UNIFESP, Pediatric,
São Paulo, Brazil
Background/Objectives: Malnutrition is highlighted as a
common condition in cancer patients. Adequate nutritional
conducts are taken from the effective nutritional evaluation,
being necessary to the presence of a screening tool, which analyzes and evaluates the nutritional risks Murphy et al. (2015)
proposed a specific screening tool for children on cancer treatment, the Screening Tool for Childhood Cancer (SCAN).
To rate the relationship between state and nutritional risk
verified through an instrument for screening children and
teenagers with cancer.
Design/Methods: A cross-sectional, retrospective study with
secondary data of 673 patients seen from August 2015 to
August 2016.The results analyzed were based on the screening performed by the nutrition team in that period and compared with the concomitant anthropometric evaluations. Parametric analyzes were performed by the STATA v.10 program.
Results: The degree of nutritional risk of cancer patients
changes according to their location and cause of hospitalization It was identified in the study that the diagnosis of nutritional risk was related to the values of BMI (Body Mass Index)
altered, being observed a significant relation between nutritional risk and body composition only in teenagers.
Conclusions: It was found that SCAN may assist clinical
practice in screening patients at nutritional risk, but further
studies should be performed to confirm their effectiveness,
especially with preschool and school children.
S354 of S518
P-410 Outcome of a Three-Week
Supplementation Program in Children and
Adolescents with Cancer and ITS Association with
Acceptance in a Clinical Trial
A. GAROFOLO1 , P.S. MAIA-LEMOS1 , F. ANCONA-LOPEZ2 ,
A.S. PETRILLI1
1 IOP/GRAACC/UNIFESP, Pediatric, São Paulo, Brazil; 2 UNIFESP,
Pediatric, São Paulo, Brazil
Background/Objectives: Malnutrition in cancer patients
impairs prognosis, increases the costs of treatment and
decreases quality of life. To study protocol compliance and
nutritional outcome in malnourished patients with cancer
after a 3-week oral supplementation program and the association of that outcome with type of supplement and severity
of malnutrition at admission.
Design/Methods: This clinical trial included patients with
1 year old or above, followed during anticancer therapy.
They were divided in two groups: mild and severe malnutrition. The severely malnourished received only the industrialized oral supplements (IOS) for three weeks, whereas the
mildly malnourished were randomized to receive IOS or nonindustrialized oral supplementation (NIS) for three weeks.
The supplement supplied 45% of the daily energy requirements. A new approach to intervention (NAI) was indicated
in the severely malnourished group, if no adequate nutritional
response was achieved and in the mildly malnourished under
IOS if the subjects developed severe malnutrition.
Results: One hundred and seventeen patients completed the
follow up: 58 severely and 59, mildly malnourished. Adequate nutritional outcome was observed in 38% of those with
a severe condition; therefore 62% had a NAI. The same analyses showed that 2.8% of the mild malnutrition IOS group
and 22.7% of the NIS group required NAI (p<0.05). IOS
and severity of malnutrition were significantly associated with
nutritional outcome; IOS demonstrated better outcome and
the severity of malnutrition worse outcome.
Conclusions: These results suggest that IOS could minimize
nutritional deficit, mainly in patients with mild malnutrition
and the severity of malnutrition was associated with worse
nutritional outcomes.
P-411 Beyond Supportive Care: A Collaboration
to Improve the Intensive Care Management of
Critically ILL Pediatric Oncology Patients in
Resource-Limited Settings
E. Dray1 , R. Mack2 , D. Soberanis3 , C. Rodriguez-Galindo4 , A.
Agulnik5
1 Dartmouth
Hitchcock Medical Center, Pediatric Intensive Care Unit, West
Lebanon, USA; 2 Unidad Nacional de Oncologia Pediatrica, Intensive Care,
Guatemala City, Guatemala; 3 Unidad Nacional de Oncologia Pediatrica,
SIOP ABSTRACTS
Nursing Education, Guatemala City, Guatemala; 4 St. Jude Children's
Research Hospital, St. Jude Global, Memphis, USA; 5 St. Jude Children's
Research Hospital, St. Jude Global/Intensive Care, Memphis, USA
Background/Objectives: Hospitalized children with cancer
are a high-risk population who frequently require critical care
and intensive interventions. Survival for children with cancer in low and high-resource settings is dependent on early
recognition of cancer diagnoses, timely implementation of
treatment protocols, management of side effects, and prevention of deterioration. In recent years, survival for pediatric
oncology patients with critical illness in high-resource centers
has improved drastically. Resource-limited hospitals, however, continue to be challenged by this population, resulting
in poor inpatient outcomes and high mortality.
Design/Methods: Since 1998, the Asociación de HematoOncología Pediátrica Centroamericana (AHOPCA) has
demonstrated that multi-center collaboration can improve
outcomes for children with cancer in low- and middle-income
countries. Using the AHOPCA infrastructure, St. Jude Children's Research Hospital sponsored a multidisciplinary
conference on February 25th 2017 to identify challenges to
the care of pediatric oncology patients with critical illness
in resource-limited settings and identify opportunities for
multidisciplinary collaboration.
Results: Over 47 nurses, oncologists, and intensivists
attended the conference from all ten AHOPCA member countries. The sessions focused on quality improvement methods
and the intensive care experience at each hospital to elucidate
challenges and goals. The group identified several major challenges to the provision of critical care to pediatric oncology
patients in resource-limited settings: lack of adequate physical, personnel, and educational resources, inadequate institutional support, and provider resistance to allowing access to
intensive care resources for these patients. The group identified over 27 multidisciplinary projects to address these challenges, fitting into the framework of topics addressing Quality
Improvement, Research, Education, and Activism.
Conclusions: This meeting represents the first multidisciplinary conference focused on the intensive care of pediatric oncology patients in Central America. This experience demonstrated that resource-limited hospitals face similar challenges in caring for this population. The challenges identified can be addressed by innovative solutions
formed as a result of multidisciplinary and multi-institutional
collaborations.
P-412 Evaluation of a Nutritional
Supplementation Program for Pediatric Oncology
Patients with Malnutrition in Lilongwe, Malawi
SIOP ABSTRACTS
I. Mtete-Kumwenda1 , M. Butia-Mutai1 , P. Wasswa1 , M. Chasela1 ,
M. Mtunda1 , A. Mpasa1 , S. Wachepa1 , P. Mehta2 , P. Kazembe3 , N.
El-Mallawany2
1 Kamuzu
Central Hospital, Pediatrics, Lilongwe, Malawi; 2 Texas
Children's Hospital, Pediatrics, Houston, USA; 3 Baylor College of
Medicine Children's Foundation Malawi, Pediatrics, Lilongwe, Malawi
Background/Objectives: Malnutrition is a critical comorbidity for pediatric oncology patients and increases
risk for life-threatening complications. Supportive care for
patients with malnutrition is essential. However, we encountered challenges treating pediatric oncology patients according to nutritional rehabilitation unit (NRU) clinical guidelines
in Lilongwe, Malawi, for two reasons: (1) World Health Organization malnutrition guidelines generally focus on patients
under 5 years of age, and (2) protocols often struggle to identify cancer patients with bulky tumors because the tumor
mass misleadingly contributes to the child's weight, thereby
masking malnutrition, especially in older children, for whom
weight-independent measurement of mid-upper arm circumference (MUAC) is not commonly applied.
Design/Methods: A nutritional supplementation program
was implemented at Kamuzu Central Hospital (KCH) in July
2016. All pediatric oncology patients received supplemental
feeds with porridge, regardless of nutritional status. Patients
with mild/moderate malnutrition received ready-to-use therapeutic food (RUTF) derived from peanuts, while patients with
severe malnutrition received therapeutic milk initially, followed by RUTF. All patients underwent anthropometric measurements including weight, height, MUAC, body mass index
(BMI) and were scheduled to have follow-up evaluations. We
evaluated and describe the results of our intervention.
Results: There were 25 patients; median age was 8 years
(interquartile range 5.1-11.3). Diagnoses included solid tumor
of abdomen (36%), lymphoma (24%), other solid tumors
(24%), leukemia (16%). One patient died. Severe malnutrition was found in 48%, moderate 24%, mild 28%. Severity
was defined by BMI (52%), MUAC (20%), BMI/MUAC both
(16%), and presence of pitting edema (12%). Re-evaluation of
weight at 1-month/and 2-3 month intervals found: weight gain
(36%/24% at 1 month/2-3 months respectively), no change
(12%/16%), weight loss (24%/32%), and no data (28%/28%).
Conclusions: Nutritional supplementation improved weight
gain for some pediatric oncology patients with malnutrition.
However more consistent and comprehensive re-evaluation
is required, in addition to investigating causes for failure to
improve.
S355 of S518
1 Boonshoft
School of Medicine Wright State university, Medical Student 3rd
year, Dayton, USA; 2 Boonshoft School of Medicine Wright State university,
Wright State University Student, Dayton, USA; 3 Boonshoft School of
Medicine Wright State University, Public Health/Statistician, Dayton, USA;
4 Dayton Children's Hospital, Pediatric Hematology Oncology, Dayton, USA
Background/Objectives: Currently, there are over 380,000
child cancer survivors in America. Studies show this population has reduced physical activity when compared to
their peers, which has led to many comorbidities. The Children's Oncology Group (COG) Long-Term Follow-Up Guidelines include exercise recommendations for pediatric cancer
patients post treatment. The objective of this study was to
determine 1) if pediatric oncologists are aware of these recommendations, 2) their exercise counseling practices, and 3)
barriers to exercise counseling.
Design/Methods: An online survey modified from Abramson
et al. in “Personal Exercise Habits and Counseling Practices
of Primary Care Physicians: A National Survey” was sent to
attending physicians and fellows in the COG member list.
Results: Two-hundred ninety-five attending physicians and
59 fellows returned completed surveys. Almost all (99%)
believe exercise is important, but only 29% were familiar with
COG post treatment exercise recommendations. Fifty-eight
percent of attending physicians reported counseling at least
half of their patients post treatment, compared to 20% of fellows (P<0.001, chi-square test). For patients on active treatment, 40% of attendings and 9% of fellows counseled at least
half of their patients (P<0.001). Over 44% of fellows reported
not having enough time for exercise counseling, compared
to 22% of attendings (P<0.001). Of physicians who counsel
patients on active treatment, 97% counsel verbally, and 76%
recommend at least 3 days/week for 30 minutes. The more
time physicians spent counseling seemed to improve patient
compliance, especially when at least 3-5 minutes was spent.
Conclusions: Although most physicians believe exercise is
important for pediatric oncology patients, there is a gap
in knowledge of current COG recommendations. Additionally, there are no published guidelines for exercise in this
population. Further research should investigate methods to
increase physicians’ knowledge regarding exercise counseling
for pediatric cancer patients and ways to improve counseling
practices.
P-414 Supporting Transport Needs of Cancer
Patients to Reduce Treatment Abandonment
L. Burns1 , F. Pinho2 , A.A. Khaing3 , P. Freccero1
1 World
P-413 National Exercise Counseling Practices of
Pediatric Oncologists for Pediatric Cancer Patients
L.L. Yelton1 , C.L. Gupta2 , A. Stolfi3 , A. El-Sheikh4
Child Cancer, Operations, London, United Kingdom; 2 Please Take
Me There, Operations, Cambridge, United Kingdom; 3 Yangon Children's
Hospital, Paediatric Haematology-Oncology, Yangon, Myanmar Burma
Background/Objectives: The cost of transport has been identified as one of the key reasons for patients to abandon
SIOP ABSTRACTS
S356 of S518
treatment at Yangon Children's Hospital (YCH) in Myanmar.
An assessment in 2013 found abandonment to be as high as
50%. NGO Please Take Me There is working in partnership
with World Child Cancer to address this issue. A pilot project
was developed to understand the transport needs of paediatric
oncology patients at YCH.
Design/Methods: A 2 week survey was conducted to
understand barriers to accessing care. 107 interviews were
conducted and criteria were established for offering transport
support. A 4 week pilot project was then run using this
criteria. During the pilot 125 patients were supported through
172 grants. A computer programme was designed to capture
accurate data and the results were used to design a support
package with the aim of reducing abandonment.
Results: The average monthly household income of families
at YCH is $78, while total treatment-related costs amount to
>$2,200. In 40% of Burmese States, the return cost of travel
to the hospital amounted to more than monthly household
income. More than 70% of caregivers had to stop work regularly, or entirely, after diagnosis. 30 of the families had up
to 5 follow-up appointments scheduled within the period of
the project and the project team identified only one case of a
family that did not return. Families became very close to the
project team, contacting them frequently to provide updates
on their travel arrangements. Caregivers felt more connected
with the project team/social workers and often asked for support.
Conclusions: The total of providing transport costs to all
patients and families at YCH would be $88,000 per year. Providing the amount required for a round trip means that children will return for outpatient appointments and treatment,
resulting in a lower rate of abandonment.
P-415 The Feasibility of Physical Activity
Interventions during the Intense Treatment Phase
for Children and Adolescents with Cancer
S. Grimshaw1
1 Royal
Children's Hospital, Allied Health, Melbourne, Australia
Background/Objectives: Physical activity may have benefits
for children undergoing intense treatment for cancer, but such
programmes are challenging to implement. This systematic
review aimed to investigate the feasibly of physical activity
interventions during intense cancer treatment for children and
adolescents.
Design/Methods: A systematic search of seven electronic
databases (Cumulative Index to Nursing and Allied Health
Literature, Medical Literature Analysis and Retrieval System
Online, Public/Publisher MEDLINE, Psychological Information Database, Sportsdiscuss, Excerpta Medica Database,
Allied and Complementary Medicine Database) from 2005
to August 2015 was completed. The risk of bias was assessed
using the Downs and Black Checklist and The Critical
Review Form– Qualitative Studies. Results were summarised
descriptively across eight domains of feasibility: acceptability, demand, implementation, adaptation, practicality, integration, expansion and limited efficiency testing (including effectiveness).
Results: Eleven quantitative studies and one qualitative study
were identified for inclusion. Physical activity interventions
were typically supervised, individualised programmes that
prescribed a variety of activity types for hospital inpatients.
There was evidence that physical activity interventions during the intense phase of cancer treatment were acceptable to
parents and children, safe and successfully implemented. A
trend of positive effects across all aspects of functioning was
noted. Data were unavailable documenting feasibility for the
domains of integration, adaptation and expansion.
Conclusions: There is preliminary evidence that physical
activity interventions are feasible, in that they are acceptable,
safe and potentially beneficial for children with cancer but
more work needs to be done to understand the most effective
ways to implement these types of programmes.
P-416 Investigating Vincristine Neurotoxicity in
Paediatric Haematology/Oncology Patients: A Role
for Genotyping
S. Guram1 , E. Richards1 , B. Messahel1
1 Addenbrookes
Hospital- Cambridge, Paediatric Haematology and
Oncology Department, Cambridge, United Kingdom
Background/Objectives: Vincristine is a vinca alkaloid
which is used as a chemotherapeutic agent for multiple paediatric haematological and solid tumours. This is frequently
complicated by dose-dependent neurological toxicity. Studies suggest that polymorphisms of the CYP3A and ABCB1
genes contribute to vincristine-related neurotoxicity, which
may explain variation in the prevalence of this side effect and
overall prognosis. An established link between mercaptopurine toxicities and polymorphisms led to the incorporation
of targeted genetic screening into therapy, suggesting a potential for tailored vincristine treatment. We aim to identify cases
of vincristine-related neurotoxicity within our patient population, characterise trends in these toxicities and investigate any
demographic influence on these side effects.
Design/Methods: This five year retrospective study from
December 2008 to February 2014 focused on paediatric
patients presenting to our oncology unit who were undergoing
first line chemotherapy for Acute Lymphoblastic Leukaemia,
Low Grade Glioma and Wilms Tumour. These malignancies
were chosen as they had a heavy burden of vincristine in their
treatment protocols. Neurotoxicity was assessed using the
SIOP ABSTRACTS
Common Terminology Criteria of Adverse Events (CTCAE).
Patient records were studied for details of neurotoxicity using
this tool and any subsequent changes that were made to their
dosage of vincristine.
Results: Frequency: There were 66 “neurotoxic events”. A
high incidence of neurotoxic events of grade 1-3 severity
was found with 71% of patients experiencing one or more
events. Motor neurotoxicity was the modal group. Demographic: Toxicity was higher amongst females and the older
age categories. There was an ethnic variation of trend toward
increased toxicity. There was no clear relationship between
tumour type and neurotoxicity. Timing: Two thirds of all neuropathies occurred within the first three months.
Conclusions: This pilot study demonstrates a high rate of
vincristine-related neurotoxicity within a subset of the paediatric haematology and oncology population, warranting a
larger study and potential pharmacogenetic analysis.
P-417 Experience of Using Galactomannan
Testing for Diagnosis of Invasive Aspergillosis in
Immunocompromised Patients from a Tertiary
Care Centre in North India
R. H N1 , V. Dinand2 , N. Radhakrishnan1 , J. Oberoi3 , A. Sachdeva1
1 Sir
Ganga Ram Hospital, Pediatric hematology oncology, Delhi, India;
Ganga Ram Hospital, Department of Research, Delhi, India; 3 Sir
Ganga Ram Hospital, Department of Microbiology, Delhi, India
2 Sir
Background/Objectives: Invasive aspergillosis (IA) is the
most frequent and one of the most lethal invasive fungal infections in high-risk oncology patients. The diagnosis of IA is
difficult and relies in part on the detection of galactomannan
(GM).
Aims and objectives: To study the utility of GM assay in diagnosing IA in paediatric oncology, paediatric critical care and
stem cell recipients. A focus was placed on evaluating the
assay sensitivity, specificity, and negative predictive value in
paediatric patients.
Design/Methods: Retrospective analysis of febrile neutropenia or prolonged febrile episodes in non-neutropenic immunocompromised patients between 1 July 2007 to 31 October
2016 was done. Standard EORTC criteria were used for defining fungal infections. Clinical profile, GM assay, radiological imaging and need for mould active antifungal therapy was
assessed.
Results: 507 patients with 825 episodes of suspected IA
were enrolled in the study. This included 288 haematological malignancies, 78 stem cell transplant recipient and 58
non-oncological patients from paediatric ICU. 9 proven and
25 probable were observed during this period. GM assay was
considered as positive for values >1. The sensitivity, speci-
S357 of S518
ficity and negative predictive value of the assay in diagnosing
IA was 76.5%, 86.5% and 98.8% respectively.
Conclusions: Data suggests that GM assay has a very good
negative predictive value in diagnosing IA. GM EIA testing
may be useful in diagnosing and/or excluding IA in at-risk
paediatric patients, but the low incidence rate of probable
or proven IA in this study precludes the ability to make any
definitive conclusions.
P-418 Correlation Between Galactomannan
Antigen and Absolute Neutrophil Counts in
Immunosuppressed Patients with Invasive
Aspergillosis
R. H N1 , N. radhakrishnan1 , V. Dinand1 , A. Sachdeva1 , J. Oberoi2
1 Sir
2 Sir
Ganga Ram Hospital, Pediatric hematology oncology, Delhi, India;
Ganga Ram Hospital, Department of microbiology, Delhi, India
Background/Objectives: Galactomannan (GM) assay is
being used widely as a diagnostic marker for invasive
aspergillosis (IA) in immunocompromised patients. Most of
the studies of GM have involved severely neutropenic patients,
screened two or three times weekly during a neutropenic risk
period. Time to positivity of Galactomannan depends on the
neutrophil count and which is often ignored while interpreting
the results.
Aims and objectives: The aim of the study was to determine
whether the diagnostic yield of GM was comparable in neutropenic and in non-neutropenic patients with and without
microbiologically documented IA.
Design/Methods: Retrospective observational analysis. The
episodes of IA occurring in the haematology department were
retrospectively classified according to the EORTC criteria as
proven, probable or possible IA. From 1 July 2007 to 31 October 2016, patients data were analysed including the neutrophil
count and galactomannan assays.
Results: 507 patients were enrolled with 825 episodes of
suspected IA. This included 288 patients of hematological
malignancy and 78 stem cell transplant recipients. Thirty
four episodes of proven (n=9) and probable (n=25) IA
were observed. GM was considered positive if value >1
(n=131/824). 255 patients received anti-mould therapy for IA.
When ANC was compared to positivity of Galactomannan in
patients who received treatment for IA, a trend towards higher
GM positivity in lower ANC was observed, although not statistically significant. (45.8% in ANC <50/mm3 , 38.9% in 50100/mm3 , 20% in 101-200/mm3 etc.) In patients who received
mould active antifungals, median ANC in those with GM positive was 273/mm3 and those in GM negative was 330/mm3
(p=0.18). In those who were CT positive for IA, median ANC
in those with GM positive was 309/mm3 and those in GM negative was 572/mm3 (p=0.38).
SIOP ABSTRACTS
S358 of S518
Conclusions: Galactomannan may be falsely negative in
patients with ANC>500/mm3 and this should be kept in mind
while interpreting the Results:
P-420 The Efficacy and Safety of Probiotics in
People with Cancer: An Updated Systematic Review
and Meta-Analysis
H. Hassan1,2 , M. Rompola1,2 , A. Glaser1,2 , S. Kinsey1,2 , B.
Phillips2,3
1 University
P-419 Validation of a Classification System for
Treatment-Related Mortality in Children with
Cancer
H. Hassan1,2 , M. Rompola1,2 , A. Glaser1,2 , S. Kinsey1,2 , B.
Phillips2,3
1 University
of Leeds, Leeds Institute of Cancer and Pathology, Leeds,
United Kingdom; 2 Leeds Teaching Hospital NHS Trust, Depeartment of
Paediatric Haematology and Oncology, Leeds, United Kingdom;
3 University of York, Centre for Reviews and Dissemination, York, United
Kingdom
Background/Objectives: Death not directly due to cancer has
been termed “treatment-related mortality” (TRM). Appreciating the differences between TRM and disease-related death
is critical in directing strategies to improve supportive care,
interventions delivered or disease progression. However, it
is poorly defined and reported in clinical trials. Recently, a
global collaboration developed and validated a consensusbased classification tool and attribution system. This study
aimed to evaluate the newly developed consensus-based definition of TRM and cause-of-death attribution system in a single institution, at a regional paediatric oncology centre in the
North of England.
Design/Methods: Thirty medical records of the most recent
deaths in children with cancer, two and four weeks prior to
death were anonymised and presented to the participants. Two
senior physicians and two clinical research associates independently classified deaths as “treatment related mortality” or
“not treatment related” according to the algorithm developed.
When TRM occurred, reviewers applied the cause-of-death
attribution system. Inter-relater reliability was assessed using
the Kappa statistic (k).
Results: Reliability of the classification was deemed almost
perfect between CRA and consultants (k=0.86, 95% confidence interval 0.72-0.97). Ten deaths were classified as TRM;
of which infection was the most frequent cause identified.
Reviewers disagreed on the primary cause of death (e.g. respiratory vs infection) when applying the cause-of-death attribution system in 6 cases. The study identified how the algorithm may not identify TRM deaths in patients receiving noncurative therapy.
Conclusions: The classification and cause of death attribution
system could be implemented in different health care settings.
Adaptation of the classification tool in patients receiving noncurative interventions and the cause of death attribution system should be considered.
of Leeds, Leeds Institute of Cancer and Pathology, Leeds,
United Kingdom; 2 Leeds Teaching Hospital NHS Trust, Department of
Paediatric Haematology and Oncology, Leeds, United Kingdom;
3 University of York, Centre for Reviews and Dissemination, York, United
Kingdom
Background/Objectives: Probiotics are living microorganisms that confer a health benefit on the host when administered in adequate amounts. This study updates a systematic
review and meta-analysis investigating the efficacy and safety
of probiotics in adult and paediatric patients diagnosed with
cancer.
Design/Methods: An updated systematic review and
meta-analysis was undertaken (PROSPERO registration:
CRD42016050252). Randomised controlled trials (RCT),
identified through screening multiple databases were included
for analyses of efficacy. Non-randomised controlled-trials
and case reports were included for safety analysis. Outcomes
included the reduction in the incidence and severity of
diarrhoea, and adverse events. Where possible, data were
combined for meta-analysis using a random-effects model
and sub-group analysis (including children) undertaken
to investigate strains and dosage of probiotic, and patient
characteristics.
Results: Twenty one studies (N = 2,982 participants) were
included for assessment of efficacy. Results show that probiotics may reduce the incidence of diarrhoea in patients with
cancer [odds ratio (OR) = 0.52, 95% confidence interval (CI)
0.34-0.78, I-sq 36.9%, 5 studies], duration of pyrexia [standardized mean difference 0.64 days, 95% CI 053-0.77, I-sq
0.01%, 5 studies] and possibly the severity of diarrhoea for
example Common Toxicity Criteria grade 3 and 4 diarrhoea
[OR=0.51, 95% CI 0.12-2.2, I-sq 92.5%, 4 studies]. However,
more studies are required to assess the true effect. There were
insufficient data to perform subgroup analysis on children,
strains, and dosage due to marked heterogeneity. Twenty five
studies (N = 2,242) were included in the safety analysis. Five
case reports and a participant from 1 RCT showed probioticrelated bacteraemia/fungaemia/positive blood cultures.
Conclusions: There remain insufficient studies to assess the
true effect of probiotics in people with cancer. Evidence suggests probiotics may be beneficial but further study is still
required, particularly in children.
P-421 Predictive Value of Serum Angiopoietin
1/2, SFLT-1 and VEGF Levels in the Diagnosis of
Sepsis in Febrile Neutropenic Children
SIOP ABSTRACTS
I. Ilhan1 , S. Cakmakci1 , C. Sonmez2 , N. Sari1
1 Dr.
Abdurrahman Yurtaslan Ankara Oncology Training and Research
Hospital, Pediatric Hematology and Oncology, Ankara, Turkey; 2 Dr.
Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital,
Clinical Biochemistry, Ankara, Turkey
Background/Objectives: Febrile neutropenia (FN) is one
of the major causes of morbidity and mortality in patients
with cancer. Endothelial damage and dysfunction is one of
the important features of sepsis. This study sought to investigate the role of serum levels of Angiopoietin-1 (Ang-1),
Angiopoietin-2 (Ang-2), Vascular endothelial growth factor
(VEGF) and Soluble fms-like tyrosine kinase-1 (sFlt1) in predicting the risk of sepsis in febrile neutropenic children
Design/Methods: From January 2014 to December 2016,
we prospectively measured concentrations of ang-1, ang2, VEGF and sFlt1 at onset and after 48 hour of fever in
FN episodes, and evaluated the diagnostic accuracy of these
mediators as predictors of sepsis and bacteriemia.
Results: Eighty-six episodes of FN in 52 patients (F:23,
M:29, median age:7.7 years (0.7-18)) were evaluated. The
most common diagnosis were acute lymphoblastic leukemia
and osteosarcoma (%22), followed by Ewing's sarcoma (%19).
Twenty-nine FN episodes (%34) were complicated with sepsis and in 12 FN episode (%14) an microbiological agent
was isolated. At baseline, Ang-2 levels (160.57 pg/ml, range
15.64-1,111 pg/ml, p=0.02) and sFlt1 levels (1,622 pg/ml,
range 750-3,980 pg/ml, p<0.001) were higher and Ang-1(696
pg/ml, range 11.57-14,452 pg/ml, p<0.001) and VEGF levels
(128.77 pg/ml, range 0-1,001 pg/ml, p<0.001) were lower in
patient group compared to healthy individuals. Serum concentrations of Ang-2 were significantly higher at onset of fever
in patients with sepsis (med:145.82 pg/ml) than in patients
without sepsis (med:75.13 pg/ml, Mann-Whitney test, P =
0.017). There were no statistically significant differences of
Ang-1, VEGF and sFlt-1 levels in patients with noncomplicated FN compared to patients that developed sepsis and/or
bacteriemia.
Conclusions: We conclude that a high Ang-2 level at onset
of fever could be an indicative of sepsis in febrile neutropenic
patients in pediatric cancer population.
P-422 Caregiver Decision Making: A
Comprehensive Approach to “Care and Connect”
V. Inglis1 , S. Richards1 , L. Knox1 , C. Hislop1 , D. Ludwinski2
1 Solving
Kids’ Cancer Europe, Care and Connect, London, United
Kingdom; 2 Solving Kids’ Cancer, Research Advocacy, New York, USA
Background/Objectives: Families with children affected by
paediatric cancer benefit from emotional support and information to empower decision making from diagnosis and throughout disease treatment. Informed decisions are augmented by
S359 of S518
recognition of emotional needs, social well-being, and knowledge of disease and clinical research landscape. Increasingly,
more families are seeking access to clinical trials across borders when options become limited locally. A flexible multimodel approach termed “Care and Connect” for family support is a forward-thinking and unique paradigm developed to
offer comprehensive support to children and their families.
Design/Methods: The “Care and Connect” program employs
a team led by a Family Coordinator to meet the needs of
individual cancer patients and families. This crucial role provides a trusted and experienced parent-professional who listens, identifies key needs, and provides tailored support and
guidance throughout a cancer journey. The support provided
in remit of access to novel therapies at home and abroad
includes assessing and navigating the clinical trial landscape
with the guidance of a researcher/clinician network, treatment
cost negotiations, travel logistics, and annual parent education
conferences to provide insight to current research.
Results: To date more than 190 families worldwide have been
positively impacted by this model, and case studies of three
families presented demonstrate the necessity for flexibility
and illustrate the range of resources required for supportive
cancer care. This multi-model approach directly helped families in making informed decisions with regard to palliative
care, access clinical trial overseas, and improve quality of life
in survivorship.
Conclusions: Families are empowered to make informed
decisions regarding their child's cancer care when this multimodal approach of caring and connecting is applied.
P-423 Hope for Cancer Kids Insurance Program
for Childhood and Adolescent Cancer Treatment in
Kenya
I. Jaboma1
1 Kenya
Hospices and Palliative Care Association KEHPCA, HOPE FOR
CANCER KIDS, NAIROBI, Kenya
Background/Objectives: Hope for Cancer Kids (H4CK) is a
charitable organization in Kenya. One of the most successful
programs H4CK has is Health Insurance program that covers
all costs related to treating any childhood cancer in a Kenyan
public hospital.
Design/Methods: It has been made possible through National
Hospital Insurance Fund(NHIF), a government State Corporation which has provided all Kenyans citizens who have
attained the age of 18 years, with an opportunity to have access
to an, affordable, sustainable and quality health insurance.
H4CK has established a special partnership with the NHIF
to ensure the registration of all children and adolescents suffering from cancer and their families at 5 USD monthly or 60
USD yearly for the whole family, as well as orphans at a subsi-
SIOP ABSTRACTS
S360 of S518
dized rate of 5 USD monthly or 60 USD yearly per 5 orphans.
It has provided a special reduced one month activation period
for all parents registered under H4CK as opposed to the normal three month activation period for any other Kenyan.
Results: As of February 28th 2017, 294 children have benefited from this program, 2 have completed treatment successfully, 270 are still going on with treatment and 22 have died.
H4CK gets about 15-20 new patients monthly in dire need of
this support and most of the children affected in Kenya come
from poor backgrounds. Cancer treatment is very costly; however it has ensured that all children suffering from Cancer can
access treatment
Conclusions: It has resulted in giving hope and motivation to
many parents to take their children to the hospital for cancer
treatment since they are relieved of the financial burden. As a
result more children and adolescents suffering from cancer in
Kenya have been able to access treatment.
dengue haemorrhagic fever during ALL induction and consolidation chemotherapy respectively, in 2010, probably due to a
delay in diagnosing dengue fever. Investigations for dengue
were sent on day 3 or 4 of fever during the 2010 epidemic
while the same was done on day 1 of fever during the 2015
epidemic, contributing to early diagnosis and prompt management of dengue fever and no mortality in 2015.
Conclusions: A high index of suspicion should be kept for
dengue infection in immunocompromised children suffering
from malignancy during the annual epidemics. Aggressive
support is mandatory especially for those under intensive
treatment phase.
P-425 Oral Cryotherapy to Reduce the Incidence
of Severe Oral Mucositis in Children Undergoing
Hematopoietic Stem Cell Transplantation: Results
of a Randomized Clinical Trial
P-424 Clinical Severity of Dengue Fever Relates
to Treatment Intensity in Children with Malignancy
T. Kamsvåg Magnusson1 , L. von Essen2 , J. Arvidson1 , A.
Svanberg3 , K. Mellgren4 , K. Garming-Legert5 , J. Toporski6 , J.
Winiarski7 , G. Ljungman1
P. Jain1 , N. Radhakrishnan1 , V. Dinand1 , A. Sachdeva1
1 Uppsala
1 Sir
Ganga Ram Hospital- Delhi, Pediatric Hematology Oncology, Delhi,
India
Background/Objectives: Clinical spectrum of dengue fever
ranges from mild febrile illness to catastrophic haemorrhagic
fever. Managing dengue fever in children with malignancy is
often challenging. The clinical presentation, course and risk
for mortality is discussed here.
Design/Methods: We retrospectively analysed the data of
children who developed dengue fever while on treatment for a
malignancy (2009-2015). Dengue fever was diagnosed based
on NS1antigen±IgM positivity.
Results: We evaluated 21 patients (Male:female13:8; median
age 8years, range 8months-17years). Underlying diagnoses
included ALL(n=12), AML(n=2), post-HSCT(n=2) and
solid tumours(n=5). Nine were on intensive phase of treatment (4-ALL, 1 day+17 post HSCT for relapsed ALL, 1relapsed AML, and 3-solid tumours). Fever was the presenting complaint in 19/21 patients, followed by vomiting,
abdominal distension, unexplained oliguria and unexpected
fall in platelet counts. Median minimum platelet count was
6,000/mm3 (interquartile range 3,000-9,000) with a mean
time to platelet recovery of 7 days (range 3-13) in children on intensive treatment. Patients not on intensive treatment had significantly higher median minimum platelet count
of 15,000/mm3 (IQR 13,000-93,750; P=0.003) and shorter
mean time to platelet recovery (3 days, P=0.013). Significant bleeding manifestations and severe illness with plasma
leakage were found in 6/9 children on intensive treatment and
1/12 on non-intensive regimen (P=0.02). Two children died of
University, Departmend of Women's and Children's Health,
Uppsala, Sweden; 2 Uppsala University, Departmend of Women's and
Children's Health- Clinical psychology in healthcare, Uppsala, Sweden;
3 Uppsala University, Department of Medical Sciences- Hematology,
Uppsala, Sweden; 4 Sahlgrenska Academy, Department of Clinical SciencesPediatrics, Gothenburg, Sweden; 5 Karolinska Institute, Department of
Dental Medicine, Stockholm, Sweden; 6 Skåne University Hospital,
Department of Clinical Sciences- Section of Pediatric
Oncology/Hematology, Lund, Sweden; 7 Karolinska Institute, Department of
Clinical Science- Intervention and Technology, Stockholm, Sweden
Background/Objectives: Oral mucositis (OM) is a common adverse effect in hematopoietic stem cell transplantations
(HSCT). Oral cryotherapy (OC), cooling of the mouth during chemotherapy infusion, has been shown to reduce OM in
adults but the effect in children has not been evaluated. The
study aimed to examine if OC reduces the incidence of severe
OM (WHO oral toxicity score 3-4) and use of opioids in children undergoing HSCT.
Design/Methods: The study was a multicenter randomized
clinical trial. Children 4-17 years old were randomized to
either OC or standard treatment. The OC-group was instructed
to cool their mouth with ice as long as they could during
chemotherapy infusions with an intended time of at least 30
minutes. Time was recorded by a nurse after each infusion
and the child evaluated the treatment with a purpose-designed
questionnaire. Grade of mucositis was recorded using the
WHO-scale from the day of transplant to engraftment. Use
of opioids was collected from the child's medical chart. Opioid doses were converted to equivalent intravenous doses of
morphine.
Results: Forty-nine children (mean age of 10.7 + 4.2 years)
were included in the study. Twenty-six children were random-
SIOP ABSTRACTS
ized to OC and 23 to standard care. Compliance to OC varied considerably with only15 children being able to use OC
according to protocol. Severe mucositis was reported in 20
children (41 %) with no difference between the two groups.
Children used opioids for a mean of 8.7 + 7.2 days with a
mean total dose of 184 + 262 mg IV morphine. There was no
difference in the use of opioids between the two groups.
Conclusions: OC did not reduce the incidence of severe OM
or use of opioids in children undergoing HSCT. However,
compliance to OC was poor, especially among the youngest
children, which may have influenced the results.
P-426 Establihsing the Dental Needs at Diagnosis
in Pediatric Oncology Patients from Maritimes,
Canada: Results of the E-POD Study
J. Kearns1 , T. Doyle1 , K. Kulkarni2
1 IWK
Health Centre, Pediatric Dentistry, Halifax, Canada; 2 IWK Health
Centre, Pediatric Hematology Oncology- Department of Pediatrics,
Halifax, Canada
Background/Objectives: The recommendation for dental
evaluation and treatment prior to commencement of oncology
therapy is well recognized; however, data on dental needs at
diagnosis of pediatric oncology patients is very scant. This
population based study was designed to assess and report
the oral health status and dental needs of pediatric oncology
patients at the time of diagnosis, as well as the treatment provided.
Design/Methods: After ethics approval, all pediatric oncology patients from the 3 Maritime Provinces managed at the
Izaac Walton Killam (IWK) Health Centre from January 2013
to December 2015 were identified for inclusion in the study.
Part of the routine oncology care plan for patients undergoing
chemotherapy is a referral to dentistry for pre-therapy evaluation.
Data was extracted from (i) Pediatric oncology hospital
database, (ii) Dental Clinic records, and (iii) Electronic medical records. The total number of patients with and without
dental needs at time of diagnosis, treatment rendered, method
of treatment, and caries risk status (CRS) were computed.
SPSS version 24 was used for statistical analysis.
Results: Of the 172 patients, 112 (65.11%)
(male:female::1.4:1, median age: 75 months)were reviewed
by Dentistry and included in the study. Among patients
aged 0-5, 6-11 and 12-19 years, 16.3%, 60.7% and 62.9%
experienced caries respectively. Other dental pathologies
observed were: abscess (n=8), retained primary teeth (n=3),
soft tissue pathology (n=2), and previous trauma (n=2).
High CRS was observed in 56.3% (n=63) while excellent
oral hygiene only in 1.8% (n=2). Treatment was required by
42.9% (n=48) of the patients and was coordinated with other
S361 of S518
procedures in 76%. Twenty eight patients required 1 or more
extractions while 22 received sealants. Type of cancer was
not associated with incidence of caries.
Conclusions: A substantial burden of dental disease requiring
therapy was identified in our study population. Care can be
successfully delivered in a coordinated and multidisciplinary
model.
P-427 Hepatosplenic Fungal Infections in
Children with Leukemia, Risk Factors and
Outcome:A Multicentric Study
H. Kızılocak1 , R. Kebudi1,2 , G. Dikme1 , A. Kalyoncu Uçar3 , N.Y.
Özbek4 , E. Unal5 , N. Sarper6 , T. Patıroğlu5 , N. Yaralı4 , E. Zengin6 ,
Ü. Koçak7 , E. Kürekçi8 , D. Tuğcu9 , E. Uysalol10 , S. Kuruoglu3 , I.
Adaletli3 , T. Celkan1
1 Istanbul
University Cerrahpasa Medical Faculty, Pediatric
Hematology-Oncology, İstanbul, Turkey; 2 Istanbul University Oncology
Institute, Pediatric Hematology-Oncology, İstanbul, Turkey; 3 Istanbul
University Cerrahpasa Medical Faculty, Radiology, İstanbul, Turkey;
4 Ankara Pediatric Hospital, Pediatric Hematology and Oncology, Ankara,
Turkey; 5 Erciyes University Medical Faculty, Pediatric Hematology and
Oncology, Kayseri, Turkey; 6 Kocaeli University Medical Faculty, Pediatric
Hematology and Oncology, Kocaeli, Turkey; 7 Gazi University Medical
Faculty, Pediatric Hematology and Oncology, Ankara, Turkey; 8 Lösante
Hospital, Pediatric Hematology Department, Ankara, Turkey; 9 Istanbul
University İstanbul Medical Faculty, Pediatric Hematology-Oncology,
Istanbul, Turkey; 10 Kanuni Sultan Süleyman Research and Training
Hospital, Pediatric Hematology and Oncology, İstanbul, Turkey
Background/Objectives: Children with leukemia are at
increased risk for invasive fungal infections, including hepatosplenic fungal infections (HSFI). We aimed to assess the
risk factors, treatment and outcome of HSFI in children with
leukemia.
Design/Methods: We retrospectively evaluated the risk factors, diagnostic approach, treatment and outcome of HSFI in
children with leukemia in nine centers in Turkey.
Results: HSFI were seen in 26 children with leukemia (15
female, 11 male); 21 ALL (15 precursor B-ALL, 3 T-ALL,
1 biphenotypic, 1 B-ALL, 1 relapsed), four AML (1 relapse)
and one CML. All cases were diagnosed radiologically with
abdominal ultrasound, that was performed at a median of 9
(1-21) days after febril neutropenia, some also had computerized tomography and magnetic resonance imaging. Twelve
patients had hepatosplenic, five splenic and nine hepatic
involvement. Most episodes occurred at the end of induction in ALL cases. Twenty-two patients had received steroids
prior to HSFI. All cases were diagnosed during evaluation
for persistent febrile neutropenia; three cases had abdominal pain, thirteen cases had back pain extending to the
shoulder. In one patient the liver nodule was excised and
mucor was diagnosed by pathology, in five trucut biopsy
was done. All patients received broad spectrum antibiotics
due to febril neutropenia and various antifungals (liposomal
SIOP ABSTRACTS
S362 of S518
amphotericin B, caspofungin, voriconasole, micafungin,
posaconasole). Fifteen patients had radiologic/microbiology
evidence of fungal infection in other sites (11 lungs, 2 lungskidney, 1 brain, 1 esophagus). Eight patients were transferred
to ICU. Hemophagocytosis was observed in two patients. Two
patients received granulocyte suspensions. Twenty patients
recovered, six died (three due to HSFI, three due to progressive leukemia).
Conclusions: We suggest that an abdominal ultrasound
should be added to the standard recommendation of CT of
lungs, for the evaluation of persistent febrile neutropenia; to
diagnose hepatosplenic fungal infections. Mucor should be
considered in the antifungal treatment spectrum.
P-428 Folate and Vitamin B12 Deficiency in
Children with Acute Lymphoblastic Leukemia in
LMIC'S: Better Nutrition or Supplementation
S. Khera1 , A. Trehan1 , S. Attri1 , R. Jain1 , D. Bansal1
1 PGIMER,
Pediatrics, Chandigarh, India
Background/Objectives: Vitamin B12 & Folic acid (FA)
help in making the cell stroma conducive to the proliferation of the malignant clone. Lower middle income countries
(LMIC's) are fraught with malnutrition and vitamin deficiencies. Refraining from folate supplementation to patients with
malignancies in LMIC's has been questioned. We evaluated
the incidence of vitamin B12/FA deficiency in children on
therapy for Acute Lymphoblastic Leukemia (ALL).
Design/Methods: Children on therapy for ALL were randomly evaluated for serum B12 and folate levels. Serum B12
< 211pg/ml and Folate< 2 ng/ml were taken as deficient. Deficiency status was correlated to undernutrition.[Weight for age
< -2zscore (WHO)].
Results: Hundred children, age 6.5 years (5.8-7.1), 50 each
on maintenance and induction chemotherapy with 50 age/sex
matched controls were evaluated.
Induction Therapy: Eleven of 50 children (22%) were undernourished. Mean B12 levels were 331.3 pg/ml (269.3 to
393.2), with 15 (30%) being deficient, 2 being undernourished. Mean Folate levels were 9.06 ng/ml (7.67 to 10.44) with
1 child being deficient.
Maintenance Therapy: Fourteen children (28%) were undernourished. Mean B12 levels were 500.56pg/ml (419.75 - to
581.37). Deficiency: 5(10%), 3 being undernourished. Mean
Folate levels were 6.61ng/ml (5.56-7.66). Deficiency: 4 (8%),
3 being undernourished. The mean levels of Folate and B12
were lower in children who were undernourished during
maintenance.
There was no difference of B12 & Folate levels between gender and risk groups of ALL. The control group was not deficient.
Conclusions: Childhood under-nutrition in India is 45.9%
with prevalence of B12 & FA deficiency in the general population being 7-33% and 20-33%; with a higher prevalence
in the undernourished. In our cohort 25% had undernutrition.
We had 5% & 20% children with Folate & B12 deficiency.
Patients with undernutrition had greater B12/FA deficiency.
Under-nutrition remains the monster to be tackled in LMIC's.
Countering undernutrition and not supplementation is the key
in LMIC's.
P-429 Central Venous Catheter (CVC)
Dysfuction Requiring One or More Doses of Tissue
Plasminogen Activator is Associated with
Significantly Increased Need of Subsequent CVC
Placement
J. MacLean1 , T. MacDonald1 , C. Digout1 , K. Rigby1 , K. Kulkarni1
1 IWK
Health Center, Pediatric Hematology Oncology- Department of
Pediatrics, Halifax, Canada
Background/Objectives: Dysfunction (defined as inability to
flush and/or draw blood) is common complications of central
venous catheters (CVCs). Tissue plasminogen activator (tPA)
is well demonstrated to reverse CVC dysfunction. However,
the association between number of doses of tPA and requirement of CVCs is not clear. We hypothesized that requirement
of an increasing number of doses of tPA are incrementally
associated with requirement of CVCs in pediatric oncology
patients.
Design/Methods: Data was abstracted for all pediatric oncology patients from the 3 Maritime Provinces managed by
the Izaac Walton Killam (IWK) Health Centre from January
2,000 to December 2,015 after institutional ethics approval.
Patients who required ≥1 CVC were included. Data were
combined from: (i) Pediatric oncology hospital database, (iii)
Electronic medical records, (iv) Pharmacy database and (v)
IWK central line database.
Results: Of the study population (n=741) 26% (n=195)
received ≥1 doses of tPA. Fiftyseven patients received ≥2
doses of tPA. The mean number of CVCs (2.05±1.29 per individual patient, 55% of the patients needed >1 CVCs) required
by patients who received ≥1 dose of tPA was significantly
higher than the mean number of CVCs (1.52±0.95 per individual patient, 32% needed more than 1 CVC) required by
patients who did not receive tPA (p=0.0001). The mean number of CVCs (2.3±1.5 per individual patient, 60% needed
more than 1 CVC) required by patients who received ≥2 dose
of tPA was significantly higher compared to the remainder
(1.6±1 per individual patient) (p=0.001).
SIOP ABSTRACTS
Conclusions: The present study demonstrates that patients
requiring tPA for CVC dysfunction are at an incremental risk
of requiring more CVCs based on the number of tPA doses.
Our observations may indicate that requirement of tPA may
identify patients at higher risk of CVC loss. After validation,
this observation can aid in identification of high risk patients
and designing strategies for mitigation of CVC loss.
P-430 The Feasibility of an Integrated
Experiential Training Program with Coaching by
Healthcare Professionals in Hong Kong Chinese
Children with Cancer: A Phase II Study
K.W.K. Lam1 , H.C.W. Li1
1 The
Univeristy of Hong Kong, School of Nursing, hong kong, Hong Kong
S.A.R.
Background/Objectives: Literature review reflects children
with cancer failing to attain the same physical activity
levels that they had before contracting the disease. Scientific
evidence supports that regular physical activity has beneficial
effects, whereas physical inactivity induces a further increase
in fatigue, muscle catabolism and atrophy. Nevertheless,
increasing concern indicates the increased demand from
families and children, posing specific challenges for implementing interventions during the unique intense treatment
phase. This study aimed to examine the feasibility of an
integrated experiential training program with coaching
by healthcare professionals in promoting regular physical
activity, reducing fatigue and enhancing quality of life among
Hong Kong Chinese children with cancer.
Design/Methods: A randomised controlled trial (RCT), twogroup pre-test and post-test, within and between subjects
design was conducted. A total of 15 children with cancer
(9- to 18-year-olds) was randomly allocated into the experimental group (N=8) and placebo-control group (N=7). Each
participant in the experimental group received home visits
by a nursing student as a coach for 3 months. Those in the
placebo control group received an amount of time and attention (home visits by research assistants) that mimics that
received by the experimental group. The participants’ levels
of cancer-related fatigue, physical activity self-efficacy, muscle strength, depression and quality of life were assessed at
the time of recruitment and 3 months after. Semi-structured
interviews were also conducted.
Results: No statistically significant result but positive trends
were found among the outcome variables in the experimental
group. Qualitative analysis also revealed that the informants
were happy and satisfied to experience less fatigue, improvements in physical activity levels, self-efficacy, muscle strength
and mood. The integrated program was found to be feasible
with no serious adverse effect.
S363 of S518
Conclusions: An integrated experiential training program
with coaching by healthcare professionals was found to be feasible and safe among children with cancer.
P-431 Incidence and Prognosis of Septicemia
after Chemotherapy: A Multicenter Acute
Lymphoblastic Leukemia CCCG2015 Study
Y. Zhu1 , C.K. Li2 , J. Tang3 , X. Zhu4 , J. Yu5 , S. Hu6 , H. Jiang7 , C.
Li8 , X. Zhai9 , X. Ju10 , Y. Fang11 , Q. Hu12 , R. Jin13 , X. Tian14 , C.
Liang15 , N. Wang16 , H. Jiang17 , L. Sun18 , K. Pan19 , S. Shen3
1 Sichuan
University west China second hospital, Hematology Oncology,
Chengdu, China; 2 The Chinese University of Hong Kong, Paediatrics,
Hong Kong, China; 3 Shanghai Jiaotong university school of medicine
affiliated Shanghai children's medical center, Hematology Oncology,
Shanghai, China; 4 Institute of Hematology & Blood Disease Hospital
Chinese Academy of Medical Sciences Peking Union Medical College,
Hematology Oncology, Tianjin, China; 5 Chongqing medical university
affiliated children's hospital, Hematology Oncology, Chongqing, China;
6 Children's Hospital of Soochow University, Hematology Oncology, suzhou,
China; 7 Guangzhou women and children health care center, Hematology
Oncology, Guangzhou, China; 8 Southern medical university affiliated
Nanfang hospital, Pediatrics, Guangzhou, China; 9 Children's hospital of
Fudan university, Hematology Oncology, Shanghai, China; 10 Qilu Hospital
of Shandong University, Pediatrics, Jinan, China; 11 Nanjing children's
hospital affiliated to Nanjing medical university, Hematology Oncology,
Nanjing, China; 12 Huazhong University of Science and Technology Tongji
Medical college Tongji hospital, Hematology Oncology, Wuhan, China;
13 Huazhong University of Science and Technology Tongji Medical college
union hospital, Pediatrics, Wuhan, China; 14 KunMing Children's Hospital,
Hematology Oncology, Kunming, China; 15 Jiangxi provincial children's
hospital, Hematology Oncology, Nanchang, China; 16 Anhui medical
university second affiliated hospital, Pediatrics, Hefei, China; 17 Children's
hospital affiliated to Shanghai jiaotong university, Hematology Oncology,
Shanghai, China; 18 Qingdao university affiliated hospital, Hemnatology
Oncology, Qingdao, China; 19 Xi ’an northwest women and children
hospital, Hematology Oncology, Xian, China
Background/Objectives: Infection related mortality (IRM)
is an important cause of treatment failure after chemotherapy.
China Children's Cancer Group ALL2015 Study conducted a
prospective multicenter clinical trial with chemotherapy stratified according to risk groups. This study aimed at analyzing
incidence and prognosis of septicemia, and factors associated
with IRM.
Design/Methods: Regular reporting of adverse effects (AE)
and serious adverse effects (SAE) are required, septicemia
was pre-defined AE and death as SAE. Annual audit of participating sites included random checking of septicemia episodes.
Results: From 01/2015 to 12/2016, 2,543 subjects from 20
participating hospitals were recruited. A total of 290 patients
(11.4%) were reported septicemia, male to female ratio was
55:45, median age 4 years. Timing of septicemia was induction 183 cases (63%), consolidation 36 cases (12.4%), interim
maintenance/reinduction 71 cases (24.5%). Twelve patients
died and IRM rate was 4.1% (12/290), 2 patients died during induction, 2 during consolidation and 8 during interim
maintenance/reinduction. According to blood cultures, 50.2%
SIOP ABSTRACTS
S364 of S518
were gram positive (Gpositive) (staphylococcus epidermidis
12.9%, staphylococcus aureus 4.9%, streptococcus pneumonia 3.4%, enterococcus 2.3%) and 47.5% were gram negative (Gnegative) (E Coli 12.6%, pseudomonas 8.8%, klebsiella
pneumonia 8.4%, enterobacter cloacae 2.3%), 2.3% fungus
(candida non-albican). Among the 7 fatal cases, 5 were due
to Gnegative and one due to Gpositive and one due to fungus). Interim maintenance/reinduction phase was associated
with higher chance of IRM (P<0.05), there was no association with risk groups, gender and types of organisms.
Conclusions: 11.4% of patients developed septicemia after
chemotherapy, mortality rate was 4.1%. Early institution of
broad spectrum during hospital stay at induction reduced
IRM. Interim maintenance had higher IRM probably related
to out-patient management with possible delay in starting
antibiotics. Gnegative septicemia had higher IRM. Education
of parents and early attention for medical treatment during
interim maintenance should be strengthened.
Supported by VIVA Children's Cancer Foundation (Hong
Kong)
Results: The number fertility preservation consults for female
cancer patients increased annually from five in 2009 to 46
in 2016. Forty-five females underwent OTC, with the number increasing from 3 in 2011 to 13 in 2016. The majority
of patients underwent OTC prior to initiation of cancer treatment. Twenty-four patients were pre-pubertal (mean age 6.5
years, youngest patient five months of age) and 20 were postpubertal (mean age 15.2 years, oldest 22 years). No complications were noted after OTC. The number of tissue vials preserved range from four to 22. More tissue was preserved in
post-pubertal patients, than pre-pubertal.
Conclusions: Ovarian tissue cryopreservation is feasible in
both pre- and post-pubertal patients
P-433 Feasibility and Early Experience with
Testicular Tissue Cryopreservation for Boys
Undergoing Gonadotoxic Treatment
B. Lockart1 , R. Brannigan2 , K. Coyne1 , E. Johnson3 , T. Lautz4 , M.
Reimann5 , E. Rowell4 , V. Scaccia1 , H. Valli6 , K. Orwig6 , Y.
Gosiengfiao1
1 Lurie
Children's Hospital, Hematology/Oncology, Chicago, USA;
Medicine, Urology, Chicago, USA; 3 Lurie Children's
Hospital, Urology, Chicago, USA; 4 Lurie Children's Hospital, Pediatric
Surgery, Chicago, USA; 5 Lurie Children's Hospital, Pediaric Surgery,
Chicago, USA
2 Northwestern
P-432 Feasibility and Experience with Ovarian
Tissue Cryopreservation for Females Undergoing
Gonadotoxic Treatment
B. Lockart1 , K. Coyne1 , T. Lautz1 , M. Reimann2 , M. Reynolds2 , V.
Scaccia1 , K. Smith3 , E. Rowell2 , Y. Goseingfiao1
1 Lurie
Children's Hospital, Hematology/Oncology, Chicago, USA; 2 Lurie
Children's Hospital, Pediatric Surgery, Chicago, USA; 3 Northwestern
University, Reproductive Medicine, Chicago, USA
Background/Objectives: Many children and adolescents
diagnosed with cancer now survive into adulthood. With these
improved outcomes, research demonstrates families are concerned about the impact of treatment on future fertility. In
response to the increasing awareness of familial distress surrounding infertility from treatment, Ann & Robert H. Lurie
Children's Hospital initiated a fertility preservation program
in 2009. The program provides counseling, education, and fertility preservation to patients at risk for infertility due to cancer
treatment or undergoing stem cell transplant for malignant and
non- malignant conditions. Here, we report our experience
with ovarian tissue cryopreservation (OTC) in patients receiving gonadotoxic treatment, including chemotherapy, radiation, or stem cell transplant.
Design/Methods: We reviewed our data on the number of fertility preservation consults provided to female patients since
the start of the fertility preservation program in 2009. Information on OTC performed at Ann & Robert H. Lurie Children's Hospital of Chicago from January 2010 to September
2017 is reported.
6 University
of Pittsburgh, Magee Women's Research Institute, Pittsburgh,
USA
Background/Objectives: Most children and adolescents
diagnosed with cancer will survive into adulthood. With
increased survival rates, research demonstrates that families
are concerned about the impact of treatments on fertility.
In response to increasing awareness of familial distress surrounding infertility from treatment, Ann & Robert H. Lurie
Children's Hospital (LCH) initiated a fertility preservation
(FP) service in 2009. The program provides counseling, education, and FP to patients at risk for infertility due to cancer treatment or undergoing stem cell transplant for malignant
and non-malignant conditions. In August 2015 LCH opened a
testicular tissue cryopreservation (TTC) protocol. We aim to
describe our early experience with TTC.
Design/Methods: We reviewed our data on patients who
underwent TTC at LCH from August 2015 to March 2017.
Results: To date, 15 males (14 pre-pubertal, 1 post-pubertal)
have undergone TTC at LCH. Mean age at TTC was 10.03
years (range 5 months to 18 years). Ten patients underwent
TTC prior to initiation of cancer treatment. Testicular sperm
extraction was attempted on two patients prior to TTC. Of
the five patients who had received chemo, three were treated
with 2.2 gr/m2 or less of cyclophosphamide prior to TTC.
Two patients received non-gonadotoxic chemotherapy. Data
on tissue yield was available for nine pre-pubertal and two
SIOP ABSTRACTS
S365 of S518
post-pubertal patients. A mean of 11 vials of tissue per patient
were obtained (range 4-26). Undifferentiated spermatogonia
stem cells were noted in all tissue. The testicular biopsy was
well-tolerated. One patient developed an incisional infection.
these biomarkers in a risk assessment model that we will test
prospectively in a clinical trial.
Conclusions: Testicular tissue cryopreservation is safe and
feasible in pre- and post-pubertal males prior to and after initiation of chemotherapy. Viable undifferentiated spermatogonia
stem cells were found in samples from all patients undergoing
TTC at Lurie Children's Hospital.
P-435 Development of a Clinical Practice
Guideline for Assessment, Prevention and
Treatment of Pain in Children with Cancer: Phase 1
Funds for testicular tissue processing and freezing were from
the Department of Obstetrics, Gynecology and Reproductive
Sciences, University of Pittsburgh.
P-434 Predictive Value of Procalcitonin and
Interleukin-6 for Bacterial Infection in Children
with Cancer and Febrile Neutropenia
E.A.H. Loeffen1 , H.T. van der Galiën1 , W.J.E. Tissing1
1 University
of Groningen- Beatrix Children's Hospital- University Medical
Center Groningen, Department of Pediatric Oncology/Hematology,
Groningen, The Netherlands
Background/Objectives: Only a third of children with cancer
and febrile neutropenia have a bacterial infection, nevertheless standard care comprises hospitalization and intravenous
antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We
aimed to evaluate the role of Interleukin-6 (IL-6) and Procalcitonin (PCT) in diagnosing bacterial infection in children with
cancer and febrile neutropenia.
Design/Methods: The study population was derived from
a prospective database (2006-2013, IL-8 study) comprising
children with cancer who presented with febrile neutropenia.
From stored plasma samples (taken at admission and/or at
12-24 hours) we determined the PCT and IL-6 levels. Consequently, we explored their relation with presence of bacterial infection (positive blood culture, positive x-thorax or
clinical bacterial focus). We predefined cut-off values, based
on previous research, at 60 ng/L for IL-6 and 0.25 ng/mL for
PCT.
Results: Seventy-seven febrile neutropenic episodes in 55
children with cancer were included, in 18 episodes (23.4%)
a bacterial infection was documented. Both at presentation
and after 12-24 hours, median values of IL-6 as well as PCT
were significantly higher in patients with a bacterial infection
compared to patients without a bacterial infection. With both
biomarkers above cut-off values, sensitivity was 93% (with
either one this was 100%). The identified low-risk group comprised 41% of the population.
Conclusions: PCT and IL-6 are promising markers in identifying bacterial infection in children with cancer and febrile
neutropenia. In a subsequent project, we will incorporate
E.A.H. Loeffen1 , A. Font-Gonzalez2 , R.L. Mulder2 , L.L. Dupuis3 ,
M.D. Van de Wetering2 , L.C.M. Kremer2 , F. Campbell4 , W.J.E.
Tissing1 , O.B.O.T.G.W.G. Pain in Children with Cancer1
1 Beatrix
Children's Hospital- University Medical Center GroningenUniversity of Groningen, Department of Pediatric Oncology/Hematology,
Groningen, The Netherlands; 2 Emma Children's Hospital- Academic
Medical Center, Department of Pediatric Oncology, Amsterdam, The
Netherlands; 3 The Hospital for Sick Children, Department of Pharmacy and
Research Institute, Toronto, Canada; 4 The Hospital for Sick Children,
Department of Anesthesia and Pain Medicine, Toronto, Canada
Background/Objectives: High-quality evidence-based
guidelines for supportive care in children with cancer are
needed. Pain in children with cancer has been identified
as an area where many clinicians seek guidance. We aim
to develop a clinical practice guideline (CPG) for pain in
children with cancer with recommendations on 1) assessment
of pain; 2) pharmacological prevention and treatment of
a) tumor-related pain, b) treatment-related pain, and c)
procedure-related pain; and 3) physical and psychological
prevention and treatment of a) tumor- and treatment-related
pain, and b) procedure-related pain.
Design/Methods: The international and inter-professional
guideline panel is comprised of a core group and six working groups and includes 44 individuals. In phase 1, clinical questions were formulated for each topic and prioritized
(maximum 5 per working group) using GRADE methodology. The scope and possible outcomes for each clinical question were delineated. The critically important outcomes for
decision making for each clinical question were then identified via electronic voting.
Results: The six working groups prioritized a total of 25 clinical questions to be answered through systematic literature
reviews. The number of critical outcomes differed per question, with a minimum of 4 and a maximum of 13.
Conclusions: We have developed the framework for CPG
development. In the next phase, systematic literature reviews
will be undertaken and evidence-to-decision frameworks will
be used to formulate recommendations. We expect to finalize
the guideline in the spring of 2018.
P-436 Efficacy and Safety of Voriconazole
Prophylaxis in Pedeatric Patients with Acute
Myeloid Leukemia in Egypt
SIOP ABSTRACTS
S366 of S518
Y. Madney1,2 , O. arafah1,2 , H. hafez1,2 , L. Shalaby1,2 , I. zaki1,2 , H.
El-Mahalawy2
1 Children
2 National
Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt;
Cancer Institute, Pediatric Oncology, Cairo, Egypt
Background/Objectives: Patients with hematologic malignancies are at higher risk for invasive fungal infections (IFI)
and the incidence of IFI is highest among patients with acute
myeloid leukemia. Early detection and appropriate antifungal
prophylaxis can help to decrease incidence of these infections
and its related complications.
Design/Methods: A double-arms prospective and retrospective historical control arm study included 136 newly
diagnosed Acute Myeloid Leukemia patients treated at the
National Cancer Institute, Cairo university from 2011 to 2013.
Prospective group (75 Patients) received primary voriconazole prophylaxis (prophylactic arm) and compared to 60
patients retrospective control (non prophylactic arm) regarding the infectious complications and incidence of fungal infection.
Results: Median age was 5 - 6 years. Almost all primary
invasive fungal infections (IFI) occurred in lungs. Most of
IFI occurred during induction phase of chemotherapy. Primary prophylaxis with voriconazole had highly statistically
significant impact on reduction of incidence of invasive fungal infection between 2 groups (p value .001), 31 (50.8 %)
of the 61 patients in non prophylactic arm and 5 (6.6 %) of
the 75 patients enrolled in prophylactic arm developed invasive fungal infection. No statistically significant difference
was detected between the 2 groups populations for age, gender, initial TLC, Initial monocytic count, risk stratification and
previous hospitalization on incidence of invasive fungal infections. Fungal related mortality was reported in 8 patients /61
(13%) in non prophylactic arm compared to 2 patients/75 (2.6
%) in prophylactic arm. With median duration of follow up
of 10 months, the overall survival and event free survival for
the whole Group of patients at 3 years were 37.5% and 34.5%
respectively. Voriconazole had an accepted toxicity profile.
Conclusions: Anti fungal voriconazole prophyalaxis significantly reduce the incidence of fungal infections and fungal related mortality in pediatric acute myeloid leukemia
patients However, its effect on overall survival is not as
pronounced.
1 NCI,
Pediatric Oncology, CAIRO, Egypt; 2 Children Cancer Hospital
57357, Pediatric Oncology, Cairo, Egypt; 3 Children Cancer Hospital
57357- Egypt, Pediatric Oncology, Cairo, Egypt; 4 Children Cancer
Hospital 57357- Egypt, Radiology, Cairo, Egypt; 5 NCI, Clinical
Microbiology, CAIRO, Egypt
Background/Objectives: Infections are important causes of
morbidity and mortality in children undergoing antineoplastic chemotherapy especially Acute Myeloid Leukemia
(AML) patients. The overall cumulative risk for bacteremia
and invasive fungal infection (IFI ) increases during induction chemotherapy. Fluoroquinolones (FQLs) significantly
reduced infection-related mortality, fever, and clinically and
microbiologically documented infections. However, the positive effect of antibiotic prophylaxis is associated with an
increased risk of harboring FQLs-resistant bacilli after treatment.
Design/Methods: This is a comparative retrospective and
prospective study that included 136 newly diagnosed Acute
Myeloid Leukemia patients treated at the National Cancer
Institute, Cairo University from 2011 to 2013. The prospective group (Group B) received primary Voriconazole and
Levofloxacin prophylaxis and compared to the retrospective control(non prophylactic arm ) regarding the microbiological outcome and the correlation of bacteremia with
IFI.
Results: No statistically significant differences between both
groups regarding rate of gram positive bacteremia (57.9 %
in Group B, 58.6 % in group A, P value = 0.921) and gram
negative bacteremia (38.9 % in Group B, 41.4 % in group A,
P value = 0.7). Higher incidence of bacterial sepsis (50% in
group B, 36 % in group A, P value .08) and bacterial sepsis
released mortality (61% in group B, 36 % in group A, P value
.07) seen in levofloxacin prophylaxis arm group.
Conclusions: Levofloxacin prophylaxis was associated with
increased bacterial sepsis episodes and bacterial sepsis mortality in our pediatric acute myeloid leukemia patients.
P-438 CT Somatom Force: A New First-Line
Modality to Investigate and Diagnose Chest
Infections in Paediatric Oncology Patients
M. Raju1 , S. Clarke2 , C. Gowdy1 , L. McDonald1 , R. Skinner1 , C.L.
Chapple2 , R. Hill3
1 Newcastle
P-437 Impact of Antibacterial Levofloxacin
Prophylaxis on Clinical Outcome and Blood Stream
Infections during Treatment of Childhood Acute
Myeloid Leukemia
Y. Madney1,2 , O. arafa2 , H. Hafiz1,3 , I. zaky4 , H. elmahalawy5 , L.
shalaby3
upon Tyne Hospitals, Great North Children's Hospital,
Newcastle upon Tyne, United Kingdom; 2 Newcastle upon Tyne Hospitals,
Northern Medical Physics & Clinical Engineering, Newcastle upon Tyne,
United Kingdom; 3 Northern Institute for Cancer Research, Wolfson
Childhood Cancer Research Centre, Newcastle upon Tyne, United Kingdom
Background/Objectives: The sensitivity and specificity of
computer-tomography (CT) imaging, as a diagnostic tool for
investigating chest infections, is superior to plain chest x-rays
(CXR). However, greater radiation exposure, need for seda-
SIOP ABSTRACTS
S367 of S518
tion and additional practicalities precludes the use of CT as
a first-line investigation. We investigated the clinical utility
of, and radiation exposure resulting from, the new Siemens
Somatom Force scanner.
Design/Methods: We undertook a retrospective case-review
of patients with primary/relapsed acute leukaemia diagnosed after August 2012 (n=155), including 98 patients
(63%) enrolled on the UKALL 2011 trial. Clinical episodes
of suspected chest infections were defined as a febrile
patient, investigated with CXR and CT chest. Radiological
reports were reviewed, and radiation effective doses for each
patient were estimated using conversion coefficients from
the dose area product for CXR, and dose length product for
CT.
Results: Fifty-nine separate episodes of CXR followed by
CT chest were identified in 42/155 (27%) patients (median
time between CXR and CT chest; 2 days, range 1-15
days). Twenty-one (36%) CT chests were performed on the
Somatom Force scanner. CT imaging added clinically valuable information in 33/59 (56%) clinical episodes, and where
data was available, subsequent treatment changes occurred
in 17/41 patients (41.5%). Importantly, additional radiation
delivered by the Somatom Force scanner following CXR
was significantly less when compared to conventional CT
(p<0.0001 unpaired t-test; 0.89mSv mean, 0.04-2.11mSv
range versus 4.27mSv mean, 1.51mSv-10.58mSv range,
respectively).
Conclusions: CT imaging provided treatment modifying
information in >40% of acute leukaemia patients with
suspected chest infections. The Somatom Force scanner
enabled reduced investigation time, with significantly less
radiation exposure compared to conventional CT. This
versatile state-of-the-art technology has clear potential as
a first-line investigation for chest infections in a selected
population of immunocompromised patients, where early
diagnosis and appropriately directed treatment may shorten
hospital stay and improve outcomes.
P-439 A Study of Pediatric Cancer Patients Who
Interacted with their School Through Information
and Communication Technology (ICT) during
Hospitalization: The Benefits of ICT Interaction
1
2
T. Masako , S.I. Suenobu
1 Oita
University of Nursing and Health Sciences, Pediatric Nursing, Oita,
Japan; 2 Oita University Faculty of Medicine, Pediatrics and Child
Neurolgy, Yufu, Japan
Background/Objectives: This study focused on pediatric
cancer patients who used ICT during long-term inpatient
care to communicate with their school and analyzed interviews with mothers to elucidate their experiences from hos-
pital admission to re-enrollment and the benefits of ICT
interaction.
Design/Methods: This study was conducted from Jan. 2012
to Oct. 2015. Participants were six mothers of children who
underwent inpatient care for cancer and then re-enrolled in
their school. Three semi-structured interviews lasting about
30 minutes each were held with each participant. The modified grounded theory approach was used for qualitative analysis. This study was approved by the research ethics committee
of the hospital.
Results: The analysis generated a total of 9 categories. The
mothers talked about their [Confusion and difficulties at the
time of hospital admission]. They were satisfied with the
[Positive effects of the hospital school].For [Relations with
the school], mothers consistently communicated with the
school. Regarding [Effects of treatment], mothers described
the stress of witnessing their child endure the consequences
of chemotherapy. The [Benefits of interacting with the
school] included interaction that instilled a daily routine that
conformed to the school schedule. In [Assistance from nurses
in preparation for re-enrollment], mothers were satisfied with
nurses’ joint conferences. [Mothers’ concerns in anticipation
of discharge] included worries about readjustment to school.
[Support from the school] was generous in the sense that
ICT interaction had prepared the school for the child's return
and friends were cooperative in helping the child cope with
school life. [Difficulties and responsibilities of mothers after
discharge] included the difficulty of explaining their child's
illness to others.
Conclusions: The children's interactions with the school
through ICT during hospitalization were a source of reassurance in the re-enrollment process. ICT interaction was beneficial for the school because it helped prepare for the child's
return.
P-440 Incidence of Central Line Associated Blood
Stream Infections (CLABSI) in Peripherally
Inserted Tunneled Central Venous Catheters
(TCVL) Compared with Centrally Inserted TCVLS
A. McCarthy1 , D.L. Spiers1 , D.P. Moriarty1 , V. Wallace1
1 Royal
Belfast Hospital for Sick Children, Children's Oncology &
Haematology, Belfast, United Kingdom
Background/Objectives: Central line associated bloodstream infection (CLABSI) is a frequent cause of morbidity
in paediatric haematology-oncology patients and is associated
with significant healthcare costs. In our unit, single lumen
tunneled central venous catheters (tCVC) are preferentially
inserted into the brachial vein in the antecubital fossa. Traditionally placed central lines are utilised when an adequate
SIOP ABSTRACTS
S368 of S518
vein cannot be found in the arm or when a multiple lumen
line is required.
Design/Methods: We aimed to (i) determine a baseline rate
of CLABSI, (ii) to identify risk factors for infection and (iii) to
examine the differences in rates of infection between insertion
sites
A retrospective review of all patients with a tCVC inserted
between 1st January 2009 and 31st December 2015 was undertaken. Infections were defined as possible, probable or definite, as per CDC guidelines. Logistic regression analysis was
used to establish risk factors and Chi2 tests to compare rates.
Results: Out of 147 patients (mean age 6.5yrs; SD 4.5),
72 children had leukaemia and 75 solid tumours. Overall
line infection rate was 0.65 per 1000 CVC days. Infection
risk was higher in patients with haematological malignancy
(OR 18.75; p<0.001) and with double-lumen lines (OR 9.58;
p<0.005). Subgroup analysis of children with single-lumen
lines and leukaemia showed a trend to lower rate of infection
in arm lines (0.31 vs 1.03 per 1000 CVC days, p=0.06). No
change in infection risk was seen with age, timing of insertion
or neutropenia at time of insertion
Conclusions: We observed a low rate of CLABSI. Risk factors for infection in our cohort were haematological malignancy and double-lumen line. For single-lumen arm lines,
there was a very low rate of infection. Difference in infection
rates with tCVC site has not previously been described, therefore prospective monitoring is required to explore this observation further.
to December 2016 in an oncologic unit. Every procedures
were assigned with or without a preliminary OMT depending on the practitioners working day. Occurrence and duration of PDPH was assessed during 4 day by patient himself or family, using feedback form. Severity of symptoms
was assessed by self-administered visual analogical scales or
hetero-evaluation scales.
Results: A total of 61 LP were studied (27 with OMT and
34 in the group control) on 45 children with a median age of
7 years [4-12.25]. No difference was founded in PDPH incidence (70.4 % versus 70.5 %;p= 0,98). PDPH seemed to be
less severe and shorter (37% of patients had back pain > 2
days without OMT versus 17.6% with OMT, p=0.087); and
14.8% had headache > 2 days without OMT versus 8.8% with
OMT ; p=0.46). Dural and cranial dysfunctions were founded
in more than 80% of cases.
Conclusions: These results did not demonstrate a significant
benefit in using OMT in prevention of PDPH, but a tendency
to reduce intensity and duration of post LP symptoms. Dysfunctions were frequently observed in this population and
OMT deserve to be better investigated as non-pharmacologic
supportive care in pediatric oncology.
P-442 Practical Support for Children Living with
Cancer and Their Families: Increasing Adherance
and Survival Rates
L. Moore1
1 CHOC
Childhood Cancer Foundation SA, Gauteng South Region,
Saxonwold, South Africa
P-441 The Use of Osteopathic Manipulative
Treatment as a Preventive Supportive Care of
Post-Lumbar Puncture Headache: A French
Pediatric Oncology Center Experience
C. Fort1 , K. Michaux1 , I. Lucas2 , A. Berthier2 , P. Marec-berard1
1 Institute
of pediatric Onco-Hematology IHOP, Pediatric Oncology, Lyon,
France; 2 Institute of pediatric Onco-Hematology IHOP, Institut supérieur
d'osteopathie, Lyon, France
Background/Objectives: Post-lumbar puncture headache
(PDPH) is a frequent complication of lumbar puncture (LP)
defined as postural headache occurring within 48 hours of
the procedure and sometime accompanied by back pain, nausea, vomiting and dizziness. The leakage of cerebrospinal
fluid through the dural defect produced by puncture is one
of the etiologic hypothesis. Osteopathic Manipulative Treatments (OMT) on spinal column, in order to soften the dura
mater before LP, could contribute to reduce symptoms.Our
aim is to compare the incidence and severity of PDPH in children undergoing LP with or without preliminary OMT.
Design/Methods: A prospective monocentric study included
children undergoing LP for diagnosis or treatment from April
Background/Objectives: A cancer diagnosis can cause
financial stress to families and result in children not accessing
health services at a paediatric oncology unit thus decreasing
their chances of survival.
For 38 years, CHOC Childhood Cancer Foundation has been
providing holistic care and support to children living with cancer and their families. Key to this is the successful implementation of a comprehensive practical support programme as a
means of relieving the financial burden on a family, as well
as increasing adherence to treatment cycles and increasing
chances of survival.
Design/Methods: Transport funds are issued daily to families
from low-income households. Alternatively accommodation
is provided at CHOC houses for those who live very far. Both
of these ensure that children can get to and from a treatment
centre. Care bags containing toiletries, toys and a parent handbook are provided to families on admission to hospital. Information in the care bag guides parents through the treatment
cycle and where to access relevant resources. On completion
of a needs assessment families are provided with nutritional
support in the form of a food parcel for when they return home.
SIOP ABSTRACTS
Results: Transport funds and accommodation play a significant role in ensuring adherence to and completion of treatment. Empowering families with knowledge helps them to
better understand and cope with the arduous treatment cycle
and therefore adhere to treatment. Food parcels ensure that
children receive and maintain a healthy balanced diet during
treatment. Anecdotal evidence and interviews with paediatric
oncologists and CHOC beneficiaries from 5 different treatment centres in South Africa will be presented to show how
practical support contributes towards increased adherence and
chances of survival.
Conclusions: Practical support, as part of a multidisciplinary
approach to treatment, can reduce the financial burden placed
on the family, increase adherence to treatment which can
increase chances of survival for the child.
P-443 The Quest for Certainty Regarding Early
Discharge in Paediatric Low Risk Febrile
Neutropenia: A Multi-Centre Focus Group
Discussion Study Involving Patients, Parents, and
Healthcare Professionals
J. Morgan1 , R. Phillips1 , L. Stewart1 , K. Atkin2
1 University
of York, Centre for Reviews and Dissemination, York, United
Kingdom; 2 University of York, Department of Health Sciences, York, United
Kingdom
Background/Objectives: A recent systematic review found
that outpatient care for children with low risk febrile neutropenia is safe, with low rates of treatment failure. A metaethnography of qualitative studies suggested that early discharge of these patients may not be acceptable to key stakeholders. The current study aimed to explore experiences and
perceptions of patients, parents and healthcare professionals
involved in paediatric febrile neutropenia care in the United
Kingdom.
Design/Methods: Thirty-two participants were included in
eight focus group discussions in three different centres, purposively selected from a large national survey for differences
in their service structure and febrile neutropenia management.
Analysis was iterative, using a constant comparative method,
with triangulation across centres and participant groups.
Results: Participants described a quest for certainty, where
they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of
certainty provided by strict protocols. Participants assessed
risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of
risk within other situations. The benefits of certainty provided by protocols resulted in frustration at their strict constraints. The perceived benefits and harms of inpatient care
that participants had previously experienced informed their
S369 of S518
appraisals of future treatment strategies. This work demonstrated how statistics identified in systematic reviews are interpreted and used by key stakeholders to assess risk differently,
and how families in particular can view the harms of therapeutic options as different from the outcomes utilised within
the literature.
Conclusions: This study highlighted the previously underestimated harms of admission for febrile neutropenia and the
paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in caring for
these children. It justifies a reassessment of current treatment
strategies for these children and exploration of the introduction of shared decision making.
P-444 Etiology and Clinical Course of Pediatric
Febrile Neutropenia in EL Salvador
S. Mukkada1 , A. Rodriguez2 , S. Fuentes Alabi3 , R.F. Vasquez3 , F.
Marroquin3 , E. Pineda3 , P. Flynn1 , H. Hakim1 , M. Caniza1,4 , R.
Hayden2 , G. Maron1
1 St.
Jude Children's Research Hospital, Infectious Diseases, Memphis,
USA; 2 St. Jude Children's Research Hospital, Pathology, Memphis, USA;
3 Hospital Nacional de Ninos Benjamin Bloom, Oncology, San Salvador, El
Salvador; 4 St. Jude Children's Research Hospital, Global Pediatric
Medicine, Memphis, USA
Background/Objectives: Infection has been identified as one
of the key drivers of morbidity and mortality in pediatric
patients treated for cancer in low and middle income countries
(LMIC). Identifying the causative organisms and clinical evolution of patients with febrile neutropenia has critical implications for empiric therapy in these settings however access to
diagnostic testing, particularly for fungal and viral infections,
is limited.
Design/Methods: We prospectively ascertained the etiology
and clinical outcomes of a group of pediatric cancer patients
presenting with febrile neutropenia in El Salvador. Clinical,
sociodemographic and laboratory predictors of adverse clinical outcomes were additionally collected.
Results: We captured 240 febrile neutropenic episodes from
November 2011 to June 2014. Patients were febrile prior to
admission in 134 (56%) episodes; median delay to admission
was 13.6 hours (IQR 7-27 hours). Fever was categorized as
being of unknown origin in 125 (52%) of episodes, with suspected or proven bacterial etiology in 30% (n=72), fungal
in 3% (n=8), and viral etiology in 14% (n=34) of episodes.
Microorganisms were recovered in 40 evaluable episodes,
with bacteremia diagnosed in 22 episodes and a CVC associated bloodstream infection in 11 episodes. Escherichia coli
was the organism most frequently isolated from blood culture
(n=8), however, coagulase negative staphylococci were identified in 7 positive blood cultures. Mortality due to infection
SIOP ABSTRACTS
S370 of S518
(n=1, 0.04%) and intensive care unit admission (n=12, 5%)
were infrequent.
and menus appropriate to the age groups were suggestions of
themes for news approaches to nutritional counseling.
Conclusions: In this LMIC setting, the etiology of febrile
episodes is frequently unknown, however, morbidity and mortality are low, likely due to prompt empiric therapy. Increased
access to diagnostic tests, particularly for viral and fungal
organisms, may improve diagnostic precision, but their impact
on clinical outcomes and resource use remains unknown. Further investigation, including cost effectiveness analyses, will
be required to optimize management of febrile neutropenia in
LMIC.
Conclusions: Decreased appetite is the most disturbing symptom during treatment and the best way to approach the management of nutritional therapy is individualized verbal guidance. This work was guiding the management of the diet plan
in the oncopediatrics outpatient clinic, contributing to personalized and humanized care in Nutrition, involving and empowering patient/caregivers in the treatment.
P-445 Identifying the Adverse Effects of
Oncological Treatment in Pediatric Patients on
Parents/Caregivers Perception: An Important Tool
to Direct the Therapeutic Plan in Nutrition
J. Nabarrete1 , A.P. Noronha Barrére1 , M. Tanaka1 , F. Lucio1 , B.
Laselva de Sá1 , L.C. Almeida Silva1 , S.M. Fraga Piovacari1 , V.
Odone Filho2 , M. Nicastro1
1 Hospital
Israelita Albert Einstein - Centro de Oncohematologia, Serviço
de Nutrição Clínica, São Paulo, Brazil; 2 Hospital Israelita Albert Einstein Centro de Oncohematologia, Medico Oncohematologista pediátrico, São
Paulo, Brazil
Background/Objectives: There are many symptoms that
may contribute to decreased food intake during treatment, but
not all of them distress the family of the same intensity. Outpatient follow-up provides a greater moment to family participate in nutritional care. Identify which adverse effects are
more impacting and which the better nutritional counseling in
the management of them.
Design/Methods: A prospective study was conducted in July
2015. Through a questionnaire applied to parents or caregivers
when was investigated what symptoms impairs food intake of
children and which nutritional counseling them prefer to be
used to support the management of these symptoms.
Results: A total of 19 questionnaires were answered, 68%
were mothers, 16% were parents and 16% were other people. Among the most frequent diseases were 41% leukemia
followed by 22.7% Lymphomas and 11% Non-oncological
diseases (e.g., Combined Immunodeficiency Syndrome).
Decreased appetite was the symptom most cited (n=13), followed by nausea/vomiting (n=8), mucositis/pain at swallowing (n=7), dysgeusia (n=2), increased appetite (n=1) and
alteration of the gastrointestinal tract (n=1). Individual verbal guidance was the nutritional counseling more mentioned,
followed by practical nutrition workshop, written guidance
and nutrition speeches. In addition, other forms of nutritional
counseling were cited which the exchange of experiences
between patients and the practical nutrition workshops for
children. Guide on the inappetence, feeding in the phases of
life and during the treatment and the presentation of recipes
P-446 Bacterial Infections in Children Treated
for Cancer in South Africa
G. Naidu1 , A. Izu2 , R. Wainwright1 , S. Poyiadjis1 , D. MacKinnon1 ,
B. Rowe1 , S.A. Madhi3
1 University
of the Witwatersrand and Chris Hani Baragwanath Academic
Hospital, Paediatrics, Johannesburg, South Africa; 2 Medical Research
Council, Meningeal and Respiratory Pathogens Research Unit,
Johannesburg, South Africa; 3 Medical Research Council- Department of
Science/ National Research Foundation: Vaccine Preventable DiseasesFaculty of Health Science- National Institute for Communicable Diseases- a
Division of National Health Laboratory Service- Sandringham-, Meningeal
and Respiratory Pathogens Research Unit- University of the Witwatersrand,
Johannesburg, South Africa
Background/Objectives: Introduction: Bacteria commonly
cause infections in children with cancer. This is related to
chemotherapy, stage of disease, immune dysfunction, neutropenia, malnutrition, surgery, and radiotherapy.
Aim: To prospectively delineate the bacterial epidemiology
of infectious morbidity and mortality in children with cancer.
Design/Methods: Methods: Febrile episodes in children
treated for cancer were studied. A history, examination and
a full blood count with differential and a blood culture was
obtained.
Results: Results 169 patients were enrolled, 82 (42.5%) with a
haematological malignancy (HM) and 87 (51.5%) with a solid
tumour (ST), 56.8% male, median age 68.5 months and 10.6%
HIV-infected. 77.5% had at least one microbiologically confirmed septic episode (MCSE), (87.8% HM vs 67.8% ST; p<
0.001) and 528 suspected septic episodes (SSE), with a mean
of 3.1/patient (4 HM vs 2.3 ST; p<0.001). The incidence of
Gram-positive bacteraemia was (77.0 vs 43.7; p<0.001) and
Gram-negative bacteraemia was (74.5 vs 25.8; p<0.001) for
HM and ST. The incidence of MCSE in children with highrisk HM ((109) was 4.01 more than in medium-risk HM (27;
p<0.001). Children with metastatic ST had a higher incidence
(71) of MSCE compared with localized ST (29; aOR: 2.49;
p<0.001). Most children were severely malnourished (76.9%
by MUAC and 56.8% by AMA). The most frequent GPB
isolates were CONS (n=176; 59.1%), Streptococcus viridans
(n=36; 12.1%), and Enterococcus faecium (n=27, 9.1%); and
GNB isolates were Escherichia species (n=64; 26.9%) and
Acinetobacter species (38; 16%), and Klebsiella species (28;
SIOP ABSTRACTS
11.8%). There were 16.8 fungal MCSE/hundred child years,
Candida albicans (n= 28; 62.2%) and Candida parapsilosis
(n=12; 26.7%). Thirteen (7.6%) of the deaths were due to sepsis and all had a HM.
Conclusions: Advanced disease (25% of ST and 61% of NHL
had Stage 4 disease and 78% of children with ALL had highrisk disease) and intensive treatment was independently associated with sepsis.
P-447 Evaluating the Effectiveness of Ketamine
Plus Atropine as Anaesthesia for Intrathecal
Chemotherapy and Bone Marrow Aspiration at
Hospital, Vietnam
H. Nguyen Thi Kim1 , H. Chau Van1 , W. Kazuyo2
1 Hue
Central Hospital, Hue Pediatric Center, Hue, Vietnam; 2 Asian
Children Care's League - Japan, CEO, Tokyo, Japan
Background/Objectives: Ketamine and atropine have
increasingly been used in recent years as an effective form of
deep sedation/anaesthesia in children in developed countries,
but not in developing countries like Vietnam.
This pioneer trial aimed to evaluate the effectiveness of using
ketamine plus atropine as anaesthetic agents for paediatric
oncology procedures. From this study, we establish a protocol for anaesthesia in paediatric oncology procedures.
Design/Methods: A descriptive and prospective study on 103
paediatric patients of both sexes (64 males and 39 females)
aged 7 months to 14 years (median age: 4.0 ± 3.3 years)
and with body weight between 4.5 to 40 kg was carried out
from January 2015 to March 2017. The patients had been
diagnosed with either acute lymphoblastic leukaemia or acute
myeloid leukaemia. They underwent intrathecal chemotherapy and bone marrow aspirations for diagnostic as well as
therapeutic purposes.
Results: The total number of procedures was 381. Bone
marrow aspiration was performed 163 times and intrathecal
chemotherapy given 218 times. 99.7% procedures were successfully. The dose of ketamine and atropine used 1.83 ± 0.25
mg/kg and 0.100 ± 0.013 mg respectively. The time taken for
anaesthesia to wear off was short: 8.5 ± 7.3 minutes. Only
0.26% experienced apnoea, hypotension; 3.1% convulsion;
0.9% nystagmus, and hyperactivity; 1.5% excess salivation,
and dreaming; 3.2 % vomiting; none of the patients had laryngospasm or transient rash. Most of the patients’ parents were
satisfied with the use of anaesthetics.
Conclusions: This is a pioneer trial for children in Vietnam. 2
mg/kg intravenous ketamine and 0.1 mg atropine were found
to be effective and suitable dose in children requiring deep
sedation for painful procedures and produce only minimal
side effects. We established a protocol with the above doses
S371 of S518
and continue to apply this in order to reduce pain, trauma, and
complications and to practice safely.
P-448 Feasibility of Testing Physical Function in
Children with Cancer during Intense Treatment in
the Respect Study and Challenges in Clinical
Practice
M.K.F. Nielsen1 , J.F. Christensen2 , K. Schmiegelow1,3 , T.
Thorsteinsson1 , L.B. Andersen4,5 , M. Faber1 , J. Nersting1 , H.B.
Larsen1
1 Copenhagen University Hospital Rigshospitalet, Department of Pediatrics
and Adolescent Medicine, Copenhagen, Denmark; 2 Copenhagen University
Hospital Rigshospitalet, Centre of Inflammation and Metabolism / Centre
for Physical Activity Research CIM/CFAS, Copenhagen, Denmark;
3 Institute of Clinical Medicine- Faculty of Medicine, University of
Copenhagen, Copenhagen, Denmark; 4 Norwegian School of Sport Sciences,
Department of Sports Medicine, Oslo, Norway; 5 Campus Sogndal, Western
Norway University of Applied Sciences, Røyrgata, Norway
Background/Objectives: Children with cancer exhibit
reduced physical function during and following treatment.
The “Rehabilitation including Social and Physical activity
and Education in Children and Teenagers with Cancer”
(RESPECT) study examines multimodal rehabilitation intervention initiated from diagnosis including physical activity
intervention. Here we discuss feasibility and barriers of
physical function evaluation.
Design/Methods: Seventy-five children (aged 6-18 years
[mean age: 11.3 ±3.1 y]), 61.3% boys diagnosed with cancer from the intervention group were included. At diagnosis
and after three months, participants were scheduled to perform a test-battery including timed up and go (TUG), sit-tostand (STS), flamingo balance, handgrip strength, and cardiopulmonary exercise test (CPET) on a bicycle ergometer.
Results: During the first 3 months 69 (92%) Of 75 children completed at least one test. Adherence rates were 66.7%
for TUG, 71.3% for STS, 77.3% for balance and 80.7% for
handgrip strength. CPET was associated with several barriers, and overall 25.3% of the tests were completed. Failure to complete CPETs was mainly (80.4%) due to medical restrictions (e.g. physician restrictions or side effects)
with motivational and logistic reasons accounting for only
8 and 11.6%, respectively. In 607 completed tests one serious adverse event was observed, with one child who fainted
briefly after CPET. Preliminary results show no change in
VO2 peak (mL/kg/min), and max watt (p>0.1). STS and balance trended to be impaired (P=0.07 and P=0.06 respectively)
and a significant decrease in handgrip strength (p=0.03) and
TUG (p=0.046) were observed.
Conclusions: Evaluation of physical function in childhood
cancer is safe and generally feasible and the children are motivated to participate. However strenuous tests such as CPET
are accompanied by several barriers such as physician restric-
SIOP ABSTRACTS
S372 of S518
tions, side effects and logistic challenges. The preliminary
results suggest that physical activity may prevent a further
impairment of CPET during early treatment. Despite the intervention, strength and TUG declined.
P-449 Outcomes of Events to Support Pediatric
Cancer Patients’ Siblings - Through Collaboration
with a Pediatric Hospital and Nursing University J. Nonaka1 , S. Oka1 , M. Yonayama1 , M. Yamazaki1 , K. Wada2
1 Kanagawa
University of Human Services Faculty of Health & Social Work
School of, Nursing, Yokosuka, Japan; 2 Nursing Care Children Fukushima
Medical University School of Nursing, Nursing, Fukushima, Japan
Background/Objectives: This study examined the outcomes
of sibling support events we held through collaboration with a
hospital specializing in pediatrics and a nursing university.To
examine the contents and outcomes of the events we held at
a hospital specializing in pediatrics annually for 2 years to
support pediatric cancer patients’ siblings.
Design/Methods: Study design: A qualitative, descriptive
study.
Data collection and analysis: The results of observation of siblings before and after the events, in addition to volunteers’ and
families’ comments and impressions, were qualitatively and
descriptively analyzed.
Ethical considerations: Before the start of each event were
provided to obtain consent.
Results: For the events, a sibling support program was developed upon deliberations among team members to clarify its
purpose, particularly points to be conveyed and appropriate
methods to convey them to siblings.The sibling support events
mainly aimed to shine a spotlight on siblings, and provide
them with an opportunity to express their emotions as a protagonist, and learn about a pediatric hospital through enjoyable play activities. The numbers of participants of the first
and second events were 14 (8 males and 6 females) and 13
(3 males and 9 females), respectively, and their age ranged
from 3 to 10 years. There were a total of 20 to 25 volunteers,
including: nursing university faculty members and students;
and CLS.
Conclusions: Future challenges of sibling support:The sibling support program was mainly designed for relatively
young children. Therefore, in the future, it may be necessary to: consider contents for other age groups, developmental tasks, and periods; use different media; and provide effective support in consideration of individual siblings’ situations.
Furthermore, as a method to enhance their self-affirmation
and -efficacy, it may also be important to provide family support, and convey families’ message to siblings. In this respect,
sibling support is likely to contribute to improved family
functions.
P-450 Promoting Treatment Adherence Among
Caregivers at the Paediatric Oncology Unit in a
Teaching Hospital, Ghana
P. Obeng1 , V. Paintsil1 , J. Dogbe1 , L. Osei-Tutu1 , B. Manlokiya1 , C.
Asiamah1 , G. Acquah1 , P. Yamoah2 , A. Osei-Nkrumah1 , L.
Adu-Gyamfi1 , R. Appiah1 , A.A. Abruquah3
1 Komfo
Anokye Teaching Hospital, Paediatric Oncology Unit- Child Health
Directorate, Kumasi, Ghana; 2 Komfo Anokye Teaching Hospital,
Department of Surgery, Kumasi, Ghana; 3 Kumasi Technical University,
Faculty of Health- Department of Pharmaceutical Sciences, Kumasi, Ghana
Background/Objectives: Practical support bears the highest
correlation with adherence. Studies suggest that structural or
functional social support correlates with patient adherence to
medical regimens. Caregivers of children with cancer may
provide medical, financial, spiritual or physical support or a
combination of all these to ensure their adherence to medications. The study objective was to find out the strategies
adopted by caregivers to promote treatment adherence in paediatric oncology in Ghana to improve treatment outcomes.
Design/Methods: The study was cross-sectional prospective conducted at the Paediatric Oncology Unit (POU) at
the Komfo Anokye Teaching Hospital (KATH), Ghana from
October to December 2016. The POU serves about 30 patients
every week. Fifteen patients out of 30 aged 12 years and below
were recruited weekly for 10 weeks. A sample size of 150 was
used for the study. Data on default, adherence and the strategies adopted by caregivers to improve treatment adherence
were obtained after informed consent. Ethical approval was
sought before the study was commenced.
Results: Default rate was 98 (65.3%). Fifty-two (34.7%)
adhered to treatment of which 37 (71.2%) shared their strategies that enhanced treatment adherence.
The strategies for adhering to treatment from the caregivers
perspective were financial and emotional support from family and friends 25 (67.6%), KATH POU 19 (51.4%), church
10 (27.0%) and colleague workers 8 (21.6%). Obtaining
loans from banks 17 (45.9%), education and counseling from
healthcare professionals at POU 8 (21.6%), motivation to save
the children 7 (18.9%) and selling of property 5(13.5%) were
also enumerated.
Conclusions: Financial and emotional support, obtaining
loans from banks, education and counseling from healthcare
professionals at POU, motivation to save the children and selling of property are the strategies adopted by caregivers to promote treatment adherence. A further study on these strategies
will inform outcome improvement interventions.
P-451 Risk Factors for Reluctance of Engagement
in a Self-Management Program Among Childhood
Cancer Survivors
M. Ogasawara1 , S. Saito2 , A. Hayashibe1
SIOP ABSTRACTS
1 Nagano
Children's Hospital, Nursing, Azumino, Japan; 2 Nagano
Children's Hospital, Hematology-oncology, Azumino, Japan
Background/Objectives: The long-term side effects in cancer survivors have been identified as a factor that reduces
patient quality of life and potentially threatens survival.
Accordingly, we have been conducting a self-management
transition program for childhood cancer survivors to provide
a better understanding of their disease and the late effects
related to treatment. Although the program teaches patients
self-management skills to become ready for care as adults,
there has been difficulty with numerous patients due to reluctance to join. We therefore conducted a single-institute study
to investigate the causes of patient reluctance.
Design/Methods: One hundred sixty-six participants were
recruited from Nagano Children's Hospital between June
2011 and March 2017. The inclusion criteria were: 1) discharge following intensive chemotherapy/radiotherapy for
childhood cancer and 2) age >6 years and able to develop
self-management skills. Questionnaire surveys were conducted to determine patient reluctance to engage in the selfmanagement program and medical records were retrospectively analyzed for subject background. Statistical analysis
was performed using the X2 test or two-tailed Fisher's exact
test according to group size.
Results: Of the 83 patients meeting the study inclusion criteria, 23 (28%) showed reluctance to engage in the program. Univariate analysis revealed that onset age <7 years
(p<0.001), absence of guardian support (p<0.001), having
received autologous stem cell transplantation (p<0.05), currently or with a history of receiving treatment related to
late effects (p<0.01), embarrassment of physical condition
(p<0.05), and cognitive or social development abnormality
(p<0.05) were significantly associated with patient hesitance
to participate in the self-management program.
Conclusions: Multiple risk factors contributed to patient
reluctance of engagement in the self-management transition
program. Resolving these issues may improve patient compliance and facilitate the development of self-management skills.
P-452 Potassium Supplementation and
Corticosteroid-Induced Neuropsychiatric Effects in
Pediatric Oncology Patients
H. Pariury1 , J. Willhoite1 , J. Michlitsch1 , A. Agrawal1
1 Childrens
Hospital and Research Center Oakland, Pediatric Hematology
Oncology, Oakland, USA
Background/Objectives: Glucocorticoids play an essential
role in the treatment of multiple pediatric malignancies and
are associated with an increase in behavioral disturbances. We
aimed to investigate the efficacy of utilizing potassium chlo-
S373 of S518
ride (KCl) supplementation to reduce corticosteroid-induced
neuropsychiatric effects among pediatric patients with acute
lymphoblastic leukemia (ALL). Although utilized anecdotally
at some institutions, no prior study has systematically reported
data of potential therapeutic benefit.
Design/Methods: The charts of pediatric patients with ALL
who received KCl supplementation with the intent to reduce
corticosteroid-induced neuropsychiatric effects from 20122016 were retrospectively reviewed, and those with baseline
and follow-up visits were analyzed. Primary outcome was the
degree of behavioral disturbances pre- and post-intervention,
based on the subjective measure of the treating physician and
parents.
Results: Seventeen children were included with a median
age of 5 years. 88.2% had pre-B ALL and the majority were
in maintenance therapy. Nine patients received dexamethasone; eight received prednisone. Patients received KCl, with
a median dose of 0.53mEq/kg/day divided BID, in conjunction with days on corticosteroids. 76.5% of parents reported
improvement in neuropsychiatric effects with KCl supplementation. No side effects were reported.
Conclusions: Oral KCl supplementation appears beneficial in
reducing corticosteroid-induced psychiatric events in children
with ALL, with no reported adverse effects. Other notable
interventions for steroid-induced neuropsychiatric symptoms
include hydrocortisone and antipsychotics, medications with
more potential secondary effects. Future prospective, randomized studies are necessary to better examine this effect with the
goal of reducing the psychosocial impact of corticosteroids on
patients and their families during ALL treatment.
P-453 Evaluation of Renal Function Using the
Level of Urinary Neutrophil Gelatinase-Associated
Lipocaline is not Predictive of Nephrotoxicity
Associated with Methotrexate-Based Chemotherapy
M. Pianovski1 , C. Almeida2 , L. Litchvan1 , D. Carmo1 , T. Tormen1
1 Hospital
Erasto Gaertner, Pediatric, Curitiba, Brazil; 2 Hospital de
Clinicas - HC/UFPR, Pediatric, Curitiba, Brazil
Background/Objectives: Methotrexate (MTX) is one of the
most widely used anti-cancer agents, and administration of
high-dose methotrexate (HDMTX) followed by folinic acid
rescue is an important component in the treatment of a variety of childhood cancers. HDMTX can be safely administered
to patients with normal renal function by the use of alkalinization, hydration and pharmacokinetically guided folinic acid
rescues. Despite these measures, HDMTX-induced renal dysfunction continues to occur. Prompt recognition and treatment
of MTX-induced renal dysfuntion are essencial to prevent
potencially life-threatening MTX-associated toxicities, especially mucositis, myelosuppression and nephrotoxicity. Delay
SIOP ABSTRACTS
S374 of S518
in the diagnosis of acute kidney injury (AKI) using convention biomarkers, like serum creatinine, has been one of the
important obstacles in applying effective early interventions.
Several new biomarkers are being evaluated in a quest for
early diagnosis of AKI, among which neutrophil gelatinaseassociated lipocalin (NGAL) appears to be promising.This
study evaluated and compared if urinary NGAL levels correlated with methotrexate induced nephrotoxicity.
Design/Methods: Single-center prospective study. Changes
in serum creatinine and urinary NGAL were compared at 0
hour, 2 hours, 6 hours and 3 days after receiving HDMTX
intravenous infusions.
Results: Seventeen pediatric cancer patients receiving
HDMTX chemotherapy were studied including 3 who developed injury, classified by Pediatric Risk Injury Failure Loss
End Stage Kidney (pRIFLE). No AKI was registered. Urinary
NGAL did not increase during or after the HD-MTX treatment.
Conclusions: There was no AKI registered by pRIFLE criteria and so NGAL can not be used as an early biomarker for
AKI in this situation.
P-454 Service Evaluation of the Clinical Value of
Routinely Testing Stools for Rotavirus Antigen in a
Regional Paediatric Oncology Unit
T. Akhtar1 , J. Cargill2 , C. Gerrard2 , F. Shaw2 , N. Cunliffe3 , R.
Cooke3 , B. Pizer1
1 Alder
Hey Children's Hospital, Paediatric Oncology, Liverpool, United
Kingdom; 2 Alder Hey Children's Hospital, Microbiology, Liverpool, United
Kingdom; 3 Alder Hey Children's Hospital, Infectious Diseases, Liverpool,
United Kingdom
Background/Objectives: Diarrhoea is common in paediatric
oncology patients; caused by non-infective or infective factors.
Rotavirus is historically the most common pathogen causing
diarrhoea. However, although stool samples are commonly
sent for virology, the value of testing in paediatric oncology
patients with diarrhoea is unclear.
We conducted a service evaluation to estimate diagnostic
yield of rotavirus testing in paediatric oncology patients. It
was felt important to undertake this review following the
introduction of UK-wide rotavirus immunisation in July 2013.
Design/Methods: Computerised microbiology records at
Alder Hey Children's Hospital from January 2010 to December 2016 (seven years) were reviewed retrospectively to examine stool testing for rotavirus antigen detection in patents
treated at a Regional Paediatric Oncology Unit. This review
focused only on rotavirus, as testing for other viruses was not
consistently undertaken. If repeat samples were submitted for
testing within a two-week period, it was assumed to be part of
the same episode and testing was not performed.
Results: A total of 1118 samples were reviewed. After rejecting repeat samples taken within two weeks, a total of 819
samples formed the basis for the analysis. Of these 819
samples, 46 (5.6%) were positive for rotavirus from a total
of 38 patients (age 0-19 years, 19 male; 19 female). The
results by year (positives/numbers tested and percentages)
were as follows: 2010 (15/141,10.6%), 2011 (10/143,6.9%),
2012 (6/132(4.5%), 2013 (8/158, 5.1%), 2014 (5/123,4.1%),
2015 (0/68,<0.1%), 2016(1/54,(1.9%).
Conclusions: A comprehensive service evaluation of all stool
tests performed for rotavirus performed in paediatric oncology patients during a 7-year period has demonstrated that
the incidence of rotavirus positivity has diminished since the
introduction of rotavirus immunisation with only one positive
test out of 122 samples in 2015/2016. Based on these results,
we suggest there is very little utility for routine rotavirus testing in children and young people with cancer presenting with
diarrhoea.
P-455 Invasive Fungal Infections in
Hemato-Oncology Pediatric Patients: A Eleven
Year Review
C. Mata Fernández1 , B. Ponce Salas1 , H. Gonzalo Pascual2 , E.
Rincón López3 , C. Garrido Colino1 , B. Santiago García3 , Y.
Aguilar de la Red1 , T. Hernández San Pelayo3
1 Hospital
Gregorio Marañón, Pediatric Onco-Hematology, 28009, Spain;
Gregorio Marañón, Pediatrics, 28009, Spain; 3 Hospital Gregorio
Marañón, Pediatric Infectious Diseases, 28009, Spain
2 Hospital
Background/Objectives: Invasive fungal infections (IFI) are
a significant cause of morbidity and mortality in children with
hematologic and malignant diseases.
Aim: To describe the epidemiology and outcome of IFIs in
our hemato-oncology unit during a eleven-year period.
Design/Methods: The medical records of pediatric patients
admitted to our hemato-oncology unit between 2006-2016
with an IFI were reviewed. Clinical characteristics of mold
and yeast infections, and their proportion over time were analyzed.
Results: 24 patients were included (62.5% males, median age
6.2 [0.6-11.9] years) in the study. Hematological malignancies were 41.7%, solid tumors 25%, and benign hematological
conditions 29.2%% Overall, 31.7% of patients had undergone
haematological stem cell transplant (HSCT),(90% allogenic),
20.8% had suffered graft versus host disease (GVHD),(60%
acute), 45.8% of them were on antifungal prophylaxis (54.5%
micafungin, 36.4% fluconazole).
Regarding outcomes, 33.3% needed PICU admission and
16.7% died.
SIOP ABSTRACTS
Molds were the most common cause of IFI (62.5%, all bronchopulmonary disease), including 2 confirmed Aspergillus.
Yeasts infections included 44.4% fungemias and 44.4% urinary infections, and were mostly caused by Candida albicans and Candida parapsilopsis. Patients with mold infections
were older (9.32 vs 3.8 years; p=0.010), had higher initial
PCR (8.85 vs 4.7mg/dl; p=0.016), higher incidence of HSCT
(66.7% vs 0%;p>0.01) and GVHD (33.3% vs 0%;p=0.066),
antifungal prophylaxis (73.3% vs 0%; p=<0.001), PICU
admission (46.6% vs 11.1%,p=0.083) and mortality (26.7%
vs 0%,p=0.066).
Comparing the first (2006-2010, 12/24 patients) and second
period (2011-2015, 12/24 patients), the latter had an increased
proportion of mold infections (33.3% vs 91.7%,p=0.007),
which coincided with higher incidence of HSCT (25% vs
58.3%,p=0.225), GVHD (8% vs 33.3%,p=0.190), and antifungal prophylaxis (25% vs 66.7%,p=0.035).
Conclusions: During the second period of time ( 2011-2016)
there has been an increased proportion of mold infections over
yeast infections, with higher severity parameters, along with
more intensive myeloablative chemotherapy regimens and an
increased survival of these diseases in the last decades.
S375 of S518
weight, 28% were stunted and 32% were wasted. Malnutrition
in children with solid tumors was 37% and in children with
hematological malignancies was 32% (p=0.27).45% children
with advanced tumors were malnourished compared to 30%
of children with early disease stage(p=0.001). Results were
non- significant for effect of socioeconomic status and effect
on treatment outcomes.
Conclusions: Prevalence of malnutrition in various studies
at diagnosis varied from 28-36%. In our patients 36% children were underweight, 28% were stunted and 32% were
wasted.Malnutrition is severe with advanced stage of the
malignancies and also when there is lag period from onset of
symptoms to starting treatment.Solid tumors are associated
with greater degree of malnutrition. There is no significant
effect of socioeconomic status on nutrition and there is no statistically significant effect of malnutrition on final outcomes.
P-457 Lifestyle Advice Provision to Teenage and
Young Adult Cancer Patients: The Perspective of
Health Professionals in the United Kingdom
G. Pugh1 , R. Hough2 , H. Gravestock3 , A. Fisher4
1 University
P-456 Prevalence of Malnutrition in Indian
Children with Malignancies- A Retrospective Study
P. Priya1 , A. Gupta1 , R. Seth1 , J. Sankar1
1 All
India Institute Of Medical Sciences, Pediatrics, Delhi, India
Background/Objectives: Malnutrition is commonly seen
in pediatric oncology patients particularly in resource poor
countries.There is paucity of data on factors affecting nutritional status and treatment outcomes with malnutrition. The
present study was done to estimate prevalence of malnutrition
in children with malignancies, to ascertain the degree of malnutrition in hematological vs. non-hematological malignancies,determine factors associated with malnutrition and follow malnourished children of various childhood cancer's for
effect on final outcomes.
Design/Methods: Retrospective review of records of children
6months to 15 years treated at the Oncology clinic at the All
India Institute of Medical Sciences, a tertiary medical institute in India, between January 2014 to December2015 was
done, Relevant data was retrieved and analysed. Children less
than 6 months, with underlying genetic diagnosis/ Immunodeficiency,with associated malabsorption syndromes or chronic
systemic diseases were excluded.
Results: Total of 542(n=542) newly diagnosed children with
malignancies were enrolled in the study period (M:F was
368:174). Children with Retinoblastoma constituted maximum number of patients (47%)followed by acute leukemia,
lymphoma and others. Of the total, 36% children were under-
College London, Department of Behavioural Science and
Health, London, United Kingdom; 2 University College Hospitals NHS
Foundation Trust, Clinical Haematology, London, United Kingdom; 3 CLIC
Sargent, Research and Policy, London, United Kingdom; 4 University
College London, Department of Behavioural Health and Science, London,
United Kingdom
Background/Objectives: There are currently no health
behaviour interventions available in the United Kingdom
to support Teenage and Young Adult Cancer Survivors
(TYACS) after a cancer diagnosis. Formative studies conducted by our group demonstrate that most UK TYACS
desire age-appropriate health behaviour information on physical activity, diet, smoking, alcohol consumption, and sun
safety, delivered in multiple formats, at various time-points
throughout the cancer pathway. Health professionals were also
identified as an important source of information for TYACS.
However, little is known about health professionals’ provision
of lifestyle advice to young people with cancer who are in their
care.
Design/Methods: An online survey was conducted to assess
TYA health professionals awareness of lifestyle guidance and
provision of lifestyle advice to TYACS in their care. Health
professionals views on lifestyle information format and delivery were also explored.
Results: Ninety-five health professionals (44% nurses; 28%
allied health professionals; 17% physicians) completed the
survey. The majority (72%) of respondents were aware of
some lifestyle guidance for cancer patients. However, less than
half of TYA health professionals (46%) were able to successfully recall the source of the guidelines and less than a third
SIOP ABSTRACTS
S376 of S518
(23-27%) reported proving specific advice to the majority of
their patients on some health behaviours. Many health professionals (38%) felt they were not the right person to provide
advice and cited lack of resources as a key barrier to advice
provision. The majority (95%) reported being interested in a
resource containing relevant lifestyle information that could
be given to young people with cancer.
Conclusions: TYA health professionals’ awareness of
lifestyle guidance and provision of advice regarding health
behaviour is sub-optimal. Clear and comprehensive guidance
written specifically for TYA health professionals could
overcome the reported barriers and improve professionals’
confidence in addressing and providing advice on lifestyle to
young people with cancer.
parts in the developed countries. Pain experience may indirectly reflect presentations of childhood cancer, and could be
a surrogate profile for tumor location, metastatic sites, the
degree of treatment intensity, likewise the context of the disease state either at diagnosis, during treatment, or at progression.
P-459 Myocardial Changes in Childhood Cancer
Patients Treated with Anthracyclines
K. Riad1 , F. Ahmad2 , R. Mohamed3 , A. Ali1 , A. Morsy1 , H.
Farghaly2
1 South
Egypt Cancer Institute, Pediatric Oncology, Assiut, Egypt;
University Hospital, Pediatric Department -Cardiology Unite,
Assiut, Egypt; 3 Assiut University Hospital, Clinical Oncology Department,
Assiut, Egypt
2 Children
P-458 Pain Experience Profile in Children with
Cancer: Prospective Analysis of 2216 Treatment
Days in a Developing Country
K. Riad1 , M. Mohamed2 , A. Morsy1
1 South
Egypt Cancer Institute, pediatric oncology, Assiut, Egypt; 2 South
Egypt Cancer Institute, Anesthesiology and Pain Management, Assiut, Egypt
Background/Objectives: Cancer in children is a potentially
curable disease, How to deal with pain is an integral part of
symptom management in pediatric cancer patients in general.
Proper recognition of underlying pathophysiology and various causes of pain are so essential for pain management, and
for ameliorating suffering in the realm of holistic care for children with cancer. The aim of this study is to address and meticulously analyze the spectrum of pain characteristics in children with cancer at an institutional university cancer center
to unravel pain profile in these patients as an experience for a
developing country
Design/Methods: A hospital based, prospective study was
conducted, involving pediatric cancer patients, who presented
with pain due to cancer itself or its treatment in the period
from 2013Jul to 2015 Jan. Evaluation of patients’ documented
pain cycles for pain cause, type, and location & also for pain
treatment characteristics was done.
Results: A total of 286 pain cycles was documented comprising 2216 treatment days (range 3-56 days). Disease-related
pain was the most frequent cause of pain in our study. Oral
mucosa was the most frequent site for treatment-related pain
& strongly correlated with NHL diagnosis. Leukemia was
strongly correlated with “the extremities” as a location of
bone pain. Visceral pain was most often associated with lymphomas. Neuropathic pain was the least frequent type of pain,
however, associated with higher initial pain intensity scores &
longer pain cycle duration.
Conclusions: Children with cancer in the developing countries still have more disease-related pain than their counter-
Background/Objectives: Anthracycline-induced cardiotoxicity in survivors of childhood cancer initially presenting as
sub-clinical cardiac abnormalities that, if left undetected or
untreated, can lead to clinical cardiac dysfunction. The present
study aimed to evaluate the early myocardial changes that
develop with anthracycline therapy
Design/Methods: In this prospective study the preanthracycline and 6-months postanthracycline echocardiographic
and electrocardiographic parameters were analyzed for cardiac dysfunction. The demographic information, including
age, sex, type of anthracycline, and cumulative dose, were
recorded, as well
Results: In this study, 115 patients with childhood cancer,
including 81 males (70.4%) and 34 females (29.6%) with the
mean age of 11.1±3.8 years were enrolled. Their normal baseline and 6-months postanthracycline echocardiographic and
electrocardiographic parameters were compared for myocardial changes. Doxorubicin alone was used in 91 (79%) patients
while daunorubicin alone in 24 (21%). Only 16 children (14%)
received a high dose of anthracycline (cumulative dose >
300 mg/m2 ). QTc interval significantly prolonged 6-months
after chemotherapy than the baseline readings (P<0.001).
There was a significant increase in the left ventricular dimensions, and all myocardial functional parameters were significantly deteriorated in children who received anthracycline
(P<0.001). The incidence of cardiac dysfunction found more
in female patients (20/28; 71.4%). Myocardial dysfunction
was significantly higher among children who received a high
cumulative dose of doxorubicin (P<0.001).
Conclusions: The incidence of subclinical anthracyclinerelated cardiac dysfunction is high. Children treated with
anthracycline require a long-term follow-up to identify and
establish optimal prevention and management strategies that
balance oncologic efficacy with long-term safety.
SIOP ABSTRACTS
S377 of S518
P-460 Correlation Between Multi-Drug Resistant
Organism Colonization and Blood Stream
Infections in Children with Haematolymphoid
Malignancies in a Low-Middle Income Country
P-461 The Utility of a Prognostic Scoring System
in a Resource Limited Pediatric Oncology Setting:
The Adaptation and Implementation of the
Pediatric Early Warning Score
N. Salifu1 , S. Desai1 , B. Arora1 , N. Periera1 , M. Prasad1 , G.
Chinnaswamy1 , T. Vora1 , S. Biswas2 , R. Kelkar2 , G. Narula1 , S.
Banavali1
H. Sankaran1 , V. Gopakumar2 , P. Komoravolu1
1 Tata
Memorial Hospital, Pediatric Oncology, Mumbai, India; 2 Tata
Memorial Hospital, Microbiology, Mumbai, India
Background/Objectives: Colonization with multi-drug
resistant organisms (MDRO) is associated with a higher
morbidity and mortality in children with cancer. The Expert
Group of the 4th European Conference of Infections in
Leukemia (ECIL4) developed guidelines for empirical
antibiotic therapy in febrile neutropenic patients where
‘escalation’ or ‘de-escalation’ strategies are employed based
on colonization with drug-resistant organisms among other
factors. Our unit employed a “de-escalation” policy based on
colonization, due to a high incidence of MDRO blood-stream
infections (BSI). A retrospective audit of this practice was
done to determine its usefulness.
Design/Methods: Records from Jan-2015 to Jul-2016 were
examined. Rectal swabs of all patients registered with
haemato-lymphoid malignancies were obtained within seven
days of presentation. Blood cultures were taken during febrile
episodes from peripheral veins. Central-lines were also cultured, if present. Data was collated and analyzed with descriptive analytical tools.
Results: Rectal swab positivity rate was 78.3% from 3,455
cultures. Incidence of MDRO and extended spectrum betalactamase producing organisms (ESBLO) colonization in
these was 32.0% and 36.6% respectively. Overall 6.63% of
4,490 blood cultures were positive. Paired positive rectal
swabs with positive blood cultures were 253. MDRO colonization was seen in 90(35.6%) of the 253 culture pairs,
while 95(37.5%) patients were colonized with (ESBLO).
Forty-six (51.1%) of patients with rectal MDRO colonization developed MDRO BSIs (p<0.05), while 12(13.3%) grew
ESBLO. Significant association was also seen in 24(25.3%)
patients colonized with ESBLO whose blood culture isolated organisms with same sensitivity (p<0.001). Thirtyfour (35.8%) patients colonized with ESBLO had BSIs with
MDRO.
Conclusions: There is a high incidence of MDRO and
ESBLO colonization at presentation in pediatric hematolymphoid malignancy patients at our center. In those developing BSIs with MDRO and ESBLO, baseline colonization status with these organisms was significantly correlated. A de-escalation of antibiotics strategy would be justified in management of febrile neutropenia in our subject
population.
1 Amrita
Institute of Medical Sciences, Department of Medical Oncology,
Ernakulam, India; 2 Amrita Institute of Medical Sciences, Department of
Nursing, Ernakulam, India
Background/Objectives: The use of pediatric early warning score (PEWS) systems to identify deteriorating pediatric
oncology patients in the developed world has been extensively
studied and implemented. However, many PEWS systems are
complex and difficult to implement in resource limited settings. A prospective study was performed to implement an
adapted PEWS system and reduce pediatric code events.
Design/Methods: Age-dependent physiologic parameters
and qualitative measures (heart rate, respiratory rate, respiratory distress, parental concern, comorbidity, oxygen need,
consciousness) were used to design a PEWS system. The
study period compared primary outcome measures 6 months
before and after implementation of PEWS in October 2016.
Primary outcome measures were defined as pediatric code
events, and sepsis related ICU transfers for PEWS above 5.
Sensitivity and specificity of the PEWS system were calculated at the end of the study period. Testing to determine
health care provider recognition of abnormal age-dependent
physiologic parameters was conducted before and after implementation of the PEWS system.
Results: 101 inpatient pediatric oncology admissions were
available for analysis. Statistical significance could not be
evaluated for the pediatric codes as after implementation there
were no events compared to 4 events before implementation.
The sensitivity of the PEWS system to identify patients requiring ICU admissions was 66.7% with a specificity of 100%
using a PEWS cutoff of 4. Length of ICU stay significantly
decreased (6.1 vs. 4.9 days, p=0.02) after implementation.
Provider recognition of abnormal vital signs increased by 20%
after implementation of the PEWS system.
Conclusions: To our knowledge, this is the first PEWS system
to be implemented in India. This study has demonstrated the
feasibility and benefit of a PEWS system in the Indian environment. Further studies are being done decreasing the PEWS
cutoff score to increase the sensitivity of this tool in our setting
and making this generalizable to other hospitals in India.
P-462 Antibiotic Resistance in Paediatric
Haematolgy and Oncology Patients –Glasgow
Experience: Justification for Adding
Aminoglycoside
SIOP ABSTRACTS
S378 of S518
J. Sastry1 , I. Essa1 , K. Harvey-Wood1 , A. Balfour1
1 Royal
Hospital for Children, Haematology and Oncology, Glasgow,
United Kingdom
Background/Objectives: Bacterial infections are a major
obstacle to the treatment of febrile neutropenia in paediatric haemato-oncology patients. Improvement in management strategies, including the use of broad-spectrum antibacterial drugs targeting Gram-negative bacteria, has reduced
the mortality in neutropenic patients developing blood stream
and other severe infections. However the development of
multi-resistant bacteria, such as pseudomonas aeruginosa
and methicillin-resistant Staphylococcus aureus, Vancomycin
resistant enterococcus pose a major threat for such patients.
This audit aims to determine the prevalence of antibiotic resistance in our unit, where first line agents used are Piperacillin
and tazobactam(Tazocin) and gentamicin
Design/Methods: We collected retrospectively, the results
of microbiological tests from a variety of specimen including blood cultures and the sensitivities to various antibiotics
of positive cultures, over a period of 22 months from January 2014 to October 2015. All paediatric haemato-oncology
patients admitted to the unit were included. The data was
obtained from electronic records kept in the bacteriology
department.
Results: A total of 610 positive microbiological tests were
noted during the audit period of which 207 showed resistance
to one or more antibiotics (34%). 201 blood cultures were positive out of 2217 (9%). 88 of these had resistance to at least
one drug (44%). A total of 126 positive cultures with sensitivity to Tazocin were recorded of which resistance was noted
in 37(29%). 68 positive blood cultures had tazocin sensitivity
reported of which 15 were resistant (22%). Meropenem sensitivity was reported in 121 positive cultures of which 22 were
resistant (18%) Amikacin sensitivity was reported in 96 positive cultures of which 21 were resistant (22%).
Conclusions: In view of the prevalence of high resistance
to Tazocin, the addition of gentamicin is justified in our
unit. Alternatively, single agent meropenem could be considered for those patients where gentamicin is contraindicated.Continued vigilance is essential to choose the appropriate empirical antibiotics
Background/Objectives: Invasive fungal infections (IFIs)
are an important concern in immunocompromised patients
and treatment of these infections can be difficult once established. So emphasis has been placed on strategies of prevention, such as use of high efficient particulate air filter, isolation
and use anti fungal prophylactic drugs. This audit was undertaken to study the prevalence of fungal infections among paediatric haemato-oncology patients and to determine the effectiveness of unit's antifungal prophylaxis in preventing IFIs.
Design/Methods: A retrospective audit involved all the
immunocompromised patients treated in our unit with positive fungal culture or aspergillus PCR over a six month period
between 1st February 2016 and 31st July 2016. The patients
were identified using electronic databases from microbiology and virology department. A proforma was used to collect
clinico-pathological information from the hospital electronic
patient records and case notes.
Results: 107 positive fungal cultures and or aspergillus PCR
tests were detected which translanted into 67 fungal infections from 42 patients (male 24, female 18). 62 of these were
localised (muco-cutaneous) and 5 were IFIs. 56 were candida
(31 albicans, 9 parpsilosis, 6 lambica and 10 others), 3 saccharomyces, 1 aspergillus, 1 monilla and 6 yeast species. Specimen from where fungi were cultured or detected included surface swabs, urine, stools, blood and tissue. IFIs were noted in
3(7.5%) patients (lungs, blood and spleen). IFIs resulted in
ICU admission, splenectomy, loss of CVAD and interruption
of chemotherapy. 6 patients were on anti fungal prophylaxis
and did not develop IFIs.
Conclusions: Most fungal infections were superficial (mucocutaneous). IFIs were noted in minority of patients but
resulted in adverse outcome. Children who were on anti fungal prophylaxis in this cohort, never developed IFIs although
the number was small. Unit's antifungal policy needs to be
aligned with international protocols, to prevent IFIs in those
who are at significant risk.
P-464 Cost and Pattern of Use of Supportive
Care for Pediatric Cancer Patients in Tanzania
M. Tesfaye1 , A. Saxton2 , M. Bhattacharya3 , N. Masalu4 , K.
Schroeder5
1 Duke
P-463 Prevalence of Fungal Infections in
Paediatric Haemato-Oncology Patients:
Effectiveness of Selective Antifungal Prophylaxis,
Glasgow Experience
J. Sastry1 , L. Torrens1 , K. Harvey-Wood1 , A. Balfour1 , E. Davies1
1 Royal
Hospital for Children, Haematology and Oncology, Glasgow,
United Kingdom
University, Pediatric Hematology/ Oncology, Durham, USA; 2 Duke
University, Surgery, Durham, USA; 3 Duke University, Medicine, Durham,
USA; 4 Bugando Medical Centre, Oncology, Mwanza, Tanzania; 5 Duke
University, Pediatric Hematology/ Oncology, raleigh, USA
Background/Objectives: Although supportive and preventive care play a crucial role in the successful management of
childhood cancer, little is known about the use of these interventions in low resource settings and the costs associated with
this treatment. This is essential information for the development of a pediatric cancer program. We examined the usage
SIOP ABSTRACTS
patterns and direct costs for supportive and preventive care
for the treatment of children with cancer in Tanzania at the
Bugando Medical Center, one of only two hospitals in the
country treating pediatric cancer.
Design/Methods: A retrospective chart review of hospital admissions and clinic visits from January 2010-August
2014 was performed. Utilization and cost of preventive
care (laboratory, imaging, and medications to evaluate
and prevent chemotherapy toxicity) and supportive care
(blood transfusions, antibiotics, and infection studies) were
recorded. Conversions from the local currency (Tsh) to
International Dollars (Intl. $) were performed. Tradable
goods (i.e. medications) were converted using the prevailing exchange rate (2189.06Tsh/USD). Non-tradable goods
(clinical & lab supplies). were converted using purchasing
power parity exchange rates obtained from the World Bank
(779.205Tsh/Int $).
Results: Files for 161 patients were available. For chemotherapy encounters, 82% had labs to monitor toxicity, 85% were
prescribed anti-emetics and only 27% received intravenous
fluids. Only 25% of patients receiving cardio-toxic chemotherapy had an echocardiogram. The mean cost incurred for preventive and supportive care was $153 and $43 per patient,
respectively. Taken together, these accounted for less than
20% of total treatment costs.
S379 of S518
Design/Methods: A convenience sample of patients 14-24 yo
and parents (not required to be matched dyads) provided information on demographics, treatment, and the use of and perceived benefit of 13 IM methods. The Attitudes and Beliefs
about Complementary and Alternative Medicine (ABCAM)
scale was used to rate expected benefits, perceived barriers,
and subjective norms. Descriptive statistics were used to summarize scale scores and ratings of IM use. Chi-squared and
t-tests were used to calculate relationships with IM use.
Results: Parent participants (n=140) were 82% female, 70%
non-Hispanic white, and 81% had completed at least some
college. Their children has Mage of 11 and 39% had completed treatment. AYA patients (n= 52) had a Mage of 19;
63% were male, 67% non-Hispanic white, and 50% had completed treatment. Use of IM treatment since cancer diagnosis was 51% for parents and 60% for patients. Expressive arts
therapy was the most commonly reported method among parents (26%) and patients (35%). Ratings of perceived benefit of
IM were high. Parents endorsed wanting relaxation techniques
for their children (79%); AYA patients were most interested in
massage (64%). For parents, reporting IM use was associated
with level of education (p=0.04) and subjective norm score
(p=0.003). Benefits (p=0.001), barriers (p=0.02), and subjective norms (p=0.02) scores were associated with IM use for
AYA patients.
Conclusions: Our findings show that although there is a
capacity to deliver supportive and preventive cancer care to
pediatric patients in Tanzania, these services are not always
routinely delivered to patients. The relatively low cost of these
services demonstrate their merit to be included in pediatric
cancer programs in low resource settings.
Conclusions: Use of IM is common in pediatric oncology and
should be routinely discussed with patients.
P-465 Use of and Beliefs About Integrative
Medicine in a Pediatric Oncology Clinic: Parent
and Adolescent/Young Adult Perspectives
C. Signorelli1 , C.E. Wakefield1 , J.E. Fardell1 , G. Michel2 , J.M.
Jones3 , K.H. Turpin4 , J. Emery5 , J.K. McLoone1 , R.J. Cohn1
L. Schwartz1 , D. Henry-Moss1 , O. Natalie2 , E. Butler1 , P. Nirali1 ,
L.P. Barakat1 , M. Jun3 , J. Tracey1
1 The
Children's Hospital of Philadelpia, Pediatrics/Oncology,
Philadelphia, USA; 2 Philadelphia College of Medicine, Medicine,
Philadelphia, USA; 3 Memorial Sloan Kettering Cancer Center, Integrative
Medicine, New York, USA
Background/Objectives: Integrative Medicine (IM; e.g.,
massage, acupuncture, mediation, herbs) has been explored in
adult oncology, but there is limited such research in pediatric
oncology. Understanding use of complementary therapies in
pediatric oncology, as well as beliefs, barriers, and support of
IM, can help inform how these treatments are discussed with
patients. We aimed to survey parents and adolescent/young
adult patients (AYA) to gauge their use of and perspectives
related to IM.
P-466 Improving the Quality of Follow-Up Care
for Pediatric Cancer Survivors: A Mixed-Methods
Study on Preferences for Models of Survivorship
Care
1 Sydney
Children's Hospital, Kids Cancer Centre, Randwick, Australia;
of Lucerne, Department of Health Sciences and Health Policy,
Lucerne, Switzerland; 3 Hudson Institute, Australian and New Zealand
Children's Haematology/Oncology Group, Clayton, Australia; 4 Paediatric
haematology/oncology, Department of Clinical Haematology/Oncology,
Adelaide, Australia; 5 University of Melbourne, Victorian Comprehensive
Cancer Centre, Melbourne, Australia
2 University
Background/Objectives: As the population of children surviving cancer grows, the importance of promoting essential,
lifelong, survivorship-focused care becomes critical. However, many survivors are disengaged from follow-up care,
mandating alternative models of care to encourage survivor
engagement. To facilitate this, we explored survivors’ and parents’ preferences regarding the delivery of survivorship care.
Design/Methods: Australian and New Zealand survivors and
parents (of survivors aged less than 16 years) completed surveys and optional interviews on their follow-up care prefer-
SIOP ABSTRACTS
S380 of S518
ences. We used multiple logistic regression to identify clinical/demographic associations with preferred survivorship
care.
monitored with the diagnosis of cancer in Ankara University
School of Medicine.
In this cross-sectional study, between February-November
2015, 139 pediatric cancer patients and their families were
applied the survey form face-to-face when they are inpatient
or outpatient clinic.
Results: 403 survivors (mean age: 26.8years) and 207 parents (child mean age: 12.4years) completed surveys, complemented by 107 interviews. 46% of survivors were disengaged
from care (not received cancer-related care in last 2 years), and
reported significantly greater dissatisfaction with the healthcare they were receiving (50% versus 16% of clinic attendees dissatisfied, �2=43.529, p<0.001). Survivors preferred
follow-up clinic after-hours (44.9%), and separate from pediatric patients (31.8%) and from patients on active treatment
(27.2%). End of treatment, one, and five years post-treatment
completion were equally endorsed among survivors as the
preferred timing to begin follow-up care. Survivors’ treating oncologist was the most favored professional for followup (62.5%), and primary care physicians were least preferred
(10%). Survivors who were further from diagnosis (p=0.018),
those who worried more about risk of recurrence (p=0.044),
who reported fewer late effects (p=0.011) and had more
unmet information needs (p=0.044) were more likely to prefer oncologist-led versus primary- or nurse-led survivorship
care.
Results: Mean age was 8.65±5.51(min:0.5,maks;18) years,
54.7% were male. The average age of patients which use
CAM was 10.6±5.42, while mean age was 7.9±5.39(p<0.05)
for didn't use CAM group. Patients with lower socioeconomic status were tend to use more CAM. Advanced
staged patients were found to have increased frequency of
the use of CAM. All patients participating this study have
mentioned about praying. About 27% of the patients were
using other CAM methods as well. The patients that used
CAM mostly used honey (59.5%), bee pollen/milk (56.8%)
and molasses (%45.9). Almost 38% of the families were
found to have applied for religious help for their patients
(Hodja reading holy passages which are believed to be
beneficiary). About 38% of the patients using CAM have
informed their doctor. The most common reason of not
consulting to physicians was thought of possible rejection
(78.3%).
Conclusions: Incorporating survivors’ preferences into future
models of care may improve engagement in essential followup, as well as satisfaction with care, ensuring survivorship
needs are better met. This may help reduce the long-term
physical and psychosocial burden on survivors following
treatment for pediatric cancer.
Conclusions: Most of patients are using CAM methods without the knowledge of physicians. None of the patients use
CAM instead of medical treatment. All of the patients that
admitted to hospital must be sufficiently informed,possible
side effects of CAM and should given opportunity discuss
with their doctors.
P-467 The Use of Complementary and
Alternative Medicine Among the Pediatric Cancer
Patients in Ankara University School of Medicine
Pediatric Oncology Clinic
I. Bulut1 , N. Tacyildiz2 , E. Unal3 , H. Dincaslan4 , G. Yavuz5
1 Ankara
University Med School, Pediatrics, Ankara, Turkey; 2 Ankara
Üniversity Faculty of Medicine, Pediatric Oncology, Ankara, Turkey;
3 Ankara University Med School, Pediatric Oncolgy, Ankara, Turkey;
4 Ankara University Med School, Pediatric Oncology, Ankara, Turkey;
5 Ankara University School Of Medicine -Ufuk University School of
Medicine, Pediatric Oncology, Ankara, Turkey
Background/Objectives:
Complamantary
Altarnative
Medicine (CAM) is mostly traditional treatment modalities
that most of the cancer patients may involve either informing
their doctors or not. Since some of these treatment modalities
may interfere with chemotherapy it is important to know if
the patient is getting any of them.
Design/Methods: Frequency and reasons of the use of CAM,
types of CAM method, socio-demographic characteristics of
the patients that use CAM among the children that are being
P-468 Improving Function in Pediatric Cancer
Survivors: The Lasting Impact of the Stoplight
Program
L. Tanner1
1 Children's
Hospitals and Clinics of Minnesota, Physical Medicine and
Rehabilitation Services, Minneapolis, USA
Background/Objectives: Survivors of pediatric acute lymphocytic leukemia (ALL) can have muscle strength deficits,
symptoms of peripheral neuropathy, and range of motion limitations months to years after treatment. A proactive physical therapy intervention, The Stoplight Program (SLP) was
implemented at a single institution with the goal of preventing and minimizing these deficits in body function and activity limitations. Children who completed the SLP during their
ALL treatment tested within healthy norms for developmental age. In this follow-up study, we continued to measure their
function after treatment to evaluate the longer term impact
of the SLP. The study objective was to measure body function and activity limitations in ALL survivors who completed
the SLP and compare them to a historical control group of
SIOP ABSTRACTS
ALL survivors who completed their cancer treatment before
the SLP was implemented
Design/Methods: In this quasi-experimental study, two
cohorts of pediatric ALL survivors ages 5 to 18 years were
assessed 18 to 24 months after completing ALL treatment.
Measurements were administered by a physical therapist and
included the Bruininks-Oseretsky Test of Motor Proficiency
and ankle range of motion (AROM). An independent-samples
t-test was used to assess differences between groups and correlations were analyzed between AROM and motor tests results.
Results: The historical control group and SLP intervention
group did not differ significantly in mean age (9 years) or time
off ALL treatment (20 months). The SLP group had significantly better AROM (p = .001) and scale scores for bilateral
coordination (p = .05), running speed/agility (p = .01), and
strength (p = .02). AROM had a positive correlation with survivors’ strength/agility percentile rank.
Conclusions: The SLP is an innovative, proactive physical
therapy intervention that continues to significantly impact
children after ALL treatment. Creative approaches are needed
to support the healthy development of children during and
after cancer treatment.
P-469 Barriers to Effective Nursing Pain
Management and Assessment of Children with
Cancer on the Paediatric Oncology Unit, at the
Korle-Bu Teaching Hospital, Accra Ghana
B. Tieku-Ward1 , W. Eyiah-Mensah1
1 Korle
Bu Teaching Hospital, Department of Child Health, Accra, Ghana
Background/Objectives: The level of pain assessment and
management among nurses is recently on the decline. This
study sought to find out barriers to effective pain assessment
and its management.
Design/Methods: Ten nurses who are working at the pediatric
oncology unit of Korle -Bu Teaching Hospital were randomly
selected for this study.
Results: Majority of the nurses, sixty percent was within the
age bracket group thirty- one to fourty years. Eighty percent
have obtained their bachelor's degree in nursing and majority has more than five years’ experience in oncology nursing.
The research revealed that nurses are most abreast with the
use of analgesics as pain management skills as to psychosocial and diversional therapy. Thus, unavailability of analgesics
(morphine) because some parents cannot afford, is a barrier
to effective pain management. Most often children are only
assessed at the onset of their pain when they cry or verbalize it. Twenty percent of nurses noted that pain assessment
tools are not readily available on the unit. Ninety percent of
the nurses do not find the pain assessment procedure time consuming. Sixty percent perceive that the female patients exag-
S381 of S518
gerate pain in order to get morphine, thus the fear for administering opioid. According to seventy percent of the nurses,
doctors are not willing to prescribe morphine when suggested
after a pain assessment and it is thus a barrier to further pain
management and assessment.
Conclusions: In conclusion, nurses need further education on
early identification of pain in children and infants with cancer
by the use of Behavioral Pain Assessment Scale (FLACC),
since pain is effectively managed when detected early, as well
as, to assess and manage pain consistently on the ward. Funds
should be raised to support parents in purchasing morphine.
Diversional therapy activities like puzzle games is encouraged
in the unit.
P-470 Validation of the Oncological Pediatric
Early Warning Score (O-PEWS) on Critical
Patients with Haemato-Oncological Diagnosis
A. Tondo1 , C. Rosa1 , F. Melosi1 , C. Favre1 , C. Cecchi1 , F.
Trevisan1 , V. Bertozzi1
1 Universita
degli Studi di Firenze, Pediatric Oncology and Hematology
Unit, Firenze, Italy
Background/Objectives: Patients with oncologicalhaematological diagnosis are subject to potentially fatal
complications. In the last years a scoring system has been
developed, based on rapidly assessable clinical parameters,
called Pediatric Early Warning Score (PEWS), to detect
critical events in a timely manner and rapidly activate the
emergency team. This study aims at finding an adaptation
of this system for the pediatric patients with haematooncological diagnosis, called Oncolgical-PEWS (O-PEWS),
and evaluate its accuracy in reflecting the level of clinical
impairment of the observed patients.
Design/Methods: We modified the PEWS in order to include
clinical parameters that reflect the neurocognitive, cardiovascular, respiratory and urinary state of the pediatric patients
with haemato-oncological diagnosis. A retrospective pilot
study has been conducted on twenty-six patients that required
admission in the Pediatric Intensive Care Unit (PICU), measuring the O-PEWS scores at admission and correlating those
scores with the outcome.
Results: The patients that were admitted in the PICU with
a lower score (average O-PEWS = 7/15) reached a better
outcome. The survival rate proved lower (31% vs 69%) in
patients with higher score at admission (average O-PEWS =
9/15), correlating with negative prognostic factor such as use
of mechanic ventilation and ultra-filtration.
Conclusions: This pilot study demonstrated that the
Oncological-PEWS is capable of predicting the clinical seriousness of the pediatric patients with haemato-oncological
diagnosis. We are now conducting a perspective multicenter
SIOP ABSTRACTS
S382 of S518
observational study aiming at a more consistent validation
of the O-PEWS and of its ability of precociously identify
all those patients that require an emergency consult and a
potential take on responsability of the patient by the PICU.
P-471 Alternative and Complementary Medicine
Use Among Pediatric Patients with Oncological
Diseases in a Latinamerican Country
M. Velazquez-avina1 , A. Chena-Sánchez1 , J. Peñaloza-González1
1 Hospital
Juárez de México, Pediatric Oncology, Mexico City, Mexico
Background/Objectives:
Alternative/Complementary
Medicine (ACM) refers to medical practices that are not in
accordance with the standards of the medical community.
ACM use is frequently used by patients with chronic or
catastrophic diseases, but the treating physician ignores its
use. The reported frequency of use in Mexico ranges from
30% to 84% according to various surveys.
Design/Methods: We included patients from the Pediatric
Oncology Service at our institution who had been receiving
treatment for at least three months. A structured questionnaire
was administered in person by a single interviewer (pediatric
oncologist). We recorded the cancer type, ACM used, and parent/guardian age, and education level. We present descriptive
statistics of the sample and clinical findings as means ± standard deviation, and proportion comparisons with Pearson's
chi-square test.
Results: Of the 133 parents interviewed, 84.2% used some
form of ACM. Herbs and minerals were the most frequently
used (35.3%), followed by diet and nutrition (25.6%) and
mind, body, and spirit (19.5%) therapies. The most frequent
cancers were hematological malignancies in a proportion 3:1
versus solid tumors. The parents education level was not associated with more frequent ACM use, nor did mother's age.
Father's age was significantly related to more frequent ACM
use, especially if they were 40 years-old or older.
Conclusions: Our study population used very frequently
ACM as an adjuvant therapy, in both, hematological and solid
tumors. No subject attempted to abandon conventional treatment and rely solely on ACM. This study may lead to further
studies that assess the results obtained from patients receiving
ACM.
Background/Objectives: Approximately 80% of patients
with childhood cancer and chemotherapy treatment will have
an episode of febrile neutropenia (FN). The percentage of positive blood cultures is correlated with the risk of overall infection.
The purpose of the present study is to describe the percentage
of positive blood cultures and the infectious disease agent.
Design/Methods: We reviewed all blood cultures of patients
with childhood cancer from August 2015 to December 2016 at
our institution. We described percentages of negative or positive blood cultures and identified the disease agent in case of
positive testing.
The demographic and clinical characteristics are described as
means or proportions according to variable type.
Results: We included 171 blood cultures. The patient average
age was 10.4 years. In 52% of the cultures the result was negative, and 48% were positive. Fifty-one percent of our patients
were female and 49% were male. According to the type of
cancer, high-risk acute lymphoblastic leukemia represented
42.1% of our population, osteosarcoma 22.8%, 9.9% germ cell
tumors and the rest were patients with Hodgkin disease and
rhabdomyosarcoma.
Gram positive bacteria were isolated in 53.9% of positive cultures, and Gram negative bacteria in 46.1% of positive cultures. The most frequent Gram positive bacteria was Staphylococcus epidermidis followed by Staphylococus aureus and
Staphylococcus hominis. The most frequent Gram negative
bacteria was Escherichia coli followed by Klebsiella pneumoniae, and Acinetobacter baumanii. Gram positive bacteria were more frequently isolated in female patients, whereas
Gram negative bacteria were most frequently isolated in male
patients.
Conclusions: The percentage of positive blood cultures in
our practice is relatively high compared to other series. The
most frequent infectious disease was a Gram positive agent.
Although not statistically significant, we found a difference
of disease agent according to gender.
P-473 Nutritional Status of Children with Cancer
at Diagnosis in Brazil
K. Viani1 , M. Neto Rafael1 , G. Bouchabki1 , A.C. Oliveira1 , B.
Manzoli1 , V. Oliveira1 , E. Ladas2 , R. Barr3 , V. Odone Filho4
1 Instituto
P-472 Infectious Disease Agents in Febrile
Neutropenia in Patients with Childhood Cancer at a
National Refrence Hospital
M. Velazquez-avina1 , M. Huitrón-Hernández1 , J.
Peñaloza-González1
1 Hospital
Juárez de México, Pediatric Oncology, Mexico City, Mexico
de Tratamento do Câncer Infantil ITACI- Hematology-Oncology
Division - Instituto da Criança do Hospital das Clínicas- Sao Paulo
University Medical School, Nutrition, Sao Paulo, Brazil; 2 Columbia
University, Division of Pediatric Hematology/Oncology/Stem Cell
Transplant, New York, USA; 3 McMaster University and McMaster
Children's Hospital- Hamilton Health Sciences, Department of Pediatrics,
Hamilton, Canada; 4 Instituto de Tratamento do Câncer Infantil ITACIHematology-Oncology Division - Instituto da Criança do Hospital das
Clínicas- Sao Paulo University Medical School, Department of Pediatrics,
Sao Paulo, Brazil
SIOP ABSTRACTS
Background/Objectives: The relationship between nutritional status (NS) at diagnosis and survival in pediatric oncology has been described by several authors. Considering the
overall importance of NS in these patients, the objectives of
this study were: to determine the NS of children with cancer at
diagnosis; compare the NS between patients with solid tumors
(ST), hematological malignancies (HM) and central nervous
system tumors (CNST); and compare the NS distribution by
two different anthropometric parameters.
Design/Methods: This is a retrospective cross-sectional
study. Data on weight, height and mid-upper arm circumference (MUAC) measured within 7 days of diagnosis were collected from the nutrition service records of a hospital in Sao
Paulo, Brazil. For comparison, NS was classified by both body
mass index z scores (BMIz), using WHO growth charts, and
MUAC percentiles. NS classifications by BMIz and MUAC
were compared using the Chi-square test.
Results: We included 370 patients in the study, mean
age 7.8(±5) years. The diagnoses distribution was: 56.5%
(n=209) HM, 27.8% (n=103) ST and 15.7% (n=58) CNST.
Overall, according to BMIz, 14% patients were below adequate, 79.8% adequate and 6.2% above adequate, whereas
MUAC percentiles classified 12.4% as below adequate, 78.3%
adequate and 9.32% above adequate, without statistical difference between the anthropometric parameters (p=0.726).
Regarding patients with HM, ST and CNST, the groups were
equivalent by BMIz (p=0.142). However they differed in
MUAC percentiles (p=0.006). Although HM presented no
divergence between BMIz and MUAC (p=0.698), more children with ST were under-nourished by MUAC (24.7%) than
BMIz (15.6%), p=0.075, while the reverse was true for CNST
(MUAC 7.8%, BMIz 21.8%, p=0.011).
Conclusions: The undernutrition prevalence in our study was
2 to 3 times higher than in the general population of Brazilian children/adolescents, especially in patients with ST and
CNST. MUAC appears more sensitive than BMIz as indicator of undernutrition at diagnosis for patients with ST.
P-474 Screening of Vitamin D Deficiency in
Children with cancer. Cause or Just a Consequence
of Malignancy? L.P. Xalafova, R.S. Ismayilzade
National Center of Oncology (NCO) of Azerbaijan
L. Xalafova1 , R.S. Ismayilzade1
1 Pediatric
Clinic of the National Center of Oncology (NCO) of Azerbaijan,
Baku, Azerbaijan
Background: Recent studies have identified an important
function of vitamin D (VD) in regulation of cell proliferation
and differentiation, and apoptosis. In addition vitamin D deficiency (VDD) has been linked to an increased cancer risk,
prompting us to screening of VDD in children with cancer.
S383 of S518
Procedure: From 06.02.2015 to 28.02. 2017(24 months) in
our center a survey was done of 191 children. Level of VD,
age, sex, time of sampling and presence of malignant tumor
were determined.
25-hydroxyvitamin D (25-OH-D) concentrations in the serum
were measured in all patients at the time of diagnosis
and during treatment and levels were categorized as normal (>=30ng/ml), insufficient (20-29ng/ml), or deficient
(<20ng/ml). The timing of sample collection was classified
into four seasons. The age ranged from 4 months to 21 years.
Results: We evaluated a total of 191 patients for this study:
131(68.57%) had a diagnose malignancy and 60(31.41%)
had non-malignant disorders (NMD). VDD was detected
in 101(77.1%) of the patients with malignancy. Particularly
alarming was the fact that VDD in 14(13.86%) patients was
detected prior to the start of treatment. VDI was identified
in 19 cases (14.5%), and normal levels had only 11 patients
(8.4%).The boys 59(58.42%) prevailed over girls 42(41.58%).
More than 50% of VDD were determined in children aged 715 years (54.46%). In 60 children with NMD VDD was determined in 32(53.33%) and VDI in 14(23.33%) cases.
Conclusion: Azerbaijan is a country with 2700 sunny
hours/year. Despite this, we discovered VDD cases in 77.1%
of pediatric cancer patients and 53.33% of children with NMD
in our survey. Further research is needed to determine whether
the VDD is a cause of malignancy or just a consequence of it.
Our study supports intake of vitamin D for possible prevention of cancer in children.
P-475 Verification of the Knowledge of Dietary
Therapy of the Care Team: A Strategy of
Continuing Education for a Pediatric Oncology
Hospital
L. Xavier Del Rio1 , M. Santos Murra2 , N. Duran Leite2
1 Barretos
Cancer Hospital, Nutrition, Franca, Brazil; 2 Barretos Cancer
Hospital, Nutrition, Barretos, Brazil
Background/Objectives: There are many questions related
to nutrition in the clinical practice of the multidisciplinary
team. Investigating doubts and implementing interventions
could be ways to address uncertainties and minimize errors
related to nutritional support. The aims of the study was
to investigate, evaluate and describe the knowledge related
to nutrition in the nursing and nutrition and dietetics teams
of a children's cancer hospital, before and after educational
interventions.
Design/Methods: The teams to be approached were defined,
corresponding to cupbearers/ kitchen assistants and nurses/
nursing technicians of the Intensive Care Unit, Hematopoietic
Stem Cell Transplantation and ward. Two questionnaires were
prepared, one for each team, and applied on the first day (D1).
SIOP ABSTRACTS
S384 of S518
Two interventions occurred at D7 and D14. Subjects such as
neutropenia, types of diets and feeding routes, were discussed.
A second questionnaire application occurred on the D75.
The results were analyzed with the statistical package SPSS
21.0.
Results: Forty-seven professionals participated in this study.
However, only fifteen performed the second questionnaire.
The scores obtained by the nutrition and dietetics team in
the first questionnaire were 2.0 to 6.0 points (poor to regular grades). The nursing team's scores were 1.0 to 5.0 points
in the first moment (poor to bad grades). There was a significant increase (p <0.05) in scores of the second questionnaire
for both teams, going from 5.0 to 7.0 (regular to good grades)
for the first team and 3.0 to 9.0 (bad to great grades) for the
second team. In comparison of the demographic characteristics of the nursing team, the sector and the working time were
statistically different for those who answered the second questionnaire.
Conclusions: Good retention rates have been demonstrated
for those who participated of all stages of the study, but it is
necessary to associate the theory with the practice performed
by the teams.
T R E AT M E N T A N D CA R E PA L L I AT I V E CA R E
P-476 Evaluation of the Acute Biochemical
Changes in DLBCL Patients Treated with and
Without Rituximab
K. ali1
1 National
Institute of Blood Diseases and Bone Marrow Transplantation,
Pharmacy, karachi, Pakistan
Background/Objectives: The background of conducted
study was to determine adverse implications on metabolic
profile of DLBCL patients deal with CHOP and R-CHOP.
With a concise determination of the changes in metabolic
profile correlated with dose intensity ratio, the findings
of this study will be helpful in choices for the physician
to discontinue therapy, delaying treatment or alternating
regimen.
Design/Methods: This was prospective study conducted at
National Institute of blood diseases and bone marrow transplantation. In this study baseline readings of liver enzymes,
urea, creatinine and electrolytes levels was taken and treated
as control readings. Post-treatment readings of aforesaid
parameters were taken after 20 days. Means of above readings was calculated and compared with common terminology
criteria for adverse events v3.0 2006 (CTCAE) to find the differences in biochemical parameters at baseline (control group)
and 20 days post-treatment (treatment group) to identify the
types of toxicity (mild moderate or severe) as define by v3.0
2006 (CTCAE).
Results: Among patients with CHOP therapy, significant
difference of ALP (p-value 0.009), direct bilirubin (p-value
0.034) and SGPT (p-value 0.004) was observed before and
after the treatment whereas among patients with R-CHOP no
significant difference was observed in any biochemical analysis (p-value >0.05).
Conclusions: Despite the fact, subjects at baseline metabolic
or biochemical investigation impairments should be corrected
rigorously rather than post chemotherapy effects of CHOP or
R-CHOP cycles leads to the fatal or life threatening renal and
hepatic toxicities. As far as safety is concern R-CHOP is safest
than CHOP in term of toxicities.
P-477 Parents’ Lived Experiences of Losing a
Child to Cancer; Like Being Covered in a Wet and
Black Blanket
M. Bjork1 , A. Sundler Johansson2 , I. Hallström3 , K. Hammarlund4
1 School
of Health and Welfare, CHILD research group- Department of
Nursing- Jönköping University, Jönköping, Sweden; 2 Faculty of Caring
Science, Work Life and Social Welfare- University of Borås, Borås-,
Sweden; 3 Faculty of Medicine, Department of Health Sciences- Lund
University, Lund, Sweden; 4 Division of Nursing, Department of Health and
Learning- University of Skövde, Skövde, Sweden
Background/Objectives: To elucidate parents’ lived experiences of losing a child to cancer.
Design/Methods: A hermeneutical phenomenological
approach was chosen. Five parents were interviewed and one
wrote down a narrative about the experiences of losing a
child to cancer.
Results: Through the analysis one essential theme was identified “Like being covered in a wet and black blanket”. In
relation to the essential theme, six related themes emerged
“Feeling conflicting emotions”, “Trying to get ready for the
moment of death, “Parenting continues after death”, “Keeping the spirit alive”, “Working with the sorrow” and “Wanting
to comprehend life into a new integrated whole”.
Conclusions: Losing a child to cancer is one of the most
painful situations a parent can live through. Life will forever
be changed and the parents need to find ways to learn to live
without the child. When giving palliative care to a child, the
care needs to be holistic and focus both the child and its family. For staff, it is important to meet parents more than once
after the child's death to be able to identify those in need for
extensive support.
P-478 Teamwork at End-of-Life: Developing an
Integrated Model
SIOP ABSTRACTS
S. Holm1
1 Children's
Medical Center, Psychiatry, Dallas, USA
Background/Objectives: (Abstract is part of a symposium
submission: ‘Psychosocial Care Models for End of Life and
Bereavement Support.’) Preparing for the death of a child
is exceptionally distressing for the family. To provide best
end-of-life care, it's imperative that an institutional infrastructure exist to promote highly collaborative work. This project
describes the development of an integrative interdisciplinary
palliative care team within the oncology service at a large
pediatric hospital and compares it to current standards of care.
The purpose of the team was to improve quality of care for
children at highest risk for death through cohesive assimilation of medical and psychosocial professionals already providing services in parallel.
Design/Methods: Prior to developing this team, end-of-life
care followed a traditional multidisciplinary model: the oncologist focused on medical aspects of care and referred to subspecialties for other concerns. Collaboration amongst subspecialties was inconsistent, leading to conflicting interventions,
contradictory goals of care, and moral distress. In response
to these difficulties, a group of experts developed an interdisciplinary approach to supporting families through end-of-life
using an integrated care model.
Results: An included case example to illustrates this
integrated model of end-of-life care: an adolescent girl
with metastatic alveolar Rhabdomyosarcoma; a parent with
untreated paranoid schizophrenia. This highly integrated
approach led to several improved outcomes: improved communication meant frequent crises were managed adequately,
streamlined care prevented repeated/competing interventions,
increased interdependence of psychosocial team members
allowed for focus on self-care, and unified goals led to a peaceful death experience.
Conclusions: The ultimate goal of palliative care is to identify and ameliorate suffering and at end-of-life, this seems best
achieved through the holistic care of a child and family by
a well-integrated team of specialists working toward consistent goals. Through developing this team, we learned that true
interdisciplinary collaboration improved the experience of a
child's death for the family and providers.
P-479 Palliative Radiotherapy for Pediatric
Patients: Outcome Expectations
B. Lee1 , D. Apkon2 , J. Wolfe1,3 , K. Marcus1,2,3
1 Dana-Farber/Boston
Children's Cancer and Blood Disorders Center,
Radiation Oncology, Boston, USA; 2 Brigham and Women's Hospital,
Radiation Oncology, Boston, USA; 3 Harvard Medical School, Radiation
Oncology, Boston, USA
S385 of S518
Background/Objectives: Palliative radiation therapy (pRT)
for pediatric cancer patients is often used to treat pain, neurologic symptoms, and other conditions from progressive cancer that affect quality of life. The decision to pursue additional
anti-cancer therapy towards the end of their child's life may be
a challenging one. The perceived risk versus benefit ratio may
be altered depending on parental knowledge and expectations
of pRT for their child. The goal of this study was to explore
parental expectations of pRT and whether the outcome met
their expectations.
Design/Methods: Nineteen children referred for pRT were
enrolled in a prospective IRB-approved study. At the time
of initial consultation, parents were counseled regarding the
indication for pRT and the expected outcomes of treatment.
At one to three months following treatment completion, a
questionnaire was given to parents to evaluate how the results
of treatment compared to their initial expectations of pRT.
Descriptive statistics were used to analyze the results of the
questionnaire.
Results: Compared to their initial expectations for pRT, 56%
reported that the outcome of pRT in their child was much
better than expected. 33% reported slightly better results, 6%
reported outcomes consistent with their expectations, and
7% reported that the results were slightly worse. No parents
reported that the outcome was much worse than their expectations.
Conclusions: Radiation therapy is an important modality in
palliative care for children with end-stage cancer. In this study,
we found that the large majority of parents believed that the
results of the pRT were better than expected. Our findings may
be of value for future patients whose parents must make this
difficult decision.
P-480 End of Life Care Experience at the
Pediatric Oncology Unit at the Uganda Cancer
Institute: What Role Can Oncology Nurses Play?
I. Mulyowa1
1 Uganda
Cancer Institute, Oncology, Kampala, Uganda
Background/Objectives: Although the majority of childhood cancers are curable, this is not yet true for low resource
countries. In Uganda, cancer care is only at the Uganda Cancer Institute.
Between Jan 1st and Dec 31st , there were 4,321 new cancer
cases registered and about 8% were among children. The mortality rate is 70% annually, that is every 3 in 5 children diagnosed with cancer will not survive past one year after cancer
diagnosis. Here, we review the factors contributing to poor
outcomes and potential solutions.
Design/Methods: Observation
SIOP ABSTRACTS
S386 of S518
Results: Majority of the children present with advanced disease at cancer diagnosis. The chemotherapy is prescribed for
palliative intent more frequently and high rates of complications are observed. Family involvement in decisions regarding
the role of palliative chemotherapy at end of life is low. The
concept of quality of life for cancer patients with advanced
cancer is not well perceived among caretakers and some clinicians at UCI. Nurses play an integral role, identifying symptoms, providing care coordination, and assuring clear communication.
Conclusions: Educational initiatives for patients, families and
health-care providers, are essential. The oncology nurses play
a key role in the multidisciplinary team approach to paediatric
patients at end of life care.
P-481 Palliative Care: Educational Intervention
for Nurses in Lebanon: An Attempt
M. Naifeh Khoury1 , M. Arevian1 , G. El-Khatib1 , S. Fares1
1 American
University of Beirut, Hariri School of NUrsing, beyrouth,
Lebanon
Background/Objectives: Background: Palliative Care (PC),
End –of-Life (EOL) care is evolving worldwide and in
Lebanon. PC provides as good or better outcomes than curative care alone, is cost effective, and alleviates pain and suffering for patients and caregivers. Nursing educators and leaders,
internationally and nationally indicate need to include concepts of “PC” and “ EOL” care in curricula of professional
nurses to cope with death and dying as potential outcome for
patient. Purpose: Assess the effectiveness of PC continuing
educational intervention for registered nurses (RNs) at American University Medical Center (AUBMC); recommend future
educational programs.
Design/Methods: Methods: Quasi experimental pre-posttest. Participants: Convenient sample of 45 “AUBMC” “RNs
“dealing with “PC” and “ELO” care from different clinical units. Program: 0ne-credit workshop, basics in” PC” and
“ELO” Care. Local “PC” experts provided the program. Content adapted from the Education for Physicians of End of Life
Care Curriculum (EPEC). Pre-Post- test consisted 34 multiple choice questions. Analysis: Demographic characteristics
summarized using descriptive statistics. Differences between
pre-post-tests were measured by means and standard deviations (SD) using the paired t test. A two-tailed test was used,
p-value less than 0.05 considered significant.
Results: Results Thirty nine participants completed the prepost-test: Mean pretest score was 48.53(SD = 9.23), range2965, post- test 70.05 (SD = 12.35), range 47-88. Paired t test
showed significant increase between pre and post test scores t
(38) = 11.07, p < 0.001 with 95% confidence interval for the
mean difference of (17.58, 25.45).
Conclusions: Conclusion: provide structured workshops to
“RNs” to for improving “PC” and “EOL” Care.
P-482 Implementation and Evaluation of a
Pediatric Palliative Care Educational Program
Intended for Nursing Staff of a National Reference
Pediatric Hospital in Nicaragua
R. Ortiz1 , N. Diaz1 , S. Saleh2 , C. Maendley3 , M. Chamorro4 , C.
Salazar4
1 Manuel
de Jesus Rivera- La Mascota- Children's Hospital, Pediatric
Hematology-oncology, Managua, Nicaragua; 2 Sainte Justine Pediatric
Hospital, Pediatrics, Montreal, Canada; 3 Centre Hospitalier Universitaire
Vaudois, Pediatrics, Lausanne, Switzerland; 4 Manuel de Jesus Rivera- La
Mascota- Children's Hospital, Pediatrics, Managua, Nicaragua
Background/Objectives: Pediatric Palliative Care (PPC) is
unarguably essential in both Global North and South as it
refers to universal Right to Health. Following the 2014 World
Health Assembly's resolution on Palliative Care, Nicaragua
launched in 2015 its first national Pediatric Palliative Care
Program in collaboration with two NGO's Associazione per
l'aiuto medico al Centro America and Médecins du Monde.
Objectives include healthcare workforce training and essential
drugs supply provision. Within this framework, a PPC educational program intended for nurses caring for children with life
limitng diseases at the only national referral Children's Hospital in Managua was developed.
Design/Methods: From November 2015 to December 2016,
a trained nurse educator provided 8 educational basic courses
on PPC to nurses of various departments of the pediatric
hospital. Pre-intervention tests and 6-month post-intervention
tests were administered to nurses to assess change in general
PPC knowledge. The highest possible test score was 18 points.
Comparison of mean results between pre- and post-tests was
performed.
Results: 54 nurses from 5 departments took part to the whole
8-courses educational program. The mean pre-test result was
10.45 points whereas mean post-test result was 14.60 points.
A 4.15-point difference was observed between pre- and posttest assessment of knowledge of participants.
Conclusions: Marked difference between pre- and postassessment demonstrate positive impact of this educational
program. Above all, a raised awareness regarding need for palliative care was witnessed across the hospital as the demand
for consultations increased notably. Education of health care
professionals is essential to sustainable, efficient and quality
provision of PPC. These positive outcomes open the doors
now for additional theoretical and practical training for nurses
as well as targeting other health care professionals involved in
the care of pediatric palliative care patients. Finally, there is
a need to review tools used to evaluate educational interventions in the field of palliative care.
SIOP ABSTRACTS
P-483 End-of-Life Care for Children with
Cancer: Medical Practitioners’ Training Needs
Assessment in a Resource Poor Setting
L. Osei-tutu1 , E. Sarfo Frimpong2 , V. Paintsil1 , J. Dogbe1
1 Komfo
Anokye Teaching Hospital, Child Health, Kumasi, Ghana; 2 Komfo
Anokye Teaching Hospital, Research and Development Unit, kumasi, Ghana
Background/Objectives: The Paediatric Cancer Unit of the
Child Health Department in the Komfo Anokye Teaching
Hospital, KATH is one of two main childhood cancer treatment centers in Ghana. 113 new patients visited the Unit in
2016; 78(69%) required palliation and 39(34%) died. Most
deaths, 33(84%) occurred in the hospital. We aimed to assess
the end-of-life training needs of medical practitioners in the
Department in the setting of paediatric cancers
Design/Methods: Medical practitioners completed a survey
assessing their participation, communication skills and practices in end-of-life care regarding paediatric cancer patients.
Responses were ranked on five-point Likert scales and analysed by simple proportions
Results: 30 practitioners, 20 doctors and 10 nurses completed
the survey. All participants reported ever undertaking some
end-of-life care some end-of-life responsibilities. 12(60%)
doctors and 5(50%) nurses reported not receiving any such
formal training. All doctors reported not receiving any formal instructions on having follow-up contact with families
after patient deaths compared to 5(50%) of nurses surveyed.
Most (80%) participants reported lacking formal instructions
in seeking support for themselves regarding end-of-life situations. 12(60%) doctors and 7(70%) nurses did not “feel adequately trained to undertake withdrawal or limitation of lifesustaining therapy” whereas only 9(18%) doctors and 4(40%)
nurses “felt adequately trained to provide symptom management at the end of life.” 45–60% of participants reported adequate training and experience in communicating end-of-life
issues to families while 15-30% reported feeling knowledgeable, competent and comfortable in such communications.
40% doctors compared to 50% nurses reported adequate training and experience in providing spiritual support for dying
children and their families. Only 15% of participants surveyed
felt competent and comfortable including children in discussions about preparing for death
Conclusions: Formal training in end-of-life care in the setting of paediatric cancers appears inadequate with significant
gaps in communication skills, in withdrawing or limiting lifesustaining therapy and symptom management
P-484 Palliative Care Practice in Pediatric
Oncology: A Single Center Experience in France
G. Revon-Riviere1 , J.C. Gentet1
S387 of S518
1 Hopital
Timone, Oncologie Pédiatrique, Marseille, France
Background/Objectives: Pediatric palliative care is a field
of primary importance for improvement of quality of life of
children with cancer. Our study aims to describe practice of
palliative care in our institution by studying time from inclusion to death, treatments, length of hospitalization, location of
death, use of community palliative services and symptoms in
children dying of cancer.
Design/Methods: This study is a retrospective, single center, chart review of every child treated in our institution and
deceased between June 2014 and June 2016. Symptoms were
assessed by chart examination three months before death. y.
Results: 45 patients died of cancer in two years. 34 (75.5 %)
have been discussed in palliative care staff and 25 (55 %) were
actively treated by pediatric palliative care unit. Median duration of palliative phase was 4.3 months (range: 0.03-29.80). 91
% of patients died in hospital. During that time, mean number of antineoplastic treatments was 1.8 per patient and 25 %
were included in a clinical trial. Symptoms were in order of
frequency: pain, fatigue, poor appetite and digestive disorders.
Their prevalence was underestimated in medical charts.
Conclusions: We report our palliative activity to allow
improvement in practices and resource allocation. Availability of innovative treatment for palliative purpose is high. However, there is a great variability in duration of palliative care
and use of palliative resources. Definition of a group of highrisk children requiring early initiation of palliative care as well
as standardization of palliative care assessments and interventions are necessary.
P-485 Consultation Team in Tertiary Hospital as
a Pediatric Palliative Care Model in Developing
Country– 5 Years Experience of a Single Institution
in China
J. Wang1
1 Shanghai Children's Medical Center, department of hematology/oncology,
Shanghai, China
Background/Objectives: To evaluate the feasibility and
effectiveness of palliative care consultation(PCC) team as a
service model at an oncology unit in a pediatric tertiary hospital in China.
Design/Methods: Our core palliative care consultation team
consists of a pediatric oncologist, a pediatric oncology nurse
and a social worker. Doctor is the leader of this interdisciplinary team who is responsible for a coordinated care plan
development. Patients are referred to the team from other
pediatric oncologists, and PCC team delivers palliative care
services through outpatient clinic, consultation, 7*24 hours
hotline and hospice room located in the observation ward. The
SIOP ABSTRACTS
S388 of S518
team also provides teaching and support to the health care professionals.
Results: A total of 50 patients and their families have been
referred since 2012. The referral reasons were refractory
pain (2 patients) and end-of-life care (48 patients). Diagnoses
included leukemia and solid tumor. 28 boys and 22 girls aged
from 14 months to 17 years. Among those patients for endof-life care, 18 and 1 died at community hospital and oncology ward of our hospital separately. The role of PCC team for
these cases was providing support to the local hospital and the
colleagues at our oncology unit. Another 29 patients received
the direct care of PCC team. 20 of them died at hospice room,
and 9 died at home. The main symptoms during the last month
were pain, anorexia, fatigue, dyspnea, fever, edema, infection,
bleeding, depression, fear, anxiety and insomnia. The direct
and indirect interventions of PCC team showed the positive
impact on suffering relief and death preparation.
Conclusions: The palliative care consultation team is closely
attached and provides professional support to the conventional
health care. It is well-functioning and cost saving. We conclude that this model may play an important role of pediatric palliative care in developing country where the medical
resources are insufficient.
T R E AT M E N T A N D CA R E PSYCHOSOCIAL (PPO)
P-486 Who Should Inform on Children Quality of
Life in Paediatric Oncology? Systematic Review and
Meta-Analysis of Agreement Between Respondents
C. Abate1,2 , C. Laverdière2,3 , M. Krajinovic2,3 , D. Sinnett2,3 , S.
Sultan1,2
1 Université
de Montréal, Psychology, Montreal, Canada; 2 CHU
Sainte-Justine, Hematology-Oncology, Montreal, Canada; 3 Université de
Montréal, Pediatrics, Montreal, Canada
Background/Objectives: Quality of life (QOL) is an essential component of care for children with cancer and for young
survivors and is often informed by parents or significant others. Assessing QOL reliably is difficult due to divergent child
and parent ratings. A systematic review and meta-analysis was
performed to synthesize the size of differences between child
and parent ratings on QOL at all stages of the cancer and to
identify moderators of the differences between ratings.
Design/Methods: A systematic search of PubMed,
PsycINFO, EMbase, CINALH and reference lists revealed
pertinent articles published until December 2016. Eligibility
criteria included QOL ratings of patients <19 years old during
or after cancer treatment and at least one of their parents with
a validated instrument. Two independent reviewers extracted
data and conducted quality assessments with standardized
tools, in line with PRISMA recommendations. Random
effects meta-analyses compared self-assessed and parentassessed QOL across scores and subscores: overall, physical,
psychosocial. We computed effect sizes with 95% confidence intervals. Additional analyses of differences between
QOL ratings and cancer diagnosis, cancer trajectories, and
instruments are underway.
Results: Forty-two articles were eligible out of a possible
1,139. Twenty-six percent of studies recruited children during treatment, 29% after treatment and 45% included mixed
samples. They describe 4,325 children and 4,485 parents
who differ on age at diagnosis, time since diagnosis, cancer
types and QOL measures. Median ICC for overall QOL was
0.58 (quartile range=0.48-0.72) and median Cohen's d was
0.23 (quartile range=0.14-0.44). Preliminary analyses yield
a mean moderate effect size between child and parent ratings. Moderation studies indicated that differences are associated with child age, child gender, clinical history, and parental
mood.
Conclusions: Disagreements among children and their parents highlight the importance of gathering QOL assessments
from multiple respondents to identify vulnerable patients.
Future research should explain disagreements and develop
new methods to interpret multiple reports.
P-487
The Childhood Cancer Mobile APP
A. Filander1 , U. Persson1 , M. af Sandeberg1 , L. Pettersson1 , G.
Cleve1
1 Karolinska
University Hospital, Astrid Lindgren Childrens HospitalPediatric Oncology, Stockholm, Sweden
Background/Objectives: A family in shock because their
child is diagnosed with cancer need to learn to understand the
disease and treatment, a prerequisite for them to feel confident in taking care of their child. Health care is legally obliged
to provide adequate information during a time when it is
extremely difficult to absorb. For many years families at the
children's cancer unit got their own folder with information
about childhood cancer, unit routines and instructions how to
act if the child should exhibit acute symptoms. The problem,
however, was to keep the information updated. The childhood
cancer mobile APP was developed as a complement to the verbal information, to make it possible to get answers when the
questions arise at home, to avoid mixed messages from healthcare staff and to help parents to inform other close persons.
Design/Methods: A special group of various clinical professions was formed to work with the APP together with the hospitals’ Innovation Centre and an enterprise platform. The text
in the information folder was updated and context and wording discussed in frequent meetings. Feedback from patients
SIOP ABSTRACTS
and relatives was gathered through workshops, questionnaires
and mail. Significant parts was translated into the four most
common foreign languages: English, Spanish, Somali and
Arabic, and processed in workshops for interpreters and parents.
Results: The APP was soon used by the majority of families
at the unit and is constantly developed.
Conclusions: The childhood cancer APP meet a considerable
need for parents, relatives and staff. It is crucial to take help
from experts on platform construction.
P-488 Bridging the Gap Between Treatment and
End of Life for Pediatric Patients with Cancer
S. Flowers1 , J. Hansen-Moore1 , T. Young-Saleme1 , C. Russell1 , M.
Gardner1
1 Nationwide
Children's Hospital, Pediatric Psychology, Columbus, USA
Background/Objectives: This abstract is part of a symposium submission from APA/Division 54 Hematology/Oncology/BMT SIG entitled Psychosocial Care Models
for End of Life and Bereavement Support
Nationwide Children's Hospital is the largest children's hospital in the United States. Our Psychosocial Oncology Team
developed a model of care to enhance care for dying children.
It embodies a collaborative approach with integration of medical, psychosocial, and palliative services for comprehensive,
coordinated, and integrated programing. This model assesses
and treats emotional and symptom burden, facilitates communication, provides anticipatory guidance and support to
patients/families, while facilitating staff communication and
support.
Design/Methods: Our program addresses specialized needs
of dying children in a collaborative team approach. Patients
are assessed and treated via a large comprehensive psychosocial team of providers. Anticipatory grief support is facilitated by relationships focused on continuity of care, medical decision-making, care conferences, and end-of-life conversations. We assist with patient/family communication with
family-centered rounds, advanced care planning, and legacy
building. Palliative/Oncology Rounds, team huddles, documentation, and death notification protocols were developed
to improve staff communication. Additionally, we provide
support for staff following patient deaths through debriefings/remembrances.
Results: In large programs with multiple providers, it is often
challenging to know who is providing specific services, while
ensuring that families are receiving needed care. By increasing communication between and within teams, we ensure support, enhance/streamline services, and delineate service provision.
S389 of S518
Conclusions: The Psychosocial Oncology Team at NCH has
improved communication among medical, psychosocial, and
palliative team members to enhance opportunities and provide support around a child's death. In a field with a high
level of burnout and stress, open communication and support
among team members can serve to enhance the well-being
and service provided to patients, and also reduce staff distress. A comparison between our model and the Psychosocial
Standards of Care related to palliative care and bereavement
follow-up will be reviewed.
P-489 Risk Factors and Reasons for Loss to
Follow-Up Among Families of Children with
Lymphoma in Malawi
C. Stanley1 , T. van der Gronde1 , K. Westmoreland1 , S. Ande1 , A.
Amuquandoh1 , S. Itimu1 , A. Manda1 , I. Mtete2 , M. Butia2 , A.
Mpasa2 , S. Wachepa2 , P. Wasswa2 , P. Kazembe2 , N.
El-Mallawany2 , S. Gopal1
1 UNC
Project Malawi / Kamuzu Central Hospital, Cancer Program,
Lilongwe, Malawi; 2 Baylor Children's Foundation, Oncology, Lilongwe,
Malawi
Background/Objectives: Lymphoma is the commonest pediatric cancer in sub-Saharan Africa (SSA). A principal contributing factor to suboptimal outcomes is frequent loss to
follow-up (LTFU). However, risk factors and reasons for
LTFU among families of children with lymphoma in SSA are
not clear. Our aim was to assess risk factors and reasons for
LTFU among pediatric lymphoma patients in Malawi.
Design/Methods: We conducted a mixed methods study
among children <18 years old with newly diagnosed lymphoma, prospectively enrolled between 2013 and 2016 in
Lilongwe, Malawi. All children received standardized diagnosis and treatment, and were followed for up to two years.
LTFU was defined as failure to attend a prescribed chemotherapy visit within four weeks, or post-treatment visit within
three months. Child, guardian, and household characteristics
associated with LTFU were assessed using Cox models. Semistructured interviews were conducted with primary caregivers
of children experiencing LTFU.
Results: Seventy-two children were newly diagnosed with
lymphoma, of whom 56 (78%) had Burkitt and 16 (22%)
Hodgkin lymphoma. Forty-nine (68%) were male, median age
was 10.6 years (interquartile range [IQR] 7.9–13.0), and 26
(36%) were LTFU. Lack of guardian formal education and
travel time ≥4 hours to clinic were independently associated
with LTFU, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5-8.9, p=0.005] and aHR 2.9 (95% CI
1.2-6.9, p=0.019), respectively. The most frequent reasons for
LTFU mentioned by guardians were community influence,
suboptimal clinic environment, logistical challenges, trans-
SIOP ABSTRACTS
S390 of S518
port costs, treatment side effects and toxicities, loss of hope,
alternative healers, and beliefs about cure.
Conclusions: LTFU was driven more by guardian or household characteristics than child characteristics. These findings highlight families at risk for LTFU, and opportunities to
improve retention in care for pediatric cancer patients in SSA.
P-490 Psychosocial Care Models for End of Life
and Bereavement Support
J. Hoag1 , K. Bingen1
1 Medical
College of Wisconsin, Department of Pediatrics, Milwaukee, USA
Background/Objectives:
This
proposed
symposium represents collaboration amongst the Hematology/Oncology/Blood and Marrow Transplant (BMT) Special
Interest Group of the Society of Pediatric Psychology, American Psychological Association. In 2015, the Standards for
Psychosocial Care for Children with Cancer were published
in a landmark special edition of Pediatric Blood & Cancer.
Two standards dealt with palliative care and bereavement.
While a minimum of care has been established, it remains
unclear how institutions are using these guidelines within
their existing infrastructure to improve or refine their practice
model. Therefore, the objective of this symposium is to
describe the psychosocial care models for end of life and
bereavement support across three institutions of varying
sizes, resources, and geographical diversity to aid in our
understanding of current practices.
Design/Methods: The proposed presentations reflect various
approaches to collaborative care across disciplines at end of
life to facilitate honest and respectful communication with
patients and families, improve family-centered advance care
planning, and assist with memory making. Presenters will also
discuss bereavement follow-up in their institution for families,
as well as staff.
Results: Descriptive program data will be presented, including hospital and patient demographics, composition of palliative and bereavement teams, timing of introductions and interventions, and program evaluation. Barriers to implementation
will be addressed.
Conclusions: This symposium highlights that there are various ways to implement the standards for psychosocial care for
providing end of life and bereavement care for children with
cancer and their families.
Authors of corresponding abstracts: Stacy Flowers, Jeffrey
Karst, and Suzanne Holm
P-491 Psychosocial Functioning and Risk Factors
for Siblings of Children with Cancer: An Updated
Systematic Review
K. Long1 , V. Lehmann2 , A. Carpenter3 , C. Gerhardt2 , A.
Marsland4 , M. Alderfer5,6
1 Boston
University, Psychological and Brain Sciences, Boston, USA;
Children's Hospital, Center for Biobehavioral Health,
Columbus, USA; 3 Boston University, Department of Psychological and
Brain Sciences, Boston, USA; 4 University of Pittsburgh, Psychology,
Pittsburgh, USA; 5 Nemours Children's Health System, Center for
Healthcare Delivery Science, Wilmington, USA; 6 Thomas Jefferson
University, Sidney Kimmel Medical College, Philadelphia, USA
2 Nationwide
Background/Objectives: Despite increased research, our
understanding of siblings’ psychosocial adjustment to cancer
remains limited. This updated systematic review summarizes
main findings and limitations of the current sibling literature,
provides clinical recommendations, and offers future research
directions.
Design/Methods: Searches of MEDLINE/Pubmed,
CINAHL, and PsycINFO yielded 1731 articles published
since 2008 related to siblings, psychosocial functioning, and
pediatric cancer. Of these, 103 (64 quantitative, 35 qualitative, and four mixed methods) met inclusion criteria. They
were rated for scientific merit, and findings were extracted
and synthesized
Results: While mean levels of anxiety, depression, and general adjustment (e.g., symptoms of internalizing, externalizing, or general distress) are similar across sibling and comparison samples, many siblings report moderate/severe levels of
cancer-related posttraumatic stress. School-aged siblings display poorer academic functioning and more absenteeism than
peers; their peer relationships are similar to those of comparisons. Findings regarding quality of life are mixed. Adult siblings may have a higher risk for cardiovascular disease and
engaging in risky or heavy drinking than comparisons. Risk
factors for poor adjustment include low social support, poorer
family functioning, lower income, nonwhite race, and shorter
time since diagnosis, but findings are inconsistent. Qualitative
studies report themes of siblings’ maturity, compassion, and
autonomy, along with strong negative emotions, uncertainty,
family disruptions, limited parental support, school problems,
altered friendships, and unmet needs. Conclusions are limited
because longitudinal studies are lacking, siblings are often
considered controls for patients/survivors, and sample characteristics (e.g., age, race/ethnicity, time since cancer diagnosis)
are rarely considered.
Conclusions: Despite methodological limitations, the literature indicates a strong need for sibling psychosocial care
focused on identifying at-risk siblings, facilitating family
communication about cancer, and bolstering siblings’ social
support, cancer-related knowledge, and cancer involvement.
Future research that implements longitudinal designs and
focuses on mechanisms and moderators of siblings’ adjustment would inform optimal timing and targets of siblings’
psychosocial care.
SIOP ABSTRACTS
P-492 Post-Traumatic Stress Symptoms and
Family Risk Among Adolescents and Young Adults
with Differentiated Thyroid Cancer: Prospective
Psychosocial Screening of an Underserved Cancer
Population
A. Psihogios1 , J. Baran1 , J. Pizza1 , S. Mostoufi-Moab1 , A. Bauer1 ,
L. Barakat1
1 The
Children's Hospital of Philadelphia, Pediatrics, Philadelphia, USA
Background/Objectives: Approximately 25% of AYA
with cancer report elevated post-traumatic stress symptoms
(PTSS). AYA with differentiated thyroid cancer (DTC)
are often excluded from psychosocial research and clinical
initiatives due to their good prognosis and treatment outside
of cancer centers. To enhance understanding of adaptation,
this study describes clinical rates of AYA and caregiver PTSS
and family risk, and correlates with PTSS.
Design/Methods: AYA with DTC (n=45, M age=15.0, 91.3%
female, 85.1% White) and a caregiver (n=44, 70.2% mothers)
completed questionnaires at diagnosis (T1) and 12 months
later (T2), including the PTSD Checklist-Civilian 6 (PTSS),
Psychosocial Assessment Tool (family risk), and PedsQL
(HRQOL). We evaluated clinically significant rates of PTSS
and family risk by assessing responses above established cut
points. Multiple regressions and MANOVAs examined relationships between PTSS and correlates.
Results: Among AYA, 23.8% and 11.1% reported clinically
significant PTSS at T1 and T2. Among caregivers, 22.0% and
26.7% reported clinically significant PTSS, and 36.6% and
35.0% endorsed family risk associated with intervention needs
at T1 and T2. Mean AYA HRQOL was 77.6 and 82.5 at T1 and
T2. Paired t-tests showed no significant changes in PTSS and
family risk from T1 to T2. Lower HRQOL (�=.72, p<.001)
was associated with more AYA PTSS at T1, and AYA with at
least one complication reported greater PTSS at T2 (F=5.29,
p=.04). Higher family risk was associated with greater caregiver PTSS at T1 (�=.40, p=.001) and T2 (�=.81, p=.001).
Conclusions: Comparable to other childhood cancer samples,
a subset of AYA with DTC and caregivers are at-risk for clinical levels of PTSS. The persistence of PTSS in the year postdiagnosis, combined with family risk, highlight the importance of conveying psychosocial screening to AYA treated
in the endocrine setting. AYA HRQOL was similar to other
newly diagnosed cancer patients at T1, and may be targeted to
reduce PTSS.
S391 of S518
1 University
of Calgary, Psychology, Calgary, Canada; 2 University of
Calgary, Medicine, Calgary, Canada; 3 University of Guelph, Psychology,
Guelph, Canada; 4 University of Calgary, Oncology, Calgary, Canada
Background/Objectives: Pediatric cancer patients and their
parents often stay in hospital for extended periods of time and
report disruptions in sleep. This study aims to examine objective and subjective measures of sleep quality in pediatric cancer patients and their parents, receiving overnight oncology
care.
Design/Methods: Sixteen patients (11 male; mean age=13.47
years) and 14 parents have participated. For three consecutive
days, patients and parents each wore an actigraphy watch and
completed a daily Sleep Diary. Patients also completed the
Child Depression Inventory, Multidimensional Anxiety Scale
for Children, Child Sleep Habits Questionnaire, Pediatric
Quality of Life (PedsQL) Multidimensional Fatigue Scale,
and PedsQL Generic Core. Parents additionally completed the
State Trait Anxiety Inventory for Adults, Abbreviated Pittsburgh Sleep Quality Index, Proxy PedsQL Mulidimensional
Anxiety Scale, Proxy PedsQL Generic Core, and a daily Profile of Mood States Questionnaire.
Results: Preliminary findings indicate that 80% of pediatric
oncology patients self-report symptoms of sleep disruption
and/or fatigue based upon measures of Child Sleep Habits,
Anxiety and Sleep Quality. Additionally, the PedsQL Multifatigue Scale indicated that all 16 children reported greater
general, cognitive and sleep/rest fatigue in comparison to published norms.
Conclusions: Data obtained from this research will help
to identify ways to decrease the effects of an important
physiological consequence of current cancer care practices.
Research into sleep disturbances in hospitalized pediatric
cancer patients and parents will aid in a better understanding of the developmental frameworks that guide intervention/prevention programs, providing benefit to and optimization of child and parent health during their hospital stay.
P-494 Home Physical Activity Intervention to
Improve Cognitive Late Effects in Children Treated
with Radiation for Brain Tumors: Pilot Feasibility
and Efficacy Data
P. Wolters1 , B. Abel1 , S. Martin1 , K. Smith2 , M.A. Toledo-Tamula3 ,
B. Drinkard2 , K. Chen4 , A. Kramer5 , A. Schembri6 , J. Han7
1 National
Cancer Institute, Pediatric Oncology Branch, Bethesda, USA;
Institutes of Health, Clinical Center, Bethesda, USA; 3 Leidos
Biomedical Research Inc, Clinical Research Directorate/Clinical
Monitoring Research Program- NCI Campus at Frederick, FrederickMaryland 21702, USA; 4 National Institute of Diabetes and Digestive and
Kidney Diseases, Diabetes- Endocrinology- and Obesity Branch, Bethesda,
USA; 5 Northeastern University, Mechanical and Industrial Engineering,
Boston, USA; 6 Cogstate- Inc., Clinical Science, Melbourne, Australia;
2 National
P-493 An Investigation of Parent and Child Sleep
Patterns on an In-Patient Oncology Unit
B. Russell1 , G. Narendran2 , S. Lee3 , L. Tomfohr1 , F. Schulte4
S392 of S518
SIOP ABSTRACTS
7 University
Background: Adolescents with cancer (AWC) show the
strengths of a positive attitude and sense of purpose. The
resources refer to maintain peers, school life, social relationships, and a normal life. The purpose of this study was to
develop the resources on the positive attitude and the purpose
to gain resilience in the AWC.
of Tennessee Health Sciences Center, Department of Pediatrics,
Memphis, USA
Background/Objectives: Cranial radiation therapy (CRT)
for pediatric brain tumors contributes to neurocognitive
late effects. Cognitive rehabilitation interventions are sorely
needed. Studies indicate that physical activity (PA) improves
CRT-damaged brain mechanisms and cognitive functions.
The aim of this pilot randomized controlled trial (RCT) was to
assess the feasibility and preliminary efficacy of a novel home
PA intervention in children treated with CRT for brain tumors.
Design/Methods: Children 8-17 years, >two years post-CRT,
with cognitive late effects were randomized to the Immediate
Intervention Group (IIG), which followed a 12-week home
program to increase PA then maintained PA for 12 weeks,
or the Delayed Intervention Group (DIG), which monitored
usual PA for 12 weeks followed by the 12-week program.
Psychologists taught Acceptance and Commitment Therapy
techniques to facilitate PA engagement. Participants used
accelerometers and a website to track and reward moderate-tovigorous PA (MVPA). Both groups underwent fasting blood
draws (to measure circulating growth factors), treadmill evaluations, and cognitive assessments before and after the first
12 weeks, and repeat cognitive assessments after the second 12 weeks, including Cogstate computerized tests (normative mean=100;SD=15). Participants repeated Cogstate tests
immediately after treadmill evaluations.
Results: All six children (mean age=13.8 years, 10-17)
enrolled (IIG=3;DIG=3) completed the pilot study. From
baseline to during the 12-week program, 6/6 increased weekly
MVPA (total means 41 to 130 minutes). After the treadmill
evaluations, 5/6 had improved Cogstate visual memory scores
(total means 107 to 118). The IIG showed greater increase in
visual memory scores post-intervention compared to after the
DIG 12-week post-control period (14 versus 5 points). On 5point Likert scales, participants reported liking the program
(mean=4) and finding it helpful (mean=4).
Conclusions: These pilot data suggest feasibility of an
innovative home PA intervention in children treated for
brain tumors and provides preliminary evidence of increased
MVPA and potential cognitive benefit to support a larger RCT.
Methods: Yin's descriptive case study was used. The study
was approved by the institutional review board. The semistructured interview guide was performed face-to-face by
an author in a private room. The cancer experience, coping
strategies, hope, and social support in the 4 phases (the early
inpatient, the inpatient, the near discharge, and the outpatient) were asked. The interview was lasted between 45 to 70
minutes.
Results: The 9 participants comprised; 6 males and 3 females,
12 to 18 years old, and 1 to 17 months of being an outpatient.
The interview data was classified in the resources on the positive attitude and the purpose in the 4 phases. The results were
exhibited the graphical patterns in the newly diagnosed AWC
and the other one. The average of the patterns was shown in
the temporal patterns. The wave of the positive attitude was
higher than it of the purpose. The positive attitude encountered the gently wave path with low, up, and down between
the 4 phases. The purpose was the steep one with up between
in the inpatient and the near discharge. The resources were
found that the parent(s) and the friends were used more than
the others. The parent(s) worked more in the early inpatient
phase and the friends did more after the phase.
Conclusions: The AWC used the resources depends on the
phases. They had fewer resources to make the purpose. The
some interventions may need them to make the purpose and
to improve the resilience.
Keywords: adolescents with cancer, resilience, resources,
positive attitudes, a sense of purpose
P-496 Technology Solutions to Promote
Medication Adherence: Perceptions of Parents of
Childhood Cancer Patients
C. Baggott Do not use1
1 Stanford
T R E AT M E N T A N D CA R E - N U R S I NG
P-495 Developing Resources on Positive Attitudes
and a Sense of Purpose to Gain Resilience in
Adolescents with Cancer
I. Akiko1 , K. Kamibeppu1
1 Graduate
School of Health Sciences & Nursing Faculty of Medicine, The
University of Tokyo
University, Cancer Clinical Trials Office, Palo Alto, USA
Background/Objectives: Children with cancer require complex home medication regimens, typically facilitated by their
parents. Despite the critical nature of these drugs, nonadherence to these regimens is commonplace, related to intentional
factors (e.g., avoidance of toxic effects) or unintentional factors (e.g., forgetfulness, medication errors). Medication nonadherence has been linked to poor outcomes among children
with cancer. A thorough and accurate assessment of patients’
medication use is essential. When collected in real-time, these
data can: promote early detection of untoward symptom pat-
SIOP ABSTRACTS
terns; identify patient/family misconceptions of medication
regimen details; identify patients/families who struggle with
medication adherence; and provide required data for. clinical trials. The current practice of interviewing parents to
elicit drug use over the prior weeks is time consuming and
prone to recall errors. Furthermore, this practice does not provide feedback on medication use patterns. While numerous
technology solutions (e.g., smartphones, smartwatches, electronic pillboxes) are available to promote medication adherence, their efficacy has not been evaluated. In a sample of parents of childhood cancer patients, the primary objective of this
project is to determine the challenges in existing medication
administration/recording practices and the optimal features to
include in technology solutions for medication tracking.
Design/Methods: Parents of children who are receiving
chemotherapy for cancer will participate in semi-structured
interviews to elicit their perceptions of challenges in medication adherence and their views on technology available and
potential technology solutions to facilitate medication tracking and promote adherence to medication regimens. The sample will consist of 15 mothers or fathers whose children have
received chemotherapy for at least 6 months and remain on
treatment at the time of the interview.
Results: Results will be summarized in poster format.
Conclusions: Eliciting views of challenges and solutions for
medication tracking from parents of childhood cancer patients
may inform strategies to promote successful adoption of technology solutions to promote medication adherence.
S393 of S518
of interdisciplinary communication. A questionnaire was provided to the nurses at Huda Al Masri Pediatric Cancer Department to assess nursing care and level of comfort both prior to
and post the educational sessions related to:
Chemotherapy safety
Supportive care
Patient/family education
Consistency of care
Team communication
Results: The questionnaire clearly demonstrated the confidence in nursing care that has developed through the educational interventions provided by KC. Nurses at Huda Al
Masri acknowledge the ability to safely provide care, educate the patients and families on the diagnosis and treatment
side effects and advocate for their patients in a receptive team
environment
Conclusions: Knowledge gained regarding oncologic diagnoses, processes, treatments and emergency management has
increased nursing ability to confidently provide quality care.
The success of this BJ program is now being replicated in
Gaza.
P-498 Care Plan for Mucositis in Thalassemia
Patients after Haploidenticalhematopoietic Stem
Cell Transplantation
J. Chanapai1 , P. Aimsirirak1 , S. Suksalee1 , P. Nakvijit1 , S.
Ritthisong1 , N. Wongsingrad1 , S. Pakakasama2 , P. Chiraporn1
1 Samitvej
Children's hospital, Pediatric onco/Hemato and HSCT, Bangkok,
Thailand; 2 Mahidol university, Pediatric Oncology, Bangkok, Thailand
P-497 Paying it Forward: The Shared Knowledge
of Pediatric Nursing Care from the United States to
the West Bank Palestine and Beyond
J. Bartholomew1 , M. Freha2
1 Children's
2 Huda
Mercy Hospital, Hematology/Oncology, Kansas City, USA;
Al Masri, Pediatric Oncology, Beit Jala, Palestinian Authority
Background/Objectives: Due to political and economic
forces, children with cancer in Palestine had essentially no
access to care. In 2013, the vision to develop a regional pediatric oncology center became a reality. A collaborative effort
to maximize the care available to these children was established between Kansas City (KC), United States and Beit Jala
(BJ), Palestinian Territory.
Design/Methods: A series of training sessions by nurses from
KC were provided. Initially nursing education focused on the
oncologic diseases that were anticipated to be seen and the
emergent care that would be needed. As the center in BJ developed, nursing education progressed to infection control, safe
handling of agents and patient supportive care. The focus most
recently has shifted to the development of nursing policies and
procedures to provide consistent care and in the strengthening
Background/Objectives: Background; Mucositis is a common complication in patient’ underwent hematopoietic stem
cell transplantation (HSCT).
Mucositis is graded from mild sympyoms to severe pain and
unable to eat causing nutritional insufficiency. Care plan for
mucositis may help to relief patients’ suffering and improve
their nutrition status.
Objective: To develop care plan for mucositis in thalassemic
patients after heploidentical Hematopoietic stem cell transplantation(HSCT)
Design/Methods: Methods; We retrospectively analyzed frequency and severity of mucositis in patients with Thalassemia after haploidentical Hematopoietic stem cell transplantation(HSCT) and developed care plan using the collected
data of mucositis.
Results:
1. There were 18 severe beta - thalassemic patients,with a
median age of 7.3 years (range 2.1-27 years), receiving
hematopoietic stem cells from mothers or fathers at our
insttute between January 2015 and December 2016.
SIOP ABSTRACTS
S394 of S518
2. The preparative regimen included rabbit antithymocyte
globulin, fludarabine and intravenous busulfan.
cyanoacrylate application to orders on eligible and consenting HSCT patients.
3. All of patients developed mucositis with severity of grade3
(n=8) and grade 4 (n =10).
Results: Sixty seven percent of patients who met criteria participated in the preventative application of cyanoacrylate to
the perianal area. No perianal breakdown was observed on
these four patients during their HSCT admission. The remaining two patients (33%), who did not to consent to cyanoacrylate, experienced severe IAD necessitating wound consultation and intravenous pain medication. One patient developed
incontinence after admission, prompting immediate implementation of preventative cyanoacrylate. This patient did not
develop IAD.
4. We recorded mucositis grading everyday and found that
patient suffered withmucositis during the first 2 weeks
after HSCT. Grade 1 occurred between day +2 and +4,
grade 2 between day +2 and +6, grade 3 between day +6
and +12 and grade 4 between day +8 and +16. Using this
data, we have planned for our nursing care as(1) evaluating nutrition intake and support since day +1, (2) changing
oral is intravenous medications since day +6, (3) considering parenteral nutrition since day +6,(4) weaning parenteral support and encouraging oral intake since day +16.
As a result, the median length of stay was only 22 days.
Conclusions: Using data of mucositis,We successfully developed and used our care plan for mucositis in Thalassemia
patients undergoing Hematopoietic stem cell transplantation(HSCT).
P-499 Prevention of Severe
Incontinence-Associated Dermatitis in Pediatric
Patients Undergoing Hematopoietic Stem Cell
Transplant
K. Coish1 , K. Ridgway1 , B. patteson1 , A. mahoney1 , E. Postell1 , S.
malone1
1 Children's
National Health System, Heme/Onc/HSCT unit, Washington-
DC, USA
Background/Objectives: Hematopoietic stem cell transplants (HSCT) registered nurses in our institution noted an
increased incidence of severe incontinence-associated dermatitis (IAD), defined by perianal excoriation, in diapered
patients undergoing HSCT. Myeloablative preparative regimens required for HSCT induce prolonged neutropenia,
increased risk of infection, and delayed wound healing,
increasing the risk of skin breakdown. This preventable complication causes increased pain, costs, and length of stay.
Design/Methods: Cyanoacrylate liquid skin barrier has been
used with positive outcomes to treat and expedite healing
of IAD. Through an interdisciplinary quality improvement
(QI) project, our HSCT team implemented prophylactic use
of cyanoacrylate on incontinent patients undergoing HSCT.
Patients who met eligibility and consented began prophylactic
perianal cyanoacrylate use upon admission for their myeloablative preparatory regimen. Use of cyanoacrylate continued
through engraftment. Incontinent patients receiving thiotepa
were excluded until adhesive products were permissible. Skin
and Wound Team members provided education to staff and
caregivers on application of cyanoacrylate. Providers added
Conclusions: The use of cyanoacrylate in vulnerable pediatric patients can prevent life-threatening infection due to skin
breakdown. This succesful quality initiative is innovative and
cost-effective. This project can be expanded to meet the needs
of other incontinent patients at risk for severe IAD.
P-500 Improving Patient Care for Hispanic
Pediatric Oncology Patients with Limited English
Proficiency
T. Flatt1 , T. Torres1
1 Children's
Mercy Hospital, Pediatric Hematology/Oncology, Kansas City,
USA
Background/Objectives: Caregivers of pediatric oncology
patients with limited English proficiency face challenges as
they navigate the English speaking medical system in the
US. Our objective is to present bilingual materials that have
improved patient care and compliance.
Design/Methods: This is a description of materials that have
been successfully utilized to improve patient care services
and medical compliance for Hispanic caregivers with limited
English proficiency. The materials will be demonstrated in the
poster.
Results: Bilingual patient face sheets that include cancer
diagnosis, central line details, oncology contact information
and strict instructions regarding time to collect blood cultures
and initiate antibiotics for patients with cancer are provided
to caregivers for medical visits outside of our facility. Many
patients live long distance from our main hospital with no
on-site language interpreter and this tool has decreased triage
time and shortened time to obtain antibiotics for patients with
fever and neutropenia. Bilingual medication calendars and
medication lists have improved compliance including adherence to oral chemotherapy. A bilingual oncology essentials
entailing side effects to monitor at home and parameters for
when to contact provider services. The use of bilingual pill
boxes (made by our medical team) have proven instrumental
in medication adherence in complicated experimental thera-
SIOP ABSTRACTS
peutic protocols that do not permit deviation from the protocol.
Conclusions: Appropriate bilingual materials can improve
patient care access, decrease triage times, time to antibiotic
administration and improve medication compliance.
P-501 Role of Nursing Care in the Management
of Burkitt's Lymphoma Patient During Inpatient
Stay after First Cycle of Intense Chemotherapy
Copadm Post Complications
R.N. Gill1 , H. Khan1 , N. Patrus1 , A.N. Gill1
1 Shaukat
Khanum Memorial Cancer Hospital and Research Center,
Pediatric Oncology/Hematology Inpatient department, Lahore, Pakistan
Background/Objectives: This Study permits us to know the
nursing care convention gave by nurses at Shaukat Khanum
Memorial Cancer Hospital and Research Center to the patient
with Burkitt lymphoma got first cycle of COPADM. Nurses
are challenged by the complexity of the therapy regimen &
the management of acute and long term effects & toxicities.
Nursing care include symptoms management,encouragement
and support to the patients during hospital stay
Design/Methods: We retrospectively investigated nursing
notes of 30 patient of Burkitt's lymphoma patients received
first cycle COPADM at Shaukat Khanum Memorial Cancer
Hospital and Research Center during the year December 2016
to Jan 2017. Information including age, sex, financial status
& duration of hospital stay. Common issues experienced were
completely examined. Nurse's notes were evaluated in regards
to motivational and dietary advising.
Results: 30 patients reviewed 28 were male. Median age of
diagnosis was 14 years. All of these patients were admitted though EAR after 5-7 days of post COPADM. During
hospital stay, Nurse to patient proportion was 1:6. Span of
Hospital stay was 10-14 days. Symptoms persisting for 7
days or more included Oral Mucositis (56%), Nausea (46%),
Diarrhea (29%), fever (25%). Oral intake was decreased in
62% (n=19) primary contributing element was oral mucositis
(n=18), nausea vomiting (n=14) abdominal discomfort (n=8)
and disliking the food (n=6). Persistent nursing care including regular oral care and counseling for dietary improvement. 62% patients (n=19) were encountered by psychological disturbance, eminent reasons were social separation, home
sickness, fear of disease progression & long term toxicities
of chemotherapy. Frequent counseling session by attending
nurses were conducted with active listening, employing play
therapy (n=12), provision of Cartoon Movies (n=19) & story
books (n=10)
Conclusions: Individual assessment and dedicated efforts by
nursing staff can facilitate these patients to cope with the
S395 of S518
problems encountered after receiving first cycle of intense
chemotherapy COPADM.
P-502 The Feasibility of a Tool to Systematically
Evaluate Nursing Care Needs of Children with
Cancer and Utilization of Nursing Resources
H. Hansson1 , G. Petersen1 , M. Madsen1 , P. Roland1 , A.B.
Christensen1 , M. Nøddeboe1
1 Copenhagen
University Hospital - Rigshospitalet, Paediatric Haematology
and Oncology Department, Copenhagen, Denmark
Background/Objectives: As a result of more intensive and
complex treatment regimens, our patients have increasing
multi-faceted needs for nursing care. We developed a tool
called PIMI to systematically document and measure nursing care needs of children with cancer and the use of nursing
resources. The objective of this study was to assess the feasibility of the tool and the balance between nursing care needs
and the amount of nursing resources the needs demand.
Design/Methods: PIMI is recorded daily and comprises two
parts: 1) a classification in which the patient's needs for nursing care are evaluated and placed in one of six care categories, which refers to an optimal number of nurses needed
to meet the patient's needs, and 2) a comparison of the optimal number of nurses with the actual number of nurses available. The inter-rater reliability was studied and it will be statistically validated in 2017. Data were collected for 179 days
at our pediatric hematology oncology ward with 21-inpatient
beds between February and December 2016 and were analyzed with descriptive statistics.
Results: The ward had 150 days (84%) below the optimal
nursing staffing, 3 days on the optimal level, and 26 days
(14%) above the level. The daily average was: 17 in-patient
children (range 9-23), the optimal number of nurses needed:
10 (range 5-16), the actual number of nurses in nursing care:
8 (range 5-11), and number of nurses in nursing care with <
1 year of experience: 2 (range 0-6).
Conclusions: PIMI is easy and accurate to use. The results
document that the children's needs for nursing care do not
match with the actual staffing level. PIMI can be used to the
daily allocation of nurses based on the children's nursing care
needs, and to manage nursing resources most appropriate in
the long-term.
P-503 A Meta-Analysis and Systematic Review of
the Effect of Low-Level Laser Therapy in Pediatric
Chemotherapy-Induced Oral Mucositis
M. He1 , N. Shen2 , J. Sun2
SIOP ABSTRACTS
S396 of S518
1 Shanghai
Children's Medical Center, Hematology and Oncology,
Shanghai, China; 2 Shanghai Children's Medical Center, Nursing
Department, Shanghai, China
and a normal life. The purpose of this study was to develop
the resources to gain the positive attitude and the purpose
(resilience) in adolescents with cancer (AWC).
Background/Objectives: Background
Design/Methods: Yin's descriptive case study was used. The
data were analyzed with the pattern-matching logic. This
study was approved by the institutional review board. The
physicians identified potential participants from their appointment list. The semi-structured interview guide and Social Network Map were used to assess. The tools were performed faceto-face by an author in a private room and lasted between 45
to 90 minutes and occurred while the participants were waiting for the results of a blood test. The interview proceeded
from a broad and safe question to a specific and sensitive one.
The participants were asked about the cancer experience, positive coping, hope and social support. The same researcher
conducted the all interviews. The demographic and the health
information were obtained form the patient charts.
Oral mucositis is one of the most frequent complications after
chemotherapy, occurring in approximately 52% to 80% of
children receiving treatment for cancer. Recently, it has been
suggested that the use of low-energy laser could reduce the
grade of oral mucositis and alleviate the symptoms. Most of
recommendations were made for adult patients, not pediatric
patients. Data about effect of low-level laser therapy in pediatric patients is limited.
Objective
To synthesize the available clinical evidences on the effects
of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy-induced oral mucositis (OM).
Design/Methods: A meta-analysis was performed using trials identified through Pubmed (1966 to March 2017), EMbase
(1980 to March 2017), Cochrane Library (up to 2016), CNKI
(in Chinese, 1980 to March 2017). Data on occurrence, duration and severity of oral mucositis were collected. All randomized controlled studies and clinical controlled studies comparing LLLT to routine qualified prevention or treatment during
or after chemotherapy were critically appraised and analyzed.
Results: We found 5 qualified clinical trials with a total of
295 pediatric patients; methodological quality was acceptable. After meta-analysis, there was a significant preventive
effect of LLLT with a relative risk at 0.34 (95% CI, 0.12 to
0.99) for grade II or higher OM to occur, but no significant
preventive effects with a relative risk at 0.82 (95% CI, 0.60 to
1.11) for all OM to occur. After prophylactic LLLT, the OM
severity could decrease significantly, with combined effect
size -0.54 (95% CI, -1.87,-0.03). No meta-analysis could be
done with the effect of LLLT on treatment of OM
Conclusions: Recommendation could be made to support
LLLT on prevention of OM in pediatric patients. Effect of
LLLT on treatment of OM could be promising, to decrease
pain and duration. Future research should identify the proper
characteristics of LLLT and determine feasibility in the clinical setting.
P-504 Developing Resources to Gain Resilience in
Adolescents with Cancer
K. Kamibeppu1
1 Graduate
School of Health Sciences & Nursing Faculty of Medicine- The
University of Tokyo, Department of Family Nursing, Tokyo, Japan
Background/Objectives: Positive health is defined as developing strengths and resources to gain resilience. The resources
refere to maintaining peers, school life, social relationships,
Results: The 9 participants comprised 6 malls and 3 females.
Five of them were newly diagnosed, and 4 had experienced
relapse. the ages pf the newly diagnosed participants reed
from 13 to 17 years, and the participants who had relapsed
were aged between 12 and 17 years.
Conclusions: The positive attitude and the purpose were
related to the resources.
P-505 The Scope of Practice for Advanced
Practice Nurses Working with Short Term Global
Health Programs
P. Johnson1
1 Children's
Mercy Hospital, Hematology/Oncology, Kansas City, USA
Background/Objectives: Advanced practice registered
nurses (APRNs) are an essential part of the US health care
system and many seek to volunteer for short term global
health programs to further expand their worldviews and
provide care to marginalized populations. The International
Council of Nurses (ICN) created a Scope of Practice and a
Code of Ethics to be followed for APRNs practicing internationally, however this is not widely known. In addition, many
countries do not fully recognize the APRN role and what
healthcare services they can or cannot provide.
Design/Methods: The purpose of the project was to explore
APRNs perceptions of their scope of practice and current
international standards of practice. A 21 item Survey Monkey© in 2016, was conducted among members of the American Academy of Nurse Practitioners International Special
Interest group who had participated in international short term
global health programs. Participants were asked about scope
of practice used with international practice, awareness of
practice guidelines and ethical dilemmas encountered regarding scope of practice.
SIOP ABSTRACTS
Results: Nineteen respondents qualified for the survey. Half
were family nurse practitioners and had participated in five or
more trips internationally. Over 50% believed they were recognized as an APRN but many of the countries listed do not
recognize APRNs. Over 60% followed their US scope of practice. Some expressed concerns about the number of patients
to be seen with limited resources but 90% expressed a love of
the work did not feel ethically challenged. Ethics of practice
ranged from national guidelines to personal beliefs.
Conclusions: As APRNs participate more in short term
global health programs, mindfulness of the host and country
expectations regarding scope of practice and national recognition of their role. Continued discussion of international roles
of APRNs will help increase access to vulnerable populations
and reduce stress to the providers.
P-506 A Case Study Approach to Understanding
the Value of Blogging for Social Support in Parents
of Children Who Have Completed Cancer-Directed
Treatment
M. Killela1 , S. Santacroce2
1 University
2 University
of North Carolina at Chapel Hill, Nursing, Raleigh, USA;
of North Carolina at Chapel Hill, Nursing, Chapel Hill, USA
Background/Objectives: Completion of cancer-directed
treatment contains a very stressful transition for children with
cancer and their families. The stress associated with this time
period is amplified when the social supports that are associated with regular hospitalizations and outpatient visits are less
frequent and thus a gap in the social network of families is
created. The use of social media presents a possible source of
support to fill this gap. This exploratory study aims to qualify
the types of support evident in one family's publicly available
online blog detailing their experiences in the period following
completion of cancer-directed treatment.
S397 of S518
Conclusions: This paper serves to provide information necessary for future studies in developing a nursing intervention
to widely distribute blogging as a means of improving social
support among parents and caregivers of children who have
completed cancer-directed treatment.
P-507 A Study on Preparation Utilizing a Picture
Book at Hospitalization: for Patients of 3-10 Years
Old
N. Nakagaki1
1 Wayo
Women's University, Nursing, Ichikawa, Japan
Background/Objectives: The purpose of this study is to
make clear how preparation utilizing a picture book influenced the children's coping ability when being admitted to a
hospital.
Design/Methods: The subjects of this study were eight children of 3-10 years old with leukaemia. During the children's
hospitalization, nurses explained children the necessity of
their hospitalization, visiting hour, hospital life and various
staff using a picture book. Time of the explanation was 2030 minutes. They were hospitalized for the first time in a
C ward for a hospitalization period of 3-7 days. Data was
collected on the 1st day, the 2nd day and the last day of
the hospitalization by means of participation observational
method. The children's reactions toward hospitalization were
observed. We analyzed and coded the children's reaction
focusing on the state of their hospital life. The coded results
were classified to subcategories, categories and then core
categories.
Results: The derived 7 core categories are as follows:
Design/Methods: By implementing Schaefer's theory of
social support, which differentiates among emotional support,
information support, and tangible support (1981), this paper
used directed content analysis to scrutinize blog posts written
in the six-months following cancer-directed treatment completion and to sort the content by social support domain.
[Children made up their mind to be staying in the hospital
by joining preparation during hospitalization.] [They made
an effort in order to get over loneliness staying away from
their family.] [They could spend their hospital life depending on nurses.] [They spent the hospitalization with the
relaxed feelings] [They had positive feelings toward the hospital life] [They could positively receive medical practice.]
[They persevered in the hospitalization and had the feeling of
achievement.]
Results: The most common form of social support observed
was information support in two categories: information about
medical procedures and information about family life. The
second most common form of social support was emotional
support, which was divided into expression of fear and stress
associated with both disease recurrence and the quest to
achieve a new normal. Lastly, the third form of social support, tangible support, was the least common and expressed
mostly in terms of gratitude for such support.
Conclusions: Children became able to imagine a hospitalization life somehow because they received preparation with
their family's cooperation. Children were able to communicate with a nurse by sharing a picture book in preparation for
hospitalization. Therefore children could build mutual trust
relationship with a nurse and entrust a nurse with their hospital life. We consider children can evade prospective critical
situation in hospitalization by receiving preparation utilizing
a picture book.
SIOP ABSTRACTS
S398 of S518
P-508 The Actual Situation of Preventive
Measures Against Exposure to Anticancer Drugs in
Japan
H. Petts1
J. Ogawa1 , M. Kudo2 , M. Baba3 , T. Watanabe4 , K. Sakuta2 , Y.
Ohara2
Background/Objectives: The complexity, number and cost
of medications within oncology has continued to rise.
1 Shukutoku
University, School of Nursing&Nutrition, Chiba, Japan; 2 Chiba
Children's Hospital, Nursing, Chiba, Japan; 3 Teikyo University Medical
Center, Nursing, Ichihara, Japan; 4 Chiba University Hospital, Nursing,
Chiba, Japan
Background/Objectives: A guideline on preventing occupational exposure to anticancer drugs was published in 2016 in
Japan. It is, however, insufficient to cover the pediatric oncology area. This study aimed to find the perception of occupational exposure among pediatric oncology nurses.
Design/Methods: The original questionnaires about the preventing occupational exposure were mailed to nurses working
for 104 hospitals (3 nurses from each hospital) where cancer
children were treated.
Results: Got 107 nurses (34.3%) responded including 86
nurses (80%) who reported they have hospital rules for occupational exposure. And found 78 nurses (73%) take some preventing measures for disposal of child excreta and 60 nurses of
them educate family caregivers of children about preventing
exposure.
Eighty-seven nurses (81%) take preventing measures for handling linen contaminated with excreta, while only 38 nurses
(36%) explain about doing the laundry or taking laundry home
to families. Specific exposure measures concerning the handling of excreta and linen were various, such as wearing only
gloves and using some of personal protective equipment.
Fifty-five nurses (51%) clean children at the time of diaper changing. 19 nurses (18%) apply ointment for protecting
themselves from exposure before administrating anticancer
drug to children.
Seventy-seven nurses (71%) responded that they put on gloves
for protection at the time of oral anticancer drug administration, and 64 nurses (60%) explain family caregivers about
its importance. 55 nurses(51%) take preventing measures for
handling empty bags of oral anticancer drugs.
Conclusions: It's clear that preventing exposure to anticancer
drugs for medical staff in pediatric oncology ward is not sufficient and need for guidelines specialized in childhood cancer
treatment because patient's siblings or mother who gets pregnant are much more vulnerable than ordinal adults.
1 Birmingham
Childrens Hospital, Haematology/ Oncology, Birmingham,
United Kingdom
Nurses in a busy 27 bedded Principal Treatment Centre were
reporting they were spending less time with patients at the
bedside and more time in the drug preparation rooms. Families commented they always knew where to find a nurse;
in the drug preparation room. This was compounded by the
Trust's drug administration policy required 2 trained staff for
the whole process.
The project sought to explore the possibility of pharmacy
technicians being part of this traditional nurse's role (from
preparation of a drug trolley and medicines through to the documentation of the administration being complete) thus releasing nurse's time to care in a health- economy where paediatric
nurse recruitment was challenged. Further objectives were
to improve timely delivery of medicines; reducing avoidable
medicines waste and integrate the pharmacy role into the paediatric oncology ward team;ncreasing efficiency.
Design/Methods: Initial observational studies were undertaken to identify the busiest time of day for intravenous and
oral drug administration.This time was used to focus the initial intervention with the aim of maximum impact. A training
package was disseminated for the technicians and checklists
introduced based on monographs.
Results: Each oral drug round undertaken by the nurse +
pharmacy technician has reduced from an average of taking
61minutes to 41 minutes releasing time for “nurses to care”.
Additionally there was a reduction of 1-3 medication/ prescribing errors/ near miss incidents per day.
Conclusions: The pharmacy technician – nurse combination to oral and intravenous medication administration has
improved the patient / staff experience and released nurse's
time.
There continues to be a high incident reporting culture within
the clinical area but the overall associated harm level has
reduced and a proactive protocol driven approach to safety of
medications has been embedded.
P-510 Symptom Patterns in Children Recovering
from Hematopoietic Stem Cell Transplant
C. Rodgers1 , M. Highberger2 , K. Voigt2 , K. Powers3
P-509 The Introduction and Collaboration of
Pharmacy Technicians to the Drug Adminsitration
Process with Nurses Increases Saftety and Releases
Time to Care
1 Duke
University, School of Nursing, Durham, USA; 2 Baylor College of
Medicine, Pediatrics, Houston, USA; 3 Ann & Robert H. Lurie Children's
Hospital, Stem Cell Transplant, Chicago, USA
Background/Objectives: Hematopoietic stem cell transplantation (HSCT) causes frequent and distressing symptoms that
SIOP ABSTRACTS
S399 of S518
continue through the first 100 days post HSCT, known as
the acute recovery phase. Current HSCT symptom research
focuses on symptom prevalence at specific points in time with
little evidence regarding the complexity of symptoms and
their changes over time. The primary aim of the study is to
identify symptom trajectory patterns among adolescents during acute HSCT recovery.
Design/Methods: A repeated measures design was used to
elicit symptoms experiences from 55 adolescents, age 1019 years, who received an allogeneic HSCT. After signed
consent/assent, demographic information was obtained from
the medical record and adolescents completed the Memorial
Symptom Assessment Scale (MSAS) prior to HSCT. Adolescents completed the MSAS again at one, two, and three
months post HSCT.
Results: Data collection will be completed in June. Symptom trajectories will include symptom frequency, severity, and
distress and evaluations will occur separately for these three
symptom characteristics. Descriptive statistics and standard
linear regressions will be used to examine the data over time.
Conclusions: Findings from this study will allow healthcare providers to easily recognize and even anticipate their
patients’ symptoms during acute HSCT recovery. These
providers can have meaningful symptom discussions with
their patients to provide anticipatory guidance and promote
strategies that can best help patients manage their symptoms.
tralia) interfaced with a laptop computer was used to conduct PWV measurements. Trained professionals performed
anthropometric measurements (e.g., weight, height, blood
pressure, surface distance carotid site to jugular notch and
jugular notch to femoral site) and entered them into the laptop for PWV calculation. PWV measurements were discarded
and repeated if heart rate varied >10% between carotid and
femoral site captures.
Results: Most of the 23 participants were male (52%), white
(82%), and non-Hispanic (74%) with mean age of 12.26 ±3.16
years and mean time since treatment 2.30 ±1.06 months. The
device tonometry probe failed during preparations in clinic
for the first data collection. We had a second probe on hand
and experienced no further technical issues. All participants
lay quietly on an exam table and otherwise cooperated with
PWV measurements. Femoral site captures were challenging but achieved for the 5 participants (22%) with body mass
index (BMI) z-scores >2. Plots compare PWV measurements
to reference values for healthy children by sex and age, and
show associations between PWV and BMI z-scores.
Conclusions: Measurement of PWV during clinical visits for
children who recently completed cancer therapy is feasible.
PWV measurements have potential to both inform and evaluate precision interventions to control risk for CVD in new
survivors of childhood cancer.
This study was funded by Alex's Lemonade Stand Foundation.
P-511 Feasibility of Measuring Carotid-Femoral
Pulse Wave Velocity (PWV) During Clinical Visits
to Estimate Risk for Cardiovascular Disease (CVD)
in New Survivors of Childhood Cancer
1
1
2
3
3
S. Santacroce , J. Crandell , J. Bai , J. Blatt , S. Gold
1 The
University of North Carolina at Chapel Hill, School of Nursing and
Lineberger Comprehensive Cancer Center, Chapel Hill, USA; 2 Emory
University, Nell Hodgson Woodruff School of Nursing, Atlanta, USA; 3 The
University of North Carolina at Chapel Hill, School of Medicine and
Lineberger Comprehensive Cancer Center, Chapel Hill, USA
Background/Objectives: Carotid-femoral pulse wave velocity (PWV) is an accurate non-invasive means to estimate
arterial stiffness and thus risk for CVD in adults. The study
purpose was to examine feasibility of measuring PWV during clinical visits to estimate risk for CVD in children who
recently completed cancer therapy and relate PWV measurements to reference values.
Design/Methods: Included: children aged 8-19 years and 14 months post treatment with treatment regimen that incorporated anthracyclines. Excluded: children with history of
another medical condition (e.g., diabetes) known to heighten
risk for CVD. A SphygmoCor Px device (Atcor, Sydney Aus-
P-512 Establishment of A Guideline to Facillitate
Adjustment on School Reentry for Children with
Cancer in Japan
G. Sayaka1,2 , S. Hitoshi1 , M. Kimikazu3
1 Tohoku
University Graduate School of Medicine, Department of Child
Health Nursing, miyagi, Japan; 2 National Center for Child Health and
Development, Nursing Department, tokyo, Japan; 3 National Center for
Child Health and Development, Children's Cancer Center, tokyo, Japan
Background/Objectives: Children and adolescents with cancer face the difficulty to return to schools after completion of
the therapy. There is no standard guideline for supporting to
school reentry for children with cancer in Japan.In this study,
we aim to develop a guideline for assessing the support of
school reentry for children with cancer, providing equality in
this situation in Japan.
Design/Methods: First, we identified 39 papers from an
online literature retrieval system of past 10 years using search
words such as “childhood cancer,” “chronic disease,” and
“school reentry”, and collected fundamental information to
establish a guideline. Five experts in medical care or educational research on children with cancer evaluated those papers
using the Delphi method. Subsequently, a semi-structured
interview was conducted with 6 clinical nurses who specialize
SIOP ABSTRACTS
S400 of S518
in pediatric cancer care, to confirm the validity of the guideline.
Results: Although the supporting program of school reentry
provided by hospitals in Japan varied, the basic elements were
common. In addition to scheduling of the conference, and
preparing requesting letters, we find it very important to affirm
consensus between patients and their parents in the individual
reentry plan.
The conference should be held with doctors and nurses in
charge, class teachers and supervisors, and patient and parents soon after the completion of initial treatment and at two
to four weeks before discharge. The points to be addressed in
the meeting included the information of disease to the concerned people at school, and methods to facilitate adjustment
to classmates, those concerned with schools, and the healthcare personnel involved.
Conclusions: A guideline will provide concrete methods of
school reentry for children with cancer to patients, parents,
medical staffs, and educators, which will lead to fulfilling support for pediatric cancer patients.
operation theatre. The sheltering place consists of a familiar
place, nearby the child´s hospital bed. The sheltering place
creates an atmosphere that is embracing, calm and protects
the child from the outside world. By reducing environmental
difficulties and de-dramatizing the event the sheltering place
provides a temporary opportunity to feel safe and protected,
which decreases the child´s anxiety and fear, and adapts the
situation to the children´s needs. In doing so, the sheltering
place minimizes the interference of the caring process on the
child´s daily life.
Conclusions: Working for the child´s best by creating a sheltering place during sedation for chemotherapy promotes adoption of a child-centred approach.
P-514 How Hospital Environment Influences
Children's Cancer Nursing in Japan
M. Uchida1 , S. Takeuchi1 , F. Shirai2 , Y. Ohara3 , N. Takenouchi4 ,
M. hirata5 , M. Adachi1 , Y. Takahashi1 , J. Nonaka6 , J. Ogawa7 , M.
MOri8
1 Nagano
College of Nursing, School of Nursing, Komagane, Japan;
College of Nursing, School ob Nursing, Komagane, Japan; 3 Chiba
Children's Hospital, Department of Nursing, Chiba, Japan; 4 Kanagawa
Children's Medical Center, Department of Maternal & Child Health,
Yokohama, Japan; 5 St. Luke's International Hospital, Department of
Nursing, tokyo, Japan; 6 Kanagawa University of Human Service, Child
Health Nursing, Yokosuka, Japan; 7 Shukutoku University, School of
Nursing & Nutrition, chiba, Japan; 8 University of Human Environments,
Child Health Nursing, Okazaki, Japan
2 Nagano
P-513 Working for the Child´S Best by Creating a
Sheltered Place During Chemotherapy for
Paediatric Leukaemia
C. Sjöberg1 , I.M. Carlsson1 , P. Svedberg1 , J. Källstrand Eriksson1 ,
J. Nygren1
1 Halmstad
University, School of health and Welfare, Halmstad, Sweden
Background/Objectives: Leukaemia is the most common
cancer form for children worldwide. The disease encroaches
on the child's daily life and influence on their living conditions and lifestyle. In addition to the disease itself, the treatment is an unpleasant experience that can cause pain, nausea and suffering. During treatment, the children stays at the
hospital for long and frequent periods, which has a significant effect on their everyday life. Improvement and increased
quality of care for children throughout their cancer trajectory
is important and could lead to a better experience for children
and reduced suffering related to the treatment.The objective
was to explore the caring environment in accordance to sedation for chemotherapy in paediatric leukemia.
Design/Methods: The study followed the approach of
grounded theory and were based on interviews with practitioners involved in the paediatric oncology care process
such as paediatricians (n=2), anaesthetists (n=2), child-nurses
(n=3) and nurse anaesthetists (n=5).
Results: The main concern that emerged was “creating a
sheltering place”, which means that all healthcare professionals works for the child´s best by providing sedation for
chemotherapy at the children´s department instead of the
Background/Objectives: A Japanese Society of Pediatric
Oncology Nursing study group developed “Nursing Care
Guidelines for Children with Cancer 2012” to standardize
children's cancer nursing in Japan in 2012.
In addition, we examined the degree of importance and
the frequency of each nursing practice based on the guidelines to evaluate this guideline in 2016. As a result,
nurses recognized that almost all nursing practices on
the guideline were important. However, nurses felt difficulties implementing a few nursing care despite their
recognition.
This study examines factors influencing nursing practice to
improve children's cancer nursing in Japan.
Design/Methods: We sent two different of questionnaires to
216 wards where children with cancer were hospitalized. The
questionnaire is composed of the following two categories.
1. On frequency of nursing practice
Asked how frequently they bring their practice into action
based on the 46 items in the Guidelines.
2. On their hospital environment
Asked how their team is composed, the arrangement of certified nurse specialist, and physical environment for children in
their wards.
SIOP ABSTRACTS
We analyzed answers from 56 wards that completely
answered questions from two categories, in order to see the
relationship between the frequency of nursing practice and
their hospital environment. Out of this 56 wards, 43 were university hospitals, 7 were children's hospitals and 5 were general hospitals.
For data analysis, we conducted a Mann-Whitney-U test using
SPSS statistics Ver.21.
Results: We found that the following 4 hospital environment
factors especially have strong influences to the frequency of
the nursing practice.
– The arrangement of certified nurse specialist
– The presence of “Nursing Care Guidelines 2012”in their
wards
– The presence of long-term follow-up system for children
with cancer
– The presence of teen room
S401 of S518
Results: Fifty-six patients (83.6%) had cancer and 11 (16.4%)
had inflammatory/reactive diseases. Within solid tumors
we found a reversed CD4/CD8 T-cell ratio in neuroblastic (median:0.82; n=10); adrenal (median:0.68; n=2); renal
(median:0.55; n=4) and germ cell tumors (median:0.55; n=8).
Conversely, CD4/CD8 ratio was ≥1 in soft tissue sarcomas
(median:1.2; n=7); Nasopharyngeal carcinomas (median:1.0;
n=3) and inflammatory/reactive masses (median:1.9; n=6).
There was a statistically significant difference (p<0.05)
between the percentage of T cells in soft tissue sarcomas –
median:3.0% (1.0 – 11.8) - and nasopharyngeal carcinomas –
median:32.9% (15 – 36.8); and also between nasopharyngeal
carcinomas and germ cell tumors – median:6.2% (0.2 – 36.7).
Concerning BM samples (n=27), BM infiltrated with neuroblastic tumors (n=9) had significantly more total T cells median:7.6% (3.0 – 39.0) - than non-infiltrated BM of patients
with neuroblastic tumors (n=11) – median:5.4% (2.0 – 10.8)
and also than reactive/inflammatory BM – median:5.4% (4.1
– 6.5).
Conclusions: From the results, some of the influencing factors on the nursing practice have been revealed. Enhancing
those factors in their wards will raise the quality of the nursing practice.
Conclusions: Our data showed that there are different patterns of T cell tumor infiltration according to disease categories. Such differences can relate to distinct patterns of
tumor aggressiveness. In addition, infiltrating neuroblastic
cells seem to induce an increase of total T cells in BM. Further investigation is necessary to elucidate the role of these
differences.
TREATMENT AND CARE - B IOLOGY
AND PATHOLOGY
P-516 Antitumor Activity of Flubendazole in a
Neuroblastoma Tumor Model
P-515 Characterization of the Immune Infiltrate
in Pediatric Solid Tumors by Flow Cytometry
V. Botafogo1 , C. Ferreira-Facio1 , P. Ferrão1 , L. Castro1 , E. de
Oliveira1 , M.C. Canellas1 , D. Vieira-Lopes1 , J. Almeida2 , A.
Orfao2 , E. Sobral da Costa1
1 Federal
University of Rio de Janeiro, Pediatric Institute IPPMG, Rio de
Janeiro, Brazil; 2 University of Salamanca, Cancer Research Center,
Salamanca, Spain
Background/Objectives: Interactions between cancer and
immune cells can influence treatment response and patients´
prognosis. The proposed strategy aims at characterizing the
infiltrating immune cells in solid tumors and in metastatic
sites from pediatric patients with cancer using Multiparameter Flow Cytometry (MFC).
Design/Methods: Eighty-seven samples were obtained at
diagnosis from 67 patients suspicious of pediatric cancer 44.8% males and 55.2% females. A MFC panel of markers was used for the identification and characterization of
tumor and immune cells. The Mann-Whitney U test was
used for continuous variables (SPSS, version 21.0, Chicago,
IL).
E. Cecen1 , Z. Altun1 , S. Aktas1 , E. Serinan1 , E. Kolatan2 , H. Evin1 ,
O. Yılmaz2
1 Dokuz
Eylül University, Basic Oncology, izmir, Turkey; 2 Dokuz Eylül
University, Department of Laboratory Animal Science, izmir, Turkey
Background/Objectives: Neuroblastoma is the most common extra-cranial solid tumor in children. Half of all patients
presenting with neuroblastoma have metastatic disease at the
time of diagnosis, and their overall prognosis has been poor
despite intensive therapy. Flubendazole had been demonstrated to exert activity against leukaemia, myeloma and neuroblastoma cells. The aim of the study was to investigate antitumor activity of flubendazole in a neuroblastoma.
Design/Methods: The effects of flubendazole on the C1300
neuroblastoma cell line were measured in vitro by using
MTT assay. C1300 cells were injected subcutaneously to
nude mice. Twenty male 4-week-old mice were used (5
mice each group). All the mice were divided into 4 groups.
Group I; Control group, Group II; Flubendazole group (50
mg/kg/day), Group III; Cisplatin group (16 mg/kg/day),
Group IV; Flubendazole+cisplatin group. Each group was
treated every 3 days and the next day sacrificed. Sections were
stained with hematoxylin and eosin (H&E). The electrically
SIOP ABSTRACTS
S402 of S518
evoked auditory brainstem response (EABR) was evaluated in
all mice. Statistical analysis was performed using SPSS. The
significance of the data was analyzed using Kruskal-Wallis
and Mann-Whitney-U and p-values of p < 0.05 were considered significant.
Results: Ld50 doses of flubendazole were determined and 50
mg/kg flubendazole was administered accordingly. The rates
of necrobiyosis in tumors were evaluated. Tumor necrosis
were higher in the group II, III and IV, when compared to the
group I (control) (p=0.029). Rates of tumor necrosis at group
I, II, II and IV were %5, %46.25, %48.95, %70, respectively. In
all groups, except for the control group, serum creatinin levels
were increased.
Conclusions: Flubendazole showed no more toxic effect than
cisplatin and led to cell death at similar levels with cisplatin.
Application of these data to clinical practice requires further
studies.
P-517 Low Phase Angle (PA) Values of the
Electrical Bioimpedance Analysis (BIA) in Pediatric
Patients with Cancer
A. GAROFOLO1 , K.J.T. GUEDES1 , P. MAIA-LEMOS1
1 IOP/GRAACC/UNIFESP,
Pediatric, São Paulo, Brazil
Background/Objectives: PA is direct measure of cell stability and can be interpreted as indicator of membrane integrity
and predictor of body cell mass and as a prognosis indicator of
survival in clinical situations. Its use is described as valid even
in situations with oscillations in the hydration state. To know
the PA values obtained through the BIA in patients with
cancer and to characterize the sample for this indicator, and
to compare PA values with reference values in the healthy
pediatric population.
Design/Methods: Pilot cross-sectional study with pediatric
patients diagnosed with malignant neoplasm. The study used
BIA which describes the response of living organisms to an
externally applied current. It is a measure of opposition to the
flow of the applied current through tissues.
Results: Thirty-three patients (45% on chemotherapy and/or
radiotherapy, 33% new cases and 21% on hematopoietic stem
cell transplants) were evaluated, with an average of 10 years,
19 (57.6%) were male, with no difference for age between
genders. Tumors of the central nervous system (33%) and
leukemias (21%) were the main diagnoses in the study. Disease recurrences accounted for 15% of the total. 39 % were
underweight and 51% were overweight. The BMI for the total
sample was 17.5 ± 6.1. AF had a mean of 4.79 ± 1.5, (4.78 for
females and 4.8 for males). Compared to the healthy pediatric
population, oncological patients present lower AF means (5.5
vs 4.8).
Conclusions: Despite the small number of the sample, a PA
lower than that found in the healthy pediatric population was
demonstrated. Studies have shown that low PA values in
critically ill patients are associated with poor nutritional status, poorer clinical outcome and higher mortality.
P-518 SNPS in Micrornas Associated with
Vincristine Induced Neurotoxicity in Spanish
Children with Acute Lymphoblastic Leukemia
M. Umerez1 , Á. Gutierrez-Camino1 , M. García-Ariza2 , A. Sastre3 ,
N. García de Andoin4 , A. Echebarria-Barona2 , I. Astigarraga2 , A.
Navajas5 , A. Garcia-Orad1
1 University
of the Basque Country, Genetics- Physical Anthropology and
Animal Physiology, Leioa, Spain; 2 University Hospital Cruces, Department
of Pediatrics, Bilbao, Spain; 3 University Hospital La Paz, Department of
Oncohaematology, Madrid, Spain; 4 Universitary Hospital Donostia,
Department of Paediatrics, San Sebastián, Spain; 5 BioCruces Health
Research Institute, BioCruces Health Research Institute, bilbao, Spain
Background/Objectives: Vincristine (VCR), an important
component of childhood acute lymphoblastic leukemia (ALL)
therapy, often causes sensory and motor neurotoxicity. This
neurotoxicity could lead to dose reduction or treatment discontinuation. Several studies associated peripheral neurotoxicity with polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it
is well known that these genes are regulated by microRNAs
(miRNAs) and SNPs in miRNAs could modify their levels or
function. Therefore, the aim of this study was to determine
whether SNPs in miRNAs could be associated with VCRinduced neurotoxicity.
Design/Methods: The association analysis was performed in
a cohort of 155 Spanish children with B-ALL treated with
LAL/SHOP protocol. We selected all the SNPs described in
pre-miRNAs with a MAF>1% (213 SNPs in 206 miRNAs)
that could regulate VCR PK/PD genes. Genotyping was performed with VeraCode GoldenGate platform.
Results: Statistically significant association was found
between 8 miRNA SNPs and neurotoxicity during induction
phase. The most significant result in this study was found for
the rs12402181 in the seed region of miR-3117, in which A
variant allele showed a decreased risk of peripheral neurotoxicity. This miRNA could target ABCC1 and RALBP1 VCR
transport genes.
Conclusions: In the present study we detected a SNP in the
seed region of in miR-3117, which could alter ABCC1 and
RALBP1 VCR transport genes expression and consequently
affect VCR-induced neurotoxicity in patients with pediatric
B-ALL.
This project was supported by Basque Government (IT98916).
SIOP ABSTRACTS
P-519 Expression of Wilms Tumor 1 and CD31 in
Non-Involuting Congenital Hemangioma
Q. Shu1 , Y. Shu1 , Y. Liu1
1 Children's
Hospital- Zhejiang University School of Medicine, Department
of Surgery, Hangzhou, China
Background/Objectives: To analyze the clinicopathological features of the Non-involuting congenital hemangioma
(NICH), and to evaluate the expression of Wilms tumor 1
(WT1) and CD31 in NICH.
Design/Methods: Thirty-eight patients from our hospital who
were diagnosed with NICH during January 2014 and May
2016 were included in this study. The control group included
38 patients who were diagnosed with vascular malformations
(VM). Based on the appearance of the hemangiomas (flat or
slightly bossed), NICHs were divided into two groups: bossed
group and plaque-like group. The pathological characteristics
and the expression of WT1 and CD31 were analyzed.
Results: The 38 NICH cases included 27 males and 11
females, aged 1Y6M to 10Y3M (mean 4Y10M). Immunohistochemical study showed cytoplasmic staining of WT1 in
NICH, positive in the endothelial cells and pericytes. There
was significant difference in the positive rate of WT1 expression between NICH and VM (Fisher exact probability test,
P<0.01). CD31 was intensely and diffusely expressed in all
NICHs, including the small vessels of the lobules, irregular
stellate vessels and the anomalous vessels in the fibrous tissues between the lobules. No difference in the positive rate
of CD31 expression between NICH and VM was observed.
The expression levels of both WT1 and CD31 in the plaquelike group were significantly higher than those of the bossed
group (Person �2=10.481 and 10.596, respectively, P<0.05).
The expression of WT1 positively correlated with CD31 in
NICH (Person correlation test, r=0.384, P<0.05).
Conclusions: For NICH, bossed type was more common.
WT1 and CD31 were expressed in all NICH specimens, with
different expression levels between the plaque-like type and
the bossed type. Expression of WT1 in NICH positively correlated with CD31.
S403 of S518
Background/Objectives: Osteosarcoma comprises 5% of the
tumors in children and adolescents. It is an aggressive disease
with metastatic patients evolving with very poor clinical outcomes. We hypothesized that DNA methylation changes could
be associated with the mechanisms involved with transformation and progression in osteosarcomas.
Design/Methods: We profiled DNA methylation in 28
chemotherapy-naive samples from patients with osteosarcomas and nine normal bone tissues using the Illumina HumanMethylation 450K Beadchip arrays. Methylation data were
corrected for technical bias and cellular composition effects.
Results: Supervised comparison using a Bayesian framework
linear model identified 3,146 differentially methylated CpG
sites (DMSs, pvalue<0.01 and methylation differences >10%)
between osteosarcoma and bone samples, with the majority of
CpG sites (n=1,997, 63%) showing an hypermethylated state
in osteosarcoma samples. In addition, bumphunter analysis
identified 95 differentially methylated regions (DMRs). We
found that tumors exhibited an hypermethylated state of the
DMR that controls PTEN expression. PTEN down-regulation
was associated to increased tumor growth in osteosarcoma
cells. At DMS and DMR levels, methylation changes identified here were enriched to chromatin assembly and remodeling, DNA packing and gene transcriptional control suggesting that DNA methylation may be involved with osteosarcoma
disease. They were also enriched for skeletal system morphogenesis and development potinting to the involvement of DNA
methylation with the disruption of mechanism that control
bone cell differentiation.
Conclusions: Our analysis revealed that DNA methylation
changes might be associated with cellular transformation in
osteosarcoma. These changes may be controlling expression
of genes related to biological processes involved with disruption of the correct cell differentiation and transformation.
Finally, osteosarcoma showed a tendency to an hypermethylated state compared to normal bone samples.
P-521 Changes in DNA Methylation May be
Associated with Progression of Wilms Tumors
J.V.S. Guerra1 , R.M. Azevedo2 , P.A. Faria3 , B. De Camargo2 , M.
Maschietto1
P-520 Charaterization of the Involvement of DNA
Methylation Changes in Osteosarcomas
D. Onofre Vidal1 , M. Quintero Escobar2 , A. van Helvoort Lengert1 ,
E. Boldrini3 , S.R. Morini da Silva4 , L.F. Lopes3 , M. Maschietto2
1 Barretos
Cancer Hospital, Molecular Oncology Research Center,
Barretos, Brazil; 2 Brazilian Center for Research in Energy and Materials
CNPEM, National Laboratory of Biosciences LNBio, Campinas, Brazil;
3 Barretos Children's Cancer Hospital, Barretos Children's Cancer
Hospital, Barretos, Brazil; 4 Barretos Cancer Hospital, Department of
Pathology, Barretos, Brazil
1 Brazilian
Center for Research in Energy and Materials CNPEM, National
Laboratory of Biosciences LNBio, Campinas, Brazil; 2 Research Center
National Institute of Cancer, Department of Pediatric Hematology and
Oncology Program, Rio de Janeiro, Brazil; 3 Research Center National
Institute of Cancer, Department of Pathology, Rio de Janeiro, Brazil
Background/Objectives: Wilms tumors (WTs) have a
relapse rate of ∼25%, from which long-term survival remains
approximately 50%. Blastemal predominant WT have a higer
risk of relapsing and was associated with resistance to
chemotherapy and capacity of forming distant metastasis.
SIOP ABSTRACTS
S404 of S518
DNA methylation changes could be associated with the mechanisms involved with Ws progression and resistance. We
aimed to identify the underlying mechanisms involved with
metastasis formation in WT.
Design/Methods: A comprehensive DNA methylation using
the Illumina 450K Beadchip arrays was applied to matched
kidney, WT blastemal component and metastatic tissues from
patients treated under SIOP 2001 protocol. Methylation data
was corrected for technical effects and cellular composition.
Results: A Bayesian framework linear model considering
intra-patients and inter-groups comparisons identified 904
differentially methylated positions (DMPs, adjP<0.05) WT,
kidney and metastasis. The methylation pattern of these
DMPs showed that whilst WT displayed an hypomethylation
profile compared to kidney, metastatic samples had an hypermethylated profile compared to both. DMPs were enriched
manl biological processes involved wih embronic development, morphogenesis and cellular differentiation. They
were also related to genes enriched for pathways related to
metabolism, mTOR and PI3K-AKT signaling pathways. Several genes with a role in nephrogenesis and disrupted in WT
appeared as differentially methylated in our analysis, in agreement with the literature. To identify the most differentially
methylated regions (DMRs), a Gaussian kernel algorithim
from DMRcate was applied to WT and kidney tissues. This
analysis showed 36 DMRs between WT and kidney samples,
which were located next to 28 genes, including CYP26C1 that
catalyze reactions involved in drug metabolism.
Conclusions: Altogether, we found that Wilms tumors exhibited an hypomethylated state compared to normal kidney, and
both were hypomethylated compared to metastatic samples.
These methylation changes could be controlling the expression of genes associated with Wilms tumor progression.
P-522 Identification of Receptor Tyrosine Kinases
and Downstream Signaling Pathways as Possible
Therapeutic Targets Using Phosphoprotein Arrays
J. Neradil1,2,3 , P. Macigova1 , M. Sramek1 , K. Melicharkova2,3 , P.
Mudry2 , R. Veselska1,2,3 , J. Sterba2,3
1 Masaryk
University, Dept. of Experimental Biology, Brno, Czech
Republic; 2 University Hospital Brno and School of Medicine- Masaryk
University, Department of Pediatric Oncology, Brno, Czech Republic; 3 St.
Anne's University Hospital, International Clinical Research Center, Brno,
Czech Republic
Background/Objectives: The main aim of our study is to
identify activity of the RTK signaling pathways as well as
of the downstream signaling pathways in pediatric refractory
and/or relapsed solid tumors. Primary samples of tumor tissue taken from the individual patients, as well as paired samples (i.e., primary tumor sample and relapsed tumor sample)
are analyzed in detail to find the possible targets for personal-
ized biological therapy using monoclonal antibodies and lowmolecular-weight inhibitors.
Design/Methods: The experimental approaches include the
RTK and MAPK phosphorylation protein arrays to determine
patterns of activity in these two groups of signaling transducers. These arrays allowed us to identify activities of 49 human
RTKs and 24 downstream signaling molecules.
Results: Till now (March 2017), we analyzed 157 samples
in total. 88 patients have examined primary tumors only, 31
patients both primary and relapsed tumors and 7 patients
have analyzed three subsequent tumor samples. According to
ICCC-3 classification, the most frequent tumor types were
soft tissue sarcomas, CNS tumors and bone tumors. This number of samples allowed us to perform also a detailed analysis
of RTK and downstream signaling profiles that clearly showed
that histogenetically different groups of tumors clearly differ
also in their cell signaling activities. Furthermore, we can also
demonstrate the changes in cell signaling pattern after administration of low-molecular-weight inhibitors during the course
of the disease in patients suffering with rhabdomyosarcoma,
Maffucci syndrome or multiple infantile myofibromatosis.
Conclusions: To summarize, our obtained results bring completely new information concerning the changes in RTK and
downstream activity patterns associated with the course of
disease that may be important for determination of personalized therapy for these children.
Supported by the project No. 16-34083A from the Ministry
of Healthcare of the Czech Republic.
P-523 Childhood Tumours with a High
Probability of Being Part of a Tumour
Predisposition Syndrome; Reason for Referral for
Genetic Consultation
F. Postema1 , S. Hopman1 , C. Aalfs2 , L. Berger3 , F. Bleeker2 , C.
Dommering4 , M. Jongmans5 , T. Letteboer6 , M. Olderode-Berends3 ,
A. Wagner7 , R. Hennekam8 , H. Merks1
1 Academic
Medical Center, Pediatric Oncology, Amsterdam, The
Netherlands; 2 Academic Medical Center, Clinical Genetics, Amsterdam,
The Netherlands; 3 University Medical Centre Groningen, Genetics,
Groningen, The Netherlands; 4 VU University Medical Centre, Clinical
Genetics, Amsterdam, The Netherlands; 5 Radboud University Medical
Centre, Human Genetics, Groningen, The Netherlands; 6 University Medical
Centre Utrecht, Genetics, Utrecht, The Netherlands; 7 Erasmus Medical
Centre, Clinical Genetics, Rotterdam, The Netherlands; 8 Academic Medical
Center, Pediatrics, Amsterdam, The Netherlands
Background/Objectives: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of
major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an
overview of 20 childhood tumours that in themselves should
be a reason to refer a child for genetic consultation.
SIOP ABSTRACTS
Design/Methods: We performed a PubMed search to review
the incidence of TPSs in children for 74 tumour types listed
in the International Classification of Childhood Cancer third
edition (ICCC3). The results were discussed during a national
consensus meeting with representative clinical geneticists
from all six academic paediatric oncology centres in The
Netherlands. A TPS incidence of 5% or more was considered
a high probability and therefore in itself a reason for referral
to a clinical geneticist.
Results: The literature search resulted in data on the incidence
of a TPS in 23 tumours. For 20/23 tumour types a TPS incidence of 5% or higher was reported. In addition, during the
consensus meeting the experts agreed that children with any
carcinoma should always be referred for clinical genetic consultation as well, as it may point to a TPS.
Conclusions: We present an overview of 20 paediatric
tumours with a high probability of a TPS; this will facilitate paediatric oncologists to decide which patients should
be referred for genetic consultation merely based on type of
tumour.
P-524 Concentrations of Plasma-Free Amino
Acids in Pediatric Cancers
A. Synakiewicz1 , M. Sawicka-Zukowska2 , N. Adrianowska3 ,
G. Galezowska4 , J. Ratajczyk4 , A. Owczarzak5 ,
T. Stachowicz-Stencel1
1 Medical
University of Gdansk, Department of Pediatrics- Hematology and
Oncology, Gdańsk, Poland; 2 Medical University of Bialystok, Department
of Pediatric Oncology and Hematology-, Bialystok, Poland; 3 Medical
University of Lodz, Department of Pediatrics- Oncology- Hematology and
Diabetology, Lodz, Poland; 4 Medical University of Gdansk, Department of
Environmental Toxicology, Gdańsk, Poland; 5 Medical University of
Gdansk, Department of Clinical Nutrition, Gdańsk, Poland
Background/Objectives: Pediatric cancer remains one of the
main cause of death in the pediatric population because of its
low detection rate in the early stage. No single substance is
known to be sensitive and specific enough to detect cancer
cells and play a role as an early biomarker. Malignant neoplastic diseases are metabolic conditions with unique metabolism,
thus amino acids and level alterations in plasma are considered to play a role in carcinogenesis and further course of the
disease.
Design/Methods: Seventy seven children with cancer, including 47 with hematological malignancies (leukemias, nonHodgkin and Hodgkin lymphomas) and 30 with solid tumors
(nephroblastoma, neuroblastoma, soft tissue sarcomas, malignant brain tumor, germ cell tumors) were enrolled in this multicenter study. 22 plasma-free amino acids were determined
by highperformance liquid chromatography with fluorometric detection.
S405 of S518
Results: The results revealed significant differences between
children with cancer and healthy control.
Conclusions: This report suggest that plasma-free amino acid
profiling may be used in cancer diagnoses and may be considered as an early tumor biomarker. Further study in this specific
group is necessary to verify the metabolic patterns characteristic of pediatric cancer.
P-525 A Retrospective Analysis of Molecular
Profiling of Pediatric Solid Tumors Using OmniSeq
Comprehensive
L. Wiltsie1 , A. Papanicolau-Sengos2 , C. Morrison2 , K. Kelly1 , M.
Barth1
1 Roswell
Park Cancer Institute, Pediatrics, Buffalo, USA; 2 OmniSeq LLC,
Pathology, Buffalo, USA
Background/Objectives: Tumor molecular profiling holds
the promise of personalized diagnostic, prognostic and therapeutic decision making. Due to cost and limited availability, molecular profiling data of pediatric tumors is limited. A
small number of centers have performed large scale, genome
wide screening for molecular alterations in pediatric tumors
identifying about 30-40% of pediatric tumors with potentially
actionable alterations. OmniSeq Comprehensive, a New York
State approved next-generation sequencing assay, utilizes a
targeted approach to molecular profiling that screens tumor
DNA and RNA to identify somatic variants in 144 genes
focusing on genomic alterations known to be associated with
cancer.
Design/Methods: We analyzed OmniSeq Comprehensive
profiling of high risk solid tumors and brain tumors from
pediatric patients treated in Buffalo, NY from July 2016 to
March 2017. All results were reviewed at an ongoing Pediatric Molecular Tumor Board.
Results: Tumor samples from 21 patients age 2 months-22
years were analyzed. Results were available within 2 weeks
of obtaining a sample for testing in each case. At least one
variant was identified in 17/21 (81%) of patients with a mean
of 1.6 variants/patient. Eight patients (38%) had a variant considered potentially actionable. Six patients (29%) had a lesion
targetable with an agent in clinical trials, but did not meet eligibility requirements. In one patient with inflammatory myofibroblastic sarcoma, molecular testing identified an ALK gene
fusion, not identified by FISH, that aided in identifying the
diagnosis and led to targeted therapy with crizotinib as first
line therapy.
Conclusions: OmniSeq Comprehensive identified actionable
variants in children with high risk solid and brain tumors at
a rate similar to published results for genome wide molecular
profiling approaches. The results of this pilot study highlight
SIOP ABSTRACTS
S406 of S518
the potential role of a more cost effective, targeted approach
to molecular profiling in pediatric oncology patients.
C. Karadeniz1 , L.U. Besli2 , U.Ö. Akdemir3 , U. Aydos3 , F.G.
Pinarli1 , A. Okur1 , M. Özçelik3 , I.N. Karabacak3 , U. Kocak4 , O.
Atay Kapucu3
1 Gazi
University School of Medicine, Pediatric Oncology, Ankara, Turkey;
University Cerrahpaşa School of Medicine, Nuclear Medicine,
Istanbul, Turkey; 3 Gazi University School of Medicine, Nuclear Medicine,
Ankara, Turkey; 4 Gazi University School of Medicine, Pediatric
Hematology, Ankara, Turkey
2 Istanbul
I M AGI NG
P-526 Value of PET/CT in Treatment Response
to Chemotherapy in Musculoskeletal Tumors
R. Lopez-Almaraz1 , M. Garcia-Ariza1 , J.M. De Pedro Olabarri1 , U.
Gonzalez Camacho1 , A. Echebarria Barona1 , R. Adan Pedroso1 , T.
Rodriguez Inchausti2 , I. Astigarraga Aguirre1
1 Hospital
Universitario Cruces, Pediatric Hematology and Oncology Unit,
Cruces- Bilbao, Spain; 2 Hospital Universitario Cruces, Nuclear Medicine
Service, Cruces- Bilbao, Spain
Background/Objectives: To evaluate the correlation
between anatomopathological (AP) tumour necrosis in
musculoskeletal tumours and the morpho-metabolic response
observed in 18F-FDG PET/CT.
Design/Methods: Retrospective descriptive study. We collected data on pediatric new diagnoses of bone and soft tissue sarcomas (STS) in a tertiary hospital in the last 3 years
(January 2014-January 2017).
Results: Seventeen patients were newly diagnosed during
those years: 6 (35%) with Ewing sarcoma (ES), 5 (30%)
Osteosarcoma (OS) and 6 STS, of which 5 (83%) were Rhabdomyosarcomas (RMS). Within the (ES 5/6 patients underwent PET/CT. Two presented a complete morpho-metabolic
response coinciding with a 100% AP tumor necrosis. Two
others presented a very good partial response in the imaging test, with tumour necrosis being 96 and 98% respectively.
The last patient presented a partial response in PET/CT; but
could not undergo surgery for its inoperability. In the case of
the 5 OS; only two PET/CT scans were performed at the presurgical evaluation. these presented partial response in PETCT and had a necrosis of 34% and 65% respectively. In the
STS, PET/CT was performed in 4 of 6 patients: one with complete response; but could not undergo surgery because of its
high surgical risk. In the other three patients, PET/CT showed
a good partial response with complete necrosis in two and partial necrosis in the other.
Conclusions: In our series, PET/CT is a valuable diagnostic tool for the initial extension study and to evaluate the
chemotherapy response of bone and soft tissue tumors. Further studies are needed to demonstrate their degree of direct
correlation with tumour necrosis of histological pieces.
P-527 First FDG PET/MRI Experience of Gazi
University in Pediatric Oncology
Background/Objectives: PET/MRI has recently been introduced as an alternative to PET/CT and pediatric patients are
expected to be one of the main target groups for PET/MRI,
which has considerably less ionizing radiation compared to
PET/CT. The aim of our study is to compare FDG PET/CT
and PET/MRI in our group of pediatric oncological patients
in terms of anatomical correlation of FDG positive lesions.
Design/Methods: Total 31 pediatric oncological patients
were included in our study. The median age was 9 years
(range: 6 months-15 years). Nine patients were diagnosed for
lymphoma (2 of them were Hodgkin lymphoma), 4 neuroblastoma, 3 rhabdomyosarcoma, 3 ALL, 4 Langerhans cell histiocytosis, 2 Ewing sarcoma, 2 ovarian cancer, 1 glioblastoma
multiforme, 1 pelvic germ cell tumor, 1 renal clear cell carcinoma and 1 conjunctival squamous cell carcinoma. Total 39
sequential FDG PET/CT (GE Discovery ST) and PET/MRI
(GE Signa PET/MR) examinations were performed on the
same day after injection of mean 3,3 mCi (122 MBq) FDG.
PET/MRI was performed first in 5 patients and PET/CT was
obtained first in the rest of the patients. All images were evaluated by 2 nuclear medicine physicians separately.
Results: On lesion based analysis, total 16 sequential PET/CT
and PET/MRI examinations were concordantly negative.
Among 47 FDG positive lesions in 18 sequential PET/CT
and PET/MRI examinations (maximum 5 lesions/patient), 37
were positive with both CT and MRI. Remaining 10 FDG
positive lesions (2 central nervous system, 4 bone marrow, 2
lymph nodes, 2 soft tissue lesions) could not be differentiated
using CT although it could be demarcated using MRI.
Conclusions: PET/MRI showed better anatomical correlation
in FDG positive lesions compared to PET/CT in our pediatric patients. Therefore FDG PET/MRI, with reduced ionizing radiation and better contrast resolution in soft tissue and
bone marrow, may be a preferred alternative to PET/CT in the
pediatric population.
P-528 Diffusion-Weighted Magnetic Resonance
Imaging Shows A Critical Difference Between
Supratentorial and Infratentorial Pediatric
Ependymoma
J. Murray1 , H. Head2 , A. Hoeft1 , L. Margraf3
1 Cook
Children's Health Care System, Hematology & Oncology Center,
Fort Worth, USA; 2 Cook Children's Health Care System, Radiology, Fort
SIOP ABSTRACTS
Worth, USA; 3 Cook Children's Health Care System, Pathology, Fort Worth,
USA
Background/Objectives: Magnetic resonance imaging
(MRI) features differ between various childhood brain
tumors. Advanced MRI techniques including diffusionweighted imaging (DWI) can add vital information to
conventional sequences, potentially crucial in creating an
appropriate differential diagnosis. Ependymoma, the third
most common malignant brain tumor in youth, remains
challenging with respect to an imaging differential diagnosis.
We have recognized a critical difference in DWI characteristics between supratentorial (ST) and infratentorial (IT)
ependymomas in children.
Design/Methods: Following IRB approval, we re-reviewed
the MRIs and neuropathology from 30 consecutively diagnosed children with intracranial ependymomas, 2007-2016,
abstracting for tumor location (ST vs IT), diffusion characteristics and tumor grade. Chi-square and Cramer's V tests were
applied.
Results: The mean age at diagnosis was 5 years (18 boys, 12
girls). Eighteen patients had IT tumors and 12 had ST tumors.
Ten tumors had anaplastic histology (WHO grade III) and 20
had classic histology (WHO grade II). Eleven tumors showed
restricted diffusion on DWI, and 19 did not (13 facilitated diffusion and 6 were equivalent to surrounding brain). All tumors
that showed restricted diffusion were ST; none were IT. Of
the 11 restricting tumors, 3 had anaplastic histology. Of the
13 non-restricting tumors, 4 had anaplasia. The relationship
between tumor location and restricted diffusion was significant and strongly associated (�2(1) = 26.053, p = 0.000,
Cramer's V= 0.932).
Conclusions: Diffusion-weighted imaging can supplement
conventional MRI sequences in formulating a critical differential diagnosis in children with brain tumors. Our analysis shows a dramatic difference in diffusion characteristics
between ST and IT ependymomas, independent of tumor
grade. Supratentorial tumors tend to show restricted diffusion,
but IT tumors, irrespective of grade, do not restrict. We postulate that there are physiologic tumor microenvironmental factors that account for this observation. Awareness of DWI differences in ependymoma may be helpful in refining the initial
differential diagnosis.
P-529 Correlation of Brown Fat to Disease State
in Lymphoma Patients
S. Servaes1 , L. States1 , A. Ntoulia1
S407 of S518
brown adipose tissue (BAT) with positron emission tomography/computed tomography (PET/CT) in pediatric patients
with Hodgkin lymphoma and the disease and season.
Design/Methods: In total, 126 PET/CT studies of 41 subjects
(25 boys and 16 girls) with ages ranging from 6-22 years with
diagnosed Hodgkin lymphoma were retrospectively reviewed.
The uptake and anatomic distribution of BAT were evaluated
at PET/CT scans in every subject at the time of initial diagnosis and after completion of chemotherapy. Comparisons
regarding the presence of BAT at these two time intervals were
performed between each subject using McNemar's test. Correlations of BAT presence with children's gender, anthropometric data (body mass index and height), examination parameters (FDG and Glucose) as well as season were performed.
Results: 80/126 (63.5%) of PET/CT studies showed no disease activity, whereas in 46/126 (36.5%) of PET/CT presence of Hodgkin lymphoma disease was identified. Among
patients with no active disease, in 23/80 (28.8%) PET/CT
studies there were high BAT uptake, whereas among patients
with active disease more BAT uptake was observed in 8/46
(17.4%) examinations. This difference was marginally significant (p=0.05). There was no significant relationship between
BAT uptake and the season that PET/CT study was performed
(p=0.74). Finally BAT uptake was not associated with examination parameters including the FDG dose (p=0.06).
Conclusions: Our findings show a marginal correlation
between the BAT uptake and the disease state. However, contrary to what other studies have demonstrated, in our study
BAT uptake was not associated to the season that the PET/CT
examination was performed and the FDG dosage.
P-530 Laparoscopy as a Primary Investigatory
Tool in Pediatric Abdominal Massess
O. Zakaria1
1 King
Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia
Background / Objectives: BACKGROUND: Abdominal
masses still pose as a major challenge for pediatrcialn and surgeons.
AIM OF THE WORK: This study was designated to evaluate the role of diagnostic laparoscopy in investigating equivocal pediatric masses that had undergone other imaging modalities.
Design/Methods: A combined prospective and retrospective
multicentric study for the period of 13 years from January
2005 to December 2016.
1 The
Children's Hospital of Philadelphia and The University of
Pennsylvania, Radiology, Philadelphia, USA
Inclusion Criteria: all children from 3 months of age to 15
years were studied.
Background/Objectives: The purpose of our study was to
determine if there is a relationship between the depiction of
Exclusion Criteria: those who have a documented diagnosis through other imaging modalities including sonographic
SIOP ABSTRACTS
S408 of S518
and or CT guided biopsy. All patients underwent multiport diagnostic laparoscopy for biopsy from the mass. All
specimens were hispatologically assessed using H&E staining, some specimens were immunohistochemically studied,
patients mean follow up was 3.6 years.
Results: A total of 132 of patients were recruited in this study
they were 69 males and 63 girls with the male to female ratio
of1.1:1 the age ranged from 3 month up to 15 years with
the mean age 0f 2.7 ± 0.8. Out of the total studied group
54 patients were diagnosed as neuroblastoma with the percentage of 40.9% while 66 were having nephroblastoma while
the remaining 12 (9.1%) were having non-Hodgkin's abdominal lymphoma. All patients did not show any complications
related to the procedure. Patients mean follow up was 3.6
years. Most of cases (121) with different diagnosis were clinically staged as grade I to grade II (91.7%). Neither intraoperative or post operative complications were recorded during
this technique. The mean operative time was recorded to be
72 mins ± 20 in the earliest group; yet, it has declined to be
32 ± 12 mins in the latest group due to the advancement of
the learning curve.
Conclusions: Laparoscopy is an accurate, safe and should be
used as the sole tool for biopsing solid abdominal tumors in
pediatrics.
P-531 Reliability of Elastographic Sonography in
Predicting Pediatric Cervical Lymph Node
Malignancy
O. Zakaria1
1 King
Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia
Background/Objectives: Preliminary studies suggest that
ultrasonographic (US) elastography may be useful in differentiating benign and malignant cervical lymph nodes, thereby
informing decisions to perform a biopsy and facilitating
follow-up.
The current study aimed to evaluate the accuracy and reliability of US elastography in distinguishing malignant pediatric
malignant cervical lymphadenopathy from benign lesions.
Design/Methods: A total of 177 lymph nodes in 128 children
with the age ranging form 11months to 12 years ; they were
77 males and 51 females with a ratio of 1.5:1. A preliminary
diagnosis primary head and neck cancer were examined by
B-mode sonography, power Doppler ultrasound and elastography. Elastographic patterns were determined on the distribution and percentage of the lymph node area with low elasticity (hard), with pattern 1 being an absent or very small hard
area to pattern 5, a hard area occupying the entire lymph node.
Patterns 3–5 were considered metastatic. Ultrasound guided
aspiration cytology was done for 107 lymph nodes.
Results: The majority 154 (87%) of metastatic lymph nodes
had elastography pattern 3–5. This finding was observed in
only 6 (3.4) % of the benign lymph nodes (P < 0.001). The
elastography pattern had sensitivity of 87.3%, specificity of
96.5%, PPV of 98.2%, NPV of 73.1% and overall accuracy of
91.9% in differentiation between benign and malignant lymph
nodes. On the other hand, for the B mode criteria, the best
accuracy was given to abnormal hilum (73%). The accuracy
of power Doppler ultrasound pattern was 65.8%.
Conclusions: The accuracy of sonoelastography is higher
than other sonographic modalities in elucidating the pathology and diagnosis of cervical lymphadenopathy distinguishing between benign and malignant lesions. This may replace
the lymph node biopsies in the future. Moreover, The integration of lymph node sonoelastography in the follow up of
patients with known head and neck cancer may reduce the
number of biopsies.
EPIDEMIOLOGY - PATHWAY OF
CA R E
P-532 Training of Childhood Cancer
Ambassadors: A Nurse-Led Capacity Building
Project to Improve Early Diagnosis of Childhood
Cancer in Northwest Cameroon
G. Afungchwi1 , K. Francine2 , P. Hesseling3 , V. Njamnshi4 , P.
Nana2 , J. Kaah4
1 Cameroon
Baptist Convention Health Services, Childhood Cancer
Program, Bamenda, Cameroon; 2 Mbingo Baptist Hospital, Pediatric
oncology, Mbingo, Cameroon; 3 Tygerberg children's hospital- Stellenbosch
University, Department of Childhealth, Cape Town, South Africa; 4 Banso
Baptist Hospital, Pediatric Oncology, Kumbo, Cameroon
Background/Objectives: In resource poor countries, many
children with cancer are diagnosed at late stages, which
makes cure impossible(Awadelkarim et al. 2012; Sullivan
et al. 2014).Childhood cancer symptoms are usually missed
by community health professionals due to their unfamiliarity
with these signs. Even when referred with suspicion of cancer, lack of transportation means becomes a major cause of
delay(Afungchwi et al., 2016). The objective of this project
was to promote early diagnosis and prompt treatment of childhood cancers through the use of trained ambassadors and
mobile money.
Design/Methods: Health professionals and prominent traditional healers for 6 health districts were invited to their respective district health services for training. The training included
topics on biology of cancer, the early warning signs of childhood cancer, and the availability of care for children with cancer in Cameroon. Three trainees from each health district were
SIOP ABSTRACTS
selected as Childhood cancer Ambassadors and provided with
mobile phones and mobile money accounts to transport every
suspected patient to the treatment centre.
Results: 133 health care providers (including 20 traditional
healers) were trained, and 18 ambassadors selected and
equipped for referrals. There was a 33.8 percentage point
increase(p<0.001) in knowledge about childhood cancers
among trainees and the proportion of trainees providing
health education on childhood cancers to their communities
is expected to increase from 14% to 100%(p<0.001). A total
of 9,000 childhood cancer warning signs leaflets were distributed. The cost of training was €27.2 per trainee.
Conclusions: The SanofiEspoir MCM Awards has provided
an opportunity to build capacity for childhood cancer early
diagnosis in Northwest Cameroon. This project has the potential to become a formal surveillance model for childhood cancers and, if expanded to cover the entire region, would create
a net through which no child with cancer could filter undiagnosed.
S409 of S518
When cause of death analyzed for type of diagnosis (p-value:
0.022) and stay in hospital (p-value: 0.001) and definite treatment given or not (p-value: 0.000) while 93% cases were
diagnosed before death but only 50% cases were started on
the treatment(p-value:0.016). 16% cases died within 24 hrs of
admission while 58% stayed up to 2 weeks 50% of cases has
to travel >100 KM to reach the Children's Hospital Lahore.
Conclusions: There is an urgent need of capacity building
with more centers and trained health professionals, implementation of effective infection control measures and efficient psycho social support for these families to decrease the morbidity
and mortality in this center.
P-534 Differential Survival Rates in State Funded
and Privately Funded Paediatric Oncology Units in
Johannesburg, South Africa
K. Bennett1 , J. Geel1 , N. Beringer2
1 Faculty
P-533 Challenges Faced in Pediatric
Hematology/Oncology in a Developing Country:
The Children's Hospital Lahore Pakistan
Experience
A. Ahmad1 , N. Tahira1 , M. Sadiq1 , M.Y. Kazi1
1 Children's
Hospital and Institute of Child Health, Paediatric
Haematology/Oncology, Lahore, Pakistan
Background/Objectives: In Punjab Pakistan for a 200 million population there are very few dedicated pediatric hematology/oncology centers resulting in delayed diagnosis and
poor management of majority these children. Objective of this
study was to evaluate the challenges faced in pediatric hematology/oncology services in resource limited settings like the
Children's Hospital Lahore which is a 60 bedded unit with bed
occupancy of 200% and 300 new admissions per month and
over 1000 new childhood cancer cases each year.
Design/Methods: Retrospective review of 140 cases enrolled
and died in the department from January to December 2016
for their epidemiology, diagnosis, treatment, stay in hospital
and cause of death and analyzed with SPSS17.
Results: Among 140 patients analyzed 106/140(76%) were
below 10 years with M: F ratio 2.3:1.71/140 (51%) had
their diagnosis established at admission while 131/140(93%)
had their diagnosis confirmed before they died. Only 50%
cases had their definite treatment started before they died.36%
were diagnosed as ALL,38% with solid malignancies,9% BThalassaemia Major, 9% Aplastic Anemia, 4% AML and 4%
others like MDS, Factor VII deficiency. Febrile neutropenia and sepsis was the major killer in 95/140(68%) while
45/140(32%) died due to relapse or progression of disease.
of Health Sciences - University of the Witwatersrand- Wits Donald
Gordon Medical Centre- Charlotte Maxeke Johannesburg Academic
Hospital, Department of Paediatric Oncology, Johannesburg, South Africa;
2 Faculty of Health Sciences - University of the Witwatersrand- Charlotte
Maxeke Johannesburg Academic Hospital, Department of Paediatric
Oncology, Johannesburg, South Africa
Background/Objectives: Data on survival rates of children
with cancer is only available from two South African centres.
The reported rate of 52% is lower than that reported in similar
upper-middle income settings in South America and Eastern
Europe. The aim of this study was to analyse survival rates of
all children with cancer treated in two large referral centres in
both the state and private setting.
Design/Methods: This retrospective review included all children, (0-15years) diagnosed with a malignancy at two pediatric oncology units between January 2012 and December
2016. The treatment regimens in both units were identical, the
same doctors worked in both settings and all diagnoses were
confirmed histologically. Descriptive statistics and KaplanMeier analyses with Cox regression modeling are presented.
Results: There were 599 children, 107 of whom presented
from outside South Africa. Median follow up was 1.3 years
(IQR 0.4 to 2.7). The most common cancers were leukaemias
(24.4%), brain tumors (17.7%) and lymphomas (14%). The
HIV incidence was 6%. Two-year overall survival was calculated to be 60%. The highest survival rates were in children
with Hodgkin Lymphoma, retinoblastoma and nephroblastoma, while the lowest were noted in children with osteogenic
sarcoma and neuroblastoma. Children treated at the private
institution had higher two-year survival rates than those in the
state funded hospital (68% vs 55% p=0.0004).
Conclusions: Two-year overall survival rates were higher for
children treated in the privately funded unit. This may reflect
SIOP ABSTRACTS
S410 of S518
differential access to specialist care and earlier referral in the
private setting.
P-535 Incidence of Malignant Solid Tumor in an
Adolescent Population in an Equatorian Children
Hospital
A. Borja1 , M.J. Pesantez1 , D. Franco2
1 Hospital
Axxis, Oncología Pediatrica, Quito, Ecuador; 2 Hospital
Metropolitano, Pathology, Quito, Ecuador
Background/Objectives: Approximately thirty percent of all
pediatric cancers in children and adolescents are solid tumors,
most frequent types Brain Tumor, Wilms Tumor, Neuroblastoma, Hepatoblastoma and Osteosarcoma. The differences
between solid tumors in childhood and adulthood are well
delimited but not in the transition period. Under 15 years
old, brain tumors are the most common form of solid tumors,
however, according to WHO, between 10 to 15 years old a
higher incidence of Osteosarcoma, Ewing tumor and lymphoma was found compared to children. This shows noticeable changes in solid tumor distribution when children reach
adolescence.
Objetive: To determine incidence of solid malignant tumor
in adolescents at Children Hospital in Ecuador from January
2007 to August 2013.
Design/Methods: Descriptive, retrospective study including
406 patients between 9years11months and 14years11months
old. Inclusion criteria was diagnostic of Malignant solid tumor
confirmed by Pathology area.
Results: Of 406 patients, fifty six (13.5%) were admitted
by Malignant solid tumor. Most of them were males (63
%) and the mean age at diagnosis was 11.5 years old. CNS
tumor had the highest incidence (50%) followed by Lymphoma 14%, Osteosarcoma 9%, Germ Cell tumor 9%, Ewing
Sarcoma 5%, Neuroblastoma 5%, Hepatic Adenocarcinoma
2%, undifferentiated tumors and others 6%. Distribution by
type is similar to epidemiology of malignant solid tumor
described by literature however selection bias is possible due
to enroll of population admitted in this pediatric hospital
only.
Conclusions: CNS tumors were most common malignant
tumors found. Osteosarcoma appear to be less frequent compared to international series. In addition, a greater number than expected of males were diagnosed. Although epidemiology and distribution of solid tumor in children and
adolescents are different, evidence has shown that higher
survival incomes in adolescents could be expected by better psychological support and accurate treatment in specialized pediatric centers despite of this differences in the
epidemiology.
P-536 Impact of Acute Methotrexate-Induced
Neurotoxicity on Therapy Among Pediatric Patients
with Acute Lymphoblastic Leukemia
H. Danysh1 , A. Brown1 , O. Taylor1 , J. Brackett1 , P. Lupo1 , I.
Moore2 , M.C. Hooke3 , M. Hockenberry4 , M. Scheurer1
1 Baylor
College of Medicine, Department of Pediatrics, Houston, USA;
of Arizona, College of Nursing, Tucson, USA; 3 University of
Minnesota, School of Nursing, Minneapolis, USA; 4 Duke University, School
of Nursing, Durham, USA
2 University
Background/Objectives: Acute methotrexate-induced neurotoxicity (MTX-NT) among pediatric patients with acute
lymphoblastic leukemia (ALL) often results in treatment
interruption, potentially reducing treatment efficacy. Despite
its clinical significance, the effects of MTX-NT on subsequent
treatment have not been well-described. Therefore, we evaluated the impact of acute MTX-NT on delays and modifications
to MTX treatment among pediatric patients with ALL.
Design/Methods: We identified patients treated on ALL protocols who had reached maintenance therapy at Texas Children's Hospital and University of Arizona in 2012-2017
(n=158). MTX-NT was defined as the occurrence of NTrelated symptoms (e.g., seizure, aphasia) after receiving MTX
and led to a change in MTX therapy. Difference in time from
diagnosis to start of maintenance, cumulative intravenous
MTX dose, and number of intrathecal MTX courses between
end of induction and start of maintenance were compared by
MTX-NT status using multiple linear regression and adjusting
for age at diagnosis, sex, ethnicity, and ALL risk stratification.
Results: On average, patients were 8.3 years of age at diagnosis (range: 2.5-18.0). The majority was male (57%), Hispanic (58%), and assigned to high or very high risk treatment
arms (56%). A total of 25 patients (16%) experienced acute
MTX-NT, of which three (12%) subsequently relapsed or died
during follow-up. After adjusting for demographics and risk
group, those who experienced acute MTX-NT received a 2.7
g/m2 lower dose of intravenous MTX (95% confidence interval [CI]: 0.4-5.0; p=0.024) and 2.4 fewer intrathecal MTX
courses (95% CI: 1.6-3.3; p<0.001) by the start of maintenance therapy compared to those without MTX-NT. The
occurrence of MTX-NT did not significantly delay the start
of maintenance therapy (p=0.680).
Conclusions: MTX-NT during post-induction chemotherapy for pediatric ALL results in patients receiving significantly less intravenous and intrathecal MTX. Future work is
needed to determine whether modifications to therapy following acute MTX-NT compromise treatment efficacy or outcomes, including relapse and survival.
P-537 Incidence of Childhood Leukemia in Costa
Rica from 2001 to 2013: An International
Perspective
SIOP ABSTRACTS
F. Erdmann1,2 , T. Li3 , G. Luta3 , J. Schüz2 , A.M. Mora4
1 Danish
Cancer Society Research Center, Unit of Survivorship,
Copenhagen, Denmark; 2 International Agency for Research on Cancer,
Section of Environment and Radiation, Lyon, France; 3 Georgetown
University, Department of Biostatistics- Bioinformatics and
Biomathematics, Washington- DC, USA; 4 Universidad Nacional, Central
American Institute for Studies on Toxic Substances, Heredia, Costa Rica
Background/Objectives: Higher childhood cancer incidence
rates, particularly for leukemia, have been reported in highincome countries compared to low and middle-income countries. However, estimating childhood cancer incidence globally is hampered by a lack of reliable data from developing
countries, including those from the Latin American region.
Costa Rica is one of the few developing countries with a longterm nationwide population-based cancer registry, enabling
the analysis of high-quality incidence data on childhood
leukemia.
Design/Methods: Data on incident leukemia in children
under 15 years of age reported to the National Cancer Registry of Costa Rica between 2001 and 2013 were analyzed by
leukemia type, age at diagnosis, gender, and region.
Results: During the 13-year period, a total of 832 children
with leukemia were reported, resulting in an overall agestandardized incidence rate (ASR) of 58.1/million. The maleto-female ratio was 1.2. The highest age-specific rate was
observed in children aged 1-4 years (97.7/million). The most
frequent leukemia type was lymphoid leukemia; with an ASR
of 49.1/million the observed rate ranked among the highest
in the world. A very low rate was observed for leukemia in
infants, largely driven by the low lymphoid leukemia rate.
With respect to geographical differences, higher leukemia
rates were observed in the Huetar Atlantica (69.2/million) and
Huetar Norte (68.1/million) regions. Both regions are characterized by extensive agricultural fields.
Conclusions: The patterns of childhood leukemia incidence
in Costa Rica were closer to those reported from high-income
countries than to those reported from other developing countries. Further research is needed to investigate which factors
may drive the high overall leukemia rate, the low rate observed
in infants as well as regional differences. Our study suggests
using caution when interpreting global incidence differences,
since our observations from a developing country with wellestablished pediatric oncology clinics and nationwide registration showed only small differences to incidence patterns
from high-income countries.
P-538 Epidemiology of Childhood Cancers in
Upper Egypt: Five Years Experience of the Largest
Cancer Institute Outside the Capital
A. Farrag1 , M.H. Ghzally2
S411 of S518
1 South
Egypt Cancer Institute- Assiut University, Department of Pediatric
Oncology, Assiut, Egypt; 2 Faculty of Medicine- Assiut University,
Department of Pediatrics, Assiut, Egypt
Background/Objectives: Most previous epidemiological
studies have focused on patients in developed countries, or
capitals and large cities of developing countries. People in
rural areas in developing countries may have different genetic,
environmental and life style issues.
Design/Methods: This retrospective study was performed
through review of charts of newly diagnosed children with
cancer who started treatment between 2006 and 2010 in the
Department of Pediatric Oncology in South Egypt Cancer
Institute (SECI). Analyzed data included: age, sex, diagnosis
and stage of the disease, response to initial course of therapy,
date of relapse if occurred, and last clinical results of treatment.
Results: Between 2006 and 2010, 502 children (291 males
and 211 females, 1.4:1) with malignancy started therapy in
SECI. The median age at first presentation was 5.2 years
(2 months-18 years). Diagnoses were commonly leukemia
(49%), lymphomas (24%), solid tumors (24%) and rarely brain
tumors (1%). At presentation, 62% of patients with acute lymphoblastic leukemia (ALL) were considered high risk group,
86% of patients with non-Hodgkin lymphoma (NHL) presented in late stages (III-IV), and 90% of neuroblastoma
patients presented in stage IV. After initial courses of therapy, 53%, 19%, 43% and 0% of patients with ALL, Acute
myeloid leukemia (AML), NHL, and neuroblastoma, respectively, were in complete remission. During initial courses of
chemotherapy 21%, 52%, 18% and 2% of patients with ALL,
AML, NHL, and neuroblastoma, respectively, died. About
85% of patients were compliant with therapy. Overall, the
relapse rate was 14%, median time from diagnosis till relapse
was 7 (1-43) months. Deaths were mainly therapy related
(60%). Five years overall and event free survival were 0.45
± 0.03 and 0.36 ± 0.03, respectively.
Conclusions: It is essential to establish country based cancer
registries in developing countries to enable own plans.
P-539 Early Diagnosis Improvement of Child
Cancer in South of Brazil
C. Fiori1 , A. Carla Rosa1
1 Hospital
do Câncer de Cascavel-UOPECCAN, Pediatric Oncology,
Cascavel, Brazil
Background / Objectives: Introduction: Childhood cancer is a rare disease, but the second leading cause of
death between 5 to 19 years old. Otherwise, the cure rate
reaches 70% if diagnosed early. Precoce detection considerably reduces the complications of the treatment, and contribute to increase the cure.
SIOP ABSTRACTS
S412 of S518
Objective: Evaluate the degree of tumor involvement in children and adolescents with cancer after training health professionals.
Design / Methods: Methodology: Health professionals being
trained since 2008, in partnership with the Ronald McDonald Institute, through the Early Diagnosis of Cancer Children and Adolescents Program. There were analyzed children younger than 19 years old attended from January 2008
to December 2016, at Cancer Hospital of Cascavel, Paraná,
Brazil. The Leukemias were considerated – Low Risk(LR)
and High Risk( HR) according to age and leukometry at diagnosis: LR: > 12 months and < 10 years old, < 50.000 leukocytes / mm3. HR: < 12 months and > 10 years old, > 50.000
leukocytes / mm3. In solid tumors are considerated by stage:
LR: I/II and HR: III/IV.
Results: Results 449 patients were attended in the period
from 2008 to 2016, of which 248 (55%) were considered High
Risk and 201 (45%) Low Risk. There was a predominance of
HR over LR per year, from 2009 to 2013. From 2014 until
2016, a predominance of LR over HR.
Conclusions: Comments: The preliminary analysis of the
data allows us to observe that children and adolescents with
cancer have advanced disease at diagnosis. After 2014, we
observed change in staging diagnosis of patients who are coming up with more localized disease. It is possible that this
change in the between Low Risk and High Risk disease from
2014 may be related to the training activities as a result of the
Early Diagnosis Program developed in the West, Northwest
and Southwest of Paraná since 2008.
P-540 Pediatric Population-Based Cancer
Registries in Central America: Insights Shaping
Health Policy and Epidemiological Research
S. Fuentes Alabi1 , G. Claudia2 , M. Carranza1 , T. Balcarcel2 , F.
Moreno3 , M. Metzguer4 , C. Rodriguez-Galindo5 , L. Frazier6
1 Hospital
Nacional de Niños Benjamin Bloom, Pediatric Oncology, San
Salvador, El Salvador; 2 Unidad de Oncologia Pediatrica - UNOP, Pediatric
Oncology, Guatemala, Guatemala; 3 Registro Oncopediatrico Hospitalario
de Argentina-ROHA, Hospital Based Pediatric Cancer Registry, Buenos
Aires, Argentina; 4 St. Jude Children's Research Hospital, Global Pediatric
Medicine- International Outreach Program, Memphis-TN, USA; 5 St. Jude
Children's Research Hospital, Global Pediatric Medicine-International
Outreach Program, Memphis-TN, USA; 6 Dana-Farber Cancer Institute,
Pediatric Oncology, Boston-MA, USA
Background/Objectives: Population-based cancer registries
(PBCR) provide a measure of incidence and survival rate—
essential for rational health care planning and further epidemiologic research. Before 2014, the incidence of pediatric cancer
in Guatemala and El Salvador (G & ES) was estimated based
on international models. Since 2014, G & ES has engaged in a
systematic collection of data which has yielded an epidemio-
logical profile of childhood cancer that will impact health care
systems.
Design/Methods: In 2014, the Registro Oncologia
Pediatrica-Central America (ROP-CA) was initiated in
G & ES to provide PBCR for children 0-14y. In each country,
a cancer registrar identifies cases through search of pathology
and laboratory reports, medical and radiation records. Neither
registries currently have access to death certificates. All cases
are recorded using the International Classification of DiseaseOncology, version 3. Using the International Classification
of Childhood Cancer, the age-adjusted incidence rates per
10^6 population are calculated and standardized to world
population. Incidence rates in G & ES were compared to
rates of Argentina.
Results: The overall incidence in El Salvador was 91.2/10^6
and in Guatemala 71.8/10^6, compared to an incidence of
125/10^6 in Argentina. The expected vs. observed incidence
in Guatemala is 56% and in El Salvador, 71%. In both countries, the incidence was lower than expected for neuroblastoma, retinoblastoma, renal tumors, germ cell tumors and
brain tumors; incidence of hepatic tumors was higher than
expected.
Conclusions: The ROP-CA has demonstrated that the number of children accessing pediatric cancer care is lower than
would be expected–likely due to limited access to primary
care, lack of recognition of disease in primary care, or competing mortalities. The identification of these factors has already
influenced strategies to improve access to care services for the
control of childhood cancer.
P-541 Texas Children's Cancer and Hematology
Center's Global Hope (Hematology-Oncology
Pediatric Excellence)
K. Wilson-Lewis1 , E. Ishigami1 , J. Slone2 , C. Allen2 , J. Lubega2 , P.
Wasswa2 , A. Anderson2 , N. El-Mallawany2 , G. Airewele2 , E.
Fruge2 , N. Kagoro2 , S. Pons1 , R. Weinstein1 , P. Mehta2 , D.
Poplack2
1 Texas
Children's Hospital, Cancer and Hematology Centers, Houston,
USA; 2 Baylor College of Medicine, Pediatrics, Houston, USA
Background/Objectives: Approximately 300,000 children
per year develop cancer globally. In Sub-Saharan Africa
(SSA) the majority die due to lack of or incorrect
diagnosis, lack of access to medications and inadequate
healthcare infrastructure. In contrast, over 80% of children diagnosed with cancer in the U.S. are cured. This
inequity compels us to improve pediatric cancer care in
SSA.
Design/Methods: The Texas Children's Cancer and Hematology Centers (TXCH) and Baylor College of Medicine
International Pediatric AIDS Initiative (BIPAI) have
SIOP ABSTRACTS
created a comprehensive program called Global HOPE
(Hematology-Oncology Pediatric Excellence) aimed at
building capacity and improving Pediatric Hematology/Oncology (PHO) infrastructure in selected SSA
countries.
Through partnering with local governments and key stakeholders, Global HOPE implements a country-specific model
based on local need. With a focus on in-country capacity
building, Global HOPE educates a broad array of healthcare
roles in SSA to support the delivery of high-quality, comprehensive, multi-disciplinary care. This comprehensive model
is aimed at addressing the clinical care, research, education
and administrative goals that will create a sustainable model to
improve health care access and outcomes, and stakeholder and
community involvement, in an environment of operational
excellence.
Results: Since 2007, across four SSA countries, Global
HOPE has increased the capacity of local healthcare workforce by training over 1500 healthcare workers and improved
the care of children with cancer or blood disorders demonstrating improved outcomes in each of its sites, including
increased case identification through improved diagnostics,
increased number of children receiving care and better access
to medications.
Conclusions: Global HOPE represents a first step towards
the ultimate, transformational goal of cure equity for children
with cancer and blood disorders in SSA delivered by a locally
sustainable workforce and infrastructure.
P-542 Development of the Joint Children's
Cancer Hospital Egypt (CCHE-57357)
Dana-Farber Boston Children's Hospital Pediatric
Oncology Fellowship Program
S413 of S518
lem is the quality of training and traditional methods of clinical practice where decision making is centered on the most
senior person on the team. To ensure real change, highlytrained locally based specialists with a strong emphasis on
problem-solving and critical thinking using evidence-based
approaches are needed.
Design/Methods: The Children's Cancer Hospital Egypt
(CCHE-57357) and Dana-Farber Boston Children's Hospital
(DFBCH) at Harvard Medical School developed a 30 month
pediatric oncology fellowship training program following the
American Academy of Pediatrics fellowship guidelines.The
primary objective of the program was to implement a shared
education model to develop highly educated physicians who
are able to follow evidence-based approaches and committed
to sustained practice in LMIC.
Results: DFBCH staff provide ongoing education to the fellows through visits to CCHE-57357 every 2-3 months, weekly
video sessions with the fellows for case presentation and journal clubs, and weekly conference calls with the fellowship
program staff to ensure that the goals and objectives for each
fellow and the program are met.Each of the current 15 fellows
spend 6 weeks/year in Boston participating in evidence-based
multi-disciplinary based rounds; the remainder of the curriculum takes place at CCHE-57357 and incorporates an array of
individual, small group and e-learning modules specifically
created for the program. Three classes of fellows have been
enrolled and the senior class will graduate in spring of 2017.
Conclusions: Training of fellows following the same standards as those applied to North American candidates is feasible and has the potential to advance the quality of education and expertise in LMIC. By focusing on the education of
the next generation of clinicians, the opportunity to implement many of the important principles of clinical care can be
realized.
M. Zamzam1 , H. Hanafy2 , R. Khedr2 , S. Abouelnaga3 , M.
Abdelbaki4 , L. Goumenrova5 , L. Lehmann6 , K. Houlahan7 , M.
Kieran8 , P. Pruden9
1 National
Cancer Institute - Cairo University / Children's Cancer Hospital
Egypt CCHE 57357, Pediatrics Oncology, Cairo, Egypt; 2 National Cancer
Institute - Cairo University / Children's Cancer Hospital Egypt
CCHE57357, Pediatrics Oncology, Cairo, Egypt; 3 National Cancer
Institute - Cairo University /Children's Cancer Hospital Egypt CCHE57357,
Pediatrics Oncology, Cairo, Egypt; 4 Nationwide Children's Hospital,
Pediatrics Oncology, Colmbus - Ohio, USA; 5 Dana Farber / Boston
Children Cancer Institute, Pediatric Neurosurgical Oncology, Boston, USA;
6 Dana Farber / Boston Children Cancer Institute, Pediatric Oncology/BMT,
Boston, USA; 7 Dana Farber / Boston Children Cancer Institute, Nursing
Department, Boston, USA; 8 Dana Farber / Boston Children Cancer
Institute, Pediatric Oncology / Neuroncology, Boston, USA; 9 Children's
Cancer Hospital Egypt CCHE 57357, Nursing Department, Cairo, Egypt
Medical College, Paediatrics, Mangalore, India; 2 Kasturba
Medical College Hospital, Pediatrics, Mangalore, India; 3 Kasturba
Medical College Hospital Manipal University, Pediatrics, Mangalore,
India; 4 Kasturba Medical College Hospital- Manipal University, Pediatrics,
Mangalore, India; 5 Kasturba Medical College Hospital Mangalore,
Pediatrics, Mangalore, India; 6 Kasturba Medical College, Pediatrics,
Mangalore, India
Background/Objectives: Children diagnosed with cancer in
low- and middle-income countries (LMIC) have inferior outcomes compared to those in high income countries. While
some of these issues can be resource availability, a major prob-
Background/Objectives: It is essential to know the routes of
presentation and time prior to diagnosis in primary and secondary care to avoid delay in diagnosis which plays an important role in better survival strategy in childhood cancers.To
P-543 Presentation of Children with Cancer to a
Pediatric Oncology Unit in Mangaluru, India
H. Lashkari1 , R. Shenoy2 , N. Kamath3 , J. K3 , S. Rao4 , M. Faheem3 ,
M. Kishore2 , S. Nayak2 , S. Prabhu2 , S. dsa5 , H. MM6 , K. Bhat6
1 Kasturba
SIOP ABSTRACTS
S414 of S518
describe average time taken for a child with cancer to present
and to get diagnosed in an oncology unit.
Design/Methods: It is retrospective cohort study of children
diagnosed with cancer between the 1st Jan 2014 and 31st Dec
2016 at Pediatric oncology unit, KMC Hospital Mangalore,
India. Time to presentation (TTP) was defined as time from
initial symptoms to time seen by a pediatrician. Time to diagnosis (TTD) was defined as time from initial symptoms to
diagnosis at our pediatric oncology unit. Patient pathways to
diagnosis were mapped and routes for different cancers were
compared.
Results: Total 148 children were registered with childhood
cancer during this period. The data of 104 children aged
between 0 to 16 yrs diagnosed during this period were collected. The majority of them were boys (68). Acute leukemia
was diagnosed in 67 cases and TTP varied between 2 to 45
days. Nearly two third (40/67) presented within 2 weeks of
onset of symptoms. The TTD varied between 7 to 180 days
with mean of 36 days in leukemia group. In solid tumor
group TTP was 1 to 60 days, whereas TTD varied between
8 to 105 days with an average of 42 days. Acute lymphoblastic leukaemia (ALL) with skeletal manifestations had longest
TTD (180 days). Lymphoma had TTD of 105 days with TTP
of 45 days.
Conclusions: The majority of children diagnosed with cancer
presented via referral from pediatricians, with the route varying between tumor types.This is part of ongoing study which
is looking into the challenges in diagnosing cancer, identifying a wide range of non-disease related factors potentially
delaying the diagnosis.
P-544 The Pediatric East African Clinical
Oncology Consortium (PEACOC)
J. Lubega1 , P. Scanlan2
1 Uganda
Cancer Institute, Pediatric Oncology, Kampala, Uganda;
National Hospital, Pediatrics, Dar es Salaam, Tanzania
2 Muhimbili
Background/Objectives: The survival of children with cancer in East Africa is poor due to shortages of dedicated
and standardized pediatric cancer services, skilled multidisciplinary workforce, and locally appropriate evidencebased pediatric cancer management guidelines. PEACOC is
a cooperative group of pediatric cancer centers in the six
member states of the East African Community to sustainably
improve the outcomes of children with cancer in the region.
Design/Methods: PEACOC was created in November 2016
at Ocean Road Cancer Hospital, Dar es Salaam (Tanzania) by
the pediatric oncology expert working under the auspices of
the East Africa Regional Oncology Center of Excellence that
is funded by member state loans from the African Development Bank. The Expert Working Group (EWG) noted the fol-
lowing as the topmost challenges of pediatric oncology across
all centers in East Africa: 1) Late presentation of patients with
advanced tumors and with life-threatening complications; 2)
Inconsistent access to chemotherapy; 3) Poor access to blood
products for transfusion; 4) Poor access to radiotherapy; 5)
Lack of local evidence-based treatment and supportive care
guidelines; 6) Lack of dedicated infrastructure and personnel. To foster regional collaboration and sharing resources, the
EWG agreed to form PEACOC to include all pediatric cancer
units in East Africa and various international collaborators.
Results: PEACOC will evaluate current pediatric cancer units
in East Africa including treatment guidelines, tumor-specific
epidemiology, care funding, research activity, tertiary and
specialist skills development. The Consortium will then adapt
current regional practices to best international practices to
develop guidelines for the region.
Conclusions: PEACOC will conduct cooperative group clinical trials, establish a harmonized regional pediatric cancer registry, conduct pediatric cancer training programs, and
benchmark quality of pediatric cancer care in the region.
P-545 Strategic Planning for Expansion:
Children's Cancer Hospital Egypt 57357
F. Makka1 , B. Lee2 , I. Albanti3
1 Harvard
University School of Public Health, Health Management, Boston,
USA; 2 Harvard University School of Public Health, Global Health, Boston,
USA; 3 Dana Farber Cancer Institute, Global Health Institute, Boston, USA
Background/Objectives: Pediatric cancer is a global health
problem. While low-and middle-income countries (LMIC)
plan to initiate or expand pediatric oncology services, guidance from published literature is limited due to its focus on
high-income countries and academic medical centers. As the
largest pediatric oncology hospital in the world, the Children's
Cancer Hospital Egypt (CCHE) strives to provide free care to
all without discrimination. High demand has pushed CCHE
to start the process of expanding its space and services. Our
project explored the expansion strategy at CCHE while considering its local context, with the goal of creating a generalizable resource for other LMIC to reference.
Design/Methods: We used qualitative research methods in
the form of in-depth Interviews with 24 key informants,
including members of senior management, staff at CCHE and
community members. The interviews were conducted over
two weeks in January 2017, with each session lasting 45-60
minutes. Findings were structured into a process map, a stakeholder analysis, a SWOT analysis, and a final report.
Results: CCHE faces many challenges in its progress, from
the flotation of the Egyptian currency to spatial restrictions of
its expansion. Throughout the interviews, we identified several major attributes that were instrumental in helping them
SIOP ABSTRACTS
overcome these barriers: visionary leadership, strong international collaborations, early investment in external consultants to bring in world-class best practices, and an emphasis
on extensive planning.
Conclusions: Many of the challenges present in the CCHE
expansion are also likely to be faced by other pediatric oncology facilities in LMIC seeking to expand their own pediatric
oncology units. We believe that such facilities may benefit
from the findings of our study.
S415 of S518
Conclusions: Observed incidence rates for children aged 014 years are comparable with those reported from countries
of Eastern Europe and from the National cancer registry of
Slovakia (NOR). The low rate reported for adolescents is due
to data incompleteness. Continuous monitoring of the time
trends is needed. For the future, it is important to put in place
a mechanism of data exchange with the national registry for
cancers of all ages (NOR), to improve data quality and completeness in both sources and provide reliable and detailed
data for research and public health.
Acknowledgement: National Scholarship Program of the
Slovak Republic
P-546 The Slovak Clinical Cancer Registry of
Children and Adolescents: Rationale, Organization
and Incidence in Years 2000-2012
M. Makohusová1,2,3 , E. Kaiserová1 , M. Colombet2 , E. Bubanská4 , I.
Oravkinová5 , T. Stančoková4 , J. Puškáčová1 , A. Kolenová1 , E.
Steliarova-Foucher2
1 Children's
University Hospital, Department of Pediatric Hematology and
Oncology, Bratislava, Slovak Republic; 2 International Agency for Research
on Cancer, Section of Cancer Surveillance, Lyon, France; 3 University of SS.
Cyril and Methodius, Department of Chemistry- Faculty of Natural
Sciences, Trnava, Slovak Republic; 4 Children's University Hospital- Slovak
Medical University, Department of Pediatric Oncology and Hematology,
Banská Bystrica, Slovak Republic; 5 University Children s Hospital- Pavol
Jozef Safarik University, Department of Pediatric Hematology and
Oncology, Kosice, Slovak Republic
Background/Objectives: The aim of the study was to report
on the cancer incidence and time trends in children and
adolescents (age-range 0-19) registered in the Slovak Clinical Cancer Registry of Children and Adolescents during the
period 2000-2012.
Design/Methods: The data are collected from three regional
pediatric treatment centers. All malignant, some benign and
borderline malignancies were included. This populationbased cancer registry with national coverage records detailed
clinical information on diagnosis, treatment and follow-up
of patients. The tumours were classified using International
Classification of Childhood Cancer, edition 3. Official population figures were used to calculate incidence rates.
Results: In 2000-2012, 2,071 cases were registered (agerange 0-19 years). For the age-range 0-14 (N=1,626), the
age-standardized (World standard) annual incidence rate
(ASR) was 144.6 per million person-years; the most frequent
were leukaemias (ASR=44.4), followed by CNS tumours
(ASR=31.7), lymphomas (ASR=15.4) and neuroblastomas
(ASR=13.0; N=125). Age-specific incidence rates were the
highest among infants (239.3; N=171), lower at age 1-4 years
(181.6; N=516), 5-9 (112.0; N=424), 10-14 years (116.1;
N=515) and the lowest at age 15-19 years (86.0; N=445). The
average annual increase over the study period in the age 0-14
was 1.68% (P=0.01) overall and increased for neuroblastoma
by 6.66% (P=0.02).
P-547 Demographic Survey on Pediatric Cancer
Patients in Japan after the Election of Childhood
Cancer Core Hospitals
K. Matsumoto1 , T. Takimoto2 , A. Saito3 , A. Oara4 , K. Horibe3 , E.
Hiyama5
1 National
Center for Child Health and Development, Children's Cancer
Center, Tokyo, Japan; 2 National Center for Child Health and Development,
Clinical Epidemiology Research Center for Pediatric Cancer, Tokyo, Japan;
3 National Hospital Organization Nagoya Medical Center, Clinical
Research Center, Nagoya, Japan; 4 Toho University School of Medicine,
Department of Pediatrics, Tokyo, Japan; 5 Hiroshima University,
Department of Pediatric Surgery, Hiroshima, Japan
Background/Objectives: In Japan there used to exist about
200 hospitals that cared childhood cancer arising about 2500
patients yearly. In 2013, with the aim of further integration
and to provide uniform accessibility to pediatric cancer treatment, the Ministry of Health, Labour and Welfare elected 15
core hospitals in seven regional blocks in Japan. The aim of
this study is to determine the demographic profile of childhood cancer patients in Japan before and after the election of
15 core hospitals.
Design/Methods: We collected data from the published
registry of the Japanese Society of Pediatric Hematology/Oncology, which would cover approximately 80% of the
patients with cancer in Japan. The collected data were analyzed to reveal the change before and after the election of the
core hospitals.
Results: In 2016, there exist 150 hospitals that cared pediatric
cancer patients in Japan. Among them, 55% were university
hospitals and 10% were children's hospitals. Twenty-five percent of the hospitals that cared more than 20 cases per year
(high-volume center) covered 57% of the cancer patients in
Japan. The core hospitals were elected from the high volume
centers, and covered 32% of pediatric cancer patients.
The number of hospitals that could care leukemia/lymphoma
patients decreased from 175 in 2012 to 143 in 2015. High volume centers of eukemia/lymphoma covered 23.8% patients in
Japan, which was increased from 13.8% before the election of
SIOP ABSTRACTS
S416 of S518
core hospitals. Also, the number of hospitals that could care
solid tumors, including brain tumor, decreased from 139 in
2012 to 129 in 2015. The coverage rate of solid tumor patients
by high volume centers of solid tumors increased from 31.0%
to 41.2%.
laboratory and pathology, inadequate supportive care, limited
accessibility of limb sparing surgery and prosthesis and treatment abandonment. These results will inform the development of specific strategies to solve these barriers in pediatric
solid tumors treatment in SEA.
Conclusions: Integration of the pediatric patients with solid
tumors and hematological malignancies is realizing in Japan
after the election of 15 core hospitals.
P-549 Evaluation of Maternal and Perinatal
Characteristics and Risk of Langerhans Cell
Histiocytosis in Texas, 1995-2011
P-548 Burden of Pediatric Solid Tumors
Management in South-East Asia Countries
1,2
3
4
3
C. Monsereenusorn , P. Friedrich , P. Alcasabas , C. Lam , C.
Rodriguez-Galindo3
1 Phramongkutklao
Hospital and College of Medicine, Department of
Pediatrics, Bangkok, Thailand; 2 Dana-Farber/Boston Children's Cancer
and Blood Disorders Center, Department of Pediatric Oncology, BostonMA, USA; 3 St.Jude Children's Research Hospital, Department of Global
Pediatric Medicine, Memphis- TN, USA; 4 Philippines General Hospital,
Department of Pediatrics, Manila, Philippines
Background/Objectives: Pediatric solid tumor treatment
require complex multidisciplinary care. The objective of this
study is to identify barriers to effective treatment of pediatric
solid tumors in South-East Asia (SEA) and will inform the
development targeted strategies to improve outlook for children with solid tumors in SEA.
Design/Methods: Physicians were received an individualized
email-specific link of survey. Questions in the survey included
topic: patients, care team, hospital/infrastructure, abandonment and barriers to treatment. Analysis will be done from
countries as classified by the World Bank Method as low
(LIC), low-middle (LMIC), upper-middle (UMIC), and high
income countries (HIC).
Results: The survey was sent to 66 physicians. 17 responses
(25.8%) from 17 centers (7 countries) had been received. Neuroblastoma is the most common disease that presenting with
late presentation in SEA, followed by osteosarcoma, Ewing
sarcoma, other soft tissue sarcomas. In terms of laboratory,
Methotrexate level is still not available in 50% of centers and
2 countries. More than 50% of solid tumor cases have been
encountered with inconclusive diagnosis by pathology. Infection is still a leading cause of death among SEA countries.
For surgery, limb sparing surgery is performed in less than
50% of cases, with higher rate in UMIC (P=0.045). However, external prostheses are seldom available, in particular
in LMIC (P=0.023). The rate of abandonment was highest
for bone tumors, soft tissue sarcomas and neuroblastoma. The
most important barriers for solid tumor treatment are financial
constraints, followed by commute, infection, abandonment,
fear from surgery, radiation and lacking of legal support.
Conclusions: Barriers to effective treatment of pediatric solid
tumors in SEA are late presentation, limited resources for
E. Peckham-Gregory1 , K. McClain1 , C. Allen1 , M. Scheurer1 , P.
Lupo1
1 Baylor
College of Medicine, Pediatrics- Hematology-Oncology Section,
Houston, USA
Background/Objectives: Langerhans cell histiocytosis
(LCH) is a myeloid neoplasia with a median diagnosis age
of 30 months. In studies of pediatric malignancies, maternal
and perinatal characteristics have been successfully evaluated
to determine the impact of inborn variation on disease risk.
Therefore, we reviewed population-based registry data to
determine if these factors influence the risk of LCH.
Design/Methods: The study population included children
with LCH born in Texas (n=164) for the period 1995-2011
who were identified from the Texas Cancer Registry. Birth
certificate controls were randomly selected at a ratio of 10:1
for the same period matched on birth year. We evaluated the
impact of factors identified from vital records including: gestational age, birthweight, and parental race/ethnicity. Unconditional logistic regression was used to generate adjusted odds
ratios (aOR) with 95% confidence intervals (CI) evaluating
the association between selected factors and the risk of LCH.
Results: Overall, non-Hispanic Black mothers were less
likely to give birth to offspring who developed LCH compared
to non-Hispanic White (NHW) mothers (aOR: 0.50; 95%
CI: 0.24-1.03). However, Hispanic mothers were at increased
risk of giving birth to offspring who developed LCH (aOR:
1.58; 95% CI: 1.07-2.35). Furthermore, the risk of LCH was
stronger among children born from two Hispanic parents compared to children born from two NHW parents (aOR: 1.83;
95% CI: 1.15-2.90). Mothers born in Mexico versus the U.S.
and who resided along the U.S.-Mexico border were less
likely to give birth to offspring who developed LCH (aOR:
0.66; 95% CI: 0.41-1.07 and aOR: 0.54; 95% CI: 0.29-0.98,
respectively).
Conclusions: Maternal and parental race/ethnicity were
strongly associated with LCH risk. Further, mothers who
resided along the U.S.-Mexico border at time of infant birth,
and Mexico-born mothers, were less likely to give birth to offspring who developed LCH. These findings highlight novel
risk factors that warrant assessment in future studies.
SIOP ABSTRACTS
P-550 Spectrum of Malignancies in Patients with
Neurofibromatosis (NF): Experience from the First
Greek NF-Center
K. Roka1 , M.C.S. Filippidou1 , E. Kokkinou2 , M. Tsipi3 , M.
Themistocleous4 , I. Nikas5 , K. Stefanaki6 , M. Tzetis3 , R. Pons2 , A.
Kattamis1
1 Athens
Medical School, Division of Pediatric Hematology-Oncology- First
Department of Pediatrics, Athens, Greece; 2 Athens Medical School, First
Department of Pediatrics, Athens, Greece; 3 Athens Medical School,
Medical Genetics, Athens, Greece; 4 Aghia Sophia Childrens Hospital,
Department of Neurosurgery, Athens, Greece; 5 Aghia Sophia Childrens
Hospital, Radiology Department, Athens, Greece; 6 Aghia Sophia Childrens
Hospital, Pathology Department, Athens, Greece
Background/Objectives: Neurofibromatosis(NF) type1(NF1) and type-2(NF2) are distinct genetic-clinicalsyndromes in which affected individuals develop both benign
and malignant tumors that predominantly affect the nervoussystem. In order to standardize and improve the clinical-care
of patients with NF, the first national-center of reference was
established in 1/1/2016.
Design/Methods: To describe the spectrum of malignancies
in patients with NF examined from January 2016 until
February 2017 in our NF-reference-center. Clinical diagnosis of NF1 was based on National-Institutes of Health
diagnostic-criteria(NIH,1988), while for NF2 on NationalNeurofibromatoses-Foundation-Criteria
(NNFF,1997).
Patients were evaluated from a multidisciplinary-team
including neurologist, dermatologist, oncologist, ophthalmologist as well as psychologist. Genetic-counseling was
provided in all the families and regular follow-up for the
patients was arranged.
Results: During the study-period 51 patients(age 6mo-17y,
median 8,79y) were examined and included in the analysis.
Clinical diagnosis of NF1 had 48 patients, while 3 of NF2.
Molecular-testing for NF1 was performed in all the patients,
with NF1 confirmed in 27 patients(3 de-novo-mutations),
while in 21 patients evaluation is still ongoing. Among the
51 patients, there were 4 families with 2 affected children,
while 7 patients were referred due to positive family-history.
Optic-Pathway-Gliomas(OPGs) were found in 19 patients
with NF1(39,6%), of whom 9 had visual deterioration during
follow-up and received chemotherapy. Two siblings with
NF1 and OPGs presented with non-reversible blindness.
Pilocytic-astrocytomas were diagnosed in two patients,
located in posterior-fossa and left parietal-lobe, respectively.
Neurofibromas were diagnosed in 4 patients(8.33%), one
with plexiform-neurofibroma and metastatic-malignantperipheral nerve-sheath-tumor also and one with a large
cervical neurofibroma causing mild-respiratory distress.
Bilateral vestibular-schwannomas causing mild-deafness
with previous history of two resected meningiomas were
observed in two out of three patients with NF2. Indication
S417 of S518
for oncologic intervention was needed in 27,4% of the
patients.
Conclusions: Establishment of a Multidisciplinary-Center
for Neurofibromatosis can improve clinical-care by providing necessary multidimensional-approach and contributing to
early diagnosis and timely therapeutic intervention.
The author thanks Special Account for Research Grants and
National and Kapodistrian University of Athens for funding
to attend the meeting
P-551 Organization of Medical Care for Children
with Cancer in the Regions of the Russian
Federation: The Results of External Audit
M. Rykov1 , V. Polyakov1
1 Institute
of Pediatric Oncology and Hematology FSBSI “N.N. Blokhin
RCRC”, General oncology, Moscow, Russia
Background/Objectives: The study presents the analysis of
the external audit results of the delivery of medical care in
children with cancer conducted in the regions of the Russian
Federation: Central, North-West, North-Caucasian, Volga and
South Federal Districts.
Design/Methods: The authors analyzed the clinical histories
of children with solid tumors who received specialized treatment in the oncology departments of the Regional Children's
Hospitals in the period of 2011–2015, and evaluate the available equipment and existing competence of the staff.
Results: The study revealed 374 patients (194 (51.9%) boys
and 180 (48.1%) girls) aged 0 - 17 years (mean age 5.4
years) with malignant tumors. The number of hospitalizations
- 1534, the total number of patient days - 22762, average 14.8. Patients with I stage of disease - 23 (6.1%), with II - 112
(30%), with III - 89 (23.9%) and with IV - 146 (39%), with an
unknown stage - 4 (1%). Clinical guidelines have been violated in the treatment of 46 (12.3%) patients.
Conclusions: It seems reasonable to develop recommendations that justify the expediency of the individual stages of
the treatment of patients in different regions of the Russian
Federation in accordance with their distance from the federal
center, the size and density, as well as the incidence of child
population in order to ensure optimal routing of patients and
improve the Commission. It is also necessary to strengthen
the oncology alertness of primary care physicians (pediatricians) for early detection of cancer, including during routine
inspections.
P-552 Duration Between the First Symptom and
Exact Diagnosis Time in Childhood Cancer
B. Sevinir1 , M. Demirkaya1 , M. Ertekin1 , G. Kalay1
S418 of S518
1 Uludag
University Medical Faculty, Pediatric Oncology, BURSA, Turkey
Background/Objectives: Early diagnosis promotes prognosis in childhood cancers.Our aim is to evaluate the duration
between the first symptom and exact diagnosis time in children diagnosed as lymphomas or solid tumors.
Design/Methods: The data of 759 patients applied to Uludağ
University Medical Faculty Department of Pediatric Oncology who diagnosed as lymphoma or solid tumor during
January 2005 to November 2014 was retrospectively analysed.The time from the first complaints to the apply of a physician,the time from admission to get a diagnose and total time
from the first complaints to the final diagnosis were determined.These datas were compared with age, sex and diagnosis.
Results: Median age was 84 months.The most common
diagnosis were lymphomas(22%), brain tumors (18.3%) and
germ cell tumors (10.8%). The patients’ were firstly apply
to 67.5% pediatricians, 5.3% general practitioners, 29% other
specialties. Median time of the duration between the first
admission was 15 days. Median time of the referral of the
patient to the oncology centers is 8 days and median diagnose time of the patients was 10 days. Median time between
the onset of symptoms and the final diagnosis was 55 days
(3-1254 days). The first admission time of the patiens diagnosed non-Hodgkin lymphoma (p=0.030), Hodgkin lymphoma (p=0.003), osteosarcomas (p=0.005), soft tissue
sarcomas(p=0.009) and thyroid carcinomas (p=0.001) were
more than 15 days. The first admission time of the patients
were significantly less than 15 days who diagnosed neuroblastoma (p=0.001), renal tumors(p=0.005) and hepatoblastomas
(p=0.016). The referral time of the patients with Hodgkin's
lymphomas (p=0.003) and osteosarcomas (p=0.016) were
more than 8 days.The admission time was longer than 15 days
in adolescent patients.Time to diagnosis was longer in patients
who addmited to physians other than pediatricians or pediatric
surgeons(p=0.024).
Conclusions: In our study the referral and diagnose times
are prolonged especially the physicians who rarely examine
children.
P-553 A Comprehensive Model for Developing a
Pediatric Cancer Health System in Ethiopia: A
Five-Year Experience
A. Shad1 , J. Broas2 , D. Korones3 , D. Hailu4 , M. Bonilla5 , C.
Rodriguez-Galindo6 , W. Bekele7 , S. Weitzman8 , J. Challinor9
1 Children's
Hospital at Sinai, Pediatrics- Pediatric Hematology/Oncology,
Baltimore, USA; 2 The Aslan Project, Non-Profit Organization, Washington
DC, USA; 3 Wilmot Cancer Institute – University of Rochester Medical
Center, Pediatrics- Pediatric Hematology/Oncology, Rochester, USA;
4 Tikur Anbessa Specialized Hospital, Pediatric Hematology/Oncology,
Addis Ababa, Ethiopia; 5 Jimma University Specialized Hospital, Pediatric
SIOP ABSTRACTS
Hematology/Oncology, Jimma, Ethiopia; 6 St. Jude Children's Research
Hospital, Global Pediatric Medicine, Memphis, USA; 7 Newark Beth Israel
Medical Center, Pediatric Hematology/Oncology ret., Newark, USA; 8 The
Hospital for Sick Children, Haematology/Oncology, Toronto, Canada;
9 School of Nursing – University of California San Francisco, Physiological
Nursing, San Francisco, USA
Background/Objectives: In 2012, despite an estimated 6,000
cases of pediatric cancer annually, Ethiopia had no qualified
pediatric oncologists, pediatric oncology nurses, or oncology
pharmacists and no dedicated infrastructure. Children with
cancer were intermixed with the general pediatrics population and palliative care/pain medications were rarely offered
during treatment. To address these issues, The Aslan Project,
a US non-governmental organization (NGO), introduced a
pilot project for building a pediatric cancer system at Tikur
Anbessa Specialized Hospital (TASH) in 2012. In 2015, with
St. Jude's support, Aslan opened a second Ethiopian site,
Jimma University Specialized Hospital (JUSH), serving an
area of 15 million people with no prior pediatric oncology
capacity.
Design/Methods: Aslan's model focuses on human resource
(HR) capacity building (fellowship training), infrastructure
development, and family/psychosocial support. Initially, at
TASH, Aslan provided nearly full financial support for the
project. At JUSH, Aslan refined its model to enhance local
partner ownership and improve HR training through partnerships with high-functioning LMIC institutions. Aslan prioritizes advocacy and relationship building with the Federal
Ministry of Health (FMOH).
Results: The TASH unit is robust; in November 2016, it
had 729 patient visits collectively on in- and out-patient service, and family support has reduced treatment abandonment
substantially. JUSH has treated 50+ children since August
2016 and administered 600+ doses of chemotherapy with no
significant error. The FMOH has prioritized childhood cancer, forming a National Task Force for Pediatric Cancer, and
WHO, SIOP, and CCI are engaged within the country. Other
Ethiopian hospitals have adopted Aslan's model, and training
continues in all specialties.
Conclusions: Full engagement of all stakeholders – the government, major institutions, and NGOs – is critical, largely
through building of trust and joint ownership of the project.
Continual refinement of the model is necessary to adapt to the
needs/capacity of partner institutions. Aslan's model may be
replicated successfully within other LMICs.
P-554 Launching Pointe: Use of Branding and
Social Media to Promote Pediatric Oncology
Education and Training Opportunities
J. Slone1 , M. Zobeck1 , J. Libes2 , R. Kunkel3 , N. Ranasinghe4 , J.
Geel5
SIOP ABSTRACTS
1 Baylor
College of Medicine/Texas Children's Hospital, Pediatrics,
Houston, USA; 2 University of Illinois College of Medicine, Pediatrics,
Peoria, USA; 3 Arkansas Children's Hospital, Pediatrics, Little Rock, USA;
4 Thomson Reuters, London, United Kingdom; 5 University of the
Witwatersrand- Charlotte Maxeke Johannesburg Academic Hospital,
Faculty of Health Sciences, Johannesburg, South Africa
Background/Objectives: Training a pediatric oncology
workforce is essential to providing optimal treatment to
children with cancer in low- and middle-income countries
(LMICs). While training opportunities exist, information on
them is often difficult to find. In an effort to promote global
childhood cancer education, we aimed to improve upon a previous initiative to consolidate information for providers by
developing a new and enhanced web site with a social media
campaign to increase awareness.
Design/Methods: The International Society of Paediatric
Oncology-Paediatric Oncology in Developing Countries Education and Training Working Group (SIOP-PODC ET WG)
launched an online database of training programs in October
2014. To better engage stakeholders, the site was re-branded
as the Paediatric Oncology International Network for Training and Education (POINTE) and launched a new website at
www.cancerpointe.com. A social media campaign on Facebook, Twitter and LinkedIn accompanied the new site's launch
in October 2016. Google Analytics was utilized to monitor
website traffic and reach of both sites.
Results: In the first five months after www.cancerpointe.com
was launched, page views increased compared to the same
time period of the initial site by 53% (5051 vs. 3291) and the
site was accessed from 13 more countries (95 countries vs.
82 previously). With a social media campaign that included
320 Facebook likes and 58 Twitter followers in the first five
months, social media referrals accounted for 13.9% of referrals to the new site. Without a similar campaign, only 1.8% of
traffic of the first site originated from social media.
Conclusions: Rebranding and launching a social media campaign has effectively increased web traffic and exposed new
training opportunities to healthcare providers in LMICs.
While data is lacking regarding impact on patient care, we
believe this initiative and the programs added to the site have
the ability to greatly improve the quality of education and
training.
P-555 Causes of Death In Pediatric Cancer
Patients in Mexico
L. Velasco-Hidalgo1 , M. Zapata-Tarrés1 , F. Arreguín-González2 ,
N.A. López-Facundo3 , R. Cárdenas-Cardós1 , B. Almazan-García2 ,
I. Tejocote-Romero3 , R. Rivera-Luna1 , A. Benito-Resendiz2
1 Instituto
Nacional de Pediatría, Pediatric Oncology Department, Mexico
City, Mexico; 2 Centro Médico Nacional 20 de Noviembre ISSSTE, Pediatric
Oncology Department, Mexico City, Mexico; 3 Hospital Materno Infantil
ISSEMYM, Pediatric Onology Department, Estado de México, Mexico
S419 of S518
Background/Objectives: Worldwide a higher survival rate is
reported in pediatric patients with cancer, due to: early diagnosis, better support treatment and early detection of complications. In a middle income country like Mexico, the mortality
of pediatric patients with cancer is still high.
Design/Methods: The aim was to know the frequency and the
main causes of death in pediatric patients with cancer registered in three public health institutions in Mexico from January 2007 to December 2015.
Results: Two thousand three hundred twenty-seven patients
were registered in the study period, of which 378 (16.4%)
died. One hundred and twenty patients were diagnosed with
leukemia and the rest with solid tumors. Fifty-three point fifteen percent were male. In patients with acute lymphoblastic leukemia, the treatment phase with the highest number of
deaths was in induction (48%), and the main cause of death
was toxicity (58.1%). In patients with solid tumors the treatment phase in which the highest number of deaths occurred
was neoadjuvance. 44% died from toxicity and 23% from
disease progression. There were 437 toxicity events in 258
patients with solid tumors, of which 14.6% of the patients
had septic shock as the cause of death. The time of diagnosis to death in patients with leukemia was 18.4 months compared to patients with solid tumors where it was 13.49 months
(P=0.04)
Conclusions: Most patients with acute leukemia who die are
secondary to toxicity in the induction phase. The main cause
of death in patients with solid tumors is toxicity and disease
progression. Mortality in patients with solid tumors occurs
earlier. Particular attention should be paid to the early detection of complications, to avoid mortality from these causes in
a middle income country.
P-556 Pediatric Cancer Treatment Abandonment
in Botswana: A Lower than Expected Abandonment
Rate
M. Zobeck1 , T. Gilliland2 , A. Slone1 , P. Semetsa3 , M.
Raletshegwana3 , M. Scheurer1 , P. Mehta1 , J. Slone1
1 Texas
Children's Hospital/Baylor College of Medicine, Pediatrics,
Houston, USA; 2 Baylor College of Medicine, Pediatrics, Houston, USA;
3 Princess Marina Hospital, Pediatrics, Gaborone, Botswana
Background/Objectives: Pediatric cancer treatment abandonment (TA) is a major cause of preventable morbidity
and mortality in low- and middle-income countries (LMICs).
Recent publications estimate that Sub-Saharan Africa (SSA)
has an average TA of 28%, but few comprehensive hospitalbased studies have been published. TA for Botswana has not
been measured previously. Our objective was to determine the
prevalence of TA for pediatric cancer patients at the tertiary
SIOP ABSTRACTS
S420 of S518
referral center in Botswana and investigate predisposing factors for TA from the available literature.
Design/Methods: Since 2007, the Botswana Ministry of
Health and Wellness has partnered with Baylor College of
Medicine/Texas Children's Hospital to operate the only pediatric hematology-oncology program in the country at Princess
Marina Hospital (PMH). We analyzed data from the Botswana
Pediatric Oncology Database for children diagnosed with a
malignancy at PMH between January 1, 2008 and December
31, 2015.
Results: Of the 185 patients in the cohort, seven met criteria
for abandonment (3.8%) and two (1.1%) had abandonment as
their final outcome. Of those who abandoned, four (57.1%) of
the patients were female, five (71.4%) had solid tumors including two (28.6%) osteosarcomas and two teratomas. Median
time to abandonment from diagnosis was 9.14 weeks. No statistically significant risk factors for TA were identified, including living outside the capital city, possessing private medical
aid, HIV status, metastases at diagnosis, and solid tumor outside the central nervous system.
Conclusions: It was found that the TA at PMH in Botswana
is low compared to a recently published average of estimated
TA of SSA countries, although precise comparison is difficult
due to the limited data available for the region. More research
is needed at the hospital and country levels to better quantify
the magnitude of the problem and to facilitate inter-country
comparisons that explore the regional and national risk factors
for TA at a given center.
LATE EFFECTS
children were added as a control group. All participants were
subjected to history taking, physical assessment, and laboratory investigations including urine analysis, serum creatinine,
and BUN. Estimated glomerular filtration rates (GFR) were
calculated and chronic kidney disease was diagnosed accordingly. In addition, serum Cystatin-C (Cys-C) and neutrophilgelatinase-associated Lipocalin (NGAL) were determined.
Results: Survivors of solid tumors showed evidence of subclinical CKD as compared to the control group after an average of 2.1 years after cessation of therapy. The creatinine
level between cases and control was insignificant (p-022). The
(GFR) has a median of 95.87 versus 120.55 (mL/min/1.73
m2) (p-0.006), serum Cystatin-C has a median of 0.99 versus
0.75 mg/l (p-0.025). NGAL level has a median of 381 versus
225 pg. /ml for the control group. There is a significant positive correlation between serum Cys-C and serum NGAL. (p<
0.001) and a Negative correlation between Cys-C (p-0.029)
and NGAL (p-0.006) with (GFR)
Conclusions: Subclinical renal dysfunction could be found in
survivors. Both NGAL and cystatin C altogether connected
with measured GFR. They have a higher diagnostic accuracy than serum creatinine in discriminating normal from an
early stage of renal injury. Re-assessment of the renal function in survivors can help us to promote the health of the
Survivors.
P-558 Survivor's Assistance Program:
Continuing Psychological Support for Children and
Young Adults after the Completion of their Cancer
Treatment
P-557 Renal Dysfunction in Survivors of
Egyptian Children with Solid Tumors
H. Anis1 , A. Dhaliwal1 , K. Bhattacharya1
E.R. Abdel Khalek1 , L. Sherief2 , M. Almalky3 , N. Khalifa4 , M.
Abdel Monem2
Background/Objectives: Cancer is a significant stressor for
patients and their families but after the completion of their
treatment, some survivors, siblings and caregivers develop
persistent traumatic stress reactions. Experiencing these posttraumatic stress symptoms is often part of the process of
coming to terms with a life-threatening event,some survivors
and their parents, however, require more intensive therapeutic interventions and approaches to re-enter in the society
with enhanced psychological adjustment and emotional wellbeing.
1 Faculty
of Medicine- Zagazig University, Pediatrics, Cairo, Egypt;
of Medicine-Zagazig University, Pediatrics, Zagazig, Egypt;
3 Faculty of Medicine - Zagazig University, Pediatrics, Zagazig, Egypt;
4 Faculty of Medicine-Zagazig University, Clinical Pathology, Zagazig,
Egypt
2 Faculty
Background/Objectives: Pediatric cancer survivors have a
nine-fold risk to renal injury compared to healthy children.
Little is known about long-term renal dysfunction in this vulnerable group.
The aim of this work is to detect early chronic Kidney dysfunction (CKD) in Survivors of Egyptian Children with Solid
Tumors in order to prevent any developing renal impairment.
Design/Methods: We investigated 50 children (aged 3-15
years) cured from different solid tumors, 1 to 4 years after
ending the treatment. Twenty healthy age and sex-matching
1 CanKids...
Kidscan, Pediatric Psycho-oncology Program, New Delhi, India
Design/Methods: In May 2016 Cankids has initiated a Survivor's Assistance Program which aims to identify, understand
and rectify the unique needs and challenges of survivors and
their parents that reduces the experience of trauma and issues
of survivorship. This program is a combination of special
interventions that provide the survivors and their caregivers in
distress with one-on-one therapeutic interventions and Shar-
SIOP ABSTRACTS
ing and Caring Sessions to enhance their psychological well
being.
Results: However, survivors reported to possess higher risk
of depression, low self esteem, marital and fertility issues,
mood swings, acceptance, and some degree of anxiety over
the possibility of a recurrence, serious psychiatric disorders
such as Obsessive Compulsive Disorder, Bipolar Disorder,
and Schizophrenia were found to be uncommon. Parents were
concerned about relapse, sibling issues and mood swings of
the survivors. Based on the pre and post intervention assessment, they reported greater benefits after participating in these
cognitive and behavioral stress management interventions and
showed positive psychological responses such as less anxiety and fear, enhanced self-esteem, greater feelings of relief,
peacefulness and purposefulness in their lives.
Conclusions: It must be recognized that cancer survivors do
appear to possess slightly higher risk for major depression and
other psychological complications which continues to exist
across the survivorship trajectory.This kind of ongoing cognitive and behavioural stress management interventions not only
helps in identifying issues but also resolves the psychological
complications related to surviviorship for positive outcomes.
P-559 Creation of a Survivorship Clinic for
Oncology Pediatric Patients in Medical National
Center 20 De Noviembre Issste, A Third Level
Hospital in Mexico City
F. Arreguin1 , B. Alma2 , B.R. Eduardo2 , A.G. Blanca3 , R.C.
Julieta2 , S.B. Ruben4 , P.C. Soledad4 , D.M. Martha4
1 Centro
Medico Nacional “20 de Noviembre” ISSSTE, Pediatric Oncology,
Mexico City, Mexico; 2 Centro Medico Nacional 20 de Noviembre ISSSTE,
Pediatric Oncology, Mexico, Mexico; 3 Centro Medico Nacional 20 de
Noviembre ISSSTE, Pediatric Oncology, Pediatric Oncology, Mexico;
4 Centro Medico Nacional 20 de Noviembre, Pediatric Oncology, Mexico,
Mexico
Background/Objectives: Over the last 30 years the survival
rate in childhood cancer has improved all around the world.
Currently, eight of every ten children will survive ≥5 years
beyond their diagnosis, but they will have adverse healthrelated and quality-of-life outcomes as a sequealae of their cancer treatment. The ISSSTE (Institute of Security and Social
Service for State Workers) is a third level institute in Mexico
city that takes care of 11% of Mexico‘s total population and
the Medical National Center 20 de Noviembre (CMN 20 de
Noviembre) is the main reference hospital for ISSSTE´S cancer pediatric patients. We receive around 120 new cases/year.
In March 2016 we created the first Survivorship Pediatric
Cancer Clinic as a national strategy for these vulnerable population.
Design/Methods: CMN 20 de Noviembre is the main reference third level hospital for adults and children with severe
conditions, so there is a complete routine health care clin-
S421 of S518
icians of all medical specialties. We implemented a riskbased model based on the Childhood Cancer Survivor Study
adjusted to a low income country and opened Mexico´s first
Surveillance Clinic for pediatric cancer patients.
Results: We recluted 128 cancer survivors, with a female predominance (71% vs 57%). Adolescents were the most frequent group (14-17 years old). The most common late effects
were altered pituitary disfunction, overweight and obesity,
metabolic syndrome, neurocognitive deficits, scoliosis, ovarian disfunction, infertility, neurosensory deficits and renal
insufficiency
Conclusions: The ideal approach to childhood cancer survivor care involves a risk-based model with routine health care
and a personalized plan of surveillance. It is difficult in a low
income country to do this follow up so we need to strengthen
the relation with primary care doctors, follow practice guidelines for early detection of cancer treatment morbidity and
work with expertise groups in order to maximize quality of
life outcomes. More data is needed.
P-560 Sarcopenic Obesity in Long Term
Survivors of Acute Lymphoblastic Leukemia (ALL)
R. Barr1 , T. Farncombe2 , L. Beaumont3 , A. Cranston4 , V.
Yakemchuk2 , C. Marriott2
1 McMaster
University, Pediatrics, Hamilton-Ontario, Canada; 2 Hamilton
Health Sciences, Nuclear Medicine, Hamilton, Canada; 3 McMaster
University, Nuclear Medicine, Hamilton-Ontario, Canada; 4 Hamilton
Health Sciences, Pediatrics, Hamilton, Canada
Background/Objectives: Sarcopenic obesity (a gain in fat
mass with loss of lean-especially skeletal muscle-mass) has
been reported to occur early in the treatment of ALL, and
ascribed mainly to the influence of glucocorticosteroids. This
apparent paradox risks the double jeopardy of the metabolic
and frailty syndromes during survivorship, with the associated adverse effects on overall health and survival that result
from the added burdens of morbidity and premature aging. We
sought to determine whether this clinical phenotype persists
in long term survivors.
Design/Methods: A cohort of 75 adolescents and young
adults, who were more than 10 years from diagnosis, were
enrolled in a study of bone health and body composition* . All
had been treated on Dana Farber Cancer Institute protocols.
Measures of fat mass, lean body mass, appendicular lean mass
(ALM) and their corresponding indices (I=mass/height2 )
were provided by dual energy X-ray absorptiometry (Hologic
Discovery A model) which also gave values for bone mineral
content and density. Skeletal muscle mass (SMM) was derived
from the equation SMM (kg) = (1.19 × ALM [kg])-1.65.
Results: On the basis of the fat mass index (FMI) 68% of the
females and 88% of the males were overweight or obese (the
obese proportions being 15% and 21% respectively). All but
SIOP ABSTRACTS
S422 of S518
one subject had a low SMM. Based on a positive Z score for
FMI and a negative Z score for ALMI, 44% of the subjects met
the definition of sarcopenic obesity (discordance between fat
mass and lean mass).
Conclusions: Sarcopenic obesity is prevalent in long term
survivors of ALL. Given the attendant risks of premature
aging and mortality, this finding offers encouragement to
research into prevention and amelioration of the clinical phenotype, so improving overall health and extending survival.
*Barr R et al. BMJ Open 2015; 5: e006191
P-561 Sensorineural Hearing Loss After IMRT
for Nasopharyngeal Carcinoma: Is Paediatric
Cochlea Radioresistant?
A. Bindal1 , S. Laskar1 , N. Khanna1 , S. Chaudhary2 , T. Vora3 , G.
Chinnaswamy3 , S. Kembhavi4 , S. Shah5 , M. Ramadwar6 , S.
Qureshi7 , M.A. Muckaden8 , P. Kurkure3
1 Tata
Memorial Centre, Radiation Oncology, Mumbai, India; 2 Tata
Memorial Centre, Medical Physics, Mumbai, India; 3 Tata Memorial
Centre, Pediatric Oncology, Mumbai, India; 4 Tata Memorial Centre,
Radiodiagnosis, Mumbai, India; 5 Tata Memorial Centre, Nuclear Medicine,
Mumbai, India; 6 Tata Memorial Centre, Pathology, Mumbai, India; 7 Tata
Memorial Centre, Surgical Oncology, Mumbai, India; 8 Tata Memorial
Centre, Radiation Oncology/ Palliative Medicine, Mumbai, India
Background/Objectives: To evaluate sensorineural hearing
loss (SNHL) in children with nasopharyngeal carcinoma
(NPC) treated with intensity-modulated radiation therapy
(IMRT) and cisplatin based chemotherapy (CTh).
Design/Methods: From 2005 to 2015, 95 children with NPC
were treated with neoadjuvant cisplatin based CTh followed
by IMRT to nasopharynx (70.2Gy/33fr) and neck nodal
regions and adjuvant CTh, and evaluated for late auditory toxicity in the form of SNHL. Post treatment audiograms were
available for 33 children (66 ears). A total of 55 pure tone
audiograms more than 6 months post RT were evaluated retrospectively and the SNHL grade noted on a scale of 0 to IV
according to SIOP ototoxicity criteria. Chemotherapy doses
and mean cochlear doses were analysed for association with
grade III/IV ototoxicity.
Results: The median audiological follow-up was 24 months.
SIOP grade 0,I,II,III and IV ototoxicity was observed in
45(68.2%), 0(0%), 6(9.1%), 9(13.6%) and 6(9.1%) ears
respectively, with grade III/IV accounting for 22.7% of cases.
All except three of our patients received a cumulative cisplatin dose of 400mg/m2 , and no threshold cisplatin dose was
observed to correlate with ototoxicity. The average cochlear
Dmean was 54.6±10 Gy. For patients who developed grade
III/IV SNHL it was 57.8±8.2Gy. Using the Pearson Chi
Square test a cochlear Dmean threshold of >58 Gy was
observed to be associated with higher incidence of developing
grade III/IV SNHL (p=0.045), while the dose of 45Gy failed
to show any significant association (p=0.24).
Conclusions: Severe ototoxicity was seen in 22.7% of ears in
children receiving radiation and chemotherapy and was significantly more in those receiving a mean cochlear dose of
more than 58 Gy. Suggested thresholds for radiation doses to
cochlea and cumulative cisplatin doses, from adult studies,
may not be applicable in paediatric population. Prospective
studies are required to determine the cochlear tolerance doses
in children.
P-562 The Effect of Vitamin D Levels and Fok 1
VDR Gene Polymorphism on Long Term Bone
Health in Pediatric Cancer Survivors
N. Çetingül1 , Z. Önder Siviş1 , S. Özen2 , H. Onay3 , D. Gökşen2 , Z.
Burak4 , A. Oral4 , M. Kantar1 , S. Aksoylar1 , F. Özkınay3
1 Ege
University Faculty of Medicine, Pediatric Oncology, Izmir, Turkey;
University Faculty of Medicine, Pediatric Endocrinology, Izmir,
Turkey; 3 Ege University Faculty of Medicine, Medical Genetics, Izmir,
Turkey; 4 Ege University Faculty of Medicine, Nuclear Medicine, Izmir,
Turkey
2 Ege
Background/Objectives: 25-Hydroxy-vitamin D (25-OH D)
insufficiency is common in healthy children and adolescents,
with the prevalence being %14-49 in the general population.
Survivors of childhood cancer are at increased risk for a variety of adverse medical outcomes. Potential risk factors for
imparied 25-OH D status in this population include poor diet,
exposure to chemotherapy, steroids, radiotherapy. Vitamin D
performs its effect via the nuclear vitamin D receptor (VDR),
which shows an extensive polymorphism. We studied the frequencies of the Fok 1 VDR gene polymorphism and the status
of 25-OH D and their correlation with bone mineral density
(BMD).
Design/Methods: This study included 100 pediatric cancer
survivors in the Ege University, Dept. of Pediatric Oncology. All of them were subjected to full history taking and
clinical examination. The peripheral venous blood were took
from each patient for genomic DNA extraction (Fok 1 gene),
serum 25-OH D, calcium, phosphorus, alkaline phosphatase,
parathormone levels and obtained urine calcium/creatine and
measured bone mineral density (BMD). Fok 1 gene polymorphism results were compared with a control group of Turkish
healthy people.
Results: The diagnosis of patients was 28% leukemia, 31%
lymphoma, and 41 % solid tumor. Median age of patients at
cancer diagnosis was 7.8 years, during to the study was 16.9
years. In 72% of the patients were patients 25-OH D insufficient and deficient. The Fok 1 gene polymorphism was found
in 54% of them. In 44% of BMD measure was osteopenia and
osteoporosis. Patients with solid tumors were most affected,
despite of their lack of routine exposure to steroids.
SIOP ABSTRACTS
Conclusions: In pediatric cancer survivors the frequency of
Fok 1 gene polymorphism was similar to control group. The
prevalance of 25-OH D insufficiency and deficiency in cancer
survivors were high according to general population. Prospective studies evaluating on long term bone health in survivors
of cancers are required.
P-563 Life Threatening and Fatal Late Effects in
Long Term Survivors of Childhood Cancer-Data
from after Completion of Treatment (ACT) Clinic
G. Chinnaswamy1 , M. Prasad1 , V. Dhamankar1 , T. Vora1 , G.
Narula1 , P. Kurkure1 , S. Banavali1
1 Tata
Memorial Hospital, Department of Pediatric and Medical Oncology,
Mumbai, India
Background/Objectives: Long term survivors of childhood
cancer(CCSs) are known to have a higher prevalence of life
threatening and fatal health conditions(NCI CTCAE grade
4/5) compared to the normal population. These include
second malignant neoplasms(SMN), benign second neoplasms(SN) and late recurrences. Although these have been
described in large cohorts from the US and Europe, no data is
available from LMIC.
Design/Methods: A total of 1838 CCSs have been enrolled
into the After Completion of Therapy(ACT) clinic of our hospital since 1991. Survivors are kept under follow up based on
primary disease, treatment received and expected long term
toxicities. Data regarding SMN/SN, recurrences and deaths
was obtained from the database.
Results: 1838 CCSs with a median age of 18 years(5-53)
have been followed up over a median duration 10 years(5-40).
Nearly 50% are lost to long term followup at various stages.
91(5%) CCSs were detected to have grade 4/5 toxicities-37
late recurrences, 33 SMN, 14 SN and additional 7 deaths. The
commonest tumors to have late recurrences are Hodgkin lymphoma(HL), ALL and Ewing sarcoma, mean time to recurrence being 7.3 years, multiple recurrences in some and high
subsequent mortality (>30%). The most common SMNs were
carcinomas of thyroid and parotid, others being Ewing sarcoma and osteosarcoma., with mean time to develop being
13.2 years(3-38). The commonest SNs were schwannomas
and meningiomas and in ALL and HL survivors. There were
22 documented deaths-3 due to late organ toxicities(renal
failure, cardiac failure and moyamoya disease),10 following
recurrence, 5 in SMN and 4 unrelated deaths(Rheumatic heart
disease, accident, malaria and dengue).
Conclusions: With increasing survival there is a need for long
term surveillance of CCSs for both late recurrences and second malignancies. Ascertaining the true number of these very
long term toxicities needs rigorous follow up, which is a challenge given the health system network in LMICs.
S423 of S518
P-564 Human Papillomavirus (HPV) Vaccination
Rates Among Childhood Cancer Survivors in South
Texas
L. Embry1 , A. Brennan2 , A. Shay3 , A. Grimes1
Pediatrics, San Antonio- TX, USA; 2 UTHSCSA, School of
Medicine- MS4, San Antonio- TX, USA; 3 UT Health School of Public
Health in San Antonio, Department of Health Promotion & Behavioral
Sciences, San Antonio, USA
1 UTHSCSA,
Background/Objectives: Initiatives targeting uptake of
human papillomavirus (HPV) vaccination improved rates
nationally, however HPV-related diseases remain a significant health concern. Although childhood cancer survivors are
at increased risk for HPV-related disease (particularly those
with a history of stem cell transplantation (SCT) or radiation
therapy), they are not a targeted group in population-based
initiatives. In South Texas, HPV vaccination uptake is among
the lowest in the state. Study aims included evaluation of (1)
HPV vaccination rates among pediatric cancer survivors in
South Texas, and (2) demographic and clinical factors associated with HPV vaccine uptake in this population.
Design/Methods: Retrospective chart reviews of 210 childhood cancer survivors identified patients who were potentially
eligible to receive HPV vaccination from 2006 through 2016.
Review of vaccine records through Texas ImmTrac vaccine
registry and electronic clinical records verified HPV vaccination status. Demographic and clinical variables collected
included DOB, gender, race/ethnicity, cancer diagnosis, and
cancer treatment.
Results: Of 210 records reviewed, 156 survivors were deemed
vaccine-eligible. Of these, 21 (13.5%) received at least one
vaccine, but only 9 (5.7%) completed the 3-dose series. Of
the 84 females, 19% initiated with 10.7% completing the
series. However among the 72 males, only 6.9% initiated with
no completions. Approximately 76% of the sample was Hispanic/Latino. Among them, 17 patients initiated the vaccine
series but only 7 completed. Rates of initiation and completion were also low in white and black patients. Furthermore,
patients who received high-risk therapies (radiation, SCT) did
not have increased uptake of the HPV vaccine compared to
patients receiving only chemotherapy.
Conclusions: HPV vaccination rates among childhood cancer
survivors in South Texas is lower than in the general population, both regionally and nationally. Given the increased susceptibility to secondary HPV-related malignancies, this study
demonstrates a clear need for enhanced efforts to increase
HPV vaccination rates in this at-risk population.
P-565 Investigating the Mechanisms of
Methotrexate Neurotoxicity in Patients with
Childhood Leukemia and Long-Term Survivors
SIOP ABSTRACTS
S424 of S518
V. Forster1 , J. Carr-Wilkinson2 , D. Tweddle2 , S. Nakjang2 , S.
Choufani1 , W. Rosanna1 , F. Van Delft2
1 Peter
Gilgan Centre for Research and Learning- The Hospital for Sick
Children, Genetics and Genome Biology, Toronto, Canada; 2 Newcastle
University, Northern Institute for Cancer Research, Newcastle upon Tyne,
United Kingdom
Background/Objectives: Adverse neurological events are
common (4-20%) during treatment for pediatric acute lymphoblastic leukaemia (ALL) and include seizures, stroke like
syndrome and leukoencephalopathy. In addition, chronic neurotoxicity is emerging as a worrying late effect of treatment
with long-term survivors experiencing decreased executive
function, processing speed and memory function. Survivors
are also at increased risk of experiencing learning difficulties, social withdrawal issues and inattention hyperactivity
disorders. Methotrexate, an anti-folate chemotherapy agent,
is a mainstay of pediatric leukemia treatment regimens globally and is widely implicated as a cause of these neurological side effects. We hypothesise that methotrexate disrupts
DNA methylation via effects on S-adenosyl methionine, a key
methylation component that has previously been described to
be involved in regulation of genes involved in myelination.
Design/Methods: Using both neural cell lines and oligodendrocytes derived from induced pluripotent stem cells (iPSC)
treated with methotrexate, we assayed for changes in DNA
methylation and consequential effects on gene expression
using whole-genome methylation arrays and RNAseq, respectively. Genes with corresponding methylation and expression
changes were selected for confirmation of expression by realtime qPCR and assessment of protein levels.
Results: We identified methylation and concomitant expression changes in genes involved in neurodevelopmental pathways and neurological disorders. Of particular interest was
dose-dependent demethylation and consequential increase in
gene expression of IRS1, a vital component of insulin signalling pathways, highly expressed in neural tissue and implicated in regulating cognitive performance. We also detected
altered methylation within the PLP1 gene, which encodes the
most major protein component of myelin. We identified that
increased PLP1 methylation after methotrexate treatment in
iPSC-derived oligodendrocytes resulted in a corresponding
reduction in PLP1 transcript levels and PLP1 protein.
Conclusions: Our work provides insight regarding the biological mechanisms behind methotrexate-induced neurological
side effects, implicating altered insulin signalling and myelination pathways as potential causative factors in neurotoxicity.
P-566 Mental Health of Long Term Survivors of
Childhood and Young Adult Cancer
A.J. Friend1 , R. Feltbower1 , A. Glaser1 , E. Hughes2 , K. Dye3
1 University
of Leeds, School of Medicine, Leeds, United Kingdom;
of Southampton, School of Medicine, Southampton, United
Kingdom; 3 St George's- University of London, School of Medicine, London,
United Kingdom
2 University
Background/Objectives: Survivors of young people's cancer are known to have increased risk of psychological distress including cognitive difficulties, however little is known
about emotional and behavioural problems. We aimed to collate evidence of the prevalence of mental health problems in
long-term survivors of childhood cancer.
Design/Methods: A standard systematic review was performed,excluding papers on cognitive function. We searched
the PubMed, Embase/OVID, CINAHL and Web of Science
databases using the following strategy:
(child OR children OR childhood OR teen OR teenage*
OR adolescent* OR “young adult”)
AND
(cancer OR leukaemia OR tumour OR tumor)
AND
survivor
AND
“Mental health” or “mental illness” or “psychiatric” or
“psychological” or “emotional” or “behavioural” or
“behavioral”
AND
“late effects” or “long term”
Results: Initial search results returned over 1500 papers,
after discarding papers covering cognitive function and those
exploring interventions rather than prevalence, 324 papers
remained. We found reports of increased antidepressant use
and higher rates of psychological distress in long term survivors of CYP's cancer compared to controls, although many
of these were siblings of survivors, who are likely to have
their own difficulties.The majority of data came from selfreports, which are associated with high risk of bias. There was
also data from hospital admissions for mental health problems
and analysis of prescribing data from primary care. We found
no papers reporting on primary care-diagnosed mental health
problems, despite this being the most common place for mental illness to be diagnosed and treated in many settings.
Conclusions: There is a need to more accurately ascertain the
prevalence of mental health problems in this group. Data from
primary care would significantly improve our understanding
of this issue. This would be essential for future service planning. We hope our future work linking primary care records
to cancer registries will go some way to addressing this gap in
knowledge.
P-567 Pharmacogenetic Analysis of
Treatment–Related Toxicities for Hepatoblastoma
Patients in Japan
SIOP ABSTRACTS
S425 of S518
E. Hiyama1 , S. Kumura2 , S. Kuriahra1 , M. Kawashima1 , Y. Ueda1 ,
Y. Onitake3
1 Hiroshima
University Hospital, Peditric Surgery, Hiroshima, Japan;
University, Natural Science Center for Basic Research and
Development, Hiroshima, Japan; 3 Kure Medical Center, Peditric Surgery,
Kure, Japan
2 Hiroshima
Background/Objectives: Cisplatin and anthracycline are the
most widely used anticancer agents against hepatoblastoma
(HB). The Japanese Study Group for Pediatric Liver Tumor
(JPLT)-2 study (1999-2012) was to evaluate the efficacy of
cisplatin/pirarubicin (CITA regimen) for HB. Avoidance of
treatment-related ototoxicity, cardiotoxicity, and secondary
malignancy effects is important to improve long-term outcomes for childhood HB.
Design/Methods: In JPLT-2 study, 360 HB children were eligible for inclusion. Among them, we evaluated late effects
including ototoxicity, cardiotoxicity, maldevelopment and
secondary malignancy in survived cases. Among them, in
186 patients whose germline DNA samples were available
under informed consent, genotyping was performed using
the Illumina Human Omni Express Exome-8 v.1.3 BeadChip (Illumina). A linkage disequilibrium (LD)-based singlenucleotide polymorphism (SNP) selection strategy was 60
used to identify a minimal set of informative variants. Associations between SNPs and toxicities were assessed using
logistic regression. Ototoxicity was determined by audiometry and/or auditory brain-stem response. Cardiotoxicity was
mainly determined by standardized echocardiography.
Results: Among the 186 survived cases tested these SNP
analysis, 64 ototoxicity, 17 cardiotoxicity, 36 maldevelopment
and 8 secondary malignancies were determined. The dose
of cisplatin and/or pirarubicin seemed to be correlated with
their occurrence but not significantly. We identified inherited
genetic variations in three SNPs including 6 SNPs including
ACYP2 associated with ototoxicity and in two SNPs associated with cardiotoxicity. Moreover, we find out candidates
of genetic variations correlated with maldevelopment or secondary malignancy.
Conclusions: The risk variant in these SNPs strongly predisposed these patients to toxicities including ototoxicity and cardiac toxicity using chemotherapy. These results
point to new biology underlying the late toxic effects of
palatinum/anthoracyclin agents. We should pay biological
assessment for next protocol avoiding these toxic effects of
chemotherapeutic agents.
P-568 Rare Outcomes Encountered In the Care
of Childhood Cancer Survivors: Piloting a
Methodology to Create Clinical Practice Guidelines
1
2
3
1
4
L.B. Kenney , B. Ames , D. Williams , A. Michaud , N. Ullrich ,
P. Manley1
1 Dana-Farber
/Boston Children's Hosptial, Pediatric Oncology, Boston,
USA; 2 Dartmouth Hitchcock Medical Center, Pediatric Hematology
Oncology, Hanover, USA; 3 Boston Children's Hospital, Clinical Research
Center, Boston, USA; 4 Boston Children's Hospital, Neurology, Boston, USA
Background/Objectives: Many of the clinical issues encountered in the long-term follow-up care of childhood cancer
survivors are unique to this population. Studies investigating management of these outcomes are often not available.
We piloted a consensus-based, modified Delphi-approach
methodology to develop regional guidelines for the care of
survivors and to identify areas of clinical disagreement.
Design/Methods: Members of the Consortium for New England Childhood Cancer Survivors (CONNECCS) were surveyed to identify clinical challenges encountered in care of
survivors. Five vignettes on neurologic outcomes were developed based on most frequent clinical issues described. A purposeful sample of 30 was chosen to represent specialty and
general physicians from geographically diverse CONNECCS
institutions. A systematic review of the medical literature
to identify risk factors and interventions was completed; a
summary of evidence was made available to participants. A
modified Delphi approach required three rounds of anonymous survey data collection to establish practice norms and
systematically build consensus among expert participants.
Results: All 30 participants completed the round 1 survey with 25 open-ended questions addressing practice norms
related to 5 clinical scenarios. Responses were coded and a
modal management option for each question was described.
The round 2 survey asked participants to agree/disagree with
the modal management options and to provide rational for
their responses. All 30 responded. Of the 25 management
questions, participants reached consensus on 3 (>90% agreement), conditional agreement on 11 (>90%), and disagreement on 11 (>10%). Round 3 questionnaire attempts to negotiate consensus in areas of disagreement by sharing summarizes of rationale provided by participants for their management decisions.
Conclusions: Regional experts can be successfully recruited
and retained to develop clinical practice guidelines to manage rare outcomes encountered in the care of childhood cancer survivors using a modified Delphi methodology. Areas
where management is controversial can be identified for further research.
P-569 Radiation- Associated Pulmonary
Diffusion, Restrictive and Obstructive
Abnormalities as a Function of Age in Pediatric
Cancer Survivors
F. Khan1 , A. Williams2 , D. Weiner3 , S. Dhakal4 , L. Constine4
1 University
of Rochester, School of Medicine, Rochester, USA; 2 University
of Rochester, James P Wilmot Cancer Center, Rochester, USA; 3 Children's
SIOP ABSTRACTS
S426 of S518
Hospital of Pittsburgh, Pediatric Pulmonology, Pittsburgh, USA;
4 University of Rochester, Radiation Oncology, Rochester, USA
Background/Objectives: Pulmonary dysfunction is a prevalent and potentially debilitating late effect of radiation therapy (RT) used to treat children with cancer. We postulated
that age, as a surrogate for respiratory developmental status,
might be associated with vulnerability to pulmonary injury.
Design/Methods: Sixty-one children treated at our institution with lung radiation who had undergone pulmonary function testing (PFT) between 1995-2016 were analyzed. Data
collection included age at treatment (radiation, chemotherapy, surgery), radiation dose and location, spirometry and
plethysmography results. PFTs were normalized according
to age, gender, height, and ethnicity and transformed into
standardized z-scores. Obstructive disease was defined as
zFEV1/FVC<-1.645, restrictive as zTLC<-1.645 and abnormal diffusion as zDLCO<-1.645. We determined the incidence of obstructive, restrictive, or diffusion abnormalities in
our population and estimated the relative risk of developing
pulmonary abnormalities.
Results: At a mean age of 24 years (range 12-31) and time
from diagnosis of 9 years (range 1-20), the cumulative incidence of any pulmonary abnormality was 34.4%. The incidence of diffusion abnormalities, obstructive, and restrictive
disease was 19.6%, 18% and 8.1% respectively. Those <5
years and 5-13 years at RT had more diffusing, restrictive, and
obstructive abnormalities than those >13 years. Compared
to patients >13 years, those <5 years and 5-13 years at RT
had a significantly increased risk of an abnormal PFT as follows: OR 7.71 (95% CI: 1.17, 51.06) and 3.51 (95% CI: 1.06,
11.57) respectively, p<0.035, although statistical significance
was lost after adjustment for bleomycin use and time since RT.
Further, this association remained when examining each type
of abnormality (p>0.05).
Conclusions: Pulmonary function abnormalities were common among our cohort of childhood cancer survivors treated
with lung radiation. Diffusion and obstructive disease were
more common than restrictive disease. Younger age at treatment is associated with an increasing risk of developing
pulmonary dysfunction, presumably due to developmental
immaturity.
Background/Objectives: Vision loss in context of pediatric
oncology is due to neurofibromatosis (NF1), retinoblastoma
or brain tumors. In which cases vision loss could be partial
or total, occurs immediately or as a progressive disease, touch
children in various ages and level of development. Symptoms
of vision loss are variable and determine different ways of
early intervention and psychological support.
Design/Methods: Whole oncological population in our center we search for vision deficits and assessed their special
needs, determined by specific mechanism of sensory loss.
We prepared recommendation for psychological procedures,
including: challenges in the assessment of this population,
the most effective vision functional assessment, psychological early rehabilitation and stimulation, psychological support
for parents in decisions making about their child's treatment,
rehabilitation and education.
Results: As a dynamic disease NF1 causes progression of
optic pathway gliomas and decreasing vision ability. Symptoms and grade of vision loss due to childhood brain tumors
depend on localization of lesion, e.g. posterior fossa tumor –
double vision, strabismus, nystagmus; frontal lobe – risk of
total vision loss; occipital lobe – cortical visual impairment
(CVI) or total vision loss (legal blindness); chiasma of optic
nerves – hemianopia, loss of peripheral vision (tunnel vision).
In our sample we observed also that relation between localization of brain damage (as a consequence of tumors) and vision
loss is complex and mechanism is not clear. Retinoblastoma as
a progressive disease caused gradual vision loss. Patients are
adapted to this limitation and do not show significant behavior
disturbances as the consequences of lack of sight. Child is too
small to give feedback how is sighing. Same behaviors and
reactions connected to vision loss are misdiagnosed, delayed
diagnose and confused caregivers.
Conclusions: Vision impairment in oncological population
is specific and requires special psychological procedures and
early intervention, started at the time of treatment.
P-571 Physical Activity Behavior in Children and
Adolescents Before, During and After Cancer
Treatment
M. Neu1 , S. Stössel1 , V. Rustler2 , R. Söntgerath3 , J. Däggelmann2 ,
K. Eckert4 , V. Kramp3 , F.T. Baumann5 , W. Bloch2 , J. Faber1
1 University
P-570 Vision Loss in Pediatric Oncology Due to
NF1, Retinoblastoma and Childhood Brain Tumors.
Recommendations for Psychological Intervention
J. Korzeniewska1 , B. Dembowska - Bagińska1
1 The
Children's Memorial Health Institute, Pediatric Oncology, Warsaw,
Poland
Medical Center Mainz, Center for Pediatric and Adolescent
Medicine- Department of Pediatric Hematology/Oncology/Hemostaseology,
Mainz, Germany; 2 German Sport University Cologne, Institute of
Cardiovascular Research and Sports Medicine- Department of Molecular
and Cellular Sport Medicine, Cologne, Germany; 3 Leipzig University
Hospital, Department of Pediatric Oncology- Hematology and
Hemostaseology, Leipzig, Germany; 4 University of Heidelberg, Institute of
Sport and Sport Science, Heidelberg, Germany; 5 University Hospital of
Cologne, Department I of Internal Medicine- Center of Integrated Oncology
Köln Bonn, Cologne, Germany
SIOP ABSTRACTS
Background/Objectives: Childhood Cancer is associated
with various disease- and treatment-related sequelae on physical, psychological and social levels. Previous studies showed
reduced physical activity levels in survivors after childhood cancer treatment (CCT) which may have considerable impact on child development, quality of life, social
participation and cardiovascular health. The aim of this
study was to evaluate physical activity behavior (PA) in
children and adolescents before, during and after intensive
CCT.
Design/Methods: In this prospective multicenter study, 114
children and adolescents formerly treated for any type of cancer were enrolled (mean age 11.7 (4.17-19.7) years). PA was
assessed after completion of intensive treatment phase (time
since diagnosis 3.7 (0.6-14) years) using an adapted version
of the PA questionnaire from the German KiGGS-Study. The
questionnaire included items asking for the level and intensity
of PA before and during CCT, and at time of study participation, i.e. after completion of intensive CCT. Results were
compared to 37 healthy controls (mean age 11.9 (5.4-17.3)
years).
Results: Compared to time before CCT, patients reported
significantly lower PA levels during and after CCT, evaluated by a visual analog scale (p<0.05). Healthy controls reported higher PA levels than patients after CCT
(p<0.05). Time of PA spent at a low intensity level was
lower after CCT than before (p<0.05). 31.1% of patients
did not participate in sport club activities before CCT and
51.1% after CCT whereas 2.7% of healthy controls did not
participate.
Conclusions: In conclusion, children and adolescents treated
for cancer report modified PA behavior during and after CCT
in comparison to time before CCT as well as in comparison
to healthy controls. Further studies are needed to investigate
the consequences of physical inactivity during and after CCT
and to examine subsequently how physical activity behavior
can be influenced positively.
S427 of S518
4 University
Medical Center Wuerzburg, Department of Pediatric
Hematology and Oncology, Wuerzburg, Germany; 5 University Medical
Centre Hamburg-Eppendorf, Department of Pediatric Hematology and
Oncology, Hamburg, Germany; 6 University of Essen, Pediatrics III
Oncology, Essen, Germany; 7 University Hospital of Geneva, Department of
Pediatrics and Adolescent Medicine Division of Pediatric Oncology,
Geneva, Switzerland; 8 University Children´s Hospital Rostock, Department
of Hematology Oncology, Rostock, Germany; 9 University Medical Center
Wuerzburg, Department of Neuroradiologie- Hit 2000 National Refenrence
Center, Wuerzburg, Germany; 10 University Medical Center Wuerzburg,
Department of Pediatric Neurosurgery, Wuerzburg, Germany; 11 University
of Leipzig, Department of Radiotherapy, Leipzig, Germany; 12 University of
Bonn, Department of Pediatric Oncology, Bonn, Germany
Background/Objectives: Background: Medulloblastoma
(MB), Ependymoma (ED) and Primitive neuroectodermal
tumors (PNET) in young children in are associated with an
unfavorable mental outcome after multimodal treatment.
Therefore, craniospinal radiotherapy (CSI) is often delayed or
replaced by intrathecal methotrexate (MTXi.th ) and systemic
Chemotherapy (CH-T).
Design/Methods: Procedures: Between October 2007 and
March 2017 n = 327 surviving children treated within the
HIT 2000 protocol at age of < 4 years were prospectively
assessed by two neuropsychologist from the Wuerzburg team.
The following tests were systematically applied: Kaufman
Assessment Battery for Children (K-ABC) measuring the
Mental Processing Composite (MPC), the Coloured Progressive Matrices (CPM), the Developmental Test of Visual Motor
Integration (VMI), the Tapping Test (TP) und der Continuous
Performance Test (CPT-K). Data of n = 206 patients were
included in this analysis.
Results: Results Children were stratified according to diagnosis (MB, ED, PNET), M-status (M0, M+) and clinical
response. The average IQ of all patients was: MPC IQ 84.96;
SD 1.63. However, the values differed largely among the various treatment groups.
As examples, the results of MB M+ patients (treated with systemic chemotherapy and the following RT) are shown:
DMB M+ good responder no CSI, MPC IQ 86
DMB M+ poor responder CSI, MPC IQ 61
P-572 Neuropsychological Outcome of Different
Treatments for Young Children with
Medulloblastoma, Ependymoma and PNET:
Multicenter Trial HIT 2000
H. Ottensmeier1 , P.G. Schlegel2 , J.E. Wolff3 , M. Eyrich4 , B.O.
Juhnke5 , K. von Hoff5 , S. Frahsek1 , G. Fleischhack6 , A. von
Bueren7 , C. Friedrich8 , M. Mynarek5 , A. Resch8 , M.
Warmuth-Metz9 , J. Krauss10 , R.D. Kortmann11 , U. Bode12 , J.
Kuehl†1 , S. Rutkowski5
1 University
of Wuerzburg Children´s Hospital, Department of Pediatric
Oncology, Wuerzburg, Germany; 2 University of Wuerzburg Children´s
Hospital, Department of Pediatric Oncology- Comprehensive Cancer
Center Mainfranken, Wuerzburg, Germany; 3 Cleveland Clinic Children´s
Hospital, Department of Pediatric Hematology Oncology, Cleveland, USA;
CMB M+ good responder no CSI, MPC IQ 89
CMB M+ poor responder CSI, MPC IQ 62
EP II infratentorial local RT, MPC IQ 97
EP III infratentorial local RT, MPC IQ 93
Interestingly, patients with infratentorial ED were found to
have a K-ABC within normal age range.
Conclusions: Conclusions In this longitudinal assessment of
the HIT 200 cohort, we found that multimodal therapy without CSI in MB patients resulted in improved mental outcome
as measured by K-ABC. This neuropsychological follow-up
project was supported by the German Childhood Cancer
Foundation.
SIOP ABSTRACTS
S428 of S518
P-573 Dose Metrics and Memory Performance in
Children Treated for Brain Tumor
K. Raghubar1 , M. Lamba2 , K. Cecil3 , K. Yeates4 , E.M. Mahone5 ,
M.D. Ris1
1 Baylor
2 University
College of Medicine, Pediatrics, Houston, USA;
of
Cincinnati College of Medicine, Radiation Oncology, Cincinnati, USA;
3 University of Cincinnati College of Medicine, Radiology, Cincinnati, USA;
4 Hotchkiss Brain Institute- University of Calgary, Psychology, Calgary,
Canada; 5 Kennedy Krieger Institute, Neuropsychology, Baltimore, USA
Background/Objectives: Advances in radiation oncology
provide new opportunities to study neurocognitive outcomes
of radiation therapy (RT) in pediatric patients treated for brain
tumor. Specifically, these advances allow for the consideration of the multidimensionality inherent to individualized RT
treatment planning when examining the relationship between
RT and neurocognitive outcomes. The present study investigates the relationship between biophysical and physical dose
metrics, as well as their relation to neurocognitive ability,
namely learning and memory.
Design/Methods: This study is based on a subsample (n =
20) of participants from a longitudinal, prospective, multisite study (BRISC: Brain Radiation Investigative Study Consortium). Participants included in this study were diagnosed
between the ages of 5 and 16 years and received RT following surgical intervention. Detailed dose reconstruction metrics were collected, and results from neuropsychological evaluations completed on average 29 months post-treatment are
reported. Physical (mean dose, prescribed dose, max dose)
and biophysical (generalized equivalent uniform dose, integral biological effective dose) dose metrics for the whole
brain, and right and left hippocampus were evaluated and correlated with learning and memory subtests from the Children's
Memory Scale.
Results: Biophysical dose metrics were highly correlated
with the physical metric of mean dose (all Spearman's � correlations > .82) but not prescribed dose. Although prescribed
dose was uncorrelated with measures of learning and memory, biophysical metrics and mean dose correlated with most
measures; and lateralizing findings were obtained.
Conclusions: These preliminary findings suggest limited
advantage of biophysical dose metrics over physical metrics
of mean dose when calculated for specific regions of brain.
Implications for evaluating and understanding the relation
between RT and neurocognitive functioning are discussed.
1 Children's
cancer Hospital-Egypt-57357, Research, Cairo, Egypt; 2 Armed
Forces College of Medicine, Research, Cairo, Egypt;
3 Charité-Universitätsmedizin Berlin, Medicine, Berlin, Germany
Background/Objectives: Thyroid carcinoma is a very rare
tumor in pediatric, it accounts for only 3% of all newly diagnosed childhood carcinomas in the United States according
to the SEER database. The incidence rates of thyroid carcinoma of children from 0 – 4 years of age is 0.4 per 100 000,
and up to 1.5 per 100 000 for adolescents aged from 15 to19
years. It was reported from large cohort studies that thyroid
carcinoma is associated with an increased risk of second primary malignancies after treatment. We aim to assess the risk
of subsequent malignancies among survivors of pediatric thyroid cancer.
Design/Methods: We used US SEER (Surveillance Research
Program, National Cancer Institute, Bethesda, MD, USA)
database to perform this study. SEER*STAT version 8.3.4
was used to extract data from SEER public-use database. The
cohort for this analysis consisted of pediatric cancer patients
aged less than 20 years diagnosed with a primary thyroid cancer and identified by site code ICD-0-3: C739, reported to a
SEER 9 database between 1973 and 2013 To identify subsequent malignancies in this population, a query was performed
to obtain all additional records of a new tumor diagnosis for
each patient. Subsequent malignancies occurring 5 years or
more after the original thyroid cancer diagnosis were included
except thyroid cancer as a second malignancy.
Results: A total of 38 patients diagnosed primarily with thyroid carcinoma with 42 incidence of subsequent malignancies
as 4 patients developed third malignancy. Females represents
89.4% while males represent 10.5%. The subsequent malignancies of pediatric cancer survivors diagnosed with thyroid
cancer includes many sites but high percent in both Female
breast (21.3%) and Salivary gland (13.2%).
Conclusions: Thyroid cancer is a rare tumor in childhood.
The risk of developing second malignancy between pediatric
cancer survivors mandates the presence of precise plan of
longer follow-up.
P-575 Cardiovascular Function in Adult
Survivors of Pediatric Cancer
I. Schmid1 , B. Reiner2 , J. Müller2 , A. Hager3 , A. Kühn3 , R.
Oberhoffer4 , P. Ewert3 , J. Weil3
1 Dr.
P-574 The Risk of Subsequent Malignancies
Among Survivors of Pediatric Thyroid Cancer
W.M. Rashed1,2 , M.H. Adly1 , M. Sobhy2 , M.A. Rezk2 , M. Ishak2 ,
A. El Shafie2 , M. Ali2 , A. Alfaar3
von Hauner Children's Hospital- Ludwig Maximilian University,
Pediatric Hematology and Oncology, Munich, Germany; 2 Deutsches
Herzzentrum München and Institute of Preventive Pediatrics- Technical
University of Munich, Department of Pediatric Cardiology and Congenital
Heart Disease, Munich, Germany; 3 Deutsches Herzzentrum MünchenTechnical University of Munich, Department of Pediatric Cardiology and
Congenital Heart Disease, Munich, Germany; 4 Institute of Preventive
Pediatrics- Technical University of Munich, Department of Pediatric
Cardiology and Congenital Heart Disease, Munich, Germany
SIOP ABSTRACTS
Background/Objectives: Adult survivors of pediatric cancer
are at high risk developing late cardiovascular events. The
most important risk factor is the cumulative dose of anthracycline therapy. The goal of this prospective study was to
detect any alterations regarding vascular structure, function
and exercise capacity based on the dose of anthracyclines
given.
Design/Methods: 51 survivors of pediatric cancer (25 male)
diagnosed at a median age of 12 years were examined at
an average age of 22 years (16-43 y) between 03/2015
and 01/2017. Patients with a cumulative dose of >250
mg/m2 anthracyclines were compared to patients with 100250 mg/m2 anthracyclines. All patients were asymptomatic
and in NYHA class 1. To quantify dysfunction of the left ventricle, ejection fraction (EF) was determined by echocardiography. As cardiac biomarker, the plasma N-terminal pro-brain
natriuretic protein (NT-proBNP) level was measured. In addition, cardiopulmonary exercise test was performed to detect
limitations in exercise capacity.
Results: EF was reduced (EF <55%) in 17% of male and
16% of female survivors. There was no difference between
the groups with high and moderate anthracycline dosage. NTproBNP was elevated (NT-proBNP >100 ng/ml) in 20% of
male and in 46% of female survivors. NT-proBNP was significantly higher in the group with high compared to the group
with moderate anthracyclines (p=0.03). There was no association between NT-proBNP and EF. Cardiopulmonary exercise
capacity was significantly lower in the group with high than
with moderate anthracycline dosage (p=0.005).
Conclusions: EF, NT-proBNP levels and cardiopulmonary
exercise tests are important parameters to detect early impairment of cardiovascular function in asymptomatic survivors of
childhood cancer.
Irene Schmid and Barbara Reiner contributed equally to this
work.
P-576 Late Effects of Treatment in Survivors of
Childhood Cancers: Experience from India
R. Seth1 , S. Seth2 , A. Singh1 , S. Sapra1
1 ALl
India Institute of Medical Sciences, Pediatrics, Delhi, India; 2 ALl
India Institute of Medical Sciences, Cardiology, Delhi, India
Background/Objectives: Background: With improved survival of childhood cancer, long-term cancer survivors are
increasing. Few studies have assessed the long-term morbidity after childhood cancer treatment in developing countries.
S429 of S518
ment completion clinic was done. Details of primary diagnosis, treatment received and current clinical status was noted.
The spectrum of late effects was ascertained by appropriate
investigations.
Results: Hematological malignancies comprised 25% of total
cases.Commonest primary diagnosis comprised acute lymphoblastic leukemia (ALL), retinoblastoma and Hodgkin lymphoma. The median age at evaluation and follow-up were 14
years and 8.5 years respectively. 23% (69) of the survivors
had a minimal disability (growth retardation or underweight),
13% (39) had moderate disabilities needing medical attention
(HbSAg positive, myocardial dysfunction, Azoospermia and
hypothyroidism) while 2 % (1) had major/ life threatening disabilities (mental retardation, liver disease, mortality). Eleven
patients relapsed on follow-up: of these five patients expired.
Two second malignancies were recorded in our cohort of
patients during the period of follow-up.
Conclusions: Late effects are a concern however severe disability (grade 3-5) is seen in only 2% survivors: most can be
tackled. Lifelong follow-up of childhood cancer survivors is
recommended to define accurately cancer-related morbidity,
occurrence of a secondary neoplasm, facilitate timely diagnosis and implement remedial or preventive interventions that
optimise health outcomes.. Awareness towards the existence
of late effects of cancer therapy is required among parents,
patients and health professionals
P-577 Subsequent Glioma in Survivors of
Paediatric Neoplasms
L. Shats1 , M. Belogurova1 , S. Ozerov2 , A. Ektova3 , M. Rizhova4 , I.
Doronina5 , O. Vizhlukova5 , E. Grishina6 , A. Rudneva7 , E. Erega8 ,
O. Zheludkova9 , A. Pshonkin2 , E. Kumirova2
1 Saint-Petersburg
State Paediatric Medical University, Division of
Oncology- Paediatric Oncology and Radiotherapy, St. Petersburg, Russia;
2 Dmitry Rogachev National Research Center of Pediatric HematologyOncology and Immunology, Division of Neurooncology, Moscow, Russia;
3 Dmitry Rogachev National Research Center of Pediatric HematologyOncology and Immunology, Pathology Department, Moscow, Russia; 4 N.N.
Burdenko Neurosurgical Institute- Russian Academy of Medical Sciences,
Division of Pathology, Moscow, Russia; 5 Paediatric Hospital of Murmansk,
Department of Paediatric Oncology- Haematology and Endocrinology,
Murmansk, Russia; 6 Children's Republican Clinical Hospital, Departmant
of Paediatric Oncology and Haematology, Kazan, Russia; 7 Dmitry
Rogachev National Research Center of Pediatric Hematology- Oncology
and Immunology, Consultation Department, Moscow, Russia; 8 Children's
Regional Hospital, Paediatric Oncology and Haematology, Khabarovsk,
Russia; 9 Russian Scientific Center of Radiology, Department of
Neuro-Oncology, Moscow, Russia
Objectives: To study the prevalence and spectrum of late
effects of cancer treatment in pediatric cancer survivors.
Background/Objectives: Multimodal therapy has improved
survival for most childhood tumours.The development of neoplasms subsequent to therapeutic cranial irradiation is a rare
but serious and potentially fatal complication.
Design/Methods: Methodology: Evaluation of the first 300
patients who completed 5 years of follow-up in the after treat-
Design/Methods: The analysis included 16 patients (pts) with
subsequent glioblastoma (SG) from several institutions who
SIOP ABSTRACTS
S430 of S518
underwent cranial or neck irradiation (1 case) to treat their
primary disease (acute lymphoblastic leukaemia - 12 pts,
medulloblastoma- 2 pts, choroid plexus papilloma - 1 pt, lymphoma - 1 pt.). All gliomas arose within the previous radiation
fields and satisfied the widely used criteria for the definition
of radiation induced neoplasms. The median RT dose administered was 18 Gy with the dosage ranges being 12-36 Gy.
Total body irradiation(TBI) was used in one patient with Phpositive ALL during bone marrow transplantation. Median
latency period was 7 years until diagnosis of SG. The majority of SG (13 of 16 [81%]) occurred during the initial 9 years
of follow-up, only 3 were diagnosed after 10 years. Patients
underwent surgery resection followed by standard fractionated local radiation and chemotherapy.
Results: A Kaplan-Meier analysis was used to illustrate the
overall survival (OS) curves. OS rate was 37.5±12.9% and
15.0±9.7% at 1 and 2 years respectively.
Conclusions: In case that paediatric neoplasms are treated
by standard fractionated radiation or TBI is used, radiationinduced gliomas should be considered as possible long-term
side effect. And the patients should be followed for a long
term, even longer after the period of risk for relapse of the
primary cancer has passed.
patient subgroups, as well as between the white matter lesion
(present vs. absent) subgroups.
Results: Cognitive scores appeared lower for WAIS working memory (F=6.866, p=.012), WAIS processing speed
(F=6.942, p=.011), RVDLT total (F=8.982, p=.004), BRIEF
working memory (F=6.149, p=.017) and PedSQL total score
(F=6.314, p=.015). WM lesions were present in 23.5% of
patients (vs. .02% of controls). The risk of WM lesions predicted by the Apo�4 allele, resulted in a correct categorization
of 37.5% as lesion patient (Model: � 2 = 8.708, p=.003). Neither of both factors were related to cognition.
Conclusions: Survivors of solid tumors mainly complain
about working memory, and also showed lower objective
scores for processing speed, visual memory and QoL. The heterogeneity of WM lesions suggest that the impact on cognition is different, depending on the location and type of lesion.
The ApoE genotype could be a potential biomarker for such
lesions.
P-579 Sonographic Image of Solitary Kidney in
Wilms Tumor Survivors
J. Stefanowicz1 , M. Kosiak2 , E. Adamkiewicz-Drożyńska3 , A.
Balcerska2 , A. Kurylak4
P-578 The ApoE Genotype and White Matter
Lesions in Childhood Non-CNS Tumor Survivors
C. Sleurs1 , J. Lemiere1 , G. Vercruysse1 , L. Vandenwyngaert1 , V.
Labarque1 , S. Jacobs1 , S. Sunaert2 , S. Deprez2 , A. Uyttebroeck1
1 University
2 University
Hospitals Leuven, Pediatric Oncology, Leuven, Belgium;
Hospitals Leuven, Radiology, Leuven, Belgium
Background/Objectives: ApoE is the cholesterol transporter,
playing an important role in neuronal plasticity. Given the
lack of evidence about neurodevelopment in childhood cancer patients, this study aims to explore potential brain lesions
in survivors and the link with cognition and the ApoE4 allele.
Design/Methods: We acquired neurocognitive data for survivors of pediatric solid non-CNS tumors (n=34) and agematched controls (n=34) [16-35] years. Patients were treated
since 2000. Neuropsychological assessments included intelligence, verbal and auditory memory, attentional measures.
T2*-weighted FLAIR images were investigated for white matter lesions. DNA samples were examined for the ApoE polymorphism. First, we compared behavioral scores on objective
assessments (WAIS, AVLT, RVDLT, ANT) and subjective
questionnaires (STAI, CFQ, BRIEF), with depression (BDI)
and SES as covariates. The risk for white matter lesions within
the patient group was predicted by the ApoE genotype (i.e. by
the presence vs. absence of allele �2 and �4). Cognitive scores
within the patient group were compared between the Apo�4
1 Gdansk
Medical University, Department of Pediatrics- Hematology and
Oncology, Gdańsk, Poland; 2 Medical University of Gdansk, Department of
Family Medicine, Gdansk, Poland; 3 Medical University of Gdansk,
Department of Paediatrics- Haematology- Oncology, Gdansk, Poland;
4 Department of Paediatrics- Haematology and Oncology. Ludwik Rydygier
Collegium Medicum in Bydgoszcz. Nicolaus Copernicus University in
Torun., Department of Paediatrics- Haematology and Oncology,
Department of Paediatrics- Haematology and Oncology, Poland
Background/Objectives: Study presents analysis of sonographic and laboratory parameters of solitary kidneys and
prevalence of chronic kidney disease (CKD) in Wilms tumor
survivors (WTs).
Design/Methods: 53 WTs who completed treatment for
Wilms tumor (WT) and 44 healthy individuals were enrolled
to the study.
Study protocol consists of: completing medical history,
sonographic examination of solitary kidney, estimation of
glomerular filtration rate (eGFR) with Schwartz or MDRD
formula, albumin urine excretion (ACR), blood pressure measurement.
Results: Sonographic sings of kidney damage were observed
in 21 (39,6%) WTs. Hypertrophy of solitary kidney occurred
in 71,7% of cases. Mean volume of solitary kidney was 77% of
volume of sum of two kidneys in control group. Mean eGFR
in WTs group was 117 ± 19,5 ml/min/1,73m2 vs 131 ± 12,8
ml/min/1,73m2 in control group (p<0,05). Six WTs (11,3%)
had value of eGFR below 90ml/min/1,73m2 . Increased albu-
SIOP ABSTRACTS
S431 of S518
min urine excretion (ACR > 30mg/g) was observed in 7 WTs
( 13,2%) and in 3 (6,8%) individuals in control group.
3) Reputation of CCHE: Trust in CCHE and brand awareness
(word of mouth, television ads, doctors’ recommendations).
Conclusions: Sonographic image of solitary kidney in WTs
differs from sonographic image in control group. The most
frequently detected abnormality are hyperechoic rings around
renal pyramids. There was no difference in sonographic image
of solitary kidney according to chemotherapy. Sonographic
examination in WTs ought to be performed not only to detect
eventual tumor recurrence but also to assess risk of CKD and
progressive deterioration of renal function.
4) Equity: CCHE's mission for equal access and free of charge
treatment.
Persons involved in writing the paper do not report a conflict
of interest.
CHILDHOOD CA NCER
I N T E R NAT I O NA L (C C I )
P-580 Family Members’ Perceptions Towards
Equity and Quality in Accessing Health Care
Services at Children's Cancer Hospital Egypt: A
Mixed Methods Study
M. Alattas1 , A. Hamdy2 , S. Elmeniawy2 , A. Elhaddad3 , A.
Abdelfattah3 , M. Zamzam4 , I. Albanti5
1 Boston
University School of Public Health, Global Health, Boston, USA;
Cancer Hospital Egypt 57357, Quality, Cairo, Egypt;
3 Children's Cancer Hospital Egypt 57357, Pediatric Oncology, Cairo,
Egypt; 4 Children's Cancer Hospital Egypt 57357, Healthcare Sciences
Academy, Cairo, Egypt; 5 Dana Farber Cancer Institute, The Global Health
Initiative, Boston, USA
2 Children's
Background/Objectives: Patients’ experience within the
health care system in terms of equity and quality influences
their perception to access. This project explores the referral mechanism at Children's Cancer Hospital Egypt 57357
(CCHE) in Cairo and assesses perceptions of family members
towards equity, quality, and other dimensions associated with
access to pediatric oncology care.
Design/Methods: This is a single site mixed methods study.
Data were collected through in-depth interviews using a structured interview guide which included probes, close-ended and
open-ended questions. A sample size of 100 family members
were randomly selected and interviewed. A focus group with
5 mothers and 1 father was conducted to expand on parents’
opinion on the referral process and overall experience.
Results: Respondents reported the following factors when
deciding to seek care at CCHE
1) Experience outside CCHE: Dissatisfaction with healthcare
providers’ knowledge, attitudes and behaviors; fragmented
system; and under equipped hospitals.
2) Perceived quality of CCHE services: Advanced, specialized facility; effective treatment; high survival rate.
Conclusions: Efficient patient centred referral process is a
vital element of high quality care service. Our recommendations include suggestions to increase engagement of families
into care, incorporate family members’ feedback into quality
improvement efforts, collaborate with national existing cancer centers to streamline the referral system and access, plan
an outreach program for health care providers in rural areas to
improve their communication skills, conduct follow-up surveys to expand on the public perception towards different
access elements.
P-581 The Cost of Childhood Cancer Treatment
in Jordan
I. Sultan1 , A. Al-Nassan1 , A. Mansour2 , S. Gupta3 , S. Horton4 , N.
Bhakta5
1 King
Hussein Cancer Center, Department of Pediatrics, Amman, Jordan;
Hussein Cancer Center, Department of Radiology, Amman, Jordan;
3 Hospital for Sick Children, Division of Hematology/ Oncology, Toronto,
Canada; 4 University of Waterloo School of Public Health and Health
Systems, Global Health Economics, Ontario, Canada; 5 St. Jude Children's
Research Hospital, Department of Global Pediatric Medicine, Memphis,
USA
2 King
Background/Objectives: Over the past 15 years, King Hussein Cancer Center (KHCC) has established a multidisciplinary cancer care program and become an important
regional hub for oncology. Each year, the center treats over
3500 new cancer patients from both Jordan and its surrounding regions. KHCC provides state-of-the-art medical equipment and services, including 8 operating rooms, 170 beds,
and 18 intensive care units, including 6 dedicated pediatric
ICU beds. Emerging data from KHCC has shown outcomes
for many pediatric malignancies treated by the hospital are
approaching those seen in high-income countries (HICs). The
cost of childhood cancer treatment in upper middle-income
countries (UMIC) like Jordan, however, has not been well
investigated. The aim of this research is to determine the cost
of operating a national childhood cancer treatment center in
Jordan to help prioritize future interventions for childhood
cancer treatment and provide an analytic framework to model
future costing analyses elsewhere.
Design/Methods: We will conduct a cross-sectional study to
evaluate the expenses of childhood cancer treatment covered
by the budget and financing model in Jordan. Expenditures
will be categorized by Personnel, Room and Board, Outpatient Clinic, Pharmacy, Pathology, Surgery, Radiation, and
Imaging. To estimate the unit cost per bed, we will multiply
the World Health Organization table of unit costs for a Ter-
SIOP ABSTRACTS
S432 of S518
tiary Hospital, the average length of stay at KHCC (days) and
the total number of inpatient visits per year.
Results: We will calculate total costs based on annual cases
diagnosed and admitted at KHCC. Cost-effectiveness will be
assessed by comparing costs with Disability-Adjusted LifeYears estimated from center-specific outcomes data.
Conclusions: Both the cost and cost-effectiveness results of
this study will inform policy makers and other stakeholders
in Jordan with planning, implementation and prioritization for
childhood cancer treatment programs. The described methods
also provide a template for other UMICs to conduct similar
analyses.
P-582 Building an Advocacy Campaign “Go Gold
India” for Childhood Cancer to be a Child Health
Priority in India
K. Chawla1 , P. Bagai1 , S. Sharma2 , R. Bhalla3 , C. Kumar4 , A.
Mishra1 , A. Ahuja1
1 CanKids...Kidscan,
CEPAA, Delhi, India; 2 CanKids...Kidscan, Capacity
Building & Parent & Survivor Group, Delhi, India; 3 CanKids...Kidscan,
CEPAA and Resource Mobilization, Delhi, India; 4 CanKids...Kidscan,
CEPAA & KCK, Delhi, India
Background/Objectives: No childhood cancer control plan
or policy in India. Survival outcomes estimated to be as low as
20-40%. Awareness about childhood cancer, gold color, gold
ribbon and gold glow as symbols was low. A focused advocacy campaign with a brand and to adopt new themes each
year was built, to promote Gold color as brand, just as pink is
for Breast cancer thereby engaging all stakeholders.
Design/Methods: Go Gold India campaign launched in
2015 invoking Childhood Cancer international hash tag “Act
Now for Kids with Cancer” with specific theme Taj Goes
Gold between February International Childhood Cancer Day
(ICCD) and September Childhood Cancer Awareness Month.
On ICCD children with cancer decorated Light it up Gold Taj
Mahal cut outs in 44 cancer centers lit up by hospital managements. On Nurses and Doctors’ Day pediatric oncology
professionals pinned with Gold ribbons. On Survivor Day “I
Deserve best cancer treatment, care and support” poster and
essay competition was spearheaded. Spanning 6 months, survivors pinned Gold Ribbons and ran Pledge campaign online
and offline. September saw a 5day 1500km Car Rally in Uttar
Pradesh and social mobilization campaign to bring children
parents and survivors to Agra for Taj to go Gold. The campaign is followed in Year 2 by Go Gold India–for Warriors
and Angels inspired by We are one song and using Yellow
wristbands.
Results: The Taj went Gold from September 25-27 adorned
with gold ribbons and Light it Up Gold Taj cut outs, first
ever Childhood Cancer Exhibition, 1900 children, parents at
Taj Mahal and extensive media coverage. 95,000 pledges collected from India and overseas, State Government announced
formation of Task Force and WHO India and Central Government Health Ministry pledged support.
Conclusions: Sustained and attractive advocacy campaign
with strong image and brand needs to be built up year on year
to engage stakeholders.
P-583 Impact of Early Intensive Nutritional
Intervention on Malnutrition Status in Pediatric
Cancer –Role of Non Governmental Organisation
(NGO)
G. Chinnaswamy1 , P. Bahl2 , J. Chadha2 , K. Bhanushali1 , N.
Mahakal2 , S. Jatia1 , M. Prasad1 , B. Arora1 , S. Banavali1
1 Tata
Memorial Hospital, Department of Pediatric and Medical Oncology,
Mumbai, India; 2 Cuddles foundation, Cuddles foundation, Mumbai, India
Background/Objectives: Pre-existing malnutrition in pediatric cancer patients adversely influences treatment outcomes.
Additionally, treatment toxicities has a detrimental effect on
the nutritional status. Early and aggressive nutritional intervention is found to improve nutritional status and in turn, overall outcomes. We analysed the impact of early intervention on
the nutritional status of children across 6 hospitals in India
where the nutritional intervention was supported by an NGO.
Cuddles Foundation(CF) is the only organization in India that
focuses on providing holistic nutritional intervention to children afflicted with cancer.
Design/Methods: Children with newly diagnosed cancer,
aged 0-16 years, and with coexisting severe acute malnutrition(SAM) between Jan’2016 to Dec’2016 were included
in the study. Weight(for age), Height(for age), Weight for
length, BMI, MUAC and Triceps skin fold thickness(TSFT)
were measured and their Z scores/percentiles were calculated at baseline, 1st and 3rd month of assessment. Nutritional interventions included incorporating Ready to use therapeutic food(RUTF), other Nutritional supplements including
micronutrients (Vitamin D, B12, Folate and Calcium if found
deficient) and close monitoring by dedicated nutritionists who
were recruited by the NGO.
Results: 61 newly diagnosed pediatric cancer children with
SAM, were enrolled. Mean age of the study group is 3.4
years and M:F-1:1.2. Average BMI improved from 12.3
to 13.22Kg/m2 in 4 weeks. Correspondingly the median
Weight shifted from 11.35 to 13.4 kg. Over 3 months, 77%
showed an improvement in nutritional status with intervention: 31/61(51%) converted to mild malnutrition/normal
nutrition and 16/61(26%) improved to moderate malnutrition
status while only 14/61(23%) continued to be SAM.
Conclusions: Early and aggressive nutritional intervention
in cancer children with pre-existing malnutrition signifi-
SIOP ABSTRACTS
cantly improves the nutritional status. This impacts positively on chemotherapy tolerance and long term outcomes.
NGOs (CF) focussed on holistic nutritional support can
play an important role in improving outcomes in LMICs
where malnutrition is highly prevalent in children with
cancer.
P-584 UNITE2CURE - Accelerating Drug
Development
N. Scobie1 , H. Delphine2 , C. Copland2
1 Unite2Cure,
Zoé4life, Sullens, Switzerland; 2 Unite2Cure, Kick Cancer,
Brussels, Belgium
Background/Objectives: There is growing recognition
across the parent/patient and professional community that
promising new drugs for children and teenagers with cancer are not being developed quickly enough. This is a multifaceted problem that requires an urgent co-ordinated panEuropean approach. The problem is not just medical but also
economic. Pharmaceutical companies consider the adult population their key customer base. Childhood cancers have been
neglected as they are made up of rare illnesses, none of
which offer a lucrative market for commercially developed
drugs.
Design/Methods: There are many groups and charities working for similar aims. We aim to provide a parent-led platform, that with the Accelerate Platform, will mobilize this
support. Under the banner “Unite Against Childhood and
Teenage Cancer, we aim to build upon a growing desire
for change in order to save more children with cancer and
allow others to access better, kinder new drugs. Our approach
will be to work supportively and collaboratively with all
stakeholders to share ideas and identify solutions. Together
we will amplify the voice of children and teenagers with
cancer
Results: A few basic changes to European law, as well as collaborative funding ideas could transform the situation and harness the major advances that have been made in biological
science for the benefit of children
Conclusions: The Paediatric Medicines Regulation promotes
research into all children's illnesses. However, with regard to
cancer in particular, it has not lived up to the promise it held
out to provide them with safe and efficient medicines.
Specific reforms to the PMR would ensure that every time
a drug company develops a new treatment for adults, the
drug's potential for combating childhood illnesses be evaluated. Alternative funding models also should be explored.
This would have a significant impact on the health of young
people generally, but, in particular, it would benefit those with
cancer.
S433 of S518
P-585 Factors Associated with Abandonment of
Pediatric Cancer Treatment in Peru: A Multicenter
Cohort Study
L. Vasquez1 , R. Diaz2 , S. Chavez2 , I. Maza1 , E. Hernandez2 , M.
Oscanoa1
1 Rebagliati
National Hospital, Pediatric Oncology, Lima, Peru; 2 National
Institute of Neoplastic Diseases, Pediatric Oncology, Lima, Peru
Background/Objectives: Abandonment is a major cause of
treatment failure and poor survival in children with cancer of
low and middle income countries; although in our country it is
not well documented. The aim of this study was to examine the
prevalence and associated factors of treatment abandonment
in pediatric patients with cancer.
Design/Methods: We have analyzed socio-demographic and
clinical data from the two major institutions in Peru in childhood cancer during 2012 to 2014. Definition of treatment
abandonment was used from the SIOP (International Society of Paediatric Oncology) PODC (Paediatric Oncology in
Developing Countries) Abandonment of Treatment Working
Group recommendation.
Results: A total of 1135 children diagnosed with malignant
solid tumors were retrospectively reviewed and 209 (18.4%)
abandoned treatment. Univariate logistic regression analysis
showed significant higher abandonment rates in children living in the southern (OR 2.35; p<0.001) and eastern cities of
Peru (OR 3.64; p=0.001); prolonged travel time to tertiary
center (> 5 hours; OR 2.75, p= 0.002); rural setting (OR 3.44;
p<0.001) and lack of parental formal job (OR 4.39; p= 0.001).
According to cancer diagnosis, children with retinoblastoma
had more abandonment rate (OR 1.79; p= 0.020) compared
with other solid tumors. There was a trend of decreasing abandonment rates over time (p=0.004). In multivariate regression
analyses, a rural origin and lack of formal parental employment were independently predictive of abandonment.
Conclusions: Treatment abandonment prevalence in our
country is high and closely related to socio-demographical
factors. Outcome could be substantially improved by strategies that help to prevent abandonment of therapy based on
these results.
P-586 Developing a Tiered-System of Quality of
Care Indicators for Pediatric Oncology
Resource-Limited Settings
C. Wong1 , A. Billett1 , P. Friedrich2 , L. Lehmann1 , I. Albanti1 , L.
Morrissey1 , K. Houlahan1 , C. Rodriguez-Galindo2
1 Dana-Farber/Boston
Children's Cancer and Blood Disorders Center,
Pediatric Oncology, Boston, USA; 2 St. Jude Children's Research Hospital,
Global Pediatric Medicine, Memphis, USA
SIOP ABSTRACTS
S434 of S518
Background/Objectives: Consensus is lacking on prioritization (collection, monitoring, and benchmarking) of pediatric
oncology (PO) quality of care (QoC) indicators in distinct
resource settings. Measurement of resource-specific indicators that shift from illustrating capacity to reflecting performance in cancer care delivery is needed to assess, identify
gaps, and improve QoC.
Objectives: To develop a pilot for consensus on a PO tieredsystem of indicators that measures QoC in low- and middleincome countries.
Design/Methods: Systematic and grey literature review generated potential indicators. A multidisciplinary group of
experts reached consensus through a modified Delphi process. Indicators were rated on two consecutive rounds
using a 5-point Likert scale survey (1=Strongly Agree;
5=Strongly Disagree) based on importance and feasibility
for resource-limited PO settings. For round 3, participants
individually categorized indicators applicable for each one
of four resource-based tiers ranging from basic (Tier-1) to
advanced (Tier-4), then ranked a pre-determined number
of top (60th percentile) indicators for each tier (round 4).
Roundtable discussions, review of results, and modification
of indicators followed each round. Consensus was reached
upon >65% agreement (or median <2) after consecutive
rounds.
Results: From an initial 107, consensus was reached on 10 top
indicators for Tier 1; 28, 33, and 37 for Tiers 2-4, respectively.
Indicators addressed a range of domains including safety,
supportive care, treatment abandonment, and long-term survival. Only four indicators were represented across all tiers
relating to the proportion of: patients with documented treatment plan available to all providers, hand-hygiene compliant providers, patients treated according to standardized treatment plans with monitoring of outcomes, and 5 year survival
rates.
Conclusions: The pilot led to consensus on PO QoC
indicators for resource-limited settings, but these varied
across tiers based on resource availability. Validation of
the tiered-system of indicators with a larger group of
experts and development of measurement strategies will
follow.
1 Hospital
for Sick Children, Pediatric Hematology Oncology, Toronto,
Canada; 2 Hospital for Sick Children, Information services, Toronto,
Canada
Background/Objectives: Scanning the appropriate journals
for relevant articles to stay updated and interpreting the impact
of new research is challenging in the expanding field of Pediatric Hematology Oncology. Following a pilot Journal Review
Initiative, where 20 fellows participated by screening and
appraising relevant articles in 27 journals, writing 155 summaries in 5 issues over 1 year, online expansion was proposed
to broaden educational opportunities and participation and
facilitate interactive discussions.
We aim to create an open access online interactive learning
resource of relevant current literature in Pediatric Hematology
Oncology and facilitate practice of journal screening, summarizing and critical appraisal. We hypothesize that participation
in “BestBits” initiative will improve journal reading habits,
self-efficacy in screening journals and critically appraising
journal articles, and be a convenient way to keep up to date
with new literature.
Design/Methods: A needs assessment was sent to Pediatric
Hematology Oncology fellows and staff across Canada and
they were invited to register online to participate in journal review and other learning activities. Following initial
design and development of www.bestbits.ca, the first phase
of the initiative was launched. A 2-month schedule for Journal Review was developed: assigned journals are reviewed
and relevant articles to read and appraise, selected using a
standardized framework. Summaries with interpretation are
submitted online after extensive editorial review and journal
review is posted online.
Results: Online participant surveys, editorial review and website statistics will be used to evaluate participation and provide
feedback on learning activities and processes. We will analyze
number of hours and articles read, proportion of articles read
completely and self-efficacy in staying updated of the participants.
Conclusions: Staying updated with Pediatric Hematology
Oncology literature is challenging and creating an open access
relevant resource may be useful to practitioners, and promote journal reading and critical appraisal. Further development will involve interactive virtual journal club and selfassessment educational activities.
OT HE R
P-587 The Pediatric Hematology Oncology
Bestbits Project: A Journal Review and Virtual
Journal Club Initiative
P-588 Development of the First East African
Pediatric Hematology Oncology Fellowship
Program in Uganda
N. Alexander1 , J. Brzezinski1 , N. Waespe1 , F. Bellavance2 , A.
Punnett1
E. Ishigami1 , N. Kagoro2 , J. Lubega2 , J. Slone2 , G. Airewele2 , P.
Mehta2 , K. Wilson-Lewis1 , E. Fruge2 , R. Kansiime3
SIOP ABSTRACTS
1 Texas
Children's Hospital, Cancer and Hematology Centers, Houston,
USA; 2 Baylor College of Medicine, Pediatrics, Houston, USA; 3 Baylor
College of Medicine Children's Foundation-Uganda, Pediatrics, Kampala,
Uganda
Background/Objectives: An estimated 300,000 children
develop cancer annually. With few trained Pediatric Hematology/Oncology (PHO) experts to provide care in sub-Saharan
Africa (SSA), the majority die. To sustainably improve quality of care in SSA, Texas Children's Cancer and Hematology
Centers (TXCH), and Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) partnered with the
Ministry of Health of the Republic of Uganda and 3 other
Ugandan Partners in 2015 to create the East Africa Pediatric
Hematology Oncology Training (EAPHOT) fellowship.
Design/Methods: The goal of the EAPHOT fellowship is to
increase PHO expert numbers in East Africa. The two year
curriculum includes didactics and supervised clinical experience. The program is directed by a full-time TXCH faculty in Uganda complimented by rotating TXCH faculty. The
curriculum includes online lectures together with electronic
tracking of each fellow's progress, weekly Tumor Boards with
TXCH faculty, a bi-monthly leadership seminar, and access
to the Texas Medical Center Library. The fellows can utilize
the TXCH global consultation system for immediate help with
difficult cases. The second year of fellowship focuses on clinical quality improvement and research.
Results: As of March 2017, a total of 8 fellows from Uganda,
Tanzania, and Kenya, have enrolled in the PHO fellowship
program. The online lecture system has been well received.
Fellows have accessed the didactic lectures over 111 times.
Fellows spend 4 hours weekly reviewing lectures. Positive
evaluations of faculty, lectures, and overall fellowship effectiveness were received. The EAPHOT program model has
been adopted by Makerere University College of Health Sciences (Kampala) and Uganda Cancer Institute to develop
other sub-specialty training programs.
Conclusions: The program is on track to train and build a
critical mass of PHO specialists in the East Africa region and
a similar program is planned for Botswana to train pediatric
hematologists-oncologists for the Southern Africa region.
P-589 Setting Up Strong Core Business
Infrastructure to Ensure Sustainability: East Meets
West - How to Set Up in Developing Countries,
Making Programs Sustainable
K. Wilson-Lewis1 , N. Kagoro2 , R. Bullock3 , E. Ishigami1
1 Texas
Children's Hospital, Pediatrics, Houston, USA; 2 Baylor College of
Medicine, Pediatrics, Houston, USA; 3 Texas Children's Hospital, Cancer
and Hematology, Houston, USA
Background/Objectives: In an effort to improve the outcomes of children with cancer and blood disorders in devel-
S435 of S518
oping countries, the Texas Children's Cancer and Hematology Centers Global HOPE (Hematology Oncology Pediatric
Excellence) program aims to build capacity and strengthen
healthcare infrastructure in Sub-Saharan Africa (SSA). These
activities require a significant investment of money, expertise
and other resources. Given the level of investment needed,
strong business management is critical to the overall success
of these efforts.
Design/Methods: Methods of business management vary
between settings within SSA and those of western partners. Challenges include working in bureaucratic and
under-resourced government healthcare systems. While
understanding that differences exist in business practices and
that regulations vary, it is necessary to focus on achieving the
highest level of practice possible. To that end, the approach
has been to understand local practices and regulations,
identify the differences and work with local leadership to
strengthen practices where needed. Examples of this strategy include facilities planning and maintenance, financial
management, monitoring and evaluation systems (M&E),
information systems management and general operational
management. This has been accomplished by creating and
implementing Standard Operating Procedures (SOPs) as
a means to clarify process, role, and responsibility and to
increase the transparency of business operations.
Results: The process of developing SOPs proved helpful
in obtaining stakeholder input and support for revised or
new processes. Adjustments to existing processes proved
challenging but not impossible. To date, outcomes include
improved financial reporting and management capabilties,
which has increased the confidence of program stakeholders
thus, increasing program fundability and sustainability. Additionally, advances in data collection, management and reporting for M&E have been accomplished to add breadth and
depth of information for program reporting.
Conclusions: Good business practice should be viewed as a
requirement of Global Health Programs to ensure program
success and sustainability.
P-590 Challenges in Managing Grants in Global
Settings
E. Ishigami1 , N. Kagoro2 , L. Morin2 , C. Chu2 , K. Wilson-Lewis1
1 Texas
Children's Hospital, Pediatrics, Houston, USA; 2 Baylor College of
Medicine, Pediatrics, Houston, USA
Background/Objectives: Grant funding plays a significant
role in funding global health. As a center that has quite
successfully obtained grant funding, the Texas Children's
Cancer and Hematology Centers (TXCH) has many years
of experience in traditional U.S. based grants management. While this experience has proven helpful to supporting it's rapidly expanding Global HOPE (Hematology-
SIOP ABSTRACTS
S436 of S518
Oncology Pediatric Excellence) Program, unique challenges
have required adapted approaches to grants management in
the global setting.
Design/Methods: New challenges include the complexity
of collaborations across countries, difficulty in long-distance
communication, differences in grants management, finance,
cash and procurement processes, pace of regulatory processes, and lack of resources at global sites. These challenges
were making it difficult for Principal Investigators to accomplish their projects and spend grant funding as planned. For
example, executed sub-awards from a U.S. institution to a
global institution were difficult to obtain and challenging to
implement due to reimbursement based cash flow practices.
To better manage the portfolio of global grants, the TXCH
formed a working group with representation of administrative
and research leadership, pre- and postaward staff, the PI and
other key stakeholders to review new grant opportunities and
to monitor the progress of awarded grants.
Results: This working team has served to overcome many of
the challenges through which were making grant funds difficult to spend. For example, clearer communication with the
PI and grants managers has helped to overcome roadblocks
with subawards, rebudgets and reporting. Dedicating preand postaward staff increased their project familiarity, thus
improving their response times and increasing team morale.
A key realization was the need for increased support to PIs
with global projects due to operational challenges they face in
a global setting.
Conclusions: Strong grants management is vital to the success of global health programs, where more grants management and operational support is needed to meet the unique
challenges.
the lack of local PHO expertise and reduce the cost of sending
fellows in a U.S. based institution for training, we integrated
an online didactic platform into the PHO Fellowship. This
online training comprises of web-based recorded lectures by
Texas Children's Cancer and Hematology Centers (TXCH)/
Baylor College of Medicine (BCM) exeperts accessible on
Blackboard
Design/Methods: A committee with African expertise, comprised of pediatric oncologists, hematologists, and psychosociologists, was created to spearhead the process of formatting, reviewing, and adapting lecture content to local settings.
TXCH PHO specialists were invited to create lectures covering the curriculum topics that were then edited, reviewed and
approved by the committee. Once approved, PHO specialists
voice recorded the lectures which were then uploaded as interactive tools onto Blackboard.
Results: Twenty-six faculty members from TXCH/BCM
recorded presentations that were uploaded as part of the curriculum. The fellows were subsequently exposed to numerous PHO specialties. Additionally, by not requiring Houstonbased faculty members to travel to Uganda to present, the program saved an annual expenditure of $260,000 USD.
Conclusions: The content of the lectures will be periodically
updated to ensure it remains relevant. Furthermore, at the end
of the two year fellowship, the fellows will participate in exit
surveys in order to attain feedback on their experience with
the lectures and course.
P-592 Localized Ewing's Sarcoma of the
Mandible Managed Surgically with Free Fibula
Flap Reconstruction in a Toddler
S. Mishra1 , R. Arora2 , S. Dabas3 , S. Jain4 , G. Kapoor4
P-591 Development of the Online Didactic
Training Platform for the East African Pediatric
Hematology Oncology (PHO) Fellowship Program
N. Kagoro1 , E. Ishigami2 , P. Mehta1 , J. Slone1 , J. Lubega1 , G.
Airewele1 , K. Wilson-Lewis2 , E. Fruge1
1 Baylor
College of Medicine, Pediatrics, Houston, USA; 2 Texas Children's
Hospital, Pediatrics, Houston, USA
Background/Objectives: There is a dire lack of specialists
in pediatric oncology in Africa. Literature shows that a significant number of African-born physicians migrate to highincome countries to obtain specialist clinical training and
few return. The East Africa PHO Fellowship was developed
in Uganda to build a critical mass of PHO specialists from
Uganda and the East Africa region through formal training
and accreditation. The goal of the program was to develop
a two–year PHO fellowship curriculum for local limited settings at low cost to ensure program sustainability. To address
1 Department
of Pediatric Surgical Oncology, Rajiv Gandhi Cancer Institute
and Research Centre, Delhi, India; 2 Department of Plastic and
reconstructive surgery, Rajiv Gandhi Cancer Institute and Research Centre,
Delhi, India; 3 Department of Surgical Oncology, Rajiv Gandhi Cancer
Institute and Research Centre, Delhi, India; 4 Department of Pediatric
Hematology & Oncology, Rajiv Gandhi Cancer Institute and Research
Centre, Delhi, India
Background: Ewing's sarcoma(ES) of head and neck is rare
comprising 1-4% of all cases. Jaw lesions present a distinct surgical challenge due to cosmetic inadequacy and functional impairment. We wish to present this child with ES of
mandible successfully managed with resection and free fibular flap reconstruction.
Design/ Method: Retrospective review of hospital records
Results 2 ½ years-old-boy had left jaw swelling for 2
months. Workup confirmed localized ES of left mandible upto the midline. After 4 cycles of neo-adjuvant chemotherapy (VAC/IE), there was partial response. Since radiation
posed higher long term complications, parents chose surgery.
SIOP ABSTRACTS
He underwent segmental resection of left mandible including teeth of left lower jaw up-to right 1st premolar, preserving the left angle of mandible. Frozen-section revealed
clear margins. Reconstruction was done by plastic and reconstructive surgeons using free fibular flap. Harvested vascularized fibula was remodeled by osteotomies after accurate
measurements and calculations, to give the exact shape of
excised mandible. Fixation with re-absorbable screws and
plate allowed for growth potential. Vascular anastomosis was
performed using operating-microscope and 9-0 sutures. Tracheostomy was done to prevent airway obstruction. The 7hours surgery did not require blood transfusion. He was electively ventilated for 48 hours and recovered smoothly. Tracheostomy tube was removed on 10th day. The free flap was
healthy. Histopathology showed 100% necrosis (Huvos Grade
4) with negative margins, hence radiation was avoided. Cosmetic appearance was excellent. Soft diet was resumed after
one month and chemotherapy was restarted. The child is well
5 months after surgery and awaits dental implants.
Discussion: Free fibular flap reconstruction for ES of
mandible gives an excellent cosmetic and functional result. A
thorough literature search revealed that it has been reported in
very few children younger than 3 years. Long term follow up
through puberty is recommended for any growth discrepancy
which may need distraction osteotomy.
HAEMATOLOGY - ACUTE
LYMPHOBLAST IC LEUKAEMIA
PO-001 Pediatric Acute Lymphoblastic
Leukaemia: The Journey So Far and the Long Road
Ahead
R. Chennamaneni1 , S. Bala1 , S. Gundeti1 , L. maddali1
1 Nizam's
Institute Of Medical Sciences, Medical Oncology, Hyderabad,
India
Background/Objectives:
Acute
lymphoblastic
leukaemia(ALL) is the most common childhood cancer,of which B-ALL and T-ALL account for 80% and 20%
respectively.With the recent advances in therapy and supportive care,survival rates have improved dramatically,but
are still lower in developing countries compared to developed
countries.In the present study,we analyzed the outcomes in
pediatric ALL at our institute.
Design/Methods: This is a single centre,retrospective
study.Patients with diagnosis of ALL aged from 0-21
years,who presented from January 2010 to December 2016
to our institute were evaluated.
S437 of S518
Results: A total of 240 patients were analyzed.The median
age at presentation was 12 years (5months to 21years) with
male to female ratio of 2.1:1.The median hemoglobin,
leukocyte count, platelet count were 8.2gm/dl(1.216),18000cells/�l(500-4,40,000),50,000cells/�l(40005,20,000)respectively.B-ALL and T-ALL were seen in
154(64%) and 86(36%) of patients respectively. Evaluable
cytogenetics were present in 119(50%)of patients,of which
29(24%) had high risk cytogenetics.Treatment protocols
used were MCP-841 and BFM-95 ALL.Post-induction
complete response,partial response and induction failure
were seen in 198(83%),29(12%),13(5%)patients respectively.The baseline characteristics were comparable among
B-ALL and T-ALL groups except for higher median
leukocyte count of 40,650(1600-4,40,000) in T-ALL.The
3-year event-free survival(EFS) and overall survival(OS)
of the entire study population was 52% and 58% respectively.The 3-year EFS and OS in B-ALL and T-ALL were
59%,64% and 45%,49% respectively.On univariate analysis
male sex,organomegaly,leukocyte count of >1 lakh and
lack of post-induction response had significant impact on
EFS and OS(p=0.006,0.003,0.02,0.003 for EFS respectively and p=0.005,0.01,0.04,0.001 for OS respectively).
Age,lymphadenopathy,mediastinal mass or lineage(B-ALL
vs T-ALL) had no significant impact.High risk cytogenetics
had significant impact on EFS but not OS(p=0.04 for EFS).
Conclusions: B-ALL constituted the majority in our study.
Male sex,organomegaly,>1 lakh leukocyte count and lack of
post-induction response had significant impact on outcome.3year EFS and OS was 52% and 58% which indicates that, we
have a long way to go in terms of achieving outcomes equivalent to western published literature.
PO-002 An Anusual Case of Massive
Leukoencephalitis in a Child with an Early
Meningeal Relapse of Acute Lymphoblastic
Leukemia
R. Parasole1 , G. Giagnuolo1 , A. Varone2 , F. Petruzziello1 , D.
Cicala3 , N. Marra1 , G. Maisto1 , G. Menna1
1 Santobono-Pausilipon
Hospital, Pediatric Hemato-oncology, Napoli, Italy;
Hospital, Department of Neurosciences, Napoli,
Italy; 3 Santobono-Pausilipon Hospital, Paediatric Neuroradiology Unit,
Napoli, Italy
2 Santobono-Pausilipon
Background/Objectives: Central nervous system (CNS) is
a frequent site of relapse in pediatric Acute Lymphoblastic Leukemia (ALL). Triple intrathecal therapy (TIT) with
cytarabine, methotrexate and prednisone is the mainstay therapy of CNS relapse. However, TIT may provoke significant
toxicity on CNS. We describe the case of a child with an early
isolated CNS relapse of ALL who showed massive leukoencephalopathy after the first TIT.
SIOP ABSTRACTS
S438 of S518
Design/Methods: At therapy discontinuation, during disease
restaging, the diagnostic lumbar puncture showed turbid cerebrospinal fluid (CSF) for pleocytosis (8100 cells/uL) and
cytospin confirmed the presence of blast B-cells. The patient
showed negative physical and neurological examination and
normal blood count. Suddenly, TIT was performed to reduce
the abnormal liquoral pleocytosis. To prevent toxicities from
tumor lysis syndrome, the patient received hydratation, allopurinol, desamethasone, acetazolamide and seizure prophylaxis with levetiracetam. After few hours, the patient showed
hyperthension, skin rash, hallucinations, hypothonia of lower
limb, until complete paralisis of all legs. A brain resonance
(MRI) showed diffuse hyperintensity of white matter, particularly in subcortical, cerebellar areas, optic chiasm and brainstem in T2-Flair sequences. This pattern was interpreted as
grade IV leukoencephalopathy. The child was transferred to
intensive care unit due to respiratory distress that required
intubation. A diagnostic lumbar puncture performed during
the following days showed CSF negativity.
Results: Patient persisted in deep coma for 5 days before
restart a spontaneous breathing. After waking up, he showed
rapid neurological ameliorations. Systemic chemotherapy
with high-dose MTX and IT ARA-C was restarted without
any additional neurotoxicity. Dosage of interleukin 6 levels
on CSF is ongoing.
Conclusions: The severity and rapidity of event's onset, associated with quickly CSF remission, suggests that neurotoxicity could be related to cytokine release syndrome due to massive blast lysis, rather than to direct drug damage on CNS. The
CSF IL-6 dosing could clarify the pathogenesis of the event.
PO-003 Characteristic of Nutrition Status,
Dietary Intake, Mother's Knowledge and Practices
in Feeding to Children with Cancers at Pediatric
Center, Hue Central Hospital, Vietnam
P.H. Hung1 , H. Vu Thi2
Central Hospital, Pediatric Center, Hue, Vietnam; 2 Hue Central
Hospital, Pediatric Center, Hue- Vietnam, Vietnam
1 Hue
Background/Objectives: Adequate nutrition is one of the
components of supportive and palliative care, plays an important role in success of childhood cancer treatment. However,
this issue has not been paid much attention in Vietnam.
The purpose of this study was to assess nutrition status,
dietary intake of children with cancer, knowledge and practices on children care and how mothers feed the children.
Design/Methods: A cross sectional study was conducted in
76 children with cancer aged 6 months -15 years. Children
was measured their weight and height. Food intake data were
taken and mothers were interviewed about feeding knowledge
and practices.
Results: The results showed that malnutrition accounts for
31,6% (<-2SD to -3SD was 23,7% and <-3SD to -4SD was
7,9 %), under height was 44,8% (<-2SD to -3SD was 29 %
and <-3SD to - 4SD was 15,8 %). The energy consumption
was less than 50% of the energy need by age and by disease.
Protein energy consumption rate accounts for 10%. No dietary
intake of milk was 34,6%, beef 32,6 %, eggs 19.2%.
Conclusions: Nutrition is an important part of the health of
all children, but it is especially important for children getting
cancer treatment. In our center malnutrition and under height
in children with cancer in our center were high. Nutritional
knowledges and practices on childhood cancer care and the
feeding of the mothers were quite poor. In order to improve the
situation, providing education about nutrition for the mothers
is needed.
PO-004 Successful Treatment of Acute
Biphenotypic Leukemia in Children Low-Dose
Chemotherapy in Uzbekistan
S. Ibragimova1
1 Institute
Of Hematology And Blood Transfusion, Children, Tashkent,
Uzbekistan
Background/Objectives: According to some authors, the
optimal therapeutic approach for acute biphenotypic leukemia
may include aggressive chemotherapy and stem cell transplantation, but this is not supported by serious research. The
paper assessed the effectiveness of chemotherapy protocol
ALL-MB-2008 with low-dose methotrexate in the treatment
of acute biphenotypic leukemia.
Design/Methods: There were 5 patients with biphenotypic
acute leukemia. The average age of the patients was 8,4 ± 1,3,
the ratio of the gender: 2 males, 3 females. In the immunological study of bone marrow, all patients had a blast cells linearly
mixed immunophenotype (B + myelo), on morphological and
cytochemical features of blast cells referred to lymphoblasts.
An initial data: all patients spleen was less than 4 cm, initial
leukocyte count was 30 thousand. One patient had t (9; 22)
BCR / ABL p190 and t (9; 22) BCR / ABL p210 PCR, from
the 15th day, for induction he received an additional imatinib
300 mg/m2 daily inside.
Results: Of the 300 patients with acute leukemia treated in
children's department of the Research Institute of Hematology in Uzbekistan for the period 2014-2016. 5 patients diagnosed with acute biphenotypic leukemia and treated with
ALL-based induction regimen. Early response to the 15th day
of treatment in all patients ascertained. All 5 patients went into
clinical remission after induction course. During induction
all 5 patients had severe sepsis, bronchopneumonia. On the
36th day, all patients achieved clinical remission. The patients
received consolidation chemotherapy according to plan for the
SIOP ABSTRACTS
S439 of S518
intermediate-risk group with low doses of MTX 30 mg/m2
intramuscularly weekly, with additional lumbar puncture with
three cytotoxic drugs. A median follow-up of 15.4 months.
The 2-year disease-free survival and overall survival estimates
were 100%.
PO-006 Outcome of Childhood Acute
Lumphoblastic Leukemia Over 12 Year: Local
Institutional Experience at Northwestern Region of
Kingdom of Saudi Arabia, Tabuk
Conclusions: ALL-based low-dose chemotherapy regimen
has shown high efficacy in a significant reduction in toxicity.
The use of this protocol enabled outpatient treatment.
T. Khattab1 , M. Alpakra2 , E. Hanafy3 , G. Mahmoud3 , Z.
Alzahrani4 , H. Sawi4 , N. Ahmed3 , M. Fawzy5
PO-005 Current Outcomes of Acute
Lymphoblastic Leukemia (ALL) Among Children
in Gulf Counties (GC); A Systematic Analysis
Z. Kanakkande Kandy1
1 Burjeel
Hospital, pediatric hematology and ooncology, Abu Dhabi, United
Arab Emirates
Background/Objectives: Published literature from GC on
ALL in children is scant. This comprehensive review of published literature was conducted to understand the current outcome of childhood ALL in GC.
Design/Methods: A search of Medline and EMBASE using
keywords leukemia, child, and Gulf Countries was carried out.
All studies, which reported outcomes on survival, related to
ALL published up to, 2016, are included. The results of the
searches were compared and merged. The reference list of all
included studies was searched to identify any other eligible
studies.
Results: The number of studies published is scarce. Of the
8 studies identified, 7 single centre studies and 1 multicentre
study from 4 out of 7 GC met the inclusion criteria. There were
a total of 2,780 children with ALL (32-698 children/study).
The median age at presentation was 0—4.37 years in majority of the studies. Minimum Residual Disease (MRD) was not
used in majority of cases. Treatment consisted of chemotherapy but there was considerable variation in chemotherapy use
among different canters. Different chemotherapies were used;
most commonly often without (Minimal Residual Disease)
MRD based risk stratification. There was only one multicenter
study published yet. Median overall survival (OS) was range
72-86.9% and Event Free Survival (EFS) Range 30.6-73%.
Reported rate of abandonment were limited. Data on longterm side effects was also very limited.
Conclusions: Survival outcomes of ALL in children in GC
are encouraging. Lack of publication from many centers
makes it difficult to understand current practices and outcome
from many centers. We recommend co ordinated multicentre approach in collaboration with western centers in treating
and analyzing experiences to address several questions. Role
of children cancer registry for entire Gulf Countries and its
effective use is highly recommended.
1 King
Salman Armed Forces Hospital, Prince Sultan Oncology CenterTabuk, Jeddah- 21423, Saudi Arabia; 2 Khamis Masheet Armed Forces
Hospital, Oncology, Abha, Saudi Arabia; 3 King Salman Armed Forces
Hospital, Oncology, Tabuk, Saudi Arabia; 4 King Salman Armed Forces
Hospital, Pediatrics, Tabuk, Saudi Arabia; 5 Children cancer Hospital,
Oncology, Tanta, Egypt
Background/Objectives: Childhood acute lymphoblastic
leukemia ALL cure rates reached 85%. Progress resulted
from combination chemotherapy, central nervous system preventive therapy and maintenance chemotherapy. Cytogenetic,
immunophenotyping, and early treatment response refine risk
categorization. In our center we use Children Cancer Group
CCG regimens.
Objectives: Find relapse time and site, survival percentage in
relapsed cases. Assess our event free survival EFS and overall
survival OS and Death causes.
Design/Methods: From January 2005 to December 2016 children with ALL are collected. Bone marrow BM immunophenotyping and cytogenetic data are gathered. Cerebrospinal
fluid CSF, early treatment response and post-induction minimal residual disease MRD are collected. Relapse time and
site are determined as well as EFS and OS.
Results: Sixty-six patients, male29, age range (1.5-11) year,
median 5 years. Immunophenotyping; 56/66 B-lineage ALL,
5/66 T-ALL, 3 unknown, 1 pro-B and 1 mixed-lineage. CSF
positive 7/66 (11%); cytogenetics; normal 12, hyperdiploidy
4, t(9;22) 2 and one for each MLL, Runx, TEL/AML and
trisomy-21. Early response to therapy available in 22/66;
rapid early response 19/22 (86%) and slow early response
3/22 (14%). Positive MRD post-induction 3/66 and negative 6/66. Chemotherapy was based on CCG regimens; lowrisk (1991, 1891) 31/66 (47%), intermediate-risk (1961 armC, 1882) 16/66 (24%) and high-risk (1961 arm-D) 18/66
(29%). Relapse incidence 17/66 (26%); very early 3/17, 2
combined and 1 isolated BM (2/3 survived). Early relapse;
2 BM, 2 combined, 1 CNS (4/5 survived). Late relapse;
4 BM, 4 combined, 1 CNS (5/9 survived). 11/17 (65%)
survived relapsed cases; 4 allogeneic stem cell transplant
(SCT), 2 awaiting SCT, 5 cured with second-line chemotherapy. EFS 44/66 (67%) and OS 56/66 (85%). Death causes;
5 refractory ALL, 3 toxic deaths, 1 secondary neoplasm 5
year off-therapy (Glioblastoma Multiform) and 1 died in car
accident.
Conclusions: CCG chemotherapy regimens with applying
risk stratification would have favorable outcome.
SIOP ABSTRACTS
S440 of S518
PO-007 Chromosome Abnormalities in
Childhood Cancer
V. Nwatah1 , A. Oyesakin1 , N. Ukpai1 , E. David2 , T. Wakama2 , O.
Oniyangi1
K. Lee1 , J. Kim1 , J. Seo1 , E. Choi2 , J. Kim1
2 National
1 Kyungpook
2 Daegu
National University, Pediatrics, Daegu, Republic of Korea;
Catholic University Medical Center, Pediatrics, Daegu, Republic of
Korea
Background/Objectives: Chromosome abnormalities have
been found in leukemia and solid tumor since Nowell and
Hungerford discovered the first in 1960. We reviewed the
results of 15,921 cytogenetic studies for 34 years.
Cytogenetic study had been done with various samples of
peripheral blood for clinical diagnosis of chromosomal abnormal patient or reproductive problem, of amniotic fluid or
cadaver for the genetic counseling or prenatal diagnosis and
of peripheral blood, bone marrow and/or tumor mass for the
cancer patient in the Pediatric Cytogenetic Laboratories of
Kyungpook National University Hospital, Daegu, Republic of
Korea between 1981 and 2014.
Design/Methods: The type of cancer was various. In cancer
patient the sample s were collected at diagnosis, remission and
relapse. No mitogen was applied in cancer cytogenetic study.
Trypsin-Giemsa stain for banding was applied for all chromosome preparation.
Chromosome study was done in 16,350 cases. The data were
analyzed in 15,921 excluding 429 cases of no cell growth or
no date. The samples were peripheral blood in 8,323, amniotic fluid and chorionic villi in 1,035, bone marrow (BM) and
tissue in 6,563 cases. Annual number of examine was 816 in
recent 10 years.
Results: Male to female ratio was 1:1.1. The mean age was
23.8 y/o (1 day∼89 y/o).
Of BM samples for cancer patient, numerical aberrations were
found in 217 cases (hypodiploidy; 131, hyperdiploidy; 50,
hypotriploidy; 3, hypertriploidy; 5, hypotetraploidy; 5 and
hypertetraploidy; 23) and structural abnormalities were found
in 1,092 (Philadelphia chromosome; 314, t(8:21), t(15:17),
t(1:19), t(7:11), t(8:14); 317 and partial trisomy or monosomy; 461).
Only 2 Philadelphia chromosomes were found in two childhood CML patient.
Conclusions: During cell culture study we realized a certain
factors will cause chromosome abnormalities during mitosis,
perhaps just before prophase?
Cytogenetic study for cancer patients is very convenient and
very essential tool for the diagnosis, the process of remission
and relapse classically since 1960.
PO-008 Pattern of Acute Leukemia Presentation
at a Tertiary Hospital in Nigeria
1 National
Hospital Abuja, Department of Paediatrics, Abuja, Nigeria;
Hospital Abuja, Department of Hematology, Abuja, Nigeria
Background/Objectives: Acute leukemia is a common childhood malignancy but its occurrence in low and middle income
countries are under-reported. Its pattern of presentation varies
depending on several factors. The objective of this report is to
determine the pattern of presentation of acute leukemias in
children at a tertiary hospital in Nigeria.
Design/Methods: A retrospective cross-sectional study of
children managed for acute leukemia at the Paediatric department in a 5 year period. Of 31 patients, 27 had adequate
records which were reviewed. Data collected include patient's
demographics, clinical features and treatment outcome.
Results: There were 16 males and 11 females, aged 8 months
to 16 years (mean 7.45 years ± 4.75 SD). Middle class was
the predominant socio-economic status of caregivers (51.9%).
Forty-eight percent of the patients were referred from tertiary
health centre while 40.7% were from secondary health centres. The pattern of clinical features were fever (85.2%), pallor (92.6%) and splenomegaly (51.9%). The specific leukemia
type ratio of Acute Myeloid leukemia (AML) to Acute lymphoblastic leukemia (ALL) was 1: 2.9. The parents of three
patients took their children away before commencement of
treatment, one patient completed treatment and 6 (22.2%) died
before completing treatment. Nearly half of the patients were
lost to follow up to seek alternative care while 9 (33.3%) of the
patients were in remission at last follow up. Lost to follow-up
was found not to be significantly associated with socioeconomic status, age and sex with p-values of 0.68, 0.43 and 0.56
respectively.
Conclusions: Acute lymphoblastic leukemia remain the predominant type of childhood leukemia in our setting. Majority
of the patients presented with fever and pallor moreover the
default to follow-up plagued treatment completion.
PO-009 OPG, RANKL and DKK1 in Childhood
Acute Lympoblastic Leukemia
M. Stratigaki1 , A. Sfiridaki2 , E. Athanasopoulos1 , N. Katzilakis1 , E.
Stiakaki1
1 University
of Crete- University Hospital of Heraklion, Pediatric
Hematology-Oncology, Heraklion Crete, Greece; 2 Venizeleion General
Hospital, Blood Transfusion Center, Heraklion Crete, Greece
Background/Objectives:
Acute
Lymphoblastic
Leukemia(ALL) the commonest childhood malignancy,
in many cases presents with musculoskeletal manifestations.
Bone lessions are also manifested as treatment complications.
The pathogenesis of bone disorders in children with ALL has
not been clarified thoroughly so far. Recently, the biology
of bone metabolism has been studied extensively and new
SIOP ABSTRACTS
S441 of S518
molecules are identified such as osteoprotogerin(OPG),
a protein which inhibits the loss of the bone, proteins
RANKL/RANK with osteoclastic activity and the molecule
Dickkopf (DKK1), a soluble inhibitor of the osteoblastic
activity of the Wnt/b-catenin pathway.
The study of the OPG, RANKL/RANK and DKK1 system in
childhood ALL
Design/Methods: Forty patients(24 boys), aged 1-18 years
old(mean age 7 years) with ALL (38 B- lineage) were studied.
All patients received treatment according to current ALL protocols and risk stratification group, 33 median and 7 high risk.
Three (7,5%) of them relapsed. The serum values of OPG,
RANKL and DKK1 were determined at diagnosis and the end
of treatment. Statistic analysis was made with the use of t-test
(paired t-test)
Results: A statistically significant decrease of osteoprotogerin values was estimated at the end of treatment compared to the levels at diagnosis. The RANKL and DKK1 values determined increased at the end of treatment compared
to diagnosis, without statistical signifigance. Although bone
manifestations at diagnosis or during the treatment were documented in 25% of our patients, there was no statistically significant difference in OPG, RANKL and Dkk1 values between
children with or without bone manifestations.
Mean value at Mean value at the
Diagnosis
end of treatment P value
OPG
24,4545
RANKL 804,502
14,1973
SE
< 0.0001 2,24561
876,84
identify miRNAs that can predict risk of early relapse in pediatric patients with ALL.
Design/Methods: We used the high-throughput miRNA-seq
analysis between three diagnostic bone marrow samples and
three early relapse bone marrow samples to determine miRNA
expression profiles associated with early relapse in ALL. Six
miRNAs were selected for further confirmation performed
by real time quantitative PCR on thirty-one diagnostic samples and ten early relapse samples. Apoptosis and proliferation
were analyzed using siRNA transfection, MTS assay, western
blot and flow cytometry.
Results: Our results demonstrated that miR-155-5p was upregulated in early relapse samples compared with diagnostic samples. miR-155-5p promoted cell proliferation and suppressed cell apoptosis by negatively regulating the expression of tumor suppressor-Forkhead box O3a (FOXO3a) in
ALL cells. Remarkably, miR-155-5p over-expression inhibited the expression of FOXO3a and its downstream targets bim
and p27kip1. Meanwhile, miR-155-5p knockdown induced
the expression of FOXO3a and its downstream targets. Furthermore, FOXO3a over-expression inhibited cell proliferation and induced cell apoptosis by promoting the expression
of bim and p27kip1 in ALL cells.
Conclusions: These results provide a possible underlying
molecular mechanism to explain the association between
miR-155-5p and early relapse in pediatric ALL, and suggest
that approaches to inhibit miR-155-5p expression or induce
FOXO3a expression may offer promising therapeutic strategies in the ALL early relapse treatment.
186,533
0,699218
DKK1
945,7254
1193,28
0,17037 178,895
Conclusions: According our preliminary results, a significant decrease of OPG values estimated between diagnosis and treatment completion.The precise role of OPG,
RANKL/RANK and DKK1 in childhood ALL needs further
investigation.
PO-010 Microrna-155-5P, Promoted
Proliferation and Suppressed Apoptosis by
Regulating the FOXO3A Signaling Pathway, Is
Associated with Early Relapse in Pediatric Acute
Lymphoblastic Leukemia
Y.L. Tang1 , L.B. Huang1 , C. Liang1 , X.J. Liu1 , X.Q. Luo1
1 The
First Affiliated Hospital - Sun Yat-sen University, Department of
Pediatrics, Guangzhou, China
Background/Objectives: Acute lymphoblastic leukemia
(ALL) is the most common pediatric malignancy. Treatment
effect in early recurrence of ALL is very bad, so we need to
HAEMATOLOGY - MYELOID
LEUKEMIAS, MYELODYSPLASTIC
AND MYELOPROLIFERATIVE
SY N D RO M E S
PO-011 Down Syndrome Associated Acute
Leukemia of Children in Georgia: 10-Year
Follow-Up
M. Khvedelidze1 , A. Shengelaia1 , T. Javakhadze1
1 Children
Central Hospital, Hematology/Oncology, Tbilisi, Georgia
Background/Objectives: Children with Down syndrome
(DS) have a 10 to 15-fold higher risk of developing B-cell
acute lymphoblastic leukemia (DS-ALL) and acute myeloid
leukemia (DS-AML). Despite higher treatment related toxicities, risk-based therapy for Down syndrome related childhood
acute leukemia has been widely appreciated across many clinical trials.
SIOP ABSTRACTS
S442 of S518
Design/Methods: Clinical records of 7 children with Down
syndrome associated acute leukemia, admitted over the last
10 years were retrospectively analyzed. The patients were
treated at M. Iashvili Children's Central Hospital, department
of hematology/oncology,- the only facility in Georgia providing care for children with hematological malignancies.
Results: 7 children (6 Males and 1 Female) with Down syndrome have been admitted since the January of 2005. Median
age of the patients was 27 months (range: 18-32 months),
three of them were diagnosed DS-AML and four presented
with DS-ALL.
Considering an overall number of 390 new cases of acute
childhood leukemia (ALL-307 and AML-83 cases) admitted at the hospital since 2005, Down syndrome associated
acute leukemia accounted for approximately 1.8% of all cases.
Despite widely appreciated higher risk of developing acute
megakaryocytic leukemia (AML-M7) in children with Down
syndrome, none of the analyzed DS-AML cases showed
AML-M7 morphology or phenotype. All DS-ALL patients
were diagnosed as Common ALL.
DS-AML patients were treated with AML-BFM-2004 and
DS-ALL cases with ALL-IC-BFM 2004 protocol. All DSALL patients had good treatment response and have been staying disease free. One of the DS-AML patients experienced an
induction failure and another developed bone marrow relapse
after 135 days of induction, both patients died of the disease.
Conclusions: The 10-year incidence of Down syndrome associated acute leukemia of childhood in Georgia is comparable to reported rates from other countries, although according to our data, the cases of DS-ALL outnumbered DS-AML
patients and we also observed a trend of higher event free survival of DS-ALL patients comparing to DS-AML.
year of maintenance with 6TG and Cytarabine. Remission and
relapse rates calculated with respect to risk stratification. Follow up data analyzed.
Results: 76% of the patients belonged to 1-10 years with
Male: Female ratio of 2:1. Study included 35 patients of AML
and 7 of APML. Of the 32 patients treated, 3 denied treatment. Post induction remission was seen in 56% with failure
in 44%. Post induction remission rates (MRD <0.1%) were
38%, 33% and 27% respectively and failure rates of 7%, 64%
and 28% in low, intermediate and high risk patients. None of
Low risk patients relapsed whereas 25% and 28% of patients
relapsed in intermediate and high risk respectively. Of the
6 who completed treatment 3 year overall survival was 50%
(rest 3 relapsed). Of the 32 treated patients 6 (18%) had post
induction death due to sepsis (90%), bleeding manifestation
(6%) and other causes (4%) (Hyperleukocytosis).The low survival rate is due to low socioeconomic strata, poor supportive care, and non availability of bone marrow transplantation
facility.
Conclusions: Low risk group has good remission rates with
none relapsing as yet with high percentage of relapse in intermediate and high risk group. To improve overall survival in
intermediate and high risk patients, risk based chemotherapy, optimization of supportive care and affordable transplant
facility is mandatory even in low resource set up.
PO-013 Childhood Noonan Syndrome with
FLT3-ITD-Positive Acute Myeloid Leukemia – A
Case Report
T. Sarashina1,2 , H. Goto2 , N. Miyagawa2 , T. Yokosuka2 , K.
Fukuda2 , F. Iwasaki2 , S. Hamanoue2 , M. Shiomi2 , S. Goto2 , H.
Azuma1
1 Asahikawa
PO-012 Acute Myeloid Leukemia: Correlation of
Cytogenetics and Outcome in a Tertiary Care
Pediatric Centre
M. Naseer1 , P. Ankit1 , K. Purva1 , C. Shraddha1 , K. VP1 , M.
Sangeeta1 , S. Archana1 , D. Mukesh1 , S. Nitin1 , A. Bharat1
1 Bai
Jerbai Wadia Hospital for Children, Department of Pediatric
Hemato-Oncology, Mumbai, India
Background/Objectives: Acute leukemia constitutes most
common childhood cancers worldwide and in India. Over
the past 20 years, the outcome of Acute Myeloid Leukemia
(AML) in children has improved substantially. There is limited data on childhood AML in India.
Design/Methods: Retrospective analysis of 42 patients with
AML from Jan 2012 till March 2017 was done. Demographic
data collected, Cytogenetics obtained for risk stratification
(WHO classification). Induction (7+3 & 5+2) followed high
dose cytarabine (3 cycles) as consolidation followed by 1
Medical University, Pediatrics, Asahikawa, Japan; 2 Kanagawa
Children's Medical Center, Division of Hemato-oncology/Regenerative
Medicine, Yokohama, Japan
Background/Objectives: Noonan syndrome (NS) is a
RASopathy characterized by facial dysmorphy, developmental disorder, short stature, and a wide spectrum of heart
defects. Hematologic disorders such as myeloproliferative
disease or acute lymphoid leukemia have been reported
in patients with NS. In non-syndromic patients, somatic
PTPN11 mutations may be detected in juvenile myelomonocytic leukemia (JMML), pediatric common acute lymphoid
leukemia, pediatric acute monocytic leukemia (FAB M-5).
Design/Methods: Case presentation: Here, we present a clinical and molecular characterization of a childhood NS patients
with FMS-like tyrosine kinase3- internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML).
The patient was a 12-year-old male who presented with
swollen and bleeding gums and enlarged hepatomegaly, no
splenomegaly. The complete blood count revealed thrombo-
SIOP ABSTRACTS
cytopenia and leukocytosis. Bone marrow aspiration consisted of 83.4% monoblasts, which were stained with nonspecific esterase and no peroxidase, and he was diagnosed
with AML (FAB-M5a). Moreover, genetic testing revealed
a FLT3-ITD-positive mutation. From a clinical characteristic
such as short stature and distinctive facial feature, PTPN11
mutation was detected by genetic testing, and Noonan syndrome was diagnosed. He received remission induction therapy. After short term of remission, AML relapsed during
maintenance therapy. He underwent stem cell transplantation (SCT) and died of progressive disease. Comprehensive
mutation analysis of an 88-gene panel was performed using
targeted next-generation sequencing in leukemic cells at the
onset.
Results: In our case, MLL partial tandem duplication, FLT3ITD, RUNX1 mutation were identified in the analysis.
Conclusions: FLT3-ITD-positive AML with NS is an
extremely rare case and we discuss our patient with NS and
the results of genetic analysis in leukemic cells.
HAEMATOLOGY - LYMPHOMAS
PO-014 Childhood Non-Hodgkin Lymphomas in
the West and the Southwest Regions of Algeria from
January, 2000 Till December, 2009
M. Rouaida1 , L. D2 , B. Ahmed3 , B. N4 , K. L.A5 , B. M6 , T. Hadj7 ,
T. Mahmoud8
1E
H S Emir Abdelkader, Hematology/Oncology, Oran, Algeria; 2 Service
de biostatistique- faculté de médecine d'Oran, Biostatistique, Oran,
Albania; 3 Clinique Medicale Infantile Sainte Therese,
Hematology/Oncology, Annaba, Algeria; 4 Service de biostatistique- faculté
de médecine d'Oran, Biostatistique, Oran, Algeria; 5 E.H S premier
Novembre, Hemato-Oncology, Oran, Algeria; 6 CHU Oran, Biostatistique,
Oran, Algeria; 7 C H U Oran, Hematology, Oran, Algeria; 8 C H U Oran,
Hemato-Oncology, Oran, Algeria
Background / Objectives: Summary The non-Hodgkin lymphomas (NHL) occupied the first place of cancersin childhood
during year 2003, with a 16.7 % frequency according to statistics given by the Register of cancers of Algiers.
The objective of our study is to describe the epidemiological, clinical and histological profiles of paediatric NHLin the
Western and the Southwest regions of Algeria during decade
2000 to 2009.
Design/Methods: it is an observational study from the files
of patients less than 16 years old, hospitalised in the Emir
AbdelkaderCentre (CEA) for the diagnosis of NHL.
LMNH was defined according to clinical, cytological and/or
histological criteria of the WHO.
Registration and analysis of data were performed on software
SPSS version 20.
S443 of S518
Results: 213 children were registered as LMNH over ten
years.
A peak of incidence of NHLwas observed between 2 - 8 years.
NHL are rare before the age of 2 years. The abdominal sitewas
the most frequent with a 47 % rate. Unusual sites of the disease
were observed in 11 % of patients. Stade III was predominant
in all sites of our series. Lymphoblastichistological type was
the most frequent with a 45 % rate, followed by Burkitt type
(30 %) and type T (17 %).
Conclusions: NHLare frequent in children. They are clinically different from adult NHL because of theextranodal disease. For these pathologies, early diagnosis remains a priority
in themanagement.
PO-015 PET/TC Utility in the Assessment
of the Response to Treatment in Pediatric
Lymphomas
R. Lopez-Almaraz1 , A. Echebarría Barona1 , U. Gonzalez
Camacho1 , J.M. De Pedro Olabarri1 , M. Garcia-Ariza1 , R. Adan
Pedroso1 , T. Rodríguez Inchausti-2 , I. Astigarraga Aguirre1
1 Hospital
Universitario Cruces, Pediatric Hematology and Oncology Unit,
Cruces- Bilbao, Spain; 2 Hospital Universitario Cruces, Nuclear Medicine
Service, Cruces- Bilbao, Spain
Background/Objectives: Evaluate the response to
chemotherapy (Ch) in the 18F-FDG-PET/CT of pediatric
patients with Hodgkin's Lymphoma (HL) and Non-Hodgkin's
Lymphoma (NHL) to decide the correct therapeutic attitude.
Design/Methods: Retrospective observational study of pediatric HL and NHL diagnosed in a tertiary hospital in the last
9 years (January 2008-January 2017).
Results: We reviewed 26 patients, 54% were HL (10.5years
and 65%male), 46% were NHL; of which 67% were Burkitt's
Lymphoma (6.25years and 67%male, another 25% T Lymphoblastic Lymphoma(mean 5.75years and 50%male and the
rest were anaplastic large cell lymphoma (8%). Within the
HL,30% were lymphocytic predominance; Half IA stages that
were resolved exclusively with surgery and the remainder,
IIA stages requiring Ch without radiotherapy (RT); All presented complete morpho-metabolic response in PET/CT. The
remaining 10 patients(70%) were of the classical subtype: 9
patients (stages IA,IIA,IIIA and IV) required only Ch since
some presented partial morphological response and all complete metabolic in PET/CT. A single patient with stage IV also
required RT for partial morpho-metabolic response. 100%of
patients are currently in complete remission (RC). Among
the Burkitt L, 63% (2 III-AR, 1 IV-AR, 1 III-RI and 1 I-BR)
required an increase in the risk group for presenting a partial
morpho-metabolic response (one case confirmed by biopsy)
75% currently in CR, one in treatment and one deceased.
The remaining three did not require group increase by com-
SIOP ABSTRACTS
S444 of S518
plete morpho-metabolic response after Ch induction. Within
patients with Lymphoblastic Lymphoma and anaplastic are all
in CR; But only one PET/CT scan was used to evaluate the
response
Conclusions: The use of PET/CT is very established in the
case of HL when making decisions regarding the therapeutic
attitude. Nevertheless it needs more studies in NHL. It seems
reasonable that in the presence of a partial metabolic response
to induction in In NHL, should lead to an increase in the risk
group.
PO-016 Primary Bone Lymphomas: Report of 10
Cases from a Single Center
N. Kurucu1 , C. Akyüz1 , I. Bajin1 , B. Aydın1 , A. Üner2 , A. Varan1 ,
B. Yalcin1 , M. Buyukpamukcu1 , T. Kutluk1
Primary bone lymphoma constitutes 0.7% of our NHL cases.
Lymph node involvement and polyosseous disease has worse
prognosis in adults. Multicenter studies with more cases are
necessary to determine prognostic factors in childhood bone
lymphomas.
PO-017 We Have Cases Withprimary
Gastrointestinal Lymphoma Complicated with
Intussusception, The Clinical Data were
Retrospectively and Analyzed
C. Zhang1
1 Zhengzhou
Children's Hospital, Surgical pediatric oncology, ZhengZhou,
China
1 Hacettepe
University Faculty of Medicine, Department of Pedatric
Oncology, ANKARA, Turkey; 2 Hacettepe University Faculty of Medicine,
Department of Pathology, ANKARA, Turkey
Background/Objectives: To summarize the features of children with primary gastrointestinal lymphoma complicated
with intussusception.
Background/Objectives: Primary bone lymphomas (PBL)
constitute less than 5% of all extra-nodal non-Hodgkin lymphomas (NHL). The objective of this study was to report our
institutional experience with bone lymphomas over a 35-year
period.
Design/Methods: Patients records in Children′ s Hospital of
Zhengzhou were retrieved for cases whose initial diagnosis
was intussusception and discharge diagnosis included lymphoma.Clinical data of 11 patients with primary gastrointestinal lymphoma complicated with intussusception with
extensive follow-up, treated in our department between January 2012 and December 2016, were retrospectively and
analyzed.
Design/Methods: From 1980 to 2016, 1412 children with
NHL were admitted to the Pediatric Oncology Department
of Hacettepe University. Of these, ten children with primary
bone lymphoma (except for fascial bone and cranium) were
evaluated retrospectively.
Results: There were six males and four females with a median
age of 84 months. Most common complaints were pain and
swelling. Median duration of symptoms was 2 months. Most
common tumor location was femur and tibia. Two patients had
localized lymph node involvement and two had polyosseous
disease. Histopathological subtypes were precursor T cell
lymphoma in three patients, anaplastic large cell lymphoma
in one, precursor B cell lymphoma in one and unclassified
in five. Patients were treated with various chemotherapeutic regimens according to histopathological subtype. Three
patients received radiotherapy. Recurrence was observed in
four patients within a median 17.5 months; three of which lost
the follow-up and one died with infection. Two patients died
from disease progression, three died from treatment-related
complications. Six patients (60%) are alive and disease free
at a median of 172 (42-322) months. Overall and event free
survival rates were 77% and 48%. Polyosseous disease had
shorter overall survival rates than monoosseous types (85%
vs 66.7% p:0.68).
Conclusions: Although secondary involvement of bones in
lymphoma is not uncommon, lymphomas originating from
bone are rare. Most cases are seen in the fifth-sixth decade.
Results: All 11 patients with PGIL presented as intussusception initially, age from 1.6 to 10 (10 cases>3), while intussusception appeared repeatedly in 5 cases (3 cases>3). All
11 patients received surgical treatment,among them,abnormal
lumps were found at intussusceptum in 9 cases,local intestinal wall were thicken and rigid. In 1 case, there was a suspicious focal necrosis around the rigid wall.Local resection
was performed successfully for each case without postoperative complication of intestinal obstruction, anastomotic leakage or stricture.Pathological examination revealed 6 cases
of diffuse large B-cell lymphoma and 5 of Burkitt′ s lymphoma. 1 cases was classified to be tumor stage I, the
remaining 10 cases to be stage Ⅱ.10 cases were treated with
chemotherapy, the other 1 given up treatment, and died 13
months after operation.During a median follow-up period of
25 months, tumor recurrence had not been found in these
10 cases.
Conclusions: For children with recurrent intussusception or episode at atypical age, PGIL should be concerned.Abnormal mass on intestinal wall, or intestinal wall
stiffness such as leather, or mesenteric mass should be
resected for Pathological examination. Early postoperative
chemotherapy can provide children with PGIL a good
prognosis.
SIOP ABSTRACTS
HAEMATOLOGY - STEM CELL
TRANSPLANTAT ION
(HAEMATOLOGICA L
DISEASES/TECHNIQUE AND
SUPPORT IVE CA R E )
PO-018 A Case of Congenital Dyserthropoietic
Anemia Successfully Treated with Haploidentical
Hematopoietic Stem Cell Transplantation
M. Al-Hameed1 , V. Balasa2 , S. Bahrani3 , H. Al-Hamid4 , J.
Rosenthal1
1 City
of Hope Comprehensive Cancer Center, Pediatrics
Hematology/Oncology and Hematopoietic Stem Cell Transplantation,
Duarte- CA, USA; 2 Valley Children's Hospital, Pediatric
Hematology/Oncology, Madera- CA, USA; 3 City of Hope/ Alpha Clinic,
Hematology/Oncology - T cells therapeutics, Duarte- CA, USA;
4 Providence Hospital and Medical Center, Internal Medicine, SouthfieldMI, USA
Background/Objectives: Congenital dyserythropoietic anemia (CDA) is a group of rare anemia disorders in which there
is bone marrow dyserythropoiesis and secondary hemochromatosis. CDA is classified into three major types (I, II,
III) based on bone marrow morphology, genetic mutations
and inheritance pattern. Allogenic hematopoietic stem cell
transplantation (HSCT) is the only cure for CDA and most
reported cases used HLA-identical sibling or matched unrelated donors.
Design/Methods: Case report.
Results: We report an 8 year-old male with CDA requiring monthly blood transfusion and deferasirox who was
referred to our center for HSCT evaluation. Due to lack
of HLA-identical sibling or matched unrelated donor, the
decision was made to proceed with haploidentical HSCT
from his father. The non-myeloablative conditioning regimen consisted of Antithymocyte globulin, Busulfan, and
Fludarabine. Post-transplant cyclophosphamide (ptCY) following uneventful infusion of mobilized hematopoietic stem
cells, and tacrolimus with mycophenolate-mofetil were used
for prevention of graft-vs-host disease (GVHD). Myeloid and
platelet engraftment were recorded on day +16 and day +78,
respectively. The patient tolerated the treatment well with
minimal adverse effects. Evaluation of bone marrow on day
+111 showed normo-cellular marrow(60%) with mild erythrocytic hyperplasia and adequate granulopoiesis. During the
treatment course, he experienced only few episodes of infections, mild GI-GVHD, and mild skin-GVHD that were all
resolved. One year post-HSCT, the peripheral count revealed;
WBC(4.2k/�L), hemoglobin(11.2g/dL), hematocrit(27.3%)
and platelets(143,000/�L). The patient condition remained
stable and he remains transfusion free. He resumed his normal childhood and is happily attending school.
S445 of S518
Conclusions: CDA is a rare disorder with paucity of data
regarding its management. HSCT is the only cure available
today. Our experience showed that haploidentical donors are
good alternatives when HLA-matched sibling or matched
unrelated donors are unavailable. The advancement in the
non-myeloablative conditioning regimen with the use of
ptCY, suggests that haploidentical HSCT could be an option
for CDA treatment in the future.
PO-019 Haploidentical Stem Cell
Transplantation with Post-Transplant
Cyclophosphamide for Pediatric
Relapsed/Refractory Solid Tumours: A Feasible
Direction
S. Kohli1 , S. NIVARGI2 , D. THAKKAR2 , N. RASTOGI2 , R.
MISRA2 , S. YADAV2
1 Medanta, PHO/BMT, Gurgaon, India; 2 Medanta, Pho/Bmt, Gurugram,
India
Background/Objectives: Haploidentical stem cell transplantation (SCT) with T-cell depleted grafts have been reported
in few patients with neuroblastoma whereas T cell replete
grafts and post-transplant Cyclophosphamide (PTCy) has
rarely been reported for treatment of relapsed/refractory solid
tumours, and needs to be evaluated in v/o unavailability of
donors and cost issues in developing countries assocociated
with T cell depleted grafts.We evaluated 6 such patients with
refractory solid tumours.
Design/Methods: Six patients with refractory solid tumours
were evaluated prospectively. Of these 4 patients had neuroblastoma - stage 3 to 4 disease post relapse. Fifth patient
of Ewing's sarcoma had CNS and skeletal relapse with bone
marrow involvement. Sixth patient with retinoblastoma had
hepatic and skeletal relapse. All patients were in complete
remission before SCT except two with neuroblastoma who
had partial remission. All patients with neuroblastoma
received MIBG with Bortezomib based chemotherapy
before transplant. Conditioning: All patients received Fludarabine(Flu) and cyclophosphamide(Cy) and total body
irradiation (TBI) except one patient with neuroblastoma who
received melphalan with Flu/Cy. All Patients received PTCy
as part of post-transplant GVHD prophylaxis.
Results: Post SCT one patient with neuroblastoma died due
to veno-occlusive disease and the other died due to progressive CNS disease. The third patient was in complete remission with grade 1 chronic liver GVHD on treatment and is
now 14 months post-transplant. Fourth patient of neuroblastoma relapsed 3 months post-transplant and was on palliative
chemotherapy with WRIST protocol and is now 1 year post
transplant. The patient with Ewing's sarcoma was in complete remission and is now day + 200 post HSCT with chronic
SIOP ABSTRACTS
S446 of S518
GVHD of the skin on treatment. Sixth patient with retinoblastoma has a short followup and had neutrophil engraftment on
Day + 13.
Conclusions: Haploidentical SCT with PTCy seems feasible
and efficacious for treatment of refractory solid tumours and
needs further evaluation for long term outcomes.
S O LID NO N BRAIN TUM O URS NEUROBLASTOMA
PO-021 Burden of Neuroblastoma in Developing
Countries: The Children's Hospital Lahore
Pakistan Experience
A. Ahmad1 , N. Uddin1 , F.S. Khan1
PO-020 Successful Haploidentical T Cell Replete
Peripheral Blood Stem Cell Haematopoietic Stem
Cell Transplantation in a Young Girl with Diamond
Blackfan Anemia
M. Ramzan1 , S. Katewa1
1 Manipal
Hospital, Pediatric Hematology Oncology & BMT, Jaipur, India
Background/Objectives: Diamond-Blackfan anemia (DBA)
is a rare congenital hypoplastic anemia that usually presents
in infancy and childhood. Only curative therapy for DBA is
haematopoietic stem cell transplantation (HSCT). Most published cases have used matched related and unrelated donor
HSCT with myeloablative conditioning regimens.
Design/Methods: Haploidentical HSCT in DBA is scarcely
mentioned in literature. We report a 5 years old girl who diagnosed with DBA at the age of 6 months. She was steroid
refractory and on chronic transfusion therapy.
Results: In view for non-availability of suitable donor, underwent 5/10 haploidentical mismatch related T cell replete
PBSC HSCT from ABO compatible father utilizing a
myeloablative conditioning regimen including intravenous
busulfan (total dose of 520 mg/m2 ), fludarabine (total dose of
175mg/m2 ), thiotepa (10mg/kg) and rabbit ATG (4.5 mg/kg).
She was also treated for class I and II HLA antibody (mean fluorescence index of 20000 each) followed by one cycle of fludarabine (total dose of 180mg/m2 ) and dexamethasone prior
to HSCT to prevent rejection. Repeat HLA antibody titers
were not done. Post transplant cyclophosphamide on day+3
and +4 with tacrolimus and mycophenolate mofetil were used
as GVHD prophylaxis. Total CD34+ stem cell dose was 27
x 106 /kg of recipient. Her neutrophil engrafted on day+ 15.
She had full donor chimerism post HSCT on day+30, +60,
+200 and +365. On day+78 she had steroid refractory grade
III acute gut GVHD which was non responsive to adequate
doses of etanercept, mesenchymal stem cells, basiliximab and
infliximab, but eventually it responded to equine ATG and
oral methotrexate. Her immunosuppression was weaned off
very slowly. At 12 months of follow up she had full donor
chimerism with hemoglobin of 15.2g/dl, reticulocytes of 1%
and almost complete immune reconstitution of all hematopoietic stem cells.
Conclusions: Haploidentical HSCT represents an effective
option for cure in patients with DBA.
1 The
Children's Hospital and the Institute of Child Health Lahore,
Paediatric Haematology/Oncology, Lahore, Pakistan
Background/Objectives: The Oncology Department Of The
Children's Hospital Lahore is a 60 bedded unit providing treatment to over 1000 new childhood cancer cases each year
and over 300 admissions per month with bed occupancy rate
around 200%.The aim of this retrospective study was to analyze the spectrum of Neuroblastoma and burden of high risk
malignancy on the public sector tertiary center with lack of
MIBG scan, N-Myc amplification and stem cell transplantation services.
Design/Methods: Prospective review of 70 patients with
Neuroblastoma enrolled from June 2015 to December 2016
was done. Data regarding their age, sex, type, staging and clinical features, bone and bone marrow involvement, course of
therapy and outcome after making diagnosis on tissue biopsy.
Results: Total 70 patients with age ranging from< 1 to 9 years
(Median age of 3 yrs) were included. M: F Ratio was 1.8:1,
49/70 70% of cases non-infantile and 21/70 30% with infantile
type. 15/70 (22%) had stage III at presentation while 55/70
(78%) was of stage IV. 33/70 (47%) had mainly abdominal
mass as the main presenting complaint, 5/70 (7%) as paraplegia, 5/70 as nasal polyp, neck and mediastinal involvement, 2/70 (3%) as bony masses and proptosis 25/70 (36%)
as multiple presentations. 52/70(74%) had to travel more than
100KM to reach the primary treatment center. 37/70(53%)%
had bone involvement at presentation and 49/70(70%) had
bone marrow involvement. 28/70(40%) had successfully completed the chemotherapy, 13/70(19%) abandoned treatment,
17/70 (24%) expired due to progressive disease and infections,
7/70(10%) were put on palliative Rx at presentation 5/70(7%)
on chemotherapy.
Conclusions: In resource limited settings, Neuroblastoma
stage IV is a challenging malignancy to deal with. There is
intense need of increased capacity building to diagnose and
treat them early and implementation of effective infection control measures with better survival options in these patients.
PO-022 Therapeutic Plasma Exchange for a Case
of Refractory Opsoclonus Myoclonus Ataxia
Syndrome
J. Greensher1 , J. Louie1,2 , J. Fish1,3
SIOP ABSTRACTS
1 Northwell
Health, Hofstra Northwell School of Medicine, Hempstead,
USA; 2 Long Island Jewish Medical Center, Department of Pathology Transfusion Medicine, New Hyde Park, USA; 3 Cohen Children's Medical
Center, Division of Pediatric Hematology Oncology and Stem Cell
Transplantation, New Hyde Park, USA
Background/Objectives: Opsoclonus myoclonus ataxia syndrome (OMAS) is an immune-mediated phenomenon affecting ∼3% of neuroblastoma cases. OMAS has a chronic,
relapsing-remitting course causing significant long-term morbidity. Therapeutic plasma exchange (TPE) effectively treats
other immune-mediated neurologic disorders. We present a
case of paraneoplastic OMAS that was refractory to all common treatments, but resolved after TPE.
Design/Methods: This is a case report of a 14-month-old
boy who achieved complete remission of otherwise refractory
OMAS after TPE, and a 2nd remission after undergoing TPE
for a relapse ∼3 years later.
Results: A14-month-old boy presenting with 6 weeks of
chaotic eye movements, jerking of the extremities, diminishing truncal support, trembling, loss of motor milestones, and
a mass of the celiac axis was diagnosed with intermediaterisk neuroblastoma with paraneoplastic OMAS. Two cycles
of chemotherapy, including carboplatin, etoposide, doxorubicin, and cyclophosphamide, resulted in complete cancer
remission, while the OMAS persisted. Over ∼4 years, oral
prednisone, high-dose pulse dexamethasone, monthly intravenous immunoglobulin (IVIG), 3 courses of rituximab, a
2nd course of cyclophosphamide, ∼2.5 years of adrenocorticotropic hormone, and several months of mycophenolate
mofetil were trialed without resolution of symptoms. Ultimately, the patient achieved rapid remission with initiation of
TPE, rituximab, and monthly IVIG. Following remission, he
continued monthly tapering TPE, receiving 14 treatments in
total. After over 3 years without relapse he re-presented with
OMAS following a viral illness, with no evidence of neuroblastoma recurrence. Within 1 month of restarting treatment
with TPE, oral prednisolone, IVIG, and rituximab, the patient
again achieved remission. He maintained an OMAS score of 0
after a course of 6 TPE treatments without tapering and after
weaning off of oral steroids.
Conclusions: TPE prefaced complete remission of OMAS
for a patient with highly refractory disease, initially, and
again after relapse. This important proof-of-principle case
demonstrates the potential efficacy of TPE in neuroblastomaassociated OMAS.
PO-023
Treatment of High-Risk Neuroblastoma
A. Hizhnikov1 , A. Kazancev1 , P. Kerimov1 , R. Pimenov1
1 Blokhin
Cancer Research Center, Department of thoracoabdominal
childrens oncology surgery Institute of Pediatric Oncology, Moscow, Russia
S447 of S518
Background/Objectives: To improve the results of treatment
of patients with high-risk neuroblastoma.
Design/Methods: 32 patients with high-risk neuroblastoma
received treatment from the DOG Research Institute from
2009 to 2016. The median follow-up time was 19.8 months.
The study included 21 (65.6%) boys and 11 (34.4%) girls. The
age of the patients ranged from 1.7 to 15 years, the average
age was 4.6 ± 3.3 years. Patients were divided into 2 groups
depending on the regimens of chemotherapy.he programmed
treatment included induction HT, surgical treatment, highdose CT, radiation therapy and biotherapy with retinoic acids.
Four patients from group I who did not receive a complete
response or a good partial response at the end of the phase of
induction chemotherapy received systemic radiotherapy 131IMIBG.
Results: The effectiveness of induction chemotherapy in the
I group was 94.7%, in the II group - 84.6%. Bone marrow
cleansing, with induction chemotherapy, was significantly
more frequent in group I after 1 course, in 71.5% of patients.
All patients in the I group had bone marrow sanation, 2
(15.4%) patients in the II group of bone marrow sanation were
not reached. The two-year OS of patients with stage 4 in group
I was 65.6 ± 14.0%, in group II, 43.1 ± 14.7%. The two-year
EFS in the I group was 33.4 ± 14.5%, in the II group - 23.1
± 11.7%. We found that systemic radiotherapy significantly
correlated with the absence of progression or relapse of the
disease. Radical surgery does not affect the prognosis of the
disease.
Conclusions: Induction HT with topotecan, used in group I
showed a higher direct efficacy, OS and EFS in group I were
higher. Patients who, at the end of the induction phase, have an
active residual tumor tissue determined to perform systemic
radiotherapy with 131I-MIBG.
PO-024 Dokuz Eylul University Treatment
Experience of Neuroblastoma
D. Ince1 , D. Kizmazoglu1 , R.E. Cecen1 , M. Erdem1 , S. Aktas2 , E.
Serinan2 , A. Demiral3 , R. Cetingoz3 , E. Ozer4 , H. Guleryuz5 , M.
Olguner6 , K. Mutafoglu1 , and N. Olgun1
1 Dokuz
Eylul University Institute of Oncology, Dept. of Pediatric Oncology,
Izmir, Turkey; 2 Dokuz Eylul University Institute of Oncology, Dept. of Basic
Oncology, Izmir, Turkey; 3 Dokuz Eylul University Faculty of Medicine,
Dept. of Radiation Oncology, Izmir, Turkey; 4 Dokuz Eylul University
Faculty of Medicine, Dept. of Pathology, Izmir, Turkey; 5 Dokuz Eylul
University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey;
6 Dokuz Eylul University Faculty of Medicine, Dept. of Pediatric Surgery,
Izmir, Turkey
Background/Objectives: To evaluate clinical characteristics and outcome of the Turkish Pediatric Oncology Group
(TPOG) Neuroblastoma treatment protocol for our patients
with neuroblastoma between 2000-2017.
SIOP ABSTRACTS
S448 of S518
Design/Methods: There were 89 patients with neuroblastoma, 60 of them were eligible. MYCN, 1p, 11q, 17q status were investigated. The INSS staging, COG risk stratification systems were used. TPOG-NB-2003/2009 protocols
were used. Low RG; stage1 only surgery, stage2 surgery
plus 3courses chemotherapy, stage4S 4courses chemotherapy. Intermediate RG; extra 2-4courses chemotherapy were
given. Maintanance therapy, 13-cis-RA were given for 10
weeks. High RG, 4-6courses conventional CT or high dose
CT+ ASCT. Maintenance therapy, 13cis-RA were used for 6
months.
Results: LRG-(n:12): Nine stage-1, one stage-2, two stage4S patients. One 4S-patient died. Median follow-up time:
55mos, 5-/10-years OS and EFS rates were 92%. IRG(n:23): CR achieved by primary surgery+CT in two stage-2
cases. CR achieved in three stage-4S patients by CT+delayed
surgery. Incomplete primary surgery was performed in two of
18 stage-3&4 patients; 6CR, 9PR achieved by CT+surgery,
delayed surgery was performed in four. In IRG Induction
(CT+Surgery) response was 95% CR+PR. RT was performed
to primary tumor in 5 patients and for metastasis in one.
Median follow up time 26mos (2mos-12yrs), 5-/10-yrs EFS
90%, OS 95%. HRG-(n:25): Incomplet primary surgery was
performed in 5 patients. Induction (CT+Surgery) response
was 92% CR+PR. Delayed surgery was performed in 20patients (11-complete). Radiotherapy was performed to primary tumor in 18-patients. 5-/10-yrs EFS was 30%. Nine
patients had refractory disease, six had systemic relapse.
Median relapse time was 27mos (9-58mos). Median follow
up time 46mos (4mos-14.5yrs), 5-/10-yrs OS were 58% and
31%, respectively. Two patients died related to ASCT, and 10
died with progression.
Conclusions: Neuroblastoma treatment was standartized
by TPOG-NB-protocols. Stage, MYCN-amplification, risk
groups, primary tumor site were found significantly related to
survival rates. Survival rates were acceptable and consistent
with the literature.
PO-025 Treatment of Relapse Neuroblastoma:
Dokuz Eylul University Experience
D. Ince1 , M. Erdem1 , R.E. Cecen1 , D. Kizmazoglu1 , E. Ozer2 , A.
Demiral3 , R. Cetingoz3 , S. Aktas4 , H. Guleryuz5 , M. Olguner6 , K.
Mutafoglu1 , and N.Olgun1
1 Dokuz
Eylul University Institute of Oncology, Dept. of Pediatric Oncology,
Izmir, Turkey; 2 Dokuz Eylul University Faculty of Medicine, Dept. of
Pathology, Izmir, Turkey; 3 Dokuz Eylul University Faculty of Medicine,
Dept. of Radiation Oncology, Izmir, Turkey; 4 Dokuz Eylul University
Institute of Oncology, Dept. of Basic Oncology, Izmir, Turkey; 5 Dokuz Eylul
University Faculty of Medicine, Dept. of Radiaodiagnostics, Izmir, Turkey;
6 Dokuz Eylul University Faculty of Medicine, Dept. of Pediatric Surgery,
Izmir, Turkey
Background/Objectives: To evaluate clinical characteristics
and response to treatment of patients with relapse/refractory
neuroblastoma.
Design/Methods: Medical records of 21 patients with
relapse/refractory neuroblastoma after treatment with TPOGNB 2003/2009 protocols were evaluated retrospectively. The
clinical characteristics, relapse types and treatments were
analized.
Results: Median age at relapse was 3.5yrs (6mos-11.5yrs),
M/F:3.2. One patient was in LowRG stage-4S. In HighRG
stage-3&4 patients (n:20), MYCN amplified in 6/17 patients
(35%). 17q aberation was detected in 3 of MYCN(-) cases,
del 1p was detected in one case. Shimada was unfavourable
in 15 patients. Tumor localization: surrenal (n:14), paraspinal
(n:3), midline (n:3). Metastasis sites: bone (85%), bone marrow (70%), lymph node (45%), lung (15%), CNS (%10).
There were 9 patients with refractory disease, 10 patients
with systemic relapse, one patient with primary relapse.
Median relapse time was 25mos (30-64mos). Median progression time of refractory patients was 8mos (4-39mos). Average 3 courses (1-8 courses) TCV (Topotecan, Cyclophosspamide, Vincristine) were given to 11 patients. Three courses
ICE were given to 5 patients. Topotecan, temozolamide,
metronomic treatment were given to one patient. High dose
chemotharapy+ASCT were performed to total 11 patients
(seven received TCV, 3 received ICE). Remission was not
achieved in nine patients despite HDCT+ASCT, and TCV,
ICE, metronomic therapy, RIST protocol, temozolomide were
given to these cases. Remaining two patients died. In four
refractory cases without ASCT history received TCV, ICE,
vinorelbine+temozolamide treatments. Also TCV, ICE, RIST
protocol or metronomic oral cyclophospamide/etoposide were
given as 3th line relapse treatment. Median OS for relapse
patients was 41m (6m-8yrs); 12mos-OS 48%, 18mos-OS
27%. Nine patients were followed more than 4 years.
Conclusions: Patients with relapse neuroblastoma had
advanced stage disease, unfavourable histology, and MYCN
amplification (35%). Progression free survival times prolonged up to 8 years. Relapse/refractory neuroblastoma
behave as chronic disease with different, multiple treatment
strategies.
PO-026 Treatment of Non High Risk
Neuroblastoma Patients Following Siopel Protocol
in Vietnam from 2013 to 2015
Q. Vu1 , N. Nguyen2 , L. Bui2 , H. Pham3 , C. Le4 , N. Le4 , T. Hoang5 ,
N. Ngo1 , H. Nguyen1 , L. Phung6 , V. Nguyen7 , H. Le8
1 Vietnam
Children's Hospital, Humans Genetics Department, Hanoi,
Vietnam; 2 Vietnam Children's Hospital, Oncology Department, Hanoi,
Vietnam; 3 Vietnam Children's Hospital, Surgery Department, Hanoi,
Vietnam; 4 Vietnam Children's Hospital, Radiology Department, Hanoi,
Vietnam; 5 Vietnam Children's Hospital, Pathology Department, Hanoi,
SIOP ABSTRACTS
Vietnam; 6 Vinmec International Hospital, Oncology Department, Hanoi,
Vietnam; 7 Hanoi University of Sciences- Hanoi National University,
Genetics Department, Hanoi, Vietnam; 8 Vietnam Children's Hospital,
Emergency Department, Hanoi, Vietnam
Background/Objectives: Neuroblastoma is the most popular
pediatric solid tumor in the first year. The treatment is based
on the risk stratification. In Vietnam, we now focus in treatment for non-high risk patients. So we study in neuroblastoma
patients in 3 years (2013-2015) for evaluation our results of
treatment following the SIOPEL protocol.
Design/Methods: The patients is classified in non-high risk
group using the INRG classification and treated following the
SIOPEL protocol. We followed up the patient each 6 months
after treatment to collect the information.
Results: There are 61 non-high risk patients in 3 years, in
which 54/61 patients are treated by the SIOPEL protocol.
The ratio of complete or partial response in our study at the
end of protocol and at the end of study is 61,11% and 80%,
respectively. The very low and low risk patients have the complete response. There are 3 aggressive patients in intermediate
group. The spontaneous regression is found in 3 patients (1 Ms
and 2 L2 stage). The 2 years EFS is 87,88%.
Conclusions: The SIOPEL protocol for non-high risk neuroblastoma patient is adaptive, and give the good result for
treatment on Vietnamese patients.
S449 of S518
stem cells was 2.62∼10.68*106/L, and the median follow-up
time was 14.9 months (9-32 months). All the 7 patients in stable state were in the maintenance treatment of retinoic acid.
Three cases recurrent tumor progression in 3, 5 and 5 months
after the reinfusion respectively. The other one occurred bone
marrow recurrence and intracranial metastasis 3 months after
retinoic acid chemotherapy completed.
Conclusions: HR-NB patients with 1p36 deletion had a high
risk of developing bone marrow and bone metastases, and
1/3 of them were associated with N-myc gene amplification. Autologous stem cell transplantation is a safe and effective therapeutic method. However, in 3-6 months after reinfusion and during retinoic acid maintenance therapy, tumor
progression may happen and lead to poor prognosis, suggesting the strength of systemic treatment of these patients is not
quiet enough. Therefore, close clinical monitoring was needed
after stem cell transfusion. Intensification chemotherapy in 3
months interval, a second dose of autologous stem cell transplantation may be the primary means of prevention disease
progression.
PO-028 A Single-Center Study on the Clinical
Efficacy and Progression of Neuroblastoma in
Pediatric Patients
Y. Zhang1 , D. Huang1 , W. Zhang1
PO-027 Clinical Effects of High Risk
Neuroblastoma with Chromosome 1P36 Deletion
Post Autologous Stem Cell Transplant
D. Zhang1 , B. Wang1 , Z. Yue1 , W. Zhao1 , G. Zhu1 , X. Wang1 , S.
Li1 , M. Jin1 , M. Qin1 , X. Ma1
1 Beijing
Children's Hospital Affiliated to Capital Medical University,
Hematology Oncology Center, Beijing, China
Background/Objectives: By describing the clinical features
of post autologous stem cell transplant high risk Neuroblastoma (HR-NB) patients with 1p36 deletion and their clinical
outcomes, the goal was to make further progress in better survival rate and life quality.
Design/Methods: A retrospective study of all HR-NB
patients with 1p36 deletion, who attended the pediatric hematology oncology centre from April 2014 to April 2016 and
received systematic treatment and follow-up care, was performed.
Results: A total of 11 HR-NB patients with 1p36 deletion,
all INSS-IV, were included in the study,4 were male and
7 female. The average age was 43 months. There were 11
cases with bone marrow metastasis and 10 cases with multiple bone metastasis. N-myc gene amplification was detected
in 4 patients.11 patients were treated with 4-5 courses of
chemotherapy before the operation. The amount of reinfused
1 beijing
tongren hospital - capital medical university, pediatric, Beijing,
China
Background/Objectives: Study on the clinical outcome of
NB associated with different risk factors by analyzing the clinical data of 147 NB patients collected in the past nine years at
Beijing Tongren Hospital.
Design/Methods: 147 patients of NB collected from January
2006 to January March 2015 and treated with induction and
consolidation treatment.The average following-up time was
32.15±21.05 months. We used SPSS 20.0 software for analyzinged the clinical data using SPSS 20.0 software for studying on the relationship between outcome of NB and different
risk factors..
Results: In 147 cases, 97 patients were male (65.266%), and
50 patients were female (34.8%). The average age of the
patients was (3.76±2.83) years old.The OS of 147 NB patients
was 54.4% (80/147). 67 Patients of NB were dead. The
medium survival time of patients of NB was 48.0 months.The
medium survival time of 117 patients of HR NB was 41.1 m,
and the 1 year-, 2 year-, 3year-, 4 year- and 5 year OS of them
was 69%,54%,45%,29%, and 16%. The medium survival time
of 30 patients of IR NB was 60 m, and the 1 year-, 2 year-,
3year-, 4 year- and 5 year OS of them was 92%,86%,86%,86%,
and 86%.73 patients of recurrence NB as followed up. Only
3 patients (3/73) of IR group of NB appeared recurrence
SIOP ABSTRACTS
S450 of S518
(P=0.001). The 4 year OS of 70 patients (70/117) of HR NB
with relapse was only 23%.
Conclusions: Relapse was and older age were main risk factors in NB, no matter what group. The prognosis of IR NB was
very good, but the prognosis of HR NB was poor. Therefore,
we would like to resolve these problems for better prognosis
we should diagnosis early and reduce relapse using reasonable
diagnosis and treatment technology for improving the survival
outcome of NB, special HR group patients.(improve the survival outcome?).
SOLID NON B R A I N T U MO U R S R E NA L T U M O U R S
PO-029 A Rare Cause of Renal Mass in the
Childhood: Malignant Solitary Fibrous Tumor
G. Ersoy1 , D. Tuğcu2 , B. Koç1 , C. Bayram1 , I. Odaman Al1 , F.
Akici1 , A. Ayçiçek1 , G.N. Ozdemir1
1 Kanuni
Sultan Suleyman Training and Research Hospital -, Pediatric
Hematology Oncology, Istanbul, Turkey; 2 Istanbul University School of
Medicine, Pediatric Hematology Oncology Department, Istanbul, Turkey
Background/Objectives: Solitary fibrous tumors (SFT) are
very rare, mostly benign neoplasms and originate from mesenchymal spindle cells. SFT rarely originate from kidney.
Design/Methods: Here we desciribe a case of malignant,
renal origin SFT with four local recurrences and metastases.
Results: A 12 year old male patient admitted to our clinic
with hematuria. Investigations revealed an abdominal mass of
40×42 mm and radical nephrotomy was planned. Pathological
diagnosis of the lesion was renal SFT the tumor was defined as
malignant. As the tumor was totally resected, monthly followup was planned for the patient. One year later, ultrasound
revealed a recurrent mass lesion at the primary tumor side.
It was excised totally and pathological diagnosis was same
as the primary tumor. After surgery, radiotherapy to tumor
site and salvage chemotherapy with ifosfamide, cisplatin and
etoposide were applied. No residual or recurrent mass were
found at the end of the therapy. However 3 months later, a 1 cm
noduler contrast enhanced mass lesion near L1 vertebra was
recorded at magnetic resonance imaging (MRI). The lesion
was surgically removed and diagnosed as the primary tumor.
An alternative chemotherapy protocol was applied after operation. Monthly follow-up was continued however 3 months
after recurrent masses at renal and pelvic region were found.
At surgery, 2 lesions with the sizes of 19x15x8 cm and 5,5 cm
were found and resected. An alternative chemotherapy regimen was used again. The patient was up on bevacisumab for
treatment.
Conclusions: There are 49 renal SFTs described at the literature up to time and 7 are malignant. This tumour is mostly
seen in adulthood, only 2 patients are younger than 18 years
old (4 and 18) and both of them have benign tumors. This case
is the youngest patient described in literature with malignant
solitary fibrous tumour.
PO-030 The First Local High-Dose
Chemotherapy Administration Experience in a
Metastatic Wilms Tumor Pediatric Patient with
Pleura and Lungs Involvement
E. Levchenko1 , E. Gumbatova2 , O. Mamontov1 , S. Rosengard3
1 Petrov
Research Institute of Oncology, Thoracic surgery, Saint-PetersburgPesochniy, Russia; 2 Petrov Research Institute of Oncology, Paediatric
Oncology, Saint-Petersburg- Pesochniy, Russia; 3 Petrov Research Institute
of Oncology, Anesthesiology, Saint-Petersburg- Pesochniy, Russia
Background/Objectives: Our aim is to report the first clinical
case of successful chemoperfusion of lungs and pleural cavity
in a child with Wilms tumor.
Design/Methods: In March 2014 a right kidney mass lesion
was found. Tumor resection with right nephroureterectomy
was performed in a local clinic. The patients received subsequent chemotherapy for stage III, blastemal type nephroblastoma according to SIOP 2003 protocol. In May 2015, a
routine check-up revealed an early relapse with multiple lung
metastases. Abroad 4 chemotherapy cycles with subsequent
15 Gy whole-lung irradiation and high-dose chemotherapy
with autologous hemopoietic stem cell transplantation were
performed. In May 2016 a chest CT scan revealed the second
early relapse with lungs involvement.
In June 2016 a left thoracotomy was performed. An intraoperative revision revealed two metastases in the lower lobe
and an additional subpleural lesion 3 mm in diameter. After
wedge resection of the lower lobe of the left lung the further revision yielded another centrally located lesion about
10 mm in diameter in the 6th segment. An anatomic resection of the segment was performed. Another three nodular
lesions 3 to 4 mm in diameter were found on the parietal
pleura of the diaphragm. After the partial pleurectomy the
intraoperative morphology results indicated metastatic pleural involvement by nephroblastoma. Therfore, the lung was
disconnected from circulation, blood vessels were cannulated,
and 30-minute normothermic lung perfusion with 500 mcg of
dactinomycin [1.6 mcg/cm3 × 310 cm3 (350 - SVI)] was performed. Due to the parietal pleura involvement found there
followed an additional 60-minutes hyperthermic pleural perfusion with 150 mg of cisplatin.
Results: The postoperative recovery was uneventful. The CT
scan shows no signs of lungs involvement.
SIOP ABSTRACTS
Conclusions: The case described illustrated the feasibility
and safety of local lung and pleura chemoperfusion in a heavily pretreated chemoresistant pediatric cancer patient.
PO-031 Non-Wilms' Malignant Masses of
Kidney: Experience of Few Patients with Improved
Outcome
B. kumar1 , V. upadhyaya1 , R.N. rao2 , S. kumar3
1 Sanjay
Gandhi Post Graduate Institute of Medical Sciences- LucknowUP- India, Paediatric Surgical Superspeciality, Lucknow, India; 2 Sanjay
Gandhi Post Graduate Institute of Medical Sciences- Lucknow- UP- India,
Pathology, Lucknow, India; 3 Sanjay Gandhi Post Graduate Institute of
Medical Sciences- Lucknow- UP- India, Radiodiagnosis, Lucknow, India
Background/Objectives: Wilms' tumour accounts for almost
85% while other rare renal tumours including stromal tumours
constitute only 15% of all paediatric renal masses. Differentiation is important for better outcome as each tumour has
different chemotherapy protocol. Clear cell sarcoma, Rhabdoid tumour and Ewing‘s / PNET tumour of kidney are rare
tumours, considered as UNFAVORABLE tumorus due to its
aggressive nature and late presentation.
Our aim is to present the characteristics, disease course, management and final outcome with these rare renal tumours in
few patients which showed relatively better outcome.
Design/Methods: We retrospectively reviewed the electronic
hospital, operation theatre and follow-up records of all
patients having non-Wilms' renal malignant masses between
July 2012 to July 2016; managed at our centre. Details of
patients were evaluated including demography, clinical presentations, investigations, intra-operative grading, pathology,
management, final outcome and follow-up. Last follow-up
was January 2017. Clinical examinations, ultrasonography, Xrays and CT/PET-scans were tools of follow-up.
Results: From July, 2012 to July, 2016, six patients with nonWilms' renal tumours were managed. Final diagnosis were
clear cell sarcoma in 3 patients, rhabdoid tumour in 2 patients
and Ewing's/PNET tumour in 1 patient. Almost all patients
presented in stage II/III and received neo-adjuvant chemotherapy followed by surgery and chemo/radiotherapy. One patient
with clear cell sarcoma could not be operated; showed partial response to chemotherapy and died due to chemotherapy
related toxicity. All 5 patients are under follow-up without
recurrence. Follow-up period ranged from 6 – 48 months.
Conclusions: The clinical characteristics of these rare renal
tumours are similar to that of Wilms' tumour and preoperative diagnosis is almost impossible without histopathology/immunohistochemistry, even with modern imaging techniques. Some of these tumours progress rapidly and may result
in fatal outcome. Early diagnosis and multimodal interven-
S451 of S518
tions in form of surgery/chem./radiotherapy are essential for
better outcome.
S O LID NO N BRAIN TUM O URS BON E T U M O U R S
PO-032 Ewing's Sarcoma 10-Year Experience at
the National Medical Center 20 De Noviembre
ISSSTE. A Third Level Hospital in a Low Income
Country
E. Baños1 , F. Arreguin1 , B. Almazan1 , A. Benito1 , J. Robles1
1 National
Medical Center 20 de Noviembre ISSSTE, Pediatric Oncology,
Mexico City, Mexico
Background/Objectives: Ewing sarcoma occur more frequently in the second decade of life and comprise about 4%
of pediatric tumors. With current protocols, survival for localized disease is around 60% and in metastatic disease is 25%.
Design/Methods: A descriptive, longitudinal, observational
study that included 20 patients´files with Ewing's Sarcoma at
the National Medical Center “20 de Noviembre” ISSSTE in a
period from January 2006 to December 2016.
Results: Male predominance was observed (1.8:1) ; mean age
of presentation was 9.9 years with a minimum and maximum
age of 1 and 16 years. Of the total cases 8 (40%) were osseous
and 12 (60%) were extraosseous; 9 cases were located and 11
metastasic cases, representing 45% and 55% respectively. The
duration of onset of symptoms at diagnosis varied from 1 to
24 months with an average of 3.5 months. The primary sites
of bone disease were lower extremities and lower limbs. The
primary sites of extraosseous disease were Head and Thoracic
Wall. The duration of follow-up varied from 1 month and 125
months with an average of 32.3 months; Overall survival was
85%; For patients with localized disease, overall survival was
88.9% and for metastatic disease 91%.
Conclusions: A predominance was observed in the male gender, mean age of presentation of 9.9 years said results differ
from that reported in other studies. Likewise, a predominance
of extraosseous localization was observed, and overall survival was higher than that observed in other studies.
PO-033 Clinical Presentation, Management and
Outcomes of Primary Ewing Sarcoma of the Spine
in Childhood- A Case Series
B. Dubashi1 , S. Kayal1 , A. Mukherji2
1 Jawaharlal
Institute of Postgraduate Medical Education and Research
JIPMER, Medical Oncology, Puducherry, India; 2 Jawaharlal Institute of
Postgraduate Medical Education and Research JIPMER, Radiotherapy,
Puducherry, India
SIOP ABSTRACTS
S452 of S518
Background/Objectives: Spine usually accounts for 6% of
the Primary sites in Ewing Sarcoma. They usually present
with malignant spinal cord compression necessitating early
workup and treatment. Local therapy is challenging. We are
presenting a short-case series of the clinical presentation,
management and outcomes of primary Ewing sarcoma of the
spine in children.
Design/Methods: The case records of 45 children during the
period 2013- 2016 with a diagnosis of Bone sarcoma presenting to the department of Medical Oncology in a regional
cancer centre were screened for primary spinal Ewing Sarcoma. Clinical manifestations, treatment details including
chemotherapy, surgery and radiotherapy and survival outcomes were noted.
Results: Seven children with primary spinal Ewing Sarcoma
were identified during the study period. The median age was
10 years (2-18) with M:F ratio of 3:4. Five children presented with Para-paresis of which two patients developed a
flaccid paraplegia during the work up. Primary site of presentation included Cervical (n=3), Cervical and Thoracic
(n=1), Dorso-lumbar (n=1) and Lumbosacral (n=2). Two
patients had metastasis to the bones at presentation. Three
patients underwent laminectomy with excision of the mass.
All patients received radiotherapy. Non metastatic patients
were treated with VAC/IE protocol while patients with metastasis were treated with VAC protocol. On the date of analysis, 4 patients had progressive disease during the treatment
and succumbed to illness, 2 patients completed treatment and
are alive and free of disease with no neurological deficit. One
patient is undergoing chemotherapy.
Conclusions: Primary Spinal Ewing sarcoma are rare
tumours requiring a multimodality treatment with surgery,
chemotherapy and radiotherapy. They can present with Oncologic emergency. They have a poor outcome to therapy in
terms of response and survival.
Design/Methods: This is a retrospective study of 75 pediatric
patients with Ewing Sarcoma treated in between 1996 to 2016.
Results: During a 20-year period, 75 patients were identified with Ewing Sarcoma in hospital database and their
records were analyzed retrospectively. Of the 75 patients, 45
(60%) were males, 30 (40%) were females. The mean age
was 10 years (ranging from 1year to 17 years). All of the
patients had received the same chemotherapy protocol at presentation. This protocol involved ifosfamide, etoposide, vincristine, doxorubicine, cyclophosphamide and actinomycin.
After 3 cycles of chemotherapy, surgery had been performed
for most of the patients. Radiotherapy had been performed
for the patients who had more than 10% viable cells after
pathological examinations. For these patients, chemotherapy
had been changed and continued during and after radiotherapy. The second chemotherapy protocol invoved vincristine,
cyclophosphamide and topotecan. At the presentation, 22 (29
%) patients had metastatic disease. During the follow up 16
(23 %) patients had relapsed. The 5-year event free survival
and overall survival were 46 % and 58,5 %. Metastatic disease
at presentation was the significant factor on overall survival.
Conclusions: The management of a child or adolescent with
Ewing sarcoma is best carried out in a specialized center under
the care of a multidisciplinary team, in order to obtain the
best outcome for the patient. Early diagnosis is very important
because metastatic disease at presentation reduces the overall
survival.
PO-035 Expression of TUBB3 and RRM1
Proteins as Markers of Drug Resistance to
Gemcitabine / Docetaxel Chemotherapy in
Childhood Osteosarcoma
A. Levashov1 , E. Senzhapova1 , D. Khochenkov2
1 Pediatric
PO-034 Outcome of Ewing Sarcoma in Children,
Twenty Years Experience from a Single Center in
Turkey
N. Eker1 , B. Yılmaz1 , G. Tokuc1 , E. Senay1 , B. Berk1 , O. Dogru1
1 Marmara
University, Pediatric Hematology and Oncology, Istanbul,
Turkey
Background/Objectives: Ewing sarcoma (ES) is the second
common primary bone malignancy in pediatric patients. Usually, these tumors occur in bone but sometimes they can olsa
orginate in soft tissue. These tumors are agressive and treatment involves multidurgs chemotherapy, radiotherapy and
surgery. The aim of this study was to determine outcomes of
Ewing sarcoma in pediatric patients who was treated in our
instution.
Hematology and Oncology Institution FSBI «N.N. Blokhin
Russian Cancer Research Center», Pediatric Hematology and Oncology,
Moscow, Russia; 2 Experimental Diagnostic and Treatment of Tumor
Institution FSBI «N.N. Blokhin Russian Cancer Research Center»,
Experimental Diagnostic and Treatment of Tumor, Moscow, Russia
Background/Objectives: The treatment results of refractory
childhood osteosarcoma are not satisfactory. According to the
data of different pilot trials progression-free survival curves
dramatically tend to zero with a median follow-up in 6-10
months. Role of the TUBB3 and RRM1 proteins expression as markers of drug resistance to gemcitabine / docetaxel
chemotherapy in childhood osteosarcoma is unknown.
Design/Methods: The aim of this study was to estimate
TUBB3 and RRM1 proteins expression in biopsy specimens
and tumor tissue samples with poor response (grade I and II
of tumor cells necrosis rate) after neoadjuvant chemotherapy
and surgery of the primary site.
SIOP ABSTRACTS
TUBB3 and RRM1 proteins expression was assessed by
immunohistochemical method using anti-RRM1 polyclonal
(Protein Tech) and anti-TUBB3 monoclonal (clone TU20, Santa Cruz) antibodies. TUBB3 positive specimen was
defined as weak (+), moderate (++), strong (+++) colouring of the tumor nuclei with number of positive tumor cells
above 10 percents. RRM1 positive specimen was defined as
moderate (++), strong (+++) colouring of the tumor nuclei
and cytoplasm with number of positive tumor cells above 25
percents. All patients were treated according to therapy like –
EURAMOS1.
Results: TUBB3 positive sample was revealed in 8 out of 14
(57.1%) biopsy specimens, in 3 out of 20 (15%) postoperative
specimens. RRM1 positive sample was revealed in 10 out of
14 (71.4%) biopsy specimens, in 9 out of 20 (45%) postoperative specimens. TUBB3 positive, RRM1 positive sample was
revealed in 5 out of 14 (37.5%) biopsy specimens, in 2 out of
20 (15%) postoperative specimens. There was not determined
any significant correlation between expression of these markers and metastatic status of patients.
Conclusions: These data suggest that optimal time of using
gemcitabine / docetaxel could be adjuvant chemotherapy.
PO-036 The Best Strategy as the First Line
Treatment Through Pediatric Iranian Population
with Osteosarcoma; A Retrospective Matched
Cohort Study
M. Faranoush1 , A. Mehrvar1 , M. Tashvighi1 , A.A. Hedayati Asl1 ,
M.A. Ehsani2 , N. Mehrvar3 , M. Alebouyeh1
1 MAHAK
Pediatric Cancer Treatment and Research Center, Oncology,
Tehran, Iran; 2 Tehran University of Medical Sciences, Bahrami Hospital,
Tehran, Iran; 3 Cancer Research Center, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
Background/Objectives: One of the utmost important challenges in Iranian health system is pediatric malignancies.
Osteosarcoma, the common primary bone tumor, has a low
survival rate in Iran. We designed this study to choose the best
strategy for chemotherapy. Our goal is improving the survival
rate of these patients.
Design/Methods: This study conducted as a retrospective
analytical cohort matched project. The randomized samples
implied children less than 15 years old with approved pathological report of osteosarcoma. Patients with matched inclusion criteria categorized into two groups who administered by
high dose methotrexate (HD MTX) and individuals with nonHD MTX. The failure events and survival rate of these groups
were estimated by SPSS software version 22.
Results: Fourty one eligible patients (non HD MTX (n=21)
and HD MTX (n=20) groups) with the mean age of 11.5±0.48
years were evaluated. 65.2% of patients with HD MTX and
S453 of S518
34.8% of non-HD MTX group had conferred relapse and
metastasis. The median time of events was one and nine
months through patients with HD MTX and non HD MTX
groups respectively. The 5-year survival rate of patients with
HD MTX and non-HD MTX was 18.4% versus 43.5%. Also
the median time of disease free survival rate was more in non
HD MTX patients (11.5 months versus one month).
Conclusions: Findings revealed that survival rate and delaying in failure events were more in patients who administered
by non HD MTX. As this study designed on the Iranian pediatric patients, the authors suggest on using non-HD MTX regiment for Iran pediatric osteosarcoma patients.
Acknowledgement: The authors thank staffs of medical documentation unit and research department at MPCTRC for
their services and thank the orthopedic surgeons and radiotherapy unit for providing assistance with the clinical procedures.
PO-037 Survival of Patients with Childhood
Osteosarcoma; A Single Center Experience
R.E. Senay1 , B. Yilmaz1 , N. Eker1 , A.G. Tokuc1 , O. Dogru1 , B.
Berk1
1 Marmara
University Medical Faculty, Paediatric haematology oncology,
Istanbul, Turkey
Background/Objectives: This study presents clinical outcome and midterm follow up of patients with childhood
osteosarcoma with <90 % necrosis rate according to the presence of metastasis during initial diagnosis
Design/Methods: Retrospective analysis of a prospectively
collected single center database were evaluated. Thirty one
patients with the diagnosis of osteosarcoma were enrolled
between December 1995 and February 2017. Demographic
variables, necrosis degree, rate of recurrence, rate of remission and survival were analyzed according to the presence of
metastasis during the initial diagnosis
Results: Patents age ranged between 5-19 years during The
initial diagnosis, 17 (54.8%) of them were female and,14
(45.2%) of them were male. The mean follow-up period
ranged between 4-133 months ( with an average of 41,13 ±
35 months). There were metastases in 5 cases (16,1%) and
local invasion in 1 case (3,2%) during the initial diagnosis.
Chemotherapy and surgical therapy was performed for each
patient. The rate of necrosis ranged from 5% to 100% and it
was 90% in 20 (64.5) patients. During the follow up period;
recurrence was observed in 10 (32.3%) cases, mortality was
observed in 9 (29%) and complete remission was detected in
22 (71%) of the cases. The five-years overall survival rate was
80.6% and mean survival time was 104.23 ± 10.27 months
(95% CI: 84.11-124.36). There was no statistically significant difference in survival between groups those include pres-
SIOP ABSTRACTS
S454 of S518
ence of metastasis at the time of diagnosis and <90% necrosis
in follow-up and nonmetastatic at the time of diagnosis and
<90% necrosis in follow-up (p>0,05).
Conclusions: These data shows 80% survival rate in midterm
follow up. There has been no difference demonstrated in survival according to the presence of metastasis during the initial
diagnosis.
SOLID NON B R A I N T U MO U R S SOFT TISSUE SARCOMAS
In all cases of transnasal endoscopic removal of the tumor
reached radicalism. The promise of this type of treatment
requires further study and definition of clear criteria for inclusion in the scheme and therapy protocols ENB children.
PO-039 Transnasal Endoscopic Surgery in
Complex Treatment of Soft Tissue Sarcomas in
Children
D. Buletov1 , O. Merkulov2 , V. Polyakov2 , T. Gorbunova2
1 Russian
PO-038 Transnasal Endoscopic Surgery in
Complex Treatment of Esthesioneuroblastoma in
Children
D. Buletov1 , O. Merkulov2 , T. Gorbunova2 , V. Polyakov2
1 Russian
Cancer Research Center N.N. Blokhin, head and neck tumors,
Moscow, Russia; 2 Russian Cancer Research Center N.N. Blokhin, head and
neck department, Moscow, Russia
Background/Objectives: Esthesioneuroblastoma is a rare
malignant tumor. The efficacy of transnasal endoscopic
removal of the tumor in the treatment of adult patients ENB is
not in doubt. However, the possibility of this type of surgical
treatment of ENB in children has not been studied sufficiently.
Design/Methods: From 2003 to 2016 the study included 11
patients. Mean patient age at diagnosis - 9 years. Staging
according to the TNM-classification. Stage I was determined
at 2, III - y 1, IV - in 8 cases. Intracranial spread has been
observed in 4 cases. 8 patients had got chemotherapy and
radiation therapy. Chemotherapy was included from 6 to 10
courses: Vincristine 1 mg/m2 to 1 and Day 8, cyclophosphamide 500 mg/m2 to 1 and Day 8, doxorubicin 20 mg/m2 of
2 and 4 day carboplatin 360 mg/m2 of 1 day. Chemotherapy
was administered in neoadjuvant regime 5 patients. Radiation
therapy was performed in 8 patients in the 1.8 - 2.4/day. At
the primary tumor RT 50.4 Gy was performed in 5 patients
and further irradiated lymph nodes 40 Gy in 3. Complex therapy, including surgical treatment, carried out in 7 patients.
Transnasal removal of the tumor was performed in 6 patients,
of whom one of them to remove the tumor transnasal access
was conducted twice, a second operation was performed for
recurrent disease.
Results: Currently, 6 patients (54.5%) lived from 3 months
to 13 years. One patient withdrew from the study immediately after diagnosis. Died of tumor progression - 4
(36.4%).
Conclusions: Based on our data shows the effectiveness of
integrated treatment of common stages of ENB in children.
Cancer Research Center N.N. Blokhin, head and neck tumors,
Moscow, Russia; 2 Russian Cancer Research Center N.N. Blokhin, head and
neck department, Moscow, Russia
Background/Objectives: Currently, the method of transnasal
endoscopic surgery (TEC) is becoming increasingly popular
in the treatment of nasal cavity, skull base and paramenegial
localization. This work is the first experience of TEC in children with Malignant tumors in Russia
Design/Methods: From 2015 to 2017 25 transnazal surgical operations were performed in 24 patients. 14 female
patients, 10 male patients. In 16 cases, one-stage tumor
removal was performed, in 9 cases cytoreductive tumor resection (biopsy) was performed.The youngest patient at the time
of the operation was 36 days. The oldest patient - 17 years
and 1 month.The histological composition of the neoplasms
was different: rhabdomyosarcomas, gliomas, Burkitt's lymphomas, angoimas, and others. 23 patients are alive at the
moment, 1 patient died 3 months after the end of special treatment for estezioneeroblastoma
Results: 23 patients are alive at the moment, 1 patient died
3 months after the end of special treatment for estezioneeroblastoma. Surgical complications: intraoperative - cavernous
sinus lesions - 2. There were no complications in the postoperative period
Conclusions: Endonasal surgery with the help of modern
endoscopy techniques plays an important role both in the formulation of the diagnosis, and in the subsequent treatment
and detection of relapses. In the modern world it is a method
of choosing for treatment benign neoplasm, but also malignant neoplasms of the nasal cavity, the base of the skull and
paramenengial localization. It is important to note that with
the use of these modern technologies in patients of different
ages, we have achieved the main goals of endoscopic interventions: complete visual control of performed manipulations;
safety; preservation of the mucosa and anatomical structure;
Minimal traumatism for the patient (absence of skin incisions); Easy tolerability in adults and children; The possibility
to do without a long period of rehabilitation in the postoperative period.
SIOP ABSTRACTS
PO-040 Treatment of Head and Neck Malignant
Rhabdoid Tumors with Combined Intensive
Chemotherapy and 125I Particle Implantation:
Report of 2 Cases Follow-Up for Over 2.5 Years
C. Duan1 , M. Jin1 , X. Ma1 , D. Zhang1 , W. Zhao1 , Q. Zhao1 , X.
Wang1
1 Beijing
Children's Hospital, heamatology/oncology, Beijing, China
Background/Objectives: Malignant rhabdoid tumors(MRT)
is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the
existing standard of intensive multimodal therapy, the prognosis of patients with MRT is still dismal. To add to the current
knowledge, here we report 2 cases of MRT in the head and
neck region treated with anthracycline and platinum-based
chemotherapy and brachytherapy.
Design/Methods: The clinical records of 2 patients with head
and neck MRT treated in Beijing Children's Hospital between
Oct 2011 and May 2014 were retrospectively studied.
Results: The medical records of two boys, onset age of 1.2y
and 4.5y respectively were studied. One patient with primary
tumor site at the right neck, another patient with the primary tumor site at the left neck, and metastasis to the right
nasopharynx and multiple facial bones. The primary tumors
size were 8*8cm and 6*6 cm respectively, were all stage
III, and were all unresectable. Immunohistochemical results
showed that the INI-1 were all negative. They were treated
with chemotherapy after biopsies were done.
The chemotherapy protocol was as follows: vincristine,
cyclophosphamide, doxorubicin (VDCPM1) at weeks
1,7,13,19,25, and cyclophosphamide, carboplatin, etoposide
(CPM5+CE) at weeks 4,10,16,22,28. 125 I particle implantations were done after 5 and 6 cycles of chemotherapy
respectively. The evaluation showed very good partial
remission of the tumor after the treatment completed. Both
patients had IV grade neutropenia, I-II degree anemiaand
thrombocytopenia.Both patients suffered from grade 1-2 skin
reaction after seed implantation, manifested as erythema or
mild edema of the local skin, which can be improved within
1-2 weeks. Now the follow-up time were 64 month and 34
month respectively, and the two patients remained stable.
Conclusions: Anthracycline and platinum-based intensive
chemotherapy combined with 125 I particle implantation may
be a promising treatment option for extra-renal, extra-cranial
MRT without distant metastasis.
S455 of S518
1 Aga
Khan University, oncology, karachi, Pakistan; 2 Aga Khan university,
Pediatrics and Child Health, Karachi, Pakistan
Background/Objectives: There is paucity of data regarding
demographic characteristics and outcomes of bone and soft
tissue sarcomas from the developing world including Pakistan. We analyzed the clinical features, and outcome of children with bone and soft tissue sarcomas treated over last 10
years at Aga Khan University Hospital.
Design/Methods: Records of patients treated from January
2005 to December 2015 at Aga Khan University Hospital, histologically confirmed diagnosis of bone and soft tissue sarcomas were reviewed. Kaplan-Meier curves were created to
assess overall survival (OS) and event free survival (EFS) with
relapse and death as outcome.
Results: Forty three patients were eligible. 27(62.7%) were
bone tumors with 13(48.1%) osteosarcoma, and 14(51.8%)
ewings sarcoma. There were 16(37.2%) soft tissue sarcomas
with 12(75%) rhabdomyosarcoma along with fibrosarcoma &
synovial sarcoma (12%) each respectively.
There were 11/43(25.5%) patients with metastatic disease, 4
osteosarcomas, 4 ewings and 3 rhabdomyosarcoma respectively. The median age for bone sarcoma was 12 years while
soft tissue sarcoma was 6 years. Distal Femur was the most
involved site - 10/27 (37%) in bone tumors and parameningeal
4/12 (33%) was the most common site in rhabdomyosarcoma.
There were 6/43 (13.9%) patients who received minimal to
no therapy. There were 10/43 (23%) relapses on therapy. The
estimated 5-year EFS was 43.4% (95%CI: 9.8%-73.9%) and
OS at 5 years was 54.7% (95%CI: 23.9%-77.6%).
Conclusions: Outcomes of sarcomas in the developing world
are poor due to multiple factors. Delayed presentation, poor
tolerance of therapy, poor nutritional status at baseline, abandonment of therapy and lack of easy access to medical care
due to financial constraints are some of the major factors
responsible.
PO-042 Treatment Results in Pediatric Head and
Neck Rhabdomyosarcomas: A Single Center
Experience
K. Mutafoglu1 , D. İnce1 , D. Kizmazoglu1 , Y. Olgun2 , M. Erdem1 ,
A. Demiral3 , R. Cetingoz3 , H. Guleryuz4 , E. Ozer5 , T. Erdag2 , and
N.Olgun1
1 Dokuz
PO-041 Outcome of Bone and Soft Tissue
Sarcomas in Children at a Tertiary Care Center in
Pakistan
Z. Fadoo1 , S. Resham1 , N. Mushtaq1 , A.R. Rizvi2 , S. altaf1
Eylul University Institute of Oncology, Dept. of Pediatric Oncology,
Izmir, Turkey; 2 Dokuz Eylul University Faculty of Medicine, Dept. of
Otorhinolaryngology, Izmir, Turkey; 3 Dokuz Eylul University Faculty of
Medicine, Dept. of Radiation Oncology, Izmir, Turkey; 4 Dokuz Eylul
University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey;
5 Dokuz Eylul University Faculty of Medicine, Dept. of Pathology, Izmir,
Turkey
SIOP ABSTRACTS
S456 of S518
Background/Objectives: To evaluate head and neck localized rhabdomyosarcomas in our center.
Design/Methods: Medical records of 32 patients with head
and neck localized RMS between 1988-2016, analyzed retrospectively.
Results: The median age of diagnosis was 6.5yrs (18 mos17 yrs),M/F:1.0. Localization of tumors were as follows;
parameningeal: 19, orbit:7, cheek:1, scalp:2, tongue:1,hard
palate:1. According to IRS, TNM stage distribution: stage I
(n:15), stage II(n:4), stage III(n:10), stage IV(n:3). Clinical
grouping: CG-1: 3% (n:1), CG-2: 6% (n:2), CG-3: 82% (n:26),
CG-4: 9% (n:3). The primary surgery was performed for three
patients. All other patients received chemotherapy as the initial treatment. IRS based treatment regimens were used in
24 patients, COG ARST0431 protocol was used for other 8
patients. RTwas given to all the primary sites except two who
were lost to follow up. Total resection with secondary surgery
was performed for one patient with cheek primary because
of chemo and radio-resistant tumor. The median follow-up
time was 33 mos (2 mos-17 yrs). Four patients were lost to
follow up at 8th month with disease (n:3) and at 37th month
without disease (n:1). 3-yrsOS rate was 76%, 5and10yrs OS
rates were 71%. 3yrsEFS rate was 63%, and 5, 10yrsEFS rates
were 58%. Totally 7 patients died with progressive disease
at median 26 months (10-49 mos). Two patients died with
refractory and progressive disease at 10 months. Nine patients
relapsed. Median relapse time was 19mos (6-40 mos). Three
patients with relapsed disease are alive and relapse treatment
is going on. A treatment resistant patient is alive after second
line surgery with NED. Five patients with relapsed disease
died with progression despite anticancer treatment.
Conclusions: Fourty percent of patients had advanced stage
disease, 91% of patients were in clinical group 3-4, local control was problem. Overall and event free survival rates were
acceptable.
PO-043 Successful Treatment of Tandem
High-Dose Chemotherapy with Allogeneic Stem
Cell Transplantation in Advanced Ewing Sarcoma
T. Miyamura1 , Y. Hashii1 , H. Yoshida1 , N. Naka2 , K. Hamada2 , S.
Takenaka2 , F. Isohashi3 , H. Minagawa1 , N. Nakagawa1 , T.
Fujiwara1 , K. Ozono1
1 Osaka
University Graduate School of Medicine, Pediatrics, Osaka, Japan;
University Graduate School of Medicine, Orthopedic surgery,
Osaka, Japan; 3 Osaka University Graduate School of Medicine, Radiology,
Osaka, Japan
2 Osaka
Background/Objectives: Ewing sarcoma (ES) is a rare
malignancy of bone and soft tissue. The prognosis of
advanced metastatic ES remains very poor and treatment strategy has not been established. We report two cases of advanced
ES treated by tandem high-dose chemotherapy with allo-
geneic stem cell transplantation (SCT). They survived without
disease for more than 4 years, therefore it may be an effective
treatment strategy for advanced ES.
Design/Methods: Patient 1 was a 15-year-old girl with ES
originating in right ilium with multiple lung metastases.
Patient 2 was an 11-year-old girl with ES originating in left
ilium with multiple lung metastases. They received multidrug chemotherapy and radiation therapy to the primary
legion. We then performed first high-dose chemotherapy
(VP16/CBDCA/CY) with autologous stem cell transplantation (SCT). They underwent surgical resection of primary
lesion after hematological recovery. Their treatment response
were good, and they achieved complete response. After that,
we performed second high-dose chemotherapy (CY/LPAM)
with allogeneic SCT. The donor of patient 1 was HLAmatched sibling, and severe adverse event including GVHD
was not detected. The donor of patient 2 was HLA 2 loci mismatched mother (KIR ligand mismatch). Moderate engraftment syndrome was occurred although severe GVHD was not
detected.
Results: Patients 1 and 2 survived without disease for 70
months and 54 months, respectively.
Conclusions: We reported two cases of advanced ES treated
with multi-drug chemotherapy and local radiation therapy,
plus tandem high-dose chemotherapy with autologous and
allogeneic stem cell rescue. They survived without disease
progression for more than 4 years. It was reported that ES can
express tumor antigens which can be recognized by T cells,
making allogeneic SCT an effective option. Intensive highdose tandem chemotherapy with alkylating agents and allogeneic tumor immunotherapy could be an effective treatment
strategy for advanced ES.
S O LID NO N BRAIN TUM O URS RETINOBLASTOMA
PO-044 Evaluation of Retinoblastoma Patients
Undergoing Enucleation in the Backdrop of IIRB
and AJCC TNM Classification; Clinical Features
and 5 Year Outcome Analysis
A. alkofide1 , H. Katan2 , M. Ayas1 , A. Ali1 , I. AlFawaz1 , S.K.
Siddiqui Khawar1 , G. Barria1 , M. Foudaneel3 , A.S. Alhmouz1 , S.
AlMesfer2 , Y. Khafagh4
1 King
Faisal Specialist Hopsital & Research Center, Pediatric Hematology
Oncology, riyadh, Saudi Arabia; 2 King Khaled Eye Specialist Hopsital,
Opthalmology, Riyadh, Saudi Arabia; 3 AlFaisal University, Medcial
College, Riyadh, Saudi Arabia; 4 King Faisal Specialist Hopsital &
Research Center, Oncology Center, riyadh, Saudi Arabia
SIOP ABSTRACTS
Background/Objectives: To determine the clinical profile
and outcome of patients with Retinoblastoma (Rb) who underwent unilateral or bilateral enucleation in the backdrop of
International intraocular retinoblastoma classification (ABC
Classification) and TNM Staging System.
Design/Methods: Medical charts of 58 pediatric (Age≤14
years) patients with retinoblastoma who underwent enucleation, treated at King Faisal Specialist Hospital and Research
Centre (KFSHRC), and King Khaled Eye Specialist Hospital
Riyadh, Saudi Arabia from 2012-2016 were reviewed
Results: Among the cohort, 51.7% (30) were female. Median
age at diagnosis was 20.5 months (3-97.8). Retinoblastoma
was unilateral in 51.7% (30), bilateral in 44.8% (26) and trilateral in 3.4(2) patients. One (1.7%) had metastatic disease at
presentation. 61 enucleations were performed in 58 patients.
International Classification for Intraocular Retinoblastoma
was carried out for all eyes. 43 (70.5%) were in Group E,
11(18%) Group D, 3(4.9%) Group C and A each, followed
by 1 (1.6%) in Group B. All patients underwent chemotherapy as chemoreduction and/or chemoprevention. 52 (85.2%)
received chemoreduction and, 5 (8.2%) chemoprevention
and 4 (6.6%) chemoreduction and chemoprevention. 4(6.9%)
patients received thermotherapy, 1(1.7%) cryotherapy and
1(1.7%) trans-pupillary intravenous carboplatin. Information
on TNM classification and IIRB was available on 46 patients.
9 (19.5%) of our T1, T2a patients were classified as Stage D or
Stage E. Post-enucleation 17.2% (10) of our patients received
External Beam Orbital Radiotherapy (EBORT). Of 44 evaluable cases, 93.2% (41) were in CR, 4.5(2) had stable disease
and remaining 2.3% (1) progressive disease. With 3 (5.2%)
mortalities (2 with bilateral, 1 with unilateral tumor), probability of five year overall survival for the whole cohort was
93% (0.930±0.040); 94.5% (0.945±0.038) for Group E and
80% (0.800±0.179) for Group D.
Conclusions: The IIRB is essential in making decision about
enucleation however, TNM Classification plays a pivotal role
in deciding on post-enucleation treatment for RB patients to
avoid over treatment.
PO-045 Are Bone Marrow Examination and
Lumbar Puncture Necessary in the Initial
Evaluation of Retinoblastoma?
K.T. D1 , M.Y. Chan1 , S.Y. Soh1 , A.M. Tan1 , C.M.J. Lam1 , B.L.
Quah1
1 KK
Women's and Children's hospital, Paediatric Haematology and
Oncology, Singapore, Singapore
Background/Objectives: Retinoblastoma is the commonest primary intraocular malignancy of childhood. Bone marrow examination and lumbar puncture for cerebrospinal
fluid (CSF) cytology are done together with EUA as initial
S457 of S518
metastatic work up for all patients with retinoblastoma in our
institution. However, this is not routinely practiced in some
centres.
This retrospective study aims to determine the prevalence of
metastasis at diagnosis and to evaluate the value of these
investigations in patients with retinoblastoma treated in KK
Women's and Children's Hospital, Singapore (KKH).
Design/Methods: The study was approved by Singhealth
Centralized Institutional Review Board. Retrospective analysis of patients with retinoblastoma from May 1997 to March
2017 was performed.
Results: Seventy-eight patients were included; 38 (48.7%)
boys, 40 (51.3%) girls. Forty-five (57.7%) had unilateral disease, 32 (41%) bilateral disease and 1 (1.3%) trilateral disease.
Median age at presentation was 25 months (range 1 to 107
months) for unilateral disease and 13 months (range 3 to 24
months) for bilateral disease. Two (2.6%) patients had positive family history. Four (5.1%) patients had metastatic disease at presentation to KKH. One had CSF (Cut optic nerve
showed involvement) and one had bone marrow involvement
(Blood count was abnormal) at diagnosis. One had initial
treatment overseas and presented to KKH with metastatic
relapse in bone marrow, CSF, liver and bone. The 4th patient
had suprasellar extension on MRI but no CSF positivity. Costs
for bone marrow and lumbar puncture tests were SGD 2500
to 3000 (USD 1785 to 2142).
Conclusions: The prevalence of metastasis at diagnosis is
very low at our institution. The patients with metastasis can
be picked up by other means like clinical examination, blood
counts, MRI and histology of optic nerve involvement. It is
not necessary to investigate all patients with retinoblastoma,
thus saving substantial financial and time costs for our patients
and institution.
PO-046 Clinicoradiologic Features of
Retinoblastoma at National Institute of Child
Health Karachi, Pakistan
U. Imam1 , F. Ali1
1 Child
Aid Association-national Institute Of Child Health, Pediatric
Oncology, Karachi, Pakistan
Background/Objectives: Retinoblastoma is a primary intra
ocular neoplasm of childhood which is presented at a very
young age with leukocoria. This study aims to determine the
clinico radiological features of retinoblastoma over a period
of nine years from 2007 to 2015 using existing hospital record
sheets.
Design/Methods: A record of 176 children with retinoblastoma derived from hospital sheets treated at Pediatric Oncology department of National Institute of Child Health, Karachi
SIOP ABSTRACTS
S458 of S518
from January 2007 to December 2015 using specially
designed Performa after informed consent from parents.
parts such as patient related delayed diagnosis, delayed diagnosis due to the doctor and delayed treatment.
Results: Out of 176 patients with Retinoblastoma, 99 (56%)
were male and 77 (44%) were females, age range was 2- 120
months, average (mean ± S.D.) age was 42 ± 21.1 months.
50% clinically presented with orbital proptosis. 69.8% of children were referred from outside Karachi. Bilateral disease was
significantly high in children below 2 years of age (31.6%) as
compared to children above 2 years (11.5%) P< 0.05. Family history of Retinoblastoma was negative in all children
with bilateral tumors. There was a mean time lag of 11.8
months between appearance of first symptom and consultation with the Oncologist. 24.4% patients were referred with
tumor recurrence after primary enucleation and its frequency
was high in children above 5 years of age [10 (52.6%) out
of 19 children] as compared to patients below 5 years [33
(21.0%) out of 157 children] (p<0.01).56 patients (32 %) had
metastatic disease and CNS involvement was noticed in 39
patients.
Results: The age of diagnosis 21day-5 years, with median
11mos. Common finding was leucocoria in 59% & strabismus in 32% of patients. Family related delay of diagnosis
was 2-450 days. median 9 days, doctor related 0 -416 days,
median 5,5 days. The total diagnosis delay range 3-640 days
median of 42.5days. The eyes were Group E 44%, Group
D 16.5%,19% Group C, 13% Group B 7,5%Group A. 64%
of patients underwent enucleation in group E & the delay
in diagnosis was longer than the other groups. In the families with low SES patient-related diagnosis delay was higher
than patient-related diagnosis delay in families with high SES
Familial RB retinoblastoma patients were diagnosed at an earlier stage,3%,71%,23% and 3% of the patients were diagnosed
by first,second, third, fourth ophthalmologist, respectively.
Conclusions: High frequency of advanced stage disease suggests late referrals to the treatment facility and a significant
percentage of children were registered with tumor recurrence,
these findings reflect lack of multidisciplinary approach in
patient management. Therefore, integrated efforts are needed
to create awareness among masses and healthcare personnel
for early referrals and uniformity in patient evaluation and
management.
PO-047 Effective Parameters at Diagnosis and
Relation of Clinical Stage of the Disease in Children
with Retinoblastoma
E. Unal Cabi1 , D. Kavlak Akar1 , N. Tacyildiz1 , H. Dincaslan1 , K.
Gunduz2 , G. Yavuz1
1 Ankara
Üniversity Faculty of Medicine, Pediatric Hematology-Oncology,
Ankara, Turkey; 2 Ankara Üniversity Faculty of Medicine, Ophthalmology,
Ankara, Turkey
Background/Objectives: RB cases are diagnosed in
advanced intraocular stages and with orbital /metastatic
disease in Turkey.We aimed to determine the duration of
diagnosis & the parameters that affect this period, with the
relation to clinical stage.
Design/Methods: We enrolled 100 RB patients. The data
obtained through a survey of the families. Patients’ files were
reviewed for the clinical stage, exact date of diagnosis, starting date of treatment, which can not be obtained from the family. In the questionnaire addressed to the parents; the parameters that could be effective during the clinical diagnosis &
stage were questioned. The duration between detection of first
symptom and diagnosis were evaluated with dividing into
Conclusions: In our study, the delay time of RB diagnosis
was shorter than some studies. However, more than half of
our patients were diagnosed at advanced intraocular stages.
We think that the most important and effective parameters in
delayed diagnosis are insufficient awareness of families and
especially healthcare workers.
S O LID NO N BRAIN TUM O URS LIVER TUMOURS
PO-048 Localized Focal Nodular Hyperplasia of
Liver in Children, 9 Cases, 5 Years Experiences
W. han1
1 Beijing
Children's Hospital, Department of Surgical Oncology, Bei Jing,
China
Background/Objectives: To evaluate the clinical diagnosis
and treatment of focal nodular hyperplasia(FNH) in children
of liver.
Design/Methods: 9 cases of focal nodular hyperplasia of liver
confirmed by operation and pathology in our hospital from
2006 to 2012 were investigated retrospectively.
Results: The age of onset ranged from 1-11 years old. Primary clinical manifestation: 3 cases for fever, 1 case for vomiting, 1 case for abnormal liver function, 1 case for abdominal distension, 2 cases for abdominal pain, 1 case for intussusception, 1 case for tumor family history (lung cancer). All
lesions were found by imaging.3 cases of alpha-fetoprotein
(AFP) measuring mildly elevated, 6 cases were normal, 1 case
of �-HCG increased, 8 cases were normal. Hepatitis B virus
infection of 1 patient was positive. Pathological performance
of 9 cases were typical, all patients underwent gross surgical
resection, no complications and death postoperatively as well
SIOP ABSTRACTS
as perioperatively. AFP decreased to normal after surgery in
3 cases, the other two cases were not investigated. Liver function abnormality ameliorated after surgery. 5-10 year followup, all patients survived with event free.
Conclusions: The genetic predisposition of FNH is not obvious. The disease can lead to abnormal liver function and
AFP. The misdiagnosis is common although not fatal. Surgical resection is important for treatment also for ruling out
the other malignancy of liver.
PO-049 Living-Related Transplantation of a
Liver in Children with Hepatoblastoma
A. Ijovskyi1 , O. Kotenko2 , G. Klymnyuk3 , O. Belokon4 , M.
Grigorian2 , M. Stezhka3 , A. Popov2 , A. Gusev2 , A. Grinenko2 , D.
Fedorov2 , A. Korshak2
1 National
Cancer Institute MPH of Ukraine, Pediatric Oncology, Kiev,
Ukraine; 2 National Institute of Surgery and Transplantology named after
O.O. Shalymov, Liver Transplantation, Kiev, Ukraine; 3 National Cancer
Institute, Department of Pediatric Oncology, Kiev, Ukraine; 4 National
Cancer Institute, Pediatric Oncology, Kiev, Ukraine
Background/Objectives: Malignant liver tumors make 1 –
2% of a number of all tumors of the child age, with yearly
incidence of 1,5 cases per million of children aged up to 15
years.
Design/Methods: At the posthoc analysis as of from 2008 to
2014 in Ukraine at the stage of surgical treatment of hepatoblastomas in children 7 living-related transplantations of a
liver were performed, among them: orthotopic transplantation
of the lateral section of a liver from the live relative donor
(mother) was executed to five patients at the stage of surgical
treatment, to one patient - hepatectomy, total pancreatectomy,
gastroduodenectomy, splenectomy, extended lymphadenectomy, esophagojejunostomy, mesocaval shunting, orthotopic
transplantation of the left lateral section of the liver from the
live relative donor (mother) with cava portal transposition,
and the transplantation concerning recurrence of hepatoblastoma after left-sided expanded hepatectomy was executed to
one patient.
Average age of children to whom the living-related transplantation of a liver was carried out made 2,7 years. Chemotherapy
according to the clinical protocol SIOPEL 3 was carried out
to all patients, group of high risk.
Results: The average time of the execution of the operation
made 14,5 hours. In the postoperative period biloma of the
resective surface of the graft developed in 1 patient, it was
removed by way of ultrasound-controlled puncture. Complete
remission of the disease was recorded in all 7 patients to
whom living-related transplantation of the liver was executed.
The five-year survival rate of patients with hepatoblastoma to
whom transplantation of the liver was executed makes 100%,
the five-year survival of the graft made 100%.
S459 of S518
Conclusions: Executing the living-related transplantation of
a liver in children with hepatoblastoma of a liver is a difficult stage of multimodality therapy demanding considerable
material and technical support and it allows to achieve good
remote results statistically authentically.
S O LID NO N BRAIN TUM O URS GERM CELL TUMOURS
PO-050 CCHE Experience in High Risk
Malignant Extracranial Pediatric Germ Cell
Tumors
O. Arafah1,2 , S. Ahmad1,2 , G. Taha3 , N. elkinaai5 , M. Elwakeel6 , W.
Rashed7 , M. essam8 , D. Elgalaly8
1 National
Cancer Institute. Cairo University, Pediatric Oncology, Cairo,
Egypt; 2 57357 Hospital. Cairo, Pediatric Oncology, Cairo, Egypt; 3 57357
Hospital. Cairo, Pediatric Oncology, Cairo, Egypt; 4 57357 Hospital. Cairo,
Surgical Oncology, Cairo, Egypt; 5 57357 Hospital. Cairo, Pathology,
Cairo, Egypt; 6 57357 Hospital. Cairo, Radiodiagnosis, Cairo, Egypt;
7 57357 Hospital. Cairo, Clinical Trial Unit, Cairo, Egypt; 8 57357 Hospital.
Cairo, Clinical Research, Cairo, Egypt
Background/Objectives: Suboptimal outcomes remain for
several groups of patients with malignant extracranial germ
cell tumors (MGCTs), including patients with extragonadal
tumors, advanced and metastatic diseases. Future studies
should be directed toward intensifying therapy for those poor
risk groups with long term follow up for late effects.
Design/Methods: High risk patients with MGCTs treated at
CCHE were retrospectively analysed for epidemiological and
survival outcomes. They were treated according to the protocol adopted from AGCT01P1 for high risk from July 2007 till
end of December 2015. All patients were followed up until
June 2016.
Results: 75 out of 122 eligible patients with MGCTs were
high risk. Mean age was 4.8 years with male to female ratio
1:4. Extragonadal tumors were 56 cases (42 females and 14
males), versus 19 ovarian cases. Sacrococcygeal sites predominates in females while mediastinal followed by sacrococcygeal sites predominates in males. Main histological types in
extragonadal cases were Yolk sac tumor followed by Mixed
GCT and Germinoma. Main histological types in ovarian
cases were Dysgerminoma followed by Yolk sac tumor and
Mixed GCT. In Extragonadal sites, Five years OS were 77.8
% and 62.8 % for stage III and IV respectively while Five years
EFS were 74.3 % and 67.8 % for stage III and IV respectively.
In ovarian cases, Five years OS and EFS were 100% for stage
III and 33.3% for stage IV. No significant P value in five years
OS and EFS between those below 11 years of age and above.
Conclusions: Poor outcome for high risk (MGCTs)
necessitates more intensified therapy especially for
SIOP ABSTRACTS
S460 of S518
metastatic tumors. Improved risk stratification systems,
novel approaches and more efficient salvage protocols are
needed to improve the outcome of those poor risk patients.
PO-051 Primary Retroperitoneal/Abdominal
Germ Cell Tumour in Children: Challenges in
Management
B. kumar1 , V.D. upadhyaya1 , S. kumar2 , R.N. rao3
1 Sanjay
Gandhi Post Graduate Institute of Medical Sciences, Paediatric
Surgical Superspeciality, Lucknow, India; 2 Sanjay Gandhi Post Graduate
Institute of Medical Sciences, Radiodiagnosis, Lucknow, India; 3 Sanjay
Gandhi Post Graduate Institute of Medical Sciences, Pathology, Lucknow,
India
Background/Objectives: Primary extra-gonadal germ cell
tumours are rare and account for only 1 – 4% of all germ cell
tumours. Prognosis is usually excellent after complete excision but peri-operative management is a distinct challenge.
Aim of this study is to present peri-operative problems and
morbidity associated with management of these tumours.
Design/Methods: We retrospectively evaluated the patients
having non-renal retroperitoneal/abdominal masses from July,
2012 to July, 2016 at our centre from hospital records with
diagnosis of germ cell tumour. Details of patients were
reviewed including demography, clinical presentations, investigations, peri-operative problems, pathology, management,
final outcome and follow-up.
Results: From July, 2012 to July, 2016, 11 patients with
retroperitoneal/abdominal germ cell tumour were managed.
Diagnoses were yolk sac tumour (YST) in 3 patients and teratoma in 8 patients. 4 patients were female and age ranged
from 2.5 months to 6 years (median age 14 months). 2
patients had respiratory problems while 3 had sub acute bowel
obstructions at the time of presentation. Patients with YSTs
and 2 patients with immature teratoma received chemotherapy. Almost complete excision performed in all patients. Perioperative problems include excessive bleeding (2), excision of
part of adjacent organ (2), hypothermia and respiratory problems and chemo related toxicity (1). Adhesive bowel obstructions occurred in 5 patients with in 3 month of post surgery in
which 4 required re-explorations and adhesiolysis. 2 patients
were died while 2 were lost in follow-up. Rest patients are
under follow-up without recurrence. Follow-up period ranged
from 6 – 45 months.
Conclusions: The management of retroperitoneal/abdominal
germ cell tumour (GCT) is challenge. Various surgical difficulties and morbidity associated with resection of these
tumours depends on clinical presentation, size and site of
tumour and age of patient.
R.E. Senay1 , O. Dogru1 , A.G. Tokuc1 , N. Eker1 , B. Yilmaz1 , B.
Berk1
1 Marmara
Background/Objectives: Germ cell tumors (GCT) account
for 2-3% of childhood tumors. It is most commonly seen
under 3 years and over 12 years old. GCTs are most commonly localized in the gonads. We have examined our
patients who diagnosed and treated with GCT at our center
retrospectively.
Design/Methods: Sixty two children and adolescence who
were diagnosed and treated with GCT at our center between
1996 and 2016 analyzed retrospectively.
Results: The patients age ranged between 5 days to 17 years.
Thirty-five of patients were girls (57%) and 27 were boys
(43%). The most common tumor localization with 29(47%)
patients was gonads. Sixteen patients (25,8%) had metastatic
disease at presentation. The most common histologic subtype was mature teratoma with 14 (22%) patients and 14
patients (22%) with yolk sac tumor. Alpha-fetoprotein (AFP)
was elevated in 29 (46%) of cases whereas beta-human
chorionic gonadotropin (�-hCG) was elevated in only 4
(4%) of cases. Twenty-two cases (35%) were treated with
total surgical resection and they didn't receive chemotherapy. Six patients (10%) received radiotherapy in addition
to surgery and chemotherapy. Thirty-three patients (53,3 %)
received BEP (bleomycin, etoposide, cisplatin) as a first line
chemotherapy. During the follow up 6 (10 %) patients had
relapsed. Five years overall survival rate of our patients was
95%, retrospectively.
Conclusions: Germ cell tumors have favorable outcome in
children. These tumors can be cured with surgical resection
followed by cisplatin-based chemotherapy and radiotherapy
for selected patients. As a result of our own data analysis, it
has been found that our survival rates are similar to current
literature data.
S O LID NO N BRAIN TUM O URS RARE TUMOURS
PO-053 Intracranial Inflammatory
Myofibroblastic Tumor: Efficacy of Crizotinib
F. Chambon1 , S. Bohrer1 , J.L. Michel2 , A. Chamouine3 , M.
Jehanne1 , Y. Reguerre1
1 CHU
PO-052 Twenty Years’ Experience in the
Management of Childhood Germ Cell Tumors
University Medical Faculty, Paediatric Oncology, Istanbul,
Turkey
Félix Guyon, Pediatric Hematology-Oncology, Saint Denis De La
Reunion, Reunion; 2 Chu Félix Guyon, Pediatric Surgery, Saint Denis De La
Reunion, Reunion; 3 CH Mayotte, Pediatric Department, Mamoudzou,
Mayotte
SIOP ABSTRACTS
Background/Objectives: Inflammatory myofibroblastic
tumors (IMT) are rare tumors in children and young adults,
considered to be intermediate malignancies and rarely
metastasizing. About 50% of IMT present an anaplastic
lymphoma kinase (ALK) rearrangement. We report the case
of a 15-year-old girl, who developed a lung tumor and brain
metastasis with a limited ALK amplification, who was treated
with crizotinib.
Design/Methods: In December 2015, the patient arrived in
Mayotte hospital for cough and hemoptysis for one year. She
also had 2 seizures after her arrival. Radiological thoracic
explorations showed a 9cm tumor in the left inferior lobe and
brain MRI showed five gadolinium-enhancing brain lesions,
especially one of 6.5cm in the frontal lobe. Microscopic partial brain tumor resection was performed. The pulmonary
tumor was completely removed by lobectomy. Both pathological exams showed an IMT negative for ROS1 but overexpressing ALK with a rearranged form in 12 to 15% of cells.
Steroids (2mg/kg) alone during 2 weeks and then chemotherapy (Methotrexate/Vinblastine) were introduced but did not
improve neurological lesions. Crizotinib was initiated as compassionate at a dose of 250mg twice daily.
Results: Crizotinib is a chemical inhibitor of ALK and
mesenchymal-epithelial transition, but it also inhibits ROS1rearranged tyrosine kinase receptors. It has been shown to
be effective in non–small-cell lung carcinoma and has also
been tested successfully in other ALK-driven tumors, notably
large-cell anaplastic lymphoma and certain paediatric cancers. Previous reports suggested that crizotinib cannot cross
the blood-brain barrier and may be unable to control CNS
IMT. In this case, complete remission on brain metastasis was
achieved after 6 weeks of crizotinib despite multiple brain
localizations and low ALK positive tumor cells rate. No recurrence of thoracic nor brain lesion was observed after a year.
Conclusions: This case suggests that ALK-targeted therapy
by crizotinib may strengthen current strategies against IMTs,
even in CNS tumors.
PO-054 Treatment of Kaposiform
Hemangioendothelioma with Kasabach-Merritt
Phenomenon by Corticosteroids and Vincristine:
Experience of the Children's Hospital 1, Ho Chi
Minh, Vietnam
T. Nguyen1 , A. Phan1
1 Children's
Hospital 1, Hematology-Oncology, Ho Chi Minh, Vietnam
Background/Objectives: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with over 70%
of cases associated with Kasabach-Merritt phenomenon
(KMP), a life-threatening constellation of thrombocytopenia,
S461 of S518
coagulopathy and purpura. We reported the results of corticosteroids and vincristine in the management of KHE with
KMP.
Design/Methods: We retrospectively analyzed the medical
records of patients with KHE and KMP who were treated with
corticosteroids and vincristine at Children's Hospital 1, Ho
Chi Minh, Vietnam from January 2013 to December 2015.
Results: Six cases, median age 3 months (1-16 months)
with a male:female ratio of 1:1 were treated by corticosteroids and vincristine. All patients had large KHE developing from the lumbar region (33.3%), extremities (33.3%),
face (16.7%) and retroperitoneum (16.7%). Clinical manifestation included anemia and purpura (100%), gastrointestinal
bleeding (16.7%), infection and ulceration at the hemangioendothelioma (16.7%) and acute respiratory distress due to the
presence of tumoral compression (33.3%). At diagnosis, the
median platelet count and fibrinogen levels was 10.5x109 /L
(4-17x109 /L) and 0.8 g/L (0.6-0.9 g/L) respectively. The duration of corticosteroid therapy was 23±6 weeks. Vincristine
was given intravenously at 0.05 mg/kg per dose weekly for
four times, followed by monthly for six times. Only one out
of 6 patients with partial response had to use vincristine for
9 months. The rates of complete, partial and no response
were 50% (3/6 cases), 33.3% (2/6 cases) and 16.7% (1/6
cases) respectively with a median follow-up of 15 months.
The platelet counts normalized after 3.6 ±1.2 weeks. Fibrinogen levels returned to normal after 3.3±0.8 weeks. Reduction in size of the tumor by 50% was achieved after 4.2±0.5
weeks, and by 80% after 27.2±8.9 weeks. The recurrence rate
of KMP was 33.3% (2/6 cases). Vincristine had mild and transient side effects compared to corticosteroids.
Conclusions: First-line therapy with corticosteroids and vincristine is one of the options for unresectable KHE with KMP.
S O LID NO N BRAIN TUM O URS H I ST I O C Y TOS I S
PO-055 A Case of Juvenile Xanthogranuloma
Involving Bone Marrow During Treatment of A
Pre-B Acute Lymphoblatic Leukemia
J.E. Park1 , O.K. Noh2
1 Ajou
University School of Medicine, Pediatrics, Suwon, Republic of Korea;
University School of Medicine, Radiation Onvology, Suwon, Republic
of Korea
2 Ajou
Background/Objectives: Juvenile xanthogranuloma (JXG)
is a rare benign disorder which is one of the diseases classified as non-Langerhans cell histiocytosis, whose etiology and
pathogenesis is still unclear. JXG is generally characterized by
solitary or multiple cutaneous nodules which resolve sponta-
SIOP ABSTRACTS
S462 of S518
neously over a few years. However, it is uncommonly possible
to present extra-cutaneous disorder and progress symptomatic
systemic disorder through involving multiple organs.
Design/Methods: We review the chart a case of systemic JXG
involving bone marrow, multiple bone and skin during treatment of acute lymphoblastic leukemia.
Results: The adolescent patient suffered unexplained prolonged fever, scalp pain, hip joint pain, and right knee joint
pain for 2 weeks during treatment in the course of interim
maintenance chemotherapy. According to the pathologic findings of bone marrow, there is no evidence of leukemia relapse
but finding diffuse infiltration of histiocytes with several
Touton-type giant cells; positive for CD68, negative for CD1a,
S-100 protein. Bone and skin biopsies confirmed the same
findings. Symptoms have been resolved since maintenance
chemotherapy which included vincristine, dexamethasone, 6mercaptopurine and methotrexate. Bone marrow involvement
of JXG is very rare and has been reported to occur only less
than 1 year of age, but this case is reported in 16-years-old
boy during acute lymphoblastic leukemia treatment.
Conclusions: We experienced a systemic JXG involving bone
marrow, multiple bone and skin during treatment of acute
lymphoblastic leukemia.
BRAIN TUMOURS
Results: Fourteen infants were identified. Males were 57%.
Median age at diagnosis was 6 months (range 0-10). Most
were supratentorial and without dissemination (93% in both
cases). No CSF was positive. Astrocytic tumors represented
the largest group of tumors (50%), most of them were low
grade glioma (71%). Embryonal, neural, choroid plexus and
melanocytic tumors were 22%, 14%, 7% and 7% respectively. No ependymal tumor was reported. Therapies included
surgery 93% (partial resection 43%, biopsy 29%, and complete
resection 21%), chemotherapy 43% and high-dose chemotherapy (HDCH) 7%. No radiation therapy was administered in
any case. Survival was 57% with a median follow up of 30
months. Among the survivors, the most frequent sequelae
were neurological (75%) and ophthalmological (62.5%). Only
in one case there was no sequel.
Conclusions: In our review, survival in infants diagnosed
with CNS tumors in the first year of life was 57%, and significant sequelae were observed. Localized supratentorial masses
without dissemination was the most common presentation but
neurosurgical procedures achieved complete resection in only
21%. Radiotherapy was avoided. Management of CNS tumors
at this age is more complicated. The role of HDCH remains
to be defined.
PO-057 Diffuse Leptomeningeal Glioneuronal
Tumour: A Case Report
S. Guram1 , J. Suththanantha1 , B. Messahel1 , K. Allinson2
PO-056 Tumors of the Central Nervous System in
the First Year of Life. One Single Institution
Experience
M. Garcia-Ariza1 , A. Echebarria Barona1 , R. Lopez-Almaraz1 , R.
Adan Pedroso1 , N. Bilbao Salcines1 , A. Ricondo De Diego1 , I.
Ojinaga Niño1 , L. Galbarriatu Gutierrez2 , E. Ruiz de Gopegui
Ruiz2 , O. Aurtenetxe Saez3 , I. Martin Guerrero3 , L. Zaldumbide
Dueñas4 , A. Navajas1 , I. Astigarraga Aguirre1
1 Hospital
Universitario Cruces, Pediatric Hematology and Oncology Unit,
Cruces- Bilbao, Spain; 2 Hospital Universitario Cruces, Neurosurgery Unit,
Cruces- Bilbao, Spain; 3 Hospital Universitario Cruces, Biocruces Health
Research Institute, Cruces- Bilbao, Spain; 4 Hospital Universitario Cruces,
Pathological Anatomy Unit, Cruces- Bilbao, Spain
Background/Objectives: Central nervous system (CNS)
tumors in the first year of life are a very specific pediatric
brain tumor group, with difficulties in the diagnosis and treatment. They associate a worse prognosis and more sequelae compared to older children. We reviewed our series and
experience.
Design/Methods: A retrospective study of infants under one
year of life diagnosed with CNS tumors from 2001 to 2016.
Clinical, histological, treatment and sequelae data were collected.
1 Addenbrookes
Hospital, Department of Paediatric Oncology, Cambridge,
United Kingdom; 2 Addenbrookes Hospital, Department of Pathology,
Cambridge, United Kingdom
Background/Objectives: Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a rare brain tumor with a distinct
molecular profile and aggressive biological behavior. These
lesions often present with insidious onset and can progress
rapidly leading to death with a median survival reported as
22 months. The natural history of this rare entity is not fully
understood.
Design/Methods: We describe a rare case of DL-GNT diagnosed on post mortem. A 23 month old boy presented with
weight loss and vomiting. A MRI of the head and spine
demonstrated extensive leptomeningeal spread in the spinal
and intracranial compartments, suggestive of a neoplastic
process. A leptomeningeal biopsy revealed a low grade primary glial lesion. There were no operative options and he
was therefore commenced on treatment on the SIOP LGG2
Study. However he demonstrated progressive disease in spite
of chemotherapy both radiologically and clinically with loss
of speech and seizures. He later developed hydrocephalus and
a ventriculo-peritoneal shunt was inserted. He deteriorated
and passed away at the age of 4 years.
SIOP ABSTRACTS
S463 of S518
Results: The macroscopic, histological and molecular findings were characteristic of diffuse leptomeningeal gioneuronal tumour.
0%. Median dead time was 9.5mos (2 weeks-2yrs). One year,
18mos, and two years overall survival rates were 52%, 39%
and 13% respectively.
Immunohistochemically, the tumour cells expressed S100 and
synaptophysin. They were negative for CD34, NeuN, GFAP
and mutant IDH-1. The MIB-1 proliferation index was less
than 1%. Interphase fluorescent in situ hybridisation (iFISH)
showed a concurrent BRAF-KIAA1549 gene fusion and loss
of 1p36.
Conclusions: Diffuse pons glioma is a group of tumor in
which the helplessness experienced in treatment. Despite
radiotherapy and chemotherapy, patients are still dying. The
progression free and overall survival rates of patients were
similar to literature. But we need new therapy agents which
will improve the progression free survival rates.
Conclusions: This case demonstrates the need for biological
markers to be integrated with clinic-pathological markers in
order for both diagnostic and prognostic risk stratification.
PO-059 Into Cancer-Free World with the Use of
Mitotic Crossing Over Inhibitors
P. Ivanovski1 , L. Garavelli2 , I. Ivanovski2 , A. Ivanovski3
PO-058 Retrospective Analysis of Our Patients
with Pons Glioma
D. İNCE1 , D. Kizmazoglu1 , M. Erdem1 , A. Demiral2 , R. Cetingoz2 ,
H. Guleryuz3 , K. Mutafoglu1 , and N. Olgun1
1 Dokuz
Eylul University Institute of Oncology, Dept. of Pediatric Oncology,
Izmir, Turkey; 2 Dokuz Eylul University Faculty of Medicine, Dept. of
Radiation Oncology, Izmir, Turkey; 3 Dokuz Eylul University Faculty of
Medicine, Dept. of Radiodiagnostics, Izmir, Turkey
Background/Objectives: To evaluate characteristics and
treatment responses of with diffuse pons glioma in our center
Design/Methods: Medical files of patients with malignant
CNS tumors between 1987-2017 were analyzed retrospectively. There were 23 patients with pons glioma. Three of them
went to another center, one of them diagnosed as demyelinizan disease and other one as encephelatic lesion laterly. These
5 patients excluded and 18 patients found evaluable.
Results: The median age at diagnosis was 7 yrs (2.618yrs), M/F:1.25. Age distrubution: <5 yrs 4 patients, 510 yrs 8 patients, 10-18 yrs 6 patients. The most frequent
complaints: cranial nerve paralysis (61%), visial impairment
(56%), headache (44%), power loss (44%) and speech disorder
(%33).
Surgery was performed to extrinsic component of mass in 3
patients. Sixteen patients received radiotherapy. Two patients
died before RT, on 2th week and sixth month. RT total doses
varied between 50-60 Gy. Thirteen patients were received
chemotherapy, four patients died before chemo, an one patient
is still receiving RT. Chemotherapy protocoles were changed
over the years: MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (Nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and
bevacizumab in one patient. Median progression free survival
rate was 6mos (2weeks -18mos). Progression free survival
rate for 6mos was 82%, for one year was 22%, for 18mos was
1 Children's
University Hospital, General Pediatrics, Belgrade, Serbia;
Santa Maria Nuova-IRCCS- Reggio Emilia- Italy., Clinical
Genetics Unit- Department of Obstetrics and Pediatrics-, Reggio Emilia,
Italy; 3 University of Belgrade, Chemical Faculty, Belgrade, Serbia
2 Arcispedale
Background/Objectives: Achivment of new SIOP mission:
No Child Shoud Contract Cancer.
Design/Methods: A comprehensive reading of papers on cancer epidemiology and pathogenesis, and creating an own theory for cancer prevention.
Results: There are no literature data about neoplasms which
originate from terminally differentiated cells (TDCs) such as
Purkinje neurons, Betz neurons, and alpha motoneurons. This
indicates that carcinogenesis cannot occur in cells not having mitotic potential, and consequently there is no mitotic
crossing over (MCO) and no loss of heterozygosity (LOH),
a mechanism responsible for the disabling of tumor suppressor genes. All known cancers so far, have been derived from
cells possessing mitotic activity. Cancer is just a “privilege” of
these cells. Larger body cell burden, longer life, means more
mitoses, more MCO, more LOH and greater chances for cancer development.
Li–Fraumeni syndrome(LFS) is a rare, autosomal dominant, hereditary disorder that pre-disposes carriers to cancer development, because of germline heterozygous TP53
mutation. This mutation is present in all body cells, including TDCs. Classical and most frequent LFS malignancies are
sarcomas, cancers of the breast, brain (especially glioblastomas), adrenocortical carcinoma, leukemias and lymphomas.
Despite exaggerated predisposition for cancer development,
no cancer originating from TDCs has been seen in LFS persons, so far. In all malignant cells of all tumors in LFS,
homozygous TP53 mutation (LOH at TP53) is present, which
is generated by MCO events during mitoses of the cells.
Conclusions: Experiments on TP53+/− mice (an animal
LFS model) must be done, protecting the mice with MCO
inhibitors (rad51, rad52, rad53 inhibitors, commercially available). If these experiments result in cancer prevention, then
SIOP ABSTRACTS
S464 of S518
the scientists must search for MCO inhibitor which would be
orally supplemented to all humans during the life. Presently,
the drug of choice is Acidum Acetylsalicylicum. Before its
use as cancer chemoprevention, the molecule must be modified, to be eliminated its hemorrhagic side effects.
PO-060 Treatment Results of Who Grade III
Ependymomas at EGE University Hospital
A. Sahin1 , M. Kantar1 , H. Hekimci Ozdemir1 , K. Serra2 , S.
Aksoylar1 , N. Cetingul1 , Y. Anacak2 , T. Turhan3
1 Ege
University School of Medicine, Pediatrics- Pediatric Oncology
Division, Izmir, Turkey; 2 Ege University School of Medicine, Radiation
Oncology, Izmir, Turkey; 3 Ege University School of Medicine, Pediatric
Neurosurgery, Izmir, Turkey
Background/Objectives: Prognosis of grade III ependymoma changed over the years, and requires multi-institutional
approach. In this analysis we aimed to analyze demographic
features and treatment results of anaplastic ependymoma at
our institution.
Design/Methods: Thirteen patients aged mean 78 months
(30-192) were diagnosed to have WHO grade III ependymoma after surgery. There were 7 female, 6 male. Tumor location was infratentorial and spinal in 11 patients (85%) and
supratentorial in 2 patients.
Results: In treatment, 10 patients were amenable to grosstotal resection while, 3 underwent subtotal resection. Nine out
of 13 patients were given CS radiation therapy (54 Gy primary, 36 Gy spinal), three cranial radiation only, and one primary spinal irradiation.
As chemotherapy regimen, except two patients treated with
vincristine, procarbazine and prednisolone, other patients
were treated according to the POG posterior fossa study (cisplatinum plus etoposide for 3 cycles, cyclofosfamide plus vincristine for 8 cycles). Seven patients were also given intratecal
methotrexate weekly for leptomeningeal involvement.
Mean duration of follow-up is 114 months (5-312). During
this period three patients recurred and died of disease. In survival analysis, 5-year EFS rate is 70.5%, and OS rate is %70.5.
Conclusions: Grade III ependymomas are difficult group of
tumors. Surgery followed by radiation are the standard treatment type. In analysis, resection type or tumor site were not
significantly related with prognosis.
Turkey; 3 Gazi University School of Medicine, Pathology, Ankara, Turkey;
4 Gazi University School of Medicine, Radiation Oncology, Ankara, Turkey
Background/Objectives: To evaluate the clinical characteristics and long-term outcome of pediatric patients with
ependymoma.
Design/Methods: A total of 22 patients (13 boys and 9 girls)
with newly diagnosed ependymoma between 1993 and 2016
were retrospectively evaluated. An analysis of the demographic, histological and clinical data including the treatment modalities, follow-up and survival analyses were made.
Histopathological examination was evaluated according to
World Health Organization (WHO) classification and tumors
are classified as low-grade (WHO Grade I-II), and high-grade
(WHO Grade III) ependymomas.
Results: The median age at the time of diagnosis was 8.7
years. The median follow-up time was 17.5 months (range:
1-236 months). The most common site of ependymomas was
posterior fossa region (68.2%). Primary tumor localization
were spinal cord in 3 patients. There were thirteen and nine
patients with WHO Grade II and III histology, respectively.
Two patients had evidence of spinal metastatic disease at
diagnosis. Treatment consisted of surgery, radiotherapy, and
chemotherapy. Gross total resection and subtotal resection
were achieved in 11 (50.0%) and 10 (45.5%) cases, respectively. Radiotherapy was administered to 17 patients and 8
patients received also chemotherapy. The most frequently
used regimens were platinum-based. Three patients experienced tumor progression/relapse. Ten patients were alive
without disease. Ten year overall and event free survival rates
of all patients were %71 and %42, respectively. There were
no statistically significant differences in overall and evet-free
survivals of the patients when compared according to subgroups consisting of grade (II vs III), gross total and less than
gross total surgery, and with or without adjuvant chemotherapy (p>0.05).
Conclusions: Ependymomas are locally invasive tumors with
occasional spinal metastases. Despite multimodality treatment including surgery, radiotherapy and chemotherapy, the
event-free survival rates are not satisfactory. The role of the
chemotherapy for ependymomas needs to be defined in larger
series and clinical trials.
PO-062 Pediatric Intracranial Germ Cell
Tumors: A Single Institutional Experience
PO-061 Ependymomas in Children: A
Retrospective Analysis of 22 Cases
C. Karadeniz1 , A. Okur1 , F.G. Pinarli1 , A. Borcek2 , A. Poyraz3 , H.
Bora4
1 Gazi
2 Gazi
University School of Medicine, Pediatric Oncology, Ankara, Turkey;
University School of Medicine, Pediatric Neurosurgery, Ankara,
C. Khaiman1 , S.L. Laohasurayothin1 , K. Chiangthong1 , P.
Techavichit1 , D. Sosothikul1 , P. Seksarn1 , S. Shuangshoti2
1 King
Chulalongkorn Memorial Hospital, Division of Pediatric
Hematology and Oncology- Department of Pediatrics, Bangkok, Thailand;
2 Chulalongkorn University, Department of Pathology- Faculty of Medicine,
Bangkok, Thailand
SIOP ABSTRACTS
Background / Objectives: Background: Intracranial germ
cell tumors (IGCTs) are considered rare with highly curable
neoplasms. The incidence of IGCTs in Eastern Asia is high as
compared to western countries.
Objectives: To study clinical characteristics and outcomes of
children with IGCTs.
Design/Methods: A retrospective review in patients diagnosed with IGCTs at Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016.
Results: Eighteen patients were diagnosed with IGCTs (11
males and 7 females). Age ranged from 5 to 14 years
(median 10.5 years). Presenting symptoms were consisted of
hydrocephalus (9 patients), weakness (2 patients), diabetes
insipidus (2 patients), visual disturbances (3 patients) and
increase intracranial pressure (2 patients). Histopathological
diagnosis was germinoma in ten patients (55.6%), yolk sac
tumor in 2 patients (11.1%) and mixed germ cells in 5 patients
(27.8%).
Elevated markers were revealed in approximately 25% of
patients. Tumor sites were pineal gland (7 patients), suprasellar (5 patients) thalamic and cerebellar (1 patient each) while
the rests were multifocal. Four patients had leptomeningeal
involvement. Treatment included total removal in three, partial removal in four while the rest underwent biopsy. Adjuvant chemotherapy was given in all patients. Radiotherapy
was given in 16 patients and craniospinal radiation (CSI) was
given in leptomeningeal metastasis. With the median follow
up of 26 months, five patients experienced relapse, four of
them died of disease. Overall survival is 88.9% in germinomatous IGCT and 37% in non-germinomatous IGCTs.
Conclusions: Treatment outcomes of germinomatous IGCTs
are favourable while the outcomes of leptomeningeal metastasis and non-germinomatous IGCTs are poor. Innovation of
therapy should be developed to improve outcomes.
PO-063 Evaluation of Acute Toxicities and
Treatment Outcomes for Pediatric
Medulloblastoma Patients Treated with
Craniospinal Irradiation (CSI)
T. Mehmood1
1 Shaukat
Khanum Memorial Cancer Hospital and Research Centre,
Radiation Oncology, Lahore, Pakistan
Background/Objectives: We retrospectively report the acute
toxicities and outcomes of pediatric medulloblastoma patients
treated with CSI using cranial and spinal posterior-anterior
photon at our institution.
Design/Methods: From September 2011 to August 2013, 19
patients were treated. Standard-risk patients received 23.4
Gy (RBE) CSI and tumor bed boost to 54 Gy (RBE); high-
S465 of S518
risk (HR) 36Gy (RBE) and 55.8 Gy (RBE), respectively (2
with spine boosts of 5.4Gy (RBE) and 12.6 Gy (RBE)). All
patients received concurrent weekly vincristine. 3 HR patients
received additional daily carboplatin. Toxicities were documented according to CTCAEv4.
Results: Median age was 10.3 years (range 3.7-17.4). 11 were
female, 14 were standard-risk. At baseline, mean neuropsychological abilities across a broad range of performance based
measures and parent reported functioning were in the average range (Wechsler IQ Mean=101.86, SD=13.18, Range 76115). Most toxicities were grade 1-2 (G1-2). The only G3+
toxicities were: nausea/vomiting (G3, n=3), anorexia (G3,
n=9, max weight loss G2), decreased hemoglobin (G3, n=3),
leukopenia (G3, n=3; G4, n=1) and thrombocytopenia (G3,
n=1). The patient with G4 leukopenia also had G3 thrombocytopenia; she had high-risk medulloblastoma, treated with
spine boost, vincristine and carboplatin. G3+ bone marrow
toxicity occurred in 4/5 HR patients and all patients receiving carboplatin. Hepatic and renal toxicities were mild. Of 8
patients with available audiograms, at median 11.3 months
from end of RT (range 6.6-26.6), 5 had mild-moderate hearing loss, 3 had none. Of 8 patients for whom detailed postradiotherapy imaging was available, none had radiation necrosis. Follow-up data were available for 16 patients. At median
follow up of 13.8 months (range 3.8-24.5), 14 are alive without disease, 1 is alive with cerebellar and thecal sac recurrences, and 1 is alive with ventricular recurrence.
Conclusions: The CSI technique is safe and well-tolerated.
The observed GI, bone marrow, hepatic, and renal toxicities
depend on chemotherapy regimen.
PO-064 Clinical-Epidemiological Characteristics
of Central Nervous System Germ Cell Tumors in
Children and Adolescents at the Edgardo Rebagliati
Martins National Hospital During the Period
1998-2016
G.G. paredes1 , E. Guzman1
1 Rebagliati
Hospital, Oncology Pediatric, Lima, Peru
Background/Objectives: Brain germinal tumors are infrequents but good prognosis by multimodal treatment.
Design/Methods: Descriptive, retrospective study of brain
germinal tumor under 18 years.
Results: Population of 3,263 cases oncologics, 447 patients
with brain tumors where nine were brain germ cell tumors
during the last 18 years. Mean age 8.2 years, five boys and
four girls, male:female sex ratio 1:2. Race: indian 55.5%,
white 44.4%. Clinic: headache and vomiting 100%, diplopia
77.7%, polyuria 66.6%, ptosis and seizures 11.1%. Four
suprasellar region, three sellar region, one bifocal and one
SIOP ABSTRACTS
S466 of S518
infrasellar. Two-thirds had diabetes insipidus requiring vasopressin, 44.4% had hormone deficiencies requiring corticosteroids and thyroid hormone, one t presented low growth
hormone. At diagnosis, five patients underwent radical subtotal resection (55.5%), three patients underwent a biopsy
only and one patient underwent a gross total resection.
Histopathology: germinoma in seven patients (77.7%) and
non- germinomatous in two cases (both immature teratomas);
no patients demonstrated chromosomal deletions or translocations. Serum alpha-fetoprotein was elevated in one of
seven cases of germinomas and elevated HCG� in the two
cases of immature teratoma. The first case was an eight
years old boy diagnosed in 1998 who received radiotherapy
alone after surgery and relapse-death six months later. Since
1999, chemotherapy has been administered complementary
to surgery and radiotherapy with four courses of carboplatinetoposide, alternated with ifosfamide-etoposide. At the time
of this report, seven patients (77.7%) are alive and in remission of disease, with an overall survival of 730 months and a
median survival of 81.1 months
Conclusions: Germinal tumors of the CNS are uncommon
in Peru as opposed to germinal gonadal tumors. Brain germinal tumors are more frequent in boys, with the suprasellar
localization and the germinoma subtype being the most frequent. Chemotherapy complementary to surgery and radiotherapy demonstrates a good response and avoids the need for
a second surgery with high survival
administration there was a small homogenous enhancement
of the tumor with marked fragmentary enhancement of adjacent dura suggesting possible infiltration. No other intracranial abnormalities were noted.
Results: The bone tumor was resected totally with subsequent cranioplasty, no infiltration of the dura was observed.
In histological examination transitional meningioma (WHO
grade I) was diagnosed. In the series of following MRI examinations slowly growing subdural, extracerebral mass in the
same region was noted, One year after the iniltial surgery,
the patient was operated on again. Subdural meningioma
attached to the inner wall of the dura, was resected with
the subsequent duraplasty. Histological examination revealed
transitional meningioma (WHO grade I) identical as tumors
located within the bone. Two-years postoperative follow-up
was uneventful, with no tumor recurrence on MRI examinations.
Conclusions: Ectopic meningioma of childhood may present
as a separate tumor of the skull, without macroscopically visible crossing and destroying the dura. However it may be followed by a second, subdural extracereballar tumor of the same
histological pattern.
T R E AT M E N T A N D CA R E - SU RG E RY
(IPSO)
PO-065 Ectopic Meningioma of the Frontal Bone
in a 14-Years-Old Boy Followed by a Frontal
Subdural Meningioma - Case Report
PO-066 Sacrococcygeal Tumors in Patients with
and without Anorectal Malformations: A Single
Institution Comparative Study
K. Zakrzewski1 , E. Nowosławska1 , W. Grajkowska2 , P.P. Liberski3 ,
M. Zakrzewska3
C. Reck1 , A. Vilanova Sanchez1 , T. Maloof1 , L. Weaver1 , J.
Stanek2 , M.A. Levitt3 , R.J. Wood3 , J.H. Aldrink4
1 Polish
1 Nationwide
Mother's Memorial Hospital - Research Institute, Department of
Neurosuregry, Łódź, Poland; 2 The Children's Memorial Health Institute,
Department of Pathology, Warsaw, Poland; 3 Medical University of Łódź,
Department of Molecular Pathology and Neuropathology, Łódź, Poland
Background/Objectives: Intracranial meningiomas are relatively rare tumors in children accounting for less than 5%
of all primary brain tumors, part of them affecting patients
with genetically-dependent phakomatoses or children post
CNS irradiation. Ectopic meningiomas of the skull bone are
extremely rare entity in a pediatric population.
Design/Methods: We describe here the case of a 14-yearsold boy presented with a 6-months history of a slow-growing
solid mass of the right frontal bone. CT examination revealed
tumor, 60 x 80 mm in diameter, located within the right
frontal bone with destruction of its normal layers and visibly
marked spiculated periosteal reaction. MRI examination confirmed right frontal bone tumor, 72 x 70 x 19 mm in diameter,
slightly compressing adjacent brain structures. After contrast
Children's Hospital, Pediatric Surgery- Center for Colorectal
and Pelvic Reconstruction, Columbus, USA; 2 Nationwide Children's
Hospital, Biostatistics- Hematology/Oncology/Bone Marrow
Transplantation, Columbus, USA; 3 Nationwide Children's Hospital- The
Ohio State University College of Medicine, Pediatric Surgery- Center for
Colorectal and Pelvic Reconstruction, Columbus, USA; 4 Nationwide
Children's Hospital- The Ohio State University College of Medicine,
Pediatric Surgery, Columbus, USA
Background/Objectives: Despite variability at presentation,
sacrococcygeal tumors (SCT) in patients with and without
anorectal malformations (ARM) appear histologically similar. The purpose of this study was to identify differences in
oncologic outcomes between these two groups.
Design/Methods: A retrospective review was performed utilizing our institutional cancer database and colorectal/pelvic
reconstruction database for patients with sacrococcygeal or
presacral masses between 1990-2017. Data captured included
age at surgical resection, Altman classification, histopathology, recurrence, and follow-up.
SIOP ABSTRACTS
Results: Forty-five patients comprised our cohort, 12 had
ARM. Median age at resection was older with ARM (15
months; range 2 days to 17.7 years) than without ARM (<1
month; range 1 day to 6.9 years) (p=0.05). All patients with
ARM had Altman type 4 tumors, and histopathology included
mature teratoma (8), yolk sac tumor (1), lipoma (1), and
unknown (2). Altman classification for patients without ARM
included type 1 (9), type 2 (9), type 3 (1), type 4 (7), and
unknown (7). Histopathology for patients with SCT without
ARM included mature teratoma (20), immature teratoma (7),
malignant teratoma/germ cell tumor (4), ganglioneuroma (1),
and unknown (1). Altman classification was statistically different between the groups (p<0.0001). There were 7 recurrences, 3 with ARM (25%) at a median time of 3.6 years, and
4 without ARM (12%) at a median time of 1.8 years. Recurrences were not statistically different between the two groups
(p=0.36). Three of the recurrences were due to failure of coccyx resection (2 in the ARM group). 5 -year event free survival
was 64.3% (95% CI: 15.1% - 90.2%) in the ARM group and
86.9% (95% CI: 64.3% - 95.6%) in the no-ARM group.
Conclusions: Presacral masses in patients with ARM are
resected at a later age, are more likely to have higher Altman
classification, and have a high rate of recurrence without complete removal of coccyx at initial operation.
S467 of S518
of recurrence of the disease 26 and 21 months after surgery,
respectively. In one patient the conduit is patent at follow up
(37 months), while in 2 patients thrombosis of the conduit was
demonstrated at short term after surgery, at 30 and 45 days
respectively. In none of those patients signs of caval obstruction after thrombosis of the conduit were experienced. In all
patients the anastomosed renal veins were patent at last follow
up.
Conclusions: This is a small but interesting series, however
it's limited to pediatric patients and has a long follow-up.
Major vascular reconstructions are possible with experienced
surgeons tailoring reconstructive techniques to the anatomy
and extension of the lesions with low mobility and good longterm function.
PO-068 Systemic Response Evaluated by Curie
Score is not Correlated to the Complexity and
Outcome of Primary Tumor Resection in High-Risk
Neuroblastoma
T. Hishiki1 , Y. Kanamori2 , A. Fujino2 , T. Watanabe2 , K. Tahara2 ,
M. Ohno2 , T. Takezoe2 , C. Kiyotani3 , Y. Shioda3 , D. Tomizawa3 ,
M. Kato3 , K. Terashima3 , T. Osumi3 , O. Miyazaki4 , M. Kitamura4 ,
K. Matsumoto3
1 National
PO-067 Caval Replacement in Pediatric Surgical
Oncology: Evidences from 3 Cases
C. Grimaldi1 , A. Bertocchini1 , A. Crocoli1 , A. Castellano2 , A.
Serra2 , L. Monti3 , A. Inserra1
1 Bambino
Gesù Children's Hospital - IRCCS, Surgery, Rome, Italy;
2 Bambino Gesù Children's Hospital - IRCCS, Oncohematology, Rome,
Italy; 3 Bambino Gesù Children's Hospital - IRCCS, Radiology, Rome, Italy
Background/Objectives: Caval encasement from retroperitoneal tumors is a rare complication in pediatric malignancies. Data about extensive tumor resections with simultaneous caval replacement in adults are scant. Furthermore, only
few reports exist on in the pediatric population. In adults,
indications to this challenging surgery are mainly oncological (absent or inadequate response to chemotherapy) or clinical (treatment of symptoms of caval obstruction: renal failure,
lower limb edema). In children, this procedure is still considered a salvage treatment without clearly extablished indications.
Center for Child Health and Development, Surgical Oncology,
Tokyo, Japan; 2 National Center for Child Health and Development,
Pediatric Surgery, Tokyo, Japan; 3 National Center for Child Health and
Development, Children's Cancer Center, Tokyo, Japan; 4 National Center
for Child Health and Development, Radiology, Tokyo, Japan
Background/Objectives: The role of surgical resection in the
treatment of high-risk neuroblastoma has been a matter of
debate. Some postulated the advantage of aggressive surgery,
indicating that complete tumor resection leads to a better prognosis. However, this is questioned with the speculation that
tumors responding better to chemotherapy are likely to be
removed easily compared to chemoresistant tumors. We conducted a retrospective review of our institutional experience
to eliminate the correlation between response to induction
chemotherapy and surgical resectability
Design/Methods: Data were retrospectively collected from
our Institution Cancer Data Base from January 2009 to February 2017.
Design/Methods: Medical records of 27 patients with
metastatic neuroblastoma who underwent definitive surgery
at our institute from 2002 to 2014 were reviewed. Systemic
response to induction chemotherapy was evaluated using the
Curie score (CS), a 123I-MIBG scintigraphy-based quantitative parameter for metastatic diseases. Surgical outcome of
cases with one or more CS at the end of induction chemotherapy were compared to those whose CS were eradicated.
Results: Three patients (2 adrenal neuroblastomas, 1 renal
cell carcinoma) underwent tumor resection and inferior vena
cava (IVC) replacement. One patient with neuroblastoma
underwent a auto transplantation of the kidney. One patient is
alive a disease free 37 months after surgery. Two patients died
Results: Twenty-three cases had tumors of abdominal origin
and four had mediastinal tumors. We used IDRF, which is a
measure to predict safe resection of low- and intermediaterisk neuroblastoma, to evaluate the predicted complexity of definitive surgery. Clearance of IDRF by induction
SIOP ABSTRACTS
S468 of S518
chemotherapy did not correlate to the clearance of CS. As a
result of surgery, >90% resection was obtained in 22 cases,
while five cases resulted in <90% resection. There were no
statistical correlation between CS and extent of resection. The
presence of CS was a significant predictor of lower overall survival, whereas the extent of surgery did not affect the overall
and event-free survival.
Conclusions: A series of surgery related complications and
mortality in children treated for neuroblastoma and Wilms
tumors since the start of centralized pediatric oncological care
in The Netherlands is analyzed. Peroperative complication
rate for neuroblastoma has clearly improved since the start of
centralized care. Percentage of surgery related adverse events
for Wilms tumors is similar.
Conclusions: Our study suggests that a good response to
induction chemotherapy evaluated by Curie score does not
guarantee an easier, complete resection of the primary tumor.
There are tumors that are easy to remove in poor responders,
and vice versa. Precise evaluation using a larger cohort is warranted to verify this finding.
PO-070 Our Experience with Staged Nephron
Sparing Surgery in Synchronous Bilateral Wilms
Tumour
Z. Jenovari1 , Z. Karady2 , E. Varga2 , M. Csoka2 , T. Budi2
1 Semmelweis
University, 2nd. Department of Pediatrics, Budapest,
Hungary; 2 Semmelweis University, 2nd Department of Pediatrics,
Budapest, Hungary
PO-069 Analysis of Surgery for Pediatric Solid
Tumors after Centralization of Care in the
Netherlands
M. Jans1 , S. Terwisscha van Scheltinga1 , C. van de Ven1 , H. Heij1 ,
J. Wilde2 , G. Tytgat3 , M. Wijnen1
1 Prinsess
Máxima Center, Pediatric Surgery, Utrecht, The Netherlands;
universitaires de Genève, Pediatric Surgery, Genève,
Switzerland; 3 Prinsess Máxima Center, Pediatric Oncology, Utrecht, The
Netherlands
2 Hôpitaux
Background/Objectives: Since 2015 all surgical care for
pediatric solid tumors in The Netherlands has been centralized at the Princess Máxima Center for Pediatric Oncology
in Utrecht. The aim of this study is to evaluate surgical complications and mortality for both neuroblastoma (NBL) and
Wilms tumors (WT) since the start of centralization.
Design/Methods: A prospective observational cohort study
was conducted including all children diagnosed and treated
for either neuroblastoma or WT between 2015-2017 at the
Princess Máxima Center. Surgery related complications and
mortality were documented. Outcome was compared with our
pre-centralization cohort of pediatric solid tumors between
1998-2014.
Results: [1] Primary tumor resection for NBL was performed
in 33 children. Peroperative complication rate was 27% (vs.
42%). Short-term postoperative complication rate was 42%
(vs. 43%). Postoperative PICU support due to complications
was necessary for 3% (vs. 5%). Secondary surgery for complications was performed in 6% (vs. 8%). No surgery related
mortality occurred (vs. 2%).
[2] Surgery for WT was performed in 61 children. Peroperative complication rate was 6% (vs. 4%). No tumor rupture
occured (vs. 2%). Short-term postoperative complication rate
was 26% (vs. 19%). No postoperative PICU support for surgical complications was necessary (vs. 2%). Secondary surgery
for complications was performed in 8% (vs. 6%). No surgery
related mortality occurred (vs. 0%).
Background/Objectives: In bilateral Wilms tumour the
primer nephrectomy on the more affected side and nephron
sparing surgery on the other side was accepted method, but
follow up studies proved the worsening of kidney function.
There are no evidences yet regarding the optimal way to preserve the maximal renal tissue and to provide sufficient oncological treatment.
Design/Methods: We retrospectively analysed the data of
patients treated in our unit with synchronous bilateral Wilms
tumour in the last 10 years.
Results: 5 patients were found; all were infants at the first
admission (av. 5 month). Male/female ratio: 1/4. None had
pulmonary metastasis, or lymph node enlargement.
2 patients underwent primer surgery, the first patient bilateral enucleation, the other unilateral nephrectomy. After
chemotherapy both patient underwent further operation, the
first patient unilateral nephrectomy; the other wedge resection
of the contralateral tumour. Both patients had postoperative
chemotherapy, and both have worsening kidney function on
the follow up.
3 patients underwent staged nephron-sparing surgery started
on the less affected side after preoperative chemotherapy. The
timing of the operation was determined by regular MRI or
US. None of these patients underwent biopsy. The histology
(taken at the operation) was favorable in 2, unfavorable in
one case. The 2nd stage contralateral nephron-sparing surgery
attempted after further chemo cycles, the timing was determined by radiology, and also followed by chemotherapy. None
of the patients got radiotherapy. All but one patient is tumour
free, all has both side significant renal tissue, and all has
normal kidney function. One tumour recurrence occurred;
nephron-sparing surgery was done.
The mean follow up is 4 years (8 months-8 years)
Conclusions: The preoperative chemotherapy may decrease
the rate of nephrectomy. The staged nephron sparing surgery
SIOP ABSTRACTS
carried out after preoperative chemotherapy, with interval and
postoperative chemotherapy seems safe and effective way to
preserve the maximal amount of renal tissue.
PO-071 Outcome of Bilateral Wilms Tumor:
Experience from a Single Tertiary Care Centre
from India
B. Jindal1 , K. Sambandan1 , K.K. Govindaranjan1 , B.K. Naredi1
1 JIPMER,
Department of Pediatric Surgery, Pondicherry, India
Background/Objectives: Approximately 5-7% of children
with Wilms tumor present with bilateral disease. Bilateral WT
are usually associated with the presence of nephrogenic rests,
congenital malformations and predisposing syndromes. The
major challenge in bilateral disease is to achieve a cure and
at the same time to preserve sufficient functional renal tissue
for normal growth and development. Renal failure is major
contributor (12%) of morbidity and mortality. We planned to
review the cases of bilateral WT treated at our institute, and
factors contributing to their morbidity and mortality.
Design/Methods: Retrospective review of case records of
bilateral WT treated at our hospital, from year 2009 to 2016
and their outcome.
Results: Total of 6 cases of bilateral WT were operated over
the last 7 years. Of these six cases. Five were synchronous and
one had metachronous bilateral WT; two had syndromic association, one each with Denysh Drash Syndrome and WAGR
syndrome, of which one had additional associated horse shoe
kidney anomaly. Two underwent sequential partial nephrectomy for synchronous bilateral WT, two had simultaneous
nephrectomy and tumorectomy, and one with horse shoe kidney with bilateral WT underwent left nephrectomy and partial nephrectomy on other side. Of these six patients, three
expired, two lost to follow up and only one is doing well at
2.5 year follow up.
Conclusions: Renal failure is a major contributor of morbidity/mortality in bilateral WT and the incidence is high in
developing countries due to late presentation. The associated
glomerulopathy with Denysh Drash syndrome and WAGR
syndrome in which condition the incidence of renal failure increases to 50% and 90% respectively. Nephron sparing
surgery (NSS) should be the aim to prevent renal insufficiency,
rather than achieving a negative surgical margin which can be
dealt with radiotherapy. Sequential nephrectomy or simultaneous NSS still a debatable point which cannot be conferred
from this small study.
PO-072 Peripherally Inserted Central Catheters
by Pediatric Surgeons for Children with Cancer:
Initial Experience from a Developing Country
S469 of S518
W.E. Oliveira Júnior1 , F.F. Gonçalves1 , V. Kremer1 , R.C. Ribeiro1
1 Barretos
Childrens Cancer Hospital, Pediatric Surgery Department,
Barretos, Brazil
Background/Objectives: A long-term venous access is
essential in children when treating malignant diseases. Peripherally inserted central catheters (PICCs) have been shown to
be a valuable alternative to traditional devices providing central access for this patients. PICCs have been used for many
years in developed countries, but there are few studies focused
on pediatric oncology patients in developing countries. The
purpose of this study was to evaluate our initial experience
with PICCs specially with regard to feasibility, catheter life,
complications and reason for removal in children with cancer
in a developing country pediatric hospital.
Design/Methods: A retrospective analysis of all pediatric
oncology patients who underwent PICC line insertion by the
pediatric surgery team at our institution from March 2016 to
March 2017 were enrolled in the study. Demographic features,
primary diagnosis, catheter days, reason for removal and complications were reviewed.
Results: Forty-six PICCs were inserted into 40 children during the 12-month period. Median catheter life was 40 days,
ranging from 2 to 287 days, with a total of 3046 catheter days.
Complication rate of 6.23 per catheter days was recorded.
The common reasons for catheter removal were suspected
infection, occlusion, dislodgement, and breakage with rates
of 3.28, 2.29, 0.98, and 0.32 per 1,000 catheter days, respectively. When compared to solid tumors, hematological malignancies had a higher median catheter permanence (46 vs. 35
catheter-days), and Lymphomas showed the highest median
with 84 catheter-days.
Conclusions: PICC lines are feasible and provides reliable
long-term intranegativenous access in children suffering from
malignancies. Although better care and proper dressings are
important to minimize premature removals and suspected
infection. Education for both parents and nursing team and
guidelines are needed to improve complication rates.
PO-073
Tumour Biopsies - Reaching the Core
J. Burns1 , D. Wanaguru1 , I. Nicklaus-Wollenteit2 , S. McGuirk3 , D.
Hobin4 , S. Arul1 , M. Pachl1
1 Birmingham
Children's Hospital, Department of Paediatric Surgery and
Urology, Birmingham, United Kingdom; 2 Birmingham Children's Hospital,
Department of Histopathology, Birmingham, United Kingdom;
3 Birmingham Children's Hospital, Department of Interventional Radiology,
Birmingham, United Kingdom; 4 Birmingham Children's Hospital,
Department of Medical Oncology, Birmingham, United Kingdom
Background/Objectives: Percutaneous renal tumour biopsies are crucial in planning neoadjuvant chemotherapy and the
timing of surgical resection in the UK. The number of cores
SIOP ABSTRACTS
S470 of S518
taken is operator dependant and can result in inadequate tissue
for diagnosis or tumour rupture with consequent upstaging.
This study attempts to define the minimum number of cores
required for diagnosis and to document the incidence of
tumour rupture in relation to number of core samples taken.
Design/Methods: Biopsy technique was by the ultrasound
guided percutaneous method in all cases and using the coaxial
technique.
This was a retrospective review of prospectively collected
data. All percutaneous trucut renal tumour biopsies taken
between February 2002 and September 2016 were included
in the analysis. Those with inadequate data about the number
of cores taken were excluded.
Data on demographics, diagnosis, diagnostic adequacy and
number of cores were collected. Details of whether immunohistochemistry, genetics and tissue typing had been performed
on the biopsy tissue were also collected.
Results: Renal units biopsied N=103; M:F 55:48
Diagnosis included Wilms tumour in 90 cases and other
tumours in 13 (Mesoblastic nephroma (2); Primitive Neuroectodermal Tumour (3); Rhabdomyosarcoma (1); Nephroblastomatosis (2); oxalosis (1); normal (1); Neuroblastoma (1);
Rhabdoid (1); Desmoplastic SRCT (1)
Median number of cores (range) was 4 (1-10). There were 6
non-diagnostic biopsies which had a median (range) number
of cores 3 (1-6)
There was one tumour rupture following a biopsy and this
patient had 7 cores taken.
The lowest number of core biopsies with 100% diagnostic
accuracy was 3 and the lowest number able to give diagnosis, immunohistochemistry and genetics was 1 core.
Conclusions: Three good cores are the minimum number
required for diagnosis and this should be subjective and operator dependent. One single good core contains enough tissue
for diagnosis, immunohistochemistry and genetics.
Further investigation for other tumour sites is ongoing.
Design/Methods: to define possibilities of endosurgery in
diagnosis of tumor of thoracic and abdominal localization at
children
Results: From 2007 to 2012 with the diagnostic purpose it is
carried out the 160th operation at 153 children, from which
63 laparoscopic and 44 thoracoscopic biopsies. Except diagnostic biopsies it was executed 53 thoracoscopic resections of
lungs at 51 children for the purpose of diagnostics of progressing of a disease, confirmation of metastatic defeat or inflammatory process that made 33% of all diagnostic operations.
The age of patients varied from 2 months to 19 years. And
children about one year there were 9,8%. Duration the thoracoscopic and laparoscopic biopsies made from 20 minutes to
260 minutes, on average 59 minutes. Blood loss during diagnostic operations averaged 78,3 ml. Intraoperative complications are in 5 cases, and postoperative in – 8. After the endosurgery operations at 59,3% of patients special treatment was
carried out, 7,4% had a repeated operation, but already in radical volume and in 33,3% were written out on continuation
treatment in a residence or in profile establishment.The average time of the beginning of special treatment made 4 days.
Conclusions: Advantages of use of endosurgery in children's
oncology are: early terms of the beginning of special treatment, small injury, the minimum blood loss, low number of
postoperative complications, early activation of the patient
and reduction of terms staying in a hospital, good cosmetic
effect. Performance the endosurgery of operations at children
with malignant tumors it is possible aged from several weeks,
thus the oncological principles of performance of surgery
aren't broken, and also the age of the child isn't the limiting
factor for performance the endosurgery of operations.
PO-075 Severe Combined Immunodeficiency
(SCID) Mimicking as a Neuroblastoma Stage MS
(NB-MS)
C. Sánchez-Montenegro1 , A. Lizano-Contreras1 , S. Vega-Salas1 ,
M. Sánchez-Salazar2 , M. Delgado-Avendaño2 , Y.
Gamboa-Chaves2 , J.C. Barrantes-Zamora3 , G. Ivankovich-Escoto4 ,
D. Matus-Obregón4 , G. Lazo-Páez4 , B. Valverde-Rojas5
1 Hospital
PO-074 Possibilities of Endosurgery in Diagnosis
of Tumor Diseases of of Thoracic and Abdominal
Localization at Children
D. Rybakova1
1 Federal
State Budgetary Institution “Russian Cancer Research Center. NN
Blokhin ”of the Ministry of Health of Russia, Children oncology, Moscow,
Russia
Background/Objectives: Diagnostic endosurgery is successfully approved in adult oncology and there are data on use of
this method in children oncology in foreign literature.
Nacional de Niños “Dr.Carlos Sáenz Herrera”, Pediatric
Surgical Oncology- Oncology Service- Department of
Hematology-Oncology, San José, Costa Rica; 2 Hospital Nacional de Niños
“Dr.Carlos Sáenz Herrera”, Pediatric Medical Oncology- Oncology
Service- Department of Hematology-Oncology, San José, Costa Rica;
3 Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera”, Pediatric
Surgical Oncology & Pediatric Medical Oncology- Oncology ServiceDepartment of Hematology-Oncology, San José, Costa Rica; 4 Hospital
Nacional de Niños “Dr.Carlos Sáenz Herrera”, Department of Pediatric
Immunology and Rheumatology, San José, Costa Rica; 5 Hospital Nacional
de Niños “Dr.Carlos Sáenz Herrera“, Flow Cytometry Service- Laboratory
of Specialized Studies and Research, San José, Costa Rica
Background/Objectives: Neuroblastoma MS has specific
characteristics including presence ≤18 months of age and
SIOP ABSTRACTS
S471 of S518
metastases to liver, skin, or bone marrow. The aim is present
a case were a primary immunodeficiency was the etiology for
the clinical findings in a child suspected of Neuroblastoma
MS (NB-MS).
C. Rinaldo1 , J. Vigholm1 , H. Haapa Hybinette1 , Y. Copeland
Wahlo1 , P. Kogner1 , M. Heyman1 , C. Petersen1 , A. Harila Saari1 , I.
Øra1
Design/Methods: Retrospective analysis of the medical
record of a patient admitted in the National Children's Hospital (Costa Rica), which was first examined by the Oncology
Service and subsequently diagnosed/treated by the Pediatric
Immunology and Rheumatology Department (SIRP).
Background/Objectives: Today approximately 20% of pediatric cancer patients will experience treatment failure and die
of disease. Huge efforts from academics and pharmaceutics
have resulted in many potential compounds to be clinically
tested. ITCC – Innovative Therapies for Childhood Cancer is
the umbrella organization for experimental clinical trials in
Europe and currently 51 centers participate.
Results: A 4-months-old female, with 2 previous admissions
due to bronchiolitis and oxygen dependence, consulted for
irritability, fever, and diarrhea. The mother mentioned 15
days of evolution of skin nodules. On physical examination
hepatomegaly and subcutaneous nodules were documented.
Abdominal ultrasound documented a solid nodule in the right
adrenal gland, hepatomegaly with multiple disseminated solid
nodular lesions. Upon clinical suspicion of NB-MS, biopsy
of a subcutaneous nodule and bone marrow aspirate/biopsy
were performed. Skin biopsy did not report malignancy but
cultured Nocardia farcinica. Bone marrow aspirate reported
absence CD4/CD8 lymphocytes, and therefore assessment of
the SIRP was requested. Review of previous blood counts
showed persistent lymphopenia (<200/�l). Patient required
hospitalization (Intensive Care Unit) for infections treatment:
subcutaneous nodule/tracheobronchial aspirate with Nocardia farcinica, septicemia due to Granulicatela adiacens, tracheobronchial aspirate with Candida albicans and BCGitis. Peripheral blood lymphocyte subsets count was compatible with Severe Combined Immunodeficiency (SCID) T- BNK+. Follow-up abdominal ultrasound showed multiple hepatic non-vascularized calcified nodules and a right adrenal
gland´s nodule partially organized with microcalcifications.
The patient received a bone marrow transplant from her HLA
identical mother, 3 months after diagnosis.
1 Karolinska
University Hospital, Pediatric oncology, Stockholm, Sweden
AIMS:To enable all Swedish pediatric patients with relapse or
refractory cancer to be included into early phase clinical trials
of precision medicine against their disease with the long term
aims to increase survival rates and quality of life for children
and adolescents with cancer.
Design/Methods: The innovative clinical trial unit at the
Pediatric Oncology unit at Karolinska University Hospital
in Stockholm was accredited as an ITCC center in January
2016. Two senior consultants and two experienced pediatric
oncology research nurses were appointed, all 50% for the time
being. The need for additional research nurses and administrative staff is a priority for 2017.
Results: The Working Plan is largely defined including designation of the organization structure, requirement of human
resources, facilities, financial requirements, and education of
the staff. The administrative work of a yearly opening of 3–4
clinical trials with approvals to the competent authorities and
ethical board is finalized. 17 first patients have been enrolled
in the INFORM study. Financial support has increased with
the help of Barncancerfonden, Entrepreneurs of good and others (additional applications are pending).
Conclusions: The blood count should be assessed for all
neonatal/infant masses, to rule out leukopenia (Immunodeficiencies) before thinking about malignancy. Not all the classic
features of NB-MS should be classified as neoplastic origin
without ruling out other pathologies.
Conclusions: Initiation and management of a Phase I/II clinical trial unit for pediatric cancer patients in Sweden is of
utmost significance. To be part of the future development
of pediatric cancer treatment will stimulate clinicians and
researchers to plan and conduct their own experimental trial
questions. The unit is of important educational benefit for
young health care staff during their specialization prior to
pediatric cancer positions.
T R E AT M E N T A N D CA R E - N E W
DRUGS/EXPER I ME N TA L
THERAPEUTICS
T R E AT M E N T A N D CA R E S UP P O RT IVE CARE
PO-076 Early Evaluation of Precision Medicine
Efficiency for Swedish Children and Adolescents
with Cancer
PO-077 Venous Thromboembolism in Children
with Cancer
Y. Aguilar de la Red1 , B. Ponce Salas1 , C. Mara Fernandez1 , J.
Huerta Aragonés1 , E. Cela de Julian1
SIOP ABSTRACTS
S472 of S518
1 Pediatric
Oncohematology Section., Pediatric. Gregorio Marañón General
University Hospital, Madrid, Spain
Background/Objectives: Cancer may be considered as a
hypercoagulable state and therefore, venous thromboembolism is a frequent complication in adulthood. Even though
it is also frequent in pediatric oncology patients, risk factors
and prophilaxis/treatment are not so well described.
Design/Methods: We analysed 12 patients (0-16 years old)
from 2011-2017, who presented a thrombosis or venous
thromboembolism (VTE) during cancer treatment or the follow up.
Results: 12 patients were studied, 8 were female (66.6%).
Median age at diagnosis of cancer was 7.2 years old (DS
5.02). Median time from cancer diagnosis to VTE was 8.13
months(DS 11.6). Symptoms were only present in 16.7%
of them. Underlying malignancies were: 8 solid tumours
(66,6%)(Wilms tumour the most frequent, -37,5%-), 4 acute
leukemias(33,3%) -3 lymphoblastic, 1 acute promyelocytic
leukemia(APL)-. The most common risk factor was the presence of a central venous catheter(CVC) (75%)-8 patients(41,7% Port-a-cath), hospitalization in 25% -4-, recent surgery
in 16% -2-, recent treatment with corticosteroids (33%)-4-,
with asparaginase (16 %)-2-, mechanical ventilation (16%)-2-.
7 of 10 patients (70%) were non-0 blood group. Only 8patients
had inherited thrombophilic factors studied, only 2 had any of
them. Obesity and sepsis were not risk factors for VTE in our
study.
5 patients (41,7%) received specific treatment for the VTE, all
of them with enoxaparin at VTE diagnosis. On 3 of them therapy was substituted afterwards by acenocumarol. The duration of therapy in 2 patients(16.7%) was longer than specific
malignancy treatment.
Regarding results, 6(50%) of the VTE were completely
resolved, 1 patient died during APL induction treatment.
Conclusions: Children with cancer are at risk to develop secondary VTE. In our small study, most common risk factors
described were having a CVC placed, and solid tumour versus
haematologic malignancy. There is still much to be learned
about risk factors and the need of specific guidelines for treatment and prophylaxis.
PO-078 Dietary Management of Chylothorax
Secondary to Mediastinal Lymphadenopathy in a
Patient with Leukaemia
M.J. Crowley1 , D.I. Sinha2 , D.M. Caswell3 , C. Barton1
1 Alder
Hey Children's Hospital NHS Foundation Trust, Department of
Paediatric Oncology, Liverpool, United Kingdom; 2 Alder Hey Children's
Hospital NHS Foundation Trust, Department of Paediatric Respiratory
Medicine, Liverpool, United Kingdom; 3 Alder Hey Children's Hospital NHS
Foundation Trust, Department of Paediatric Haematology, Liverpool,
United Kingdom
Background/Objectives: We report the case of a teenage
patient newly diagnosed with T cell acute lymphoblastic leukaemia, presenting with chylous pleural effusions
secondary to significant mediastinal lymphadenopathy. We
describe our experience in the management of the condition,
and a review of current literature.
Design/Methods: As the patient continued to receive
chemotherapy to treat his leukaemia, a conservative medical approach was taken, with intensive dietetic input to institute a minimal fat diet, incorporating an exchange system.
The major dietetic challenge was providing sufficient calorie and protein intake, requiring fat free nutritional supplements (e.g. paediasure plus juice) which the patient found
unpalatable. Subsequently, supplemental parenteral nutrition
was commenced. As his clinical condition improved, fat content of the diet was gradually increased. Parenteral nutrition
was stopped and medium chain triglyceride supplements were
added, with relaxation of dietary restrictions based on clinical
assessment.
Results: Eventually, the chylothorax fully resolved both clinically and radiologically, through conservative management
alone. The patient struggled significantly with dietary restriction, requiring significant nutritional counselling and adaptation of his diet to aid compliance.
Conclusions: There are no best practice guidelines for the
management of chylothorax. A single systematic review from
2015 identifies a lack of consensus in management options,
with the strongest evidence coming from case reports, which
are highly heterogeneous, and lacking in clinical detail. This
case report provides greater detail on the crucial role of
dietetic support in managing chyle leak, lacking in previous
reports. Further research is needed to generate robust clinical
guidance.
PO-079 The Management of Fever in Children
with Cancer in the North of Scotland
T. Lawes1 , J. Calley1 , L. Adam1 , N. Abdelrazig1 , H. Bishop1 , N.
Ahmad1
1 Royal
Aberdeen Children's Hospital, Department of Paediatric Oncology,
Aberdeen, United Kingdom
Background/Objectives: Outcomes in children with cancer
continue to improve but febrile neutropenia remains a major
cause of mortality. Early recognition and treatment- particularly rapid antibiotic administration- improves outcomes,
whilst appropriate de-escalation of care can allow safe discharge. Standards of care have been proposed by both the
National Institute for Health and Care Excellence (NICE) and
the Managed Service Network (MSN) for Children & Young
People with Cancer in Scotland. Our aim was to audit the management of fever in paediatric oncology patients presenting to
SIOP ABSTRACTS
the tertiary centre in the North of Scotland and implement a
quality improvement (QI) intervention to support care delivery.
Design/Methods: A retrospective criterion-based sample of
the first 50 episodes of fever retrieved from case notes of paediatric oncology patients treated in the years 2013-2015 was
analysed for performance against key standards in clinical
assessment, early intervention, and escalation/de-escalation
decisions.
Results: The management of 52 episodes from 13 patients
were analysed of which 28 were febrile neutropenia and 24
febrile non-neutropenia. Within the target time of 60 minutes
89% of patients were assessed by a doctor, 69% of blood cultures were performed and 64% of empirical antibiotics were
administered. Those with a paediatric early warning score ≥
2 were seen earlier, and were more likely to receive antibiotics within the target time (100% vs. 55%, P= 0.013). There
was 98% adherence to local empirical antibiotic policy. 61%
and 93% of patients were de-escalated appropriately at 24 and
48-96 hours respectively.
Conclusions: Clinical assessment and intervention within the
first 60 minutes was identified as our key target area for
QI. A febrile neutropenia management proforma has been
developed. This is being implemented as part of a wider QI
project alongside updates to family information, reinforcement of emergency care standards by multi-disciplinary team
scenario-based training, and implementation of a programme
of regular audit.
PO-080 Parental Decision Making and Quality of
Life in Children with Cancer
M.H. Chen1 , L.H. Huang-2 , W.Y. Hu2 , Y.L. Lee2 , K.P. Yao3 , Y.C.
Chang4
1 Tzu
Chi University of Science and Technology, nursing, Hualien, Taiwan
R.O.C.; 2 National Taiwan University, nursing, Taipei, Taiwan R.O.C.;
3 National Taiwan University, psychology, Taipei, Taiwan R.O.C.; 4 Tamkang
University, Mathematicis, Taipei, Taiwan R.O.C.
Background/Objectives: This study purpose to explore the
family‘s parental treatment decision making and quality of life
of having a child diagnosed with cancer in the hospital.
Design/Methods: The institutional review board at the hospital approved all study procedures. Research design using a
Indepth interviews and focus group discussions approach in
was parents of children diagnosed with cancer in the hospital.Using a participant observation study approach for data
collection and themes were uncovered from each interview
data set and rigorous methods to data analysis. Record the
data with the process recording in interview and participant
observation. Data analysis by authors and parent.
S473 of S518
Results: The cancer treatment decisions made by the parents
while their hospitalized children are being treated for cancer
mainly include choosing the appropriate hospitals and treatment process. There are fourth themes of the quality of life:
(1)Physiologically: Their sleep is disturbed due to the treatments of the children; They are more prone to feeling tired
or catching a cold.(2) Psychologically: They are concerned
about (a) the side effects of the treatments on the children, and
(b) the children's emotional changes under the invasive treatments; Feeling guilty when the other children in the family are
being neglected; Feeling difficult reconciling the demands of
work and caring for the sick children.(3) The changes in everyday lives: The diets are mainly composed of self-grown food;
Timely isolations in the home environments; Living in one's
tribe.(4) Using the support system: The mutual support among
husbands, wives, siblings, and paramedical staff.
Conclusions: It was expected that findings of the study could
provide family members and paramedical staff be the positive
force supporting the healing of children.
PO-081 Correlation Between Neck
Circumference and ARM Muscle Area in Children
and Adolescents with Malignant Neoplasms
R.L. Ferretti1 , P.S. Maia-Lemos1 , K.J.T. Guedes1 , E.M.M. Caran1
1 Pediatric
Oncology Institute - IOP/GRAACC/UNIFESP, Pediatric, Sao
Paulo, Brazil
Background/Objectives: Malnutrition in children and adolescents with malignant neoplasms may be underestimated in
the diagnosis of the disease when considering only the Body
Mass Index. Anthropometric measures are able to detect early
malnutrition. Neck circumference (NC) is a simple, inexpensive, and easily applicable measure in clinical practice. Arm
Muscular Area (AMA) is recognized in the literature as a good
indicator of muscle mass depletion. The main objective of this
study is to verify if there is a correlation between the measurement of NC AMA.
Design/Methods: A cross-sectional study that evaluated children and adolescents between 0 and 20 years of age with
malignant neoplasms at a Specialized Pediatric Oncology
Institute from October 2015 to June 2016. The measurements
of NC were evaluated and, for AMA calculation, arm circumference and skinfold triceps, all performed by trained evaluators, following anthropometric techniques standardized by
the literature. The chi-square test was performed to verify the
association between inadequacy of AMA and the sexes, with
significance level p <0.05. The correlation between NC and
AMA was performed through the Pearson correlation.
Results: Among 647 patients, 42,66% (276) were females.
The mean age for females was 8.65 (± 5.78) and for males
was 9.07 (± 6.08). The correlation between NC and AMA
SIOP ABSTRACTS
S474 of S518
was linear positive and strong (r=0.80), with a higher correlation coefficient for males than for females (r=0.84 vs r=0.74).
There was a significant difference between the sexes and inadequacy of AMA (p=0.01).
Conclusions: It was concluded that there is a strong correlation between NC and AMA, with a higher outcome for males.
In addition, NC is a simple measure, easy to apply and very
useful in clinical practice.
PO-082 Emplacement of Single-Lumen
Subcutaneous Port by Angio-Radiology Service:
Our Experience in the Last Ten Years
A. De Lucio1 , M. gonzalez1
1 yes,
Hematology-Oncology Department, Sta. Cruz de Tenerife, Spain
Background/Objectives: Emplacement of single-lumen subcutaneous port (SSQP) in pediatric patients is a daily routine. In last years, it has also been used not only in oncologic
patients but also in children with chronic diseases with little
complications.
Design/Methods: Medical records of pediatric patients (≤15
years of age) who underwent SSQP at our Hospital between
2005 and 2015 by Angio-radiology Service. Variables analyzed included gender, age at diseases’ diagnostic, disease,
time between diagnosis and collocation, absolute neutrophils
and platelets count before procedure, vein used and complications in those years.
Results: A total of 121 SSQPs placed in 105 patients (65
males and 40 females). Eighty four cases were malignant diseases (80%) and 21 no malignant (20%). Acute lymphoblastic/myeloblastic leukemia and lymphoma were the most common diagnosis (40%). Median age at diagnosis was 5.8 years
(1m-14.8 years).Time between diagnostic and collocation was
11.2 days in malignant cases (excluding two cerebral tumors
and an opsoclonus syndrome). In the other group, it was 12.3
months.
Right internal jugular vein was used as the first location in all
the cases. Median absolute neutrophil count before procedure
was 6147/mm3 (range 0–181,000) while median platelet was
261,384/mm3 (range 9,000-835,000). Median weight was 27
Kilogram (range 4-77.5).
A total of 34 patients (32.3%) had some complication: 16
catheter malfunction (81.2% solved with urokinase), 20 local
positive blood cultures, 6 with hematoma or skin infection,
2 broken system and 1 hemotorax. During first month, there
were 13 patients with any complication (5 within first week,
2 of them during procedure).
New SSQP was placed in 13 patients for different causes
(56.2% infections, 25% catheter broken/malfunction and
12.5% relapse after years).
Conclusions: We conclude that SSQP is useful and safe in
all pediatric patients with a low risk of complications. Their
early collocation does not carry additional complications in
comparison with other Services.
PO-083 Assessment of the Use of Parenteral
Nutritional in Intensive and Semi Intensive Therapy
Units Pediatric Oncology
B.C. Elias1 , P. dos Santos Maia Lemos2 , N. Dorascenzi Magri
Teles1
1 Instituto
de Oncologia Pediatrica, Nutrition, São Paulo, Brazil; 2 Instituto
de Oncologia Pediátrica, Nutrition, São Paulo, Brazil
Background/Objectives: Parenteral nutritional (PN) consists
in provide the macro and micronutrients directly into the circulatory system for patients who are unable to receive enteral
nutritional therapy (ENT). Considering that patients under
cancer treatment undergo intensive treatments that compromise nutritional status, PN is an alternative to meet the
patient's current needs. The present study had the goal to evaluate the use of PN in intensive care units (ICU) and pediatric
oncology special care units (SCU).
Design/Methods: Retrospective observational study performed at a pediatric oncology institute, which included
patients aged 0 to 18 years old, hospitalized in the ICU and
SCU for more than 24 hours using PN.
Results: In a sample of 565 hospitalizations, 3,5% of patients
had indication of PN. The main clinical diagnoses were
tumors of the Central Nervous System (40%) and Osteosarcomas (15%). The main indication for PN was to the diagnosis of Typhlitis (35%). According the Body Mass Index, 60%
had malnutrition and 40% eutrophy. Using the Arm Circumference, 30% were below adequate. The fasting time until the
beginning of the PN ranged from 2 to 16 days. Hydroelectrolytic disorders, hemodynamic instability and scheduling of
exams were the main reasons for prolonged fasting until early
onset of PN.
Conclusions: In cases where the enteral route is contraindicated, PN may provide better control of complex disease
states, but studies analyzing its practice in pediatric oncology
patients are scarce, indicating that more studies are needed.
PO-084 Use of Apheresis Platelet Concentrates:
One Center Experience
Z. salcioglu1 , G. Ersoy1 , K. sanli2 , G. Aydogan1 , F. Akici1 , E.
Uysalol1 , B. Koc1 , E. Yılmaz1 , C. Bayram1 , A. Ayçiçek1 , G.N.
Ozdemir1
1 Kanuni
Sultan Suleyman Training and Research Hospital -, Pediatric
Hematology Oncology, Istanbul, Turkey; 2 Kanuni Sultan Suleyman Training
and Research Hospital -, Blood Bank Department, Istanbul, Turkey
SIOP ABSTRACTS
S475 of S518
Background/Objectives: Thrombocytopenia is a commonly
encountered problem for patients who are treated with
chemotherapeutic agents. These patients are transfused by
random donor platelets (RDPs) or apheresis derived platelets
(ADPs) for bleeding or prophylaxis
2016 to 5th August, 2016, in which initially observation was
made on nurses’ assessment of 48 cytotoxic administration
follow-up patients. In second phase staffs were being asked to
demonstrate management of extravasation in simulated based
setting.
Design/Methods: This study is continued between 01 January
2012 and 30 April 2014 to assess indications to use ADPs
instead of RDPs, in pediatric hematology and oncology clinic.
Patients’ data are collected retrospectively from blood bank
records and patients’ registry of our hospital database.
Results: Around 82% of patients were being assessed for condition of last cannulated site, however only 3% of discoloration of IV sites were identified and being notified to physicians on floor. On hands on management of extravasation only
70% of nurses were able to aspirate residual cytotoxics from
skin and 30% were comfortable in injecting hydrocortisone at
extravsated site.
Results: ADPs are reserved for 56 patients whose age
between 1 to 16 years old. ALL is the most common
patient group (36 patients:64,3 %), followed by the AML
(12 patients:21,4 %), Wilms’ tumor (3 patients), Glanzmann thrombasthenia (2 patients), non-Hodgkin Lymphoma
(2 patients), neuroblastoma (1 patient) respectively. ADPs
ordered per patient are 1 to 20 (med:6,6±4,1). ADPs are prepared as two bags mostly in form of 4+4 (92,1%), followed
by 6+6 (4,5%) and 8+8 (2,2%) forms respectively. Apheresis
thrombocyte was used mostly for prophylaxis no:265 (74,6%)
and no:90 (25,4%) for bleeding. No mortality from bleeding
is observed during study period. Platelet counts before transfusion were between 1000-86000/mm3 (med: 26.000/mm3 ).
30 complete unit ADPs (8,4%) and 12 one bag ADPS are disposed due to expired date of use.
Conclusions: Preparation of ADP from single donor is an
expensive procedure. Usage of upcoming expiration dated
thrombocyte concentrates must be monitored closely by blood
bank. As a result it is understood that our clinic need to revise
the indications of thrombocyte concentrates use and need to
focus on education about thrombocyte concentrate use.
PO-085 Assessing Nurses’ Knowledge and Skills
on Identification and Management of Cytotoxic
Induced Extravasation in Oncology Day Care in a
Tertiary Care Hospital- Via Clinical Audit
A. Feroz
1
1 Aga
Khan University Hospital, Ibne Zohar Daycare Oncology, Karachi,
Pakistan
Background/Objectives: Incidences of extravasations are
being monitored as a key quality indicator in oncology areas,
however to work more towards precision, a need for assessment of knowledge and hands on capacity of nurses in identifying and early managing of cytotoxic extravasation was identified.
Design/Methods: Clinical Audit was the identified strategy
for assessment, with the help of existing best practice institutional guideline, checklist was being developed; piloted on
oncology nurses not working in day care oncology, and validity was gained. A clinical audit was performed from 15th July,
Conclusions: A strong need for hands on training for extravasation assessment and management is being identified for
oncology nurses. Video based and simulated based learning
can be taken as a strategy for training of oncology nurses on
rare occurring situations like extravasation.
PO-086 An Assessment of Central Line
Associated Blood Stream Infections (CLABSI) in
Southern Vietnam
R. Huynh1 , V.S. Nguyen1 , C. Assanasen2
1 UTHSCSA,
2 UTHSCSA,
Long School of Medicine, San Antonio- Texas, USA;
Pediatric Hematology/Oncology, San Antonio- Texas, USA
Background/Objectives: Though Vietnam has become one
of the top 10 fastest growing economies globally, as an LMIC
it still needs improvement in pediatric oncology care. Survival
rates as low as 5% have been reported in Vietnam in 2008, and
although it has risen beyond this point, the rates remain well
below that of their Western developed counterparts. This low
survival rate has been attributed to differences in chemotherapy treatments as well as inexperience with supportive care
preventative measures such as central line associated blood
stream infection (CLABSI) monitoring.
Design/Methods: Medical directors at three institutions in
Ho Chi Minh City Vietnam (City Children's Hospital, Children's Hospital #2, and Children's Hospital #1) were surveyed to determine how central line infections were identified and monitored in their pediatric hematology/oncology
patient populations. Questions included whether the director
was familiar with the recent ASPIC guidelines for the prevention of CLABSIs, monitoring policies, and current estimates. Education of staff using a train-the-trainer approach
was implemented with the development of infrastructure and
policies to monitor rates long term. Staff members surveyed
also provide insight into gaps in care.
Results: Though limited by many resources, two surveyed
institutions reported the majority of their pediatric oncology
patients used central lines regularly. One hospital had not
yet begun caring for pediatric oncology patients. All three,
SIOP ABSTRACTS
S476 of S518
however, did not have current policies or procedures in place
for CLABSI monitoring. Estimated infection rates reported
varied widely ranging from 10-30%. Hospital directors have
viewed initial responses to supportive care training positively.
Direct observation revealed inconsistencies and unanticipated
problems, such as ineffective occlusive dressing adhesive
within the humid environment.
Conclusions: There are no reports on the CLABSI rates
in pediatric cancer hospitals within southern Vietnam. Our
report represents the initiation and commitment toward this
quality improvement effort. As improvement takes place over
time, further details will be provided.
PO-087 Hospital Construction or
Person-to-Person Transmission is the Source of
Pneumocystis Jiroveci Pneumonia Outbreaks in
Pediatric Acute Leukemia Under Prophylaxis?
K.S. Lee1 , D.E. Roh1 , H.R. Suh1 , S.Y. Min1 , T.K. Jo1 , J.K. Suh1 ,
J.Y. KIM1
1 Kyungpook
National University Hospital, Department of Pediatrics,
Daegu, Republic of Korea
Background/Objectives: After the era of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis, PCP
is decreasing and rare. However, there are limited reports
about transmission and disease courses of PCP in pediatric
immunocompromised patients under TMP/SMX prophylaxis. Recently a cluster of PCP was reported in a hospital
construction setting, we investigated this study to assess the
risk factors of PCP outbreaks.
Design/Methods: We retrospectively reviewed the medical
records of pediatric patients who were diagnosed with hematologic malignancies and solid tumor and received chemotherapy at Kyungpook National University Children's hospital between October 2014 and March 2017. Among the
patient diagnosed pneumonia during chemotherapy, medical
records of patients who did not respond to empirical antibiotics therapy for community acquired pneumonia or hospital
acquired pneumonia were reviewed. Clinical characteristics
were reviewed.
Results: From October 2014 to March 2017, four patients
who received chemotherapy and TMP/SMX prophylaxis were
diagnosed as proven or suspected PCP. All cases occurred
within 3 months period from August to December 2016 under
the hospital construction. The duration of each episode overlapped in time suggesting the possibility of person-to-person
transmission. They were on chemotherapy with acute lymphoblastic leukemia, one on consolidation and the other three
on maintenance chemotherapy. Three PCP patients during
maintenance chemotherapy were clinically improved after
TMP/SMX treatment and adjuvant corticosteroid therapy.
The PCP patient during consolidation chemotherapy expired
due to progressive acute respiratory distress syndrome and
pneumothorax while receiving mechanical ventilator support.
Two patients showed Pneumocystis carinii PCR positive and
the other two patients showed negative results.
Conclusions: The cluster of PCP is significant in terms of
air borne and person-to-person transmission of pneumocystis
in a hospital construction setting. Considering the high morbidity and mortality of PCP, respiratory isolation of suspected
patients and construction environmental reservoirs control are
also important in addition to accurate diagnosis and early
treatment.
PO-088 Sibling Support for Children Who have
been Treated for a Cancer: A Collaborative
Approach
N. Kisby1 , N. Shaw2 , T. West2
1 Candlelighters,
Family Support, Leeds, United Kingdom; 2 Leeds Teaching
Hospitals Trust, Oncology Outreach Team, Leeds, United Kingdom
Background/Objectives: Candlelighters has been providing
support for families affected by childhood cancer for over 40
years. As part of this support, specific sibling groups for children affected by childhood cancer have been developed. These
groups are supported by wider members of the Multidisciplinary team. The overall aim in undertaking work directly
with siblings, is that every brother and sister has the opportunity to receive support within an environment in which they
feel safe and comfortable. Siblings are often viewed as the
‘forgotten’ group and their needs can be overlooked. As siblings try to come to terms with the severity of their brother
or sister's illness this may give rise to a number of conflicting
emotions.
Design/Methods: The Candlelighters groups offer them the
time and opportunity to be with other siblings who are in the
same situation as themselves. It also gives them the opportunity to be the focus (even for just a few hours) and opportunity
just to be themselves.
The groups provide the chance to talk with some of the professionals who are directly involved with the care of their families
enabling them to ask questions which they may feel uncomfortable asking their families for fear of upsetting them. Most
importantly it is about providing a space for the siblings to
have time out and to have fun. The groups are held once per
month alternating between children going through treatment
and bereaved siblings. Three times per year, the groups come
together for a trip. The monthly groups are held at Candlelighters (The Square).
Results: “Candlelighters are fun and help me forget stuff
going on at home”,
“Candlelighters help people make more friends” and
SIOP ABSTRACTS
“At Candlelighters you can always say your feelings”.
Conclusions: As the feedback in our results states the sibling
groups provide much needed support for all siblings affected
by childhood cancer.
PO-089 Breakthrough Disseminated Invasive
Fusariosis Fungal Infection in a Patient with Acute
Myeloid Leukemia Under Micafungin Prophylaxis,
Case Report
Y. Madney1,2 , S. Samir2 , S. Mahmoud2 , A. Salama3 , M. Gaber4 , K.
Alsheshtawi5 , L. Shalaby2
1 National
cancer institute - Cairo university -EGYPT, pediatric oncology,
CAIRO, Egypt; 2 Children cancer hospital 57357- EGYPT, Pediatric
oncology, Cairo, Egypt; 3 children cancer hospital 57357- Egypt, clinical
pathology, Cairo, Egypt; 4 children cancer hospital 57357- Egypt, clinical
microbiology, Cairo, Egypt; 5 children cancer hospital 57357- Egypt,
clinical research, Cairo, Egypt
Background/Objectives: Invasive fusariosis, though rare,
may cause disseminated infections in patients with hematological malignancies and in hematopoietic stem cell transplant
recipients. The mortality attributable to Fusarium infections
in immunocompromised patients ranges from 50% to 70%
Design/Methods: We report a case of acute myeloid
leukemia, male patient, 7 years old admitted in our hospital (Children Cancer Hospital Egypt 57357). Patient started
induction chemotherapy with micafungin prophylaxis from
d1 chemotherapy according to our policy. At day 20 induction
patient had multiple skin lesion started as erythematous raised
papules, indurated and painful with a central area of necrosis
as well as target lesions and perforated nasal septum. Patient
was shifted to broader spectrum liposomal amphotericin B.
Results: Fusarium was isolated from Blood culture, fungal screening was done including CT Chest, sinuses and
abdomen showing non specific bilateral pulmonary infiltration and sinusitis. Fundus examination was free. Biopsy taken
from skin lesion showed fungal hyphae that are septated with
branching and associated with round bulbous ends consistent
with fusarium infection. Clinical improvement with healing
and ulceration of skin lesion with resolution of pulmonary
infiltration after recovery from neutropenia. Bone marrow
aspirate done to assess response to treatment showed complete
remission. Patient discharged on voriconazole after achieving
therapeutic level. Reassessment before 2nd cycle chemotherapy showed clinical and radiological improvement, patient
kept on voriconazole as secondary prophylaxis.
Conclusions: Fusariosis though rare it should be suspected
and covered with appropriate antifungal in presence of suspected cutaneous lesions in immunocompromised patients.
Due to the lack of clinical trials and the critical role of immune
reconstitution in the outcome of fusariosis, the optimal treatment strategy for patients with severe Fusarium infection
S477 of S518
remains unclear. Reversal of immunosuppression is recommended whenever possible.
PO-090 Enteral Feeding with Gastrostomy in
Pediartic Oncology Patients: Complications and
Limits
L. Genere1 , P. Marec Berard1
1 Institut
d'hématologie et d'oncologie pediatrique IHOP, Centre Léon
Berard, Lyon, France
Background/Objectives: Nutritional state is a major prognostic factor in pediatric oncology. Enteral feeding by gastrostomy is increasingly used to prevent and treat malnutrition in
this population. The main objective of our study is to describe
immediate and late complications arising after a gastrostomy
placement procedure.
Design/Methods: We performed a retrospective monocentric observational study of children treated between 2012 and
2016 in a pediatric oncology center and who benefited from
a placement of button gastrostomy during oncological treatment.
Results: thirty three patients (17 male, 16 female), mean age
10.3 years, have benefited from a button gastrostomy placement. Fourteen were malnourished at the time of diagnosis
(42%), and 27 at the time of gastrostomy insertion (81%), –
on average 10.7 months later. Percutaneous radiologic placement was used in 66% of cases. Prophylactic antibiotics were
prescribed for 22 patients (66.7%). Enteral feeding started
on average 1.7 days after procedure. The mean delay from
insertion to removal was 21.3 months. We report 46 side
effects (1 arising in the first 15 days and 45 later) consisting in leaks (34.4%), infection requiring general (31.2%) or
local (9.4%) antibiotic treatment, vomiting (23.3%), granulation tissue formation (21.2%), bedsore(6.2%), and accidental removal (15.2%). At the time of button removal 33 % of
patients were still undernourished.
Conclusions: Gastrostomy feeding in chronic pediatric diseases is well described. In pediatric oncology, its benefit is not
clearly demonstrated and responsible for numerous late complications which could disturb oncological treatment plan.
Some of these complications could be avoided by an earlier
nutritional evaluation and support.
PO-091 Exploring Nurses’ Understanding of
Chemotherapy-Induced Nausea and Vomiting in
Paediatric Cancer Patients: A Quantitative Study
E. Neumann1
1 Birmignham
Children's Hospital NHS Foundation Trust,
Haematology/Oncology, Birmingham, United Kingdom
SIOP ABSTRACTS
S478 of S518
Background/Objectives:
Background:
Chemotherapy
remains the first-line treatment for many paediatric cancer conditions but research by Wood et al. (2015) found
chemotherapy-induced nausea and vomiting (CINV) to be
the most documented distressing side-effect of childhood
cancer treatment. Research among the adult population found
cancer nurses’ played an integral role in the management of
CINV but their knowledge and understanding was lacking.
There was no comparable data available within the paediatric
field.
Aim: To explore and understand nurses’ knowledge of CINV
and identify future learning needs, ultimately improving
patient care through improved knowledge of symptoms by
staff.
Design/Methods: Method: This quantitative study adapted a
previously used questionnaire to explore nurses’ understanding of CINV, working in a Principle Treatment Centre (PTC)
and three, Level 3 Paediatric Oncology Shared Care Units
(POSCU's) within the United Kingdom. A purposive sampling technique was utilised with a paper-based questionnaire
targeting the population of all registered nurses working at
these four sites (n=143). Results were analysed using descriptive and inferential statistics to demonstrate nurses’ overall
understanding and knowledge of CINV in relation to paediatric cancer.
Results: Results Response rate was 51%. An overall knowledge gap existed amongst nurses at all research sites and no
significant differences in the knowledge level between PTC
and POSCU nurses was observed. Nurses had no awareness
of the available assessment tools for CINV.
Conclusions: Conclusions Nurses’ knowledge on these distressing symptoms needs to be increased in order to improve
patient care and experience. The most popular choices for
receiving further education were face: face and online modules while self-directed learning featured as the least popular choice among all participants. There was a significant gap
in knowledge regarding available assessment tools, therefore
knowledge should be increased on this subject.
PO-092 Current Status and Challenges of
Support for Pediatric Cancer Patients’ Siblings An Analysis of Ward Managers’ Free Descriptions J. Nonaka1 , M. Yonayama1 , S. Oka1 , M. Yamazaki1 , M. Uchida2
1 kanagawa
University of Human Services Faculty of Health & Social Work
School of, nursing, Yokosuka, Japan; 2 Nagano College of Nursing, Nursing,
Nagano, Japan
Background/Objectives: A questionnaire survey was conducted on support for the siblings of children with diseases or
disabilities, involving ward managers, and their free descrip-
tions were analyzed to clarify the current status and challenges
of such support.
Design/Methods: subjects:Seventy ward managers supporting the siblings of children hospitalized in pediatrics throughout Japan.Data collection method and procedure: Questionnaires were distributed in envelopes to facilities which previously consented to cooperate with the study.
Analytical method: The contents of the collected descriptions
were analyzed and grouped based on semantic similarities and
differences to create categories. The approval of the research
ethics committee of the researchers’ facility was previously
obtained.
Results: Respondents’ backgrounds: Among the 70 ward
managers of hospitals specializing in pediatrics throughout
Japan, 36 of 10 facilities responded.
<Examples of in-hospital sibling support> supporting endstage pediatric patients’ siblings ; supporting siblings not
allowed to enter wards> ; supporting discharge to home ; making environmental and temporal arrangements for siblings and
families to stay together ; holding events for siblings ; providing explanations to siblings.
<Desires, expectations, systems, and organizations related to
sibling support in the in- and outpatient divisions> making
environmental and systematic arrangements for siblings and
families to stay together ; organizing systems to take care for
siblings ; developing human resources ; and performing nursing care for families. As for the status of sibling support, the
respondents noted the following issues: insufficient manpower
; the risk of infection ; individualized approaches ; alternative
equipment use.
Conclusions: The ward managers made environmental, temporal, and systematic arrangements, such as coordinating visits, and gave considerations with awareness. It was also noted
that they carefully considered appropriate methods to support
end-stage patients’ siblings, as such support was difficult, and
required sufficient consideration, highlighting the necessity of
establishing systems for ward managers to provide sibling and
family support.
PO-093 Factors Affecting Fatigue in Pediatric
Oncology Patients
A.M. Platschek1 , V. Abeln1 , B. Hero2 , T. Simon2 , H.K. Strüder1
1 German
Sport University Cologne, Institute of Movement and
Neurosciences, Cologne, Germany; 2 University of Cologne, Department of
Pediatric Oncology and Hematology- Children's Hospital, Cologne,
Germany
Background/Objectives: Cancer-related fatigue is one of the
most frequent and severe symptoms experienced by pediatric
oncology patients during treatment. Fatigue is multidimensional, with the most distressing symptoms affecting quality
SIOP ABSTRACTS
S479 of S518
of life. There is uncertainty regarding the predictive power of
physical activity prior to disease relative to other factors on
fatigue outcome in pediatric cancer patients.
Results: Two patients fulfilled the criteria. Patients received
NAC intravenously post IFO as follow: 150mg/kg hours 5-6,
50mg/kg hours 6-10 and 100mg/Kg hours 10-24.
Design/Methods: In eleven pediatric cancer patients (6
female; mean age=11.82±2.44 years) PedsQL Multidimensional Fatigue Scale questionnaire was completed during
cancer therapy. Types of cancer present in this study were
leukemia (n=3), lymphoma (n=5), sarcoma (n=2) and neuroblastoma (n=1). The standard treatment for the pediatric
patients was adjuvant chemotherapy according to national
protocols. Daily activity level before disease was retrospectively interrogated with 24 hours division self-report (active
time, sleeping, sitting, lying awake in bed) at the beginning of
treatment. Pearson correlations and Students t-test were used
to analyze the data (�=0.05).
Patient one had Relapsed Rhabdomyosarcoma and received
IFO 2400 mg/m2/day with Etoposide 100mg/m2/day on days
1,2 and 3 and Carboplatin 635mg/m2 on day 3 that was
extended for eight courses. Patient two had Osteosarcoma
previously treated with high-dose methotrexate, cisplatin and
doxorubicin for ten weeks and subsequently required oral
replacement with magnesium. She then received two courses
of IFO 2800mg/m2/day and Etoposide (100mg/m2/day) for
five days. Both patients received pre-, post-hydration and
Mesna as per institutional guidelines.
Results: Mean time between start of cancer therapy and
fatigue questionnaire was 147.55±64.46 days. Mean activity
level before disease was 5.64±2.11 hours per day and ranged
between 2.00 and 8.00 hours. Patients with higher activity
level before disease show a significant higher fatigue score
during cancer therapy (r=0.715, P=0.013), higher scores indicate lower fatigue. However, age (r=-0.356, P=0.283) and
gender (r=0.584, P=0.059) had a less severe impact on fatigue
outcome.
Conclusions: Activity status before disease seems to be a
more powerful predictor of fatigue among pediatric oncology
patients than other factors like gender or age. These findings
emphasize the importance of physical activity in lessening
side effects in cancer therapy.
PO-094 N-Acetylcysteine as a Secondary
Prophylaxis for Ifosfamide Induced Renal
Tubulopathy in Children with Solid Tumors: Case
Series
M. Rojas Vasquez1 , M. Diachinsky1 , M. Romaniuk2 , S. Mckillop2
1 Stollery
Children's Hospital, Pediatric Hematology Oncology, Edmtonon,
Canada; 2 Stollery Children's Hospital, Pediatric Hematology Oncology,
Edmonton, Canada
Background/Objectives: Ifosfamide (IFO) is a commonly
used chemotherapy agent in pediatric solid tumors. A known
side effect of IFO is renal tubulopathy (RT). There is limited data suggesting that N-acetylcysteine (NAC) can prevent
nephropathy induced by IFO. We aim to report a cohort of
children with RT secondary to IFO successfully treated with
NAC.
Design/Methods: Case series of children with solid tumors
between the ages of 0 – 17 years and RT secondary to IFO
treated with NAC.
Patient one developed RT after course 5 and patient two
after course 1. Both had significant hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia and acidosis requiring intravenous replacement of sodium chloride, potassium
phosphate and magnesium followed by two weeks of oral
replacement. Patient one received NAC on courses 6, 7 and
8 and patient two on course 2. After first course of NAC,
both patients developed mild hypophosphatemia, hypomagnesemia and acidosis with other electrolytes normal requiring few days of oral potassium, phosphate and magnesium.
Patient one did not required electrolytes replacement after
courses 7 and 8.
Conclusions: We report two patients with solid tumors with
RT secondary to IFO who responded to treatment with NAC
when given concomitantly with IFO. Prospective studies are
required to further confirm this therapeutic approach
PO-095 Intestinal Mucor Infection in a Patient
with Non-Hodgkin's Lymphoma During Induction
Chemotherapy
A. Erbay1 , F. Sarialioglu1 , N. Yazici1 , S. Ezer2 , B. Hasbay3
1 Baskent
University, Department Of Pediatric Oncology-Hematology,
Adana, Turkey; 2 Baskent University, Department Of Pediatric Surgery,
Adana, Turkey; 3 Baskent University, Department Of Pathology, Adana,
Turkey
Background/Objectives: Intestinal mucor mycosis is a very
rare and frequently a fatal condition in immuno-compromised
patients.
Design/Methods: An 8 year-old male was diagnosed as
stage III NHL in another hospital. Before admission to our
center, after first course of chemotherapy he had experienced a tumor lysis and posterior reversible ensefalopathy
syndrome (PRESS). We detected a low creatinin clearence,
panhypogammaglobulinemia, B type lymphopenia and partial response of lymphoma. Immunosupression type could
not be adressed if it was primary or secondary. Intravenous
Immunoglobulin (IVIG) was administered and B block of
SIOP ABSTRACTS
S480 of S518
BFM regimen was started. Febrile neutropenia was occured
early. Meropenem, teicoplanin and fluconazol were given as
emprical treatment. Amikacin was added for resistant fever. In
5th day of antibiotics, he had abdominal cramps and vomiting.
There were fluid levels in plain X-ray. Nasogastric decompression, metronidazol and caspofungin were started. After
3 days of conservative management for cytological improvement, laparotomy was made. In jejunal and ileal segments
there were necrosis and perforations. Ileostomy and segmentary jejunal resection were made. After 2 days, a second
surgery was made with resection of ileum with necrosis. Specimen showed mucor mycosis. Liposomal amfoterisin B was
started.
Results: After the completion of treatment for febrile neutropenia, a course of vinkristin, doxorubicin, cyclophosphamide and etoposide was given. A third surgery was done
for abcess after 40 days of the second surgery. Mucor mycosis
was again displayed in specimen.Amphotericin B was continued for 125 days. We switched to posaconazole because
of kidney functions. Chemotherapy could not be continued
due to fungal infection and nephrotoxicity. Weekly rituximab was adminestered for 4 courses. The patient is still
under follow-up with in remission for 14 months for primary
disease.
Conclusions: This patient was presented because of rare and
highly lethal fungal infection during induction treatment of
Burkitt's lymphoma. He was treated with surgical resections
and antifungal treatment.
Results: We interviewed 33patients with a terminal illness, 27
caregivers, 36staff, 25client representatives and 29community
leaders. In each site, Antivirals were used effectively. Children
valued being treated with dignity and respect without discrimination. Being supported at home reduced physical, emotional
and financial burden of traveling to and care at health facilities. Practical support and instruction in feeding and bathing
patients facilitated a good death at home with all the information given.
In each community mobile phones enabled access to clinical and social support work Client representatives and community leaders reported that caring for the HIV/AIDS children especially in poor communities was stressful, but also
rewarding, with resilience forced by having good treatment
therapies.
Conclusions: This programme was new and it was reported to
be successful because they integrated symptom control with
practical physical care, education and spiritual care for these
children. Holistic pediatric palliative care can be delivered
effectively in the face of community leaders and integrated
in public health approach.
T R E AT M E N T A N D CA R E PSYCHOSOCIAL (PPO)
PO-097 Breaking the Barrier of Childhood
Cancer Treatment Abandonment: The Case of
Ghana
T R E AT M E N T A N D CA R E PA L L I AT I V E CA R E
PO-096 Palliative Care for Children Case Study
at Taso Uganda
S. Nandaula1
1 Uganda
Cancer Institute, Palliative care and research, Kampala, Uganda
Background/Objectives: Many people live and die of pain
in Uganda. A study was done to describe family, and leaders
from different communities on the impact of each community
based service delivery and interventions. The major objective
was to see that all childern are cared for with diginity especially when diagnosed with a terminal illness
Design/Methods: Different modules were used in Uganda
and there after rapid evaluation fields techniques in each community was done, getting data from three sources: observations of clinical and the encounters, interviews with informants and the local healthy leaders not forgetting data collections and statistics
A. Sarpong1
1 Korle
Bu Teaching Hospital, Department of Child Health, Accra, Ghana
Background/Objectives: High Treatment abandonment rates
is a major contributor to treatment failure in developing countries. In 2010, 62% of children receiving treatment for cancer
abandoned treatment in Ghana. In the same year, an International Twinning project commenced. There has been a continuous decline in the number of children that interrupted treatment between 2010 and 2016. This paper assesses the factors
motivating parents to continue with treatment, despite daunting constraints; and the contributions of the Twinning Project
towards the progress made.
Design/Methods: Key project activities include training
(workshops and internships), treatment sponsorship, psychosocial support and setting up of data registers. Analysis of
data from two facility-based registers established a consistent
decline in treatment abandonment from 2010 to 2016. With
the aid of questionnaire, 42% of the parents were randomly
selected and interviewed face-to-face, between January and
December 2016. STATA (version 12) was used for the data
SIOP ABSTRACTS
analysis and descriptive statistics employed for the results presentation.
Results: A total of 285 children were presented for cancer
treatment at the two centres in 2016. Participants in the study
were 120 parents (80% females, 20% males). Majority (31%)
said treatment sponsorship was the key enabling condition
helping them continue with treatment. Psychosocial support
(peer counselling-18% and nurse-guardian counselling-17%)
were the most important factors that urged parents on. Other
factors of motivation were financial support from extended
family and other sources (8%), believe in God-(7%), and love
for the child-(6%).
Conclusions: Psychosocial support and treatment sponsorship combined were cited by two-thirds (66%) of respondents
as most important factors contributing to the lowering of treatment abandonment rates. International Twinning partnership
with activities that include training, psychosocial support and
treatment sponsorship hold the potential to lowering treatment abandonment rates in developing countries. Advocacy
for sustainable treatment funding by governments is important
if treatment abandonment could be eliminated in developing
countries.
PO-098 Setting An Agenda for Advocacy,
Research, and Care of Siblings of Children with
Cancer
M. Alderfer1 , M. Goldish on behalf of SPARCCC & Summit
participants2
1 Alfred
I duPont Hospital for Children, Center for Healthcare Delivery
Science, Wilmington, USA; 2 Sibling Partnership for Advocacy- Research
and Care in Childhood Cancer, USA
Background/Objectives: The purpose of this presentation is
to describe the process and outcome of the Sibling Research
Summit, a 1.5 day invitation-only gathering of researchers,
clinicians, advocates, community-partners and siblings of
children with cancer focused upon setting an agenda for advocacy, research, and care of siblings of children with cancer.
Design/Methods: In November 2016, the Sibling Partnership for Advocacy, Research and Care in Childhood Cancer
(SPARCCC) hosted a Sibling Research Summit in Philadelphia, with financial support from Alex's Lemonade Stand
Foundation (ALSF). After introductory remarks from members of SPARCCC and ALSF, the panel of adolescent and
young adult siblings told their stories of how cancer impacted
them and their families. The researchers, clinicians, and advocates then introduced themselves and their work. Recent systematic reviews of the sibling literature were presented and
the group set out to identify priorities for moving advocacy,
research and care of siblings of children with cancer forward.
S481 of S518
Results: Four priority areas were identified and discussed: 1)
Identifying and measuring the “ultimate costs” of childhood
cancer on siblings (i.e., psychosocial development, achievement, financial); 2) Screening siblings of children with cancer
for unmet needs and adjustment difficulties and providing
appropriate levels of care (e.g., education, monitoring, intervention); 3) Developing evidence-based interventions and
empirically evaluating new and existing community-based
interventions for siblings (e.g., oncology camps, SuperSibs);
and, 4) Advancing education and awareness within families,
communities (e.g., schools) and the healthcare system
regarding psychosocial issues faced by siblings in families of
children with cancer and influencing healthcare policy (i.e.,
including siblings in family-centered care).
Conclusions: Progress is being made in understanding and
addressing the psychosocial needs of siblings of children with
cancer, however, coordinated international collaborations of
key stakeholders are needed to propel these efforts forward.
We acknowledge the generous support of ALSF and CIGNA
and whole-heartedly thank all Sibling Research Summit participants.
PO-099 Exploring Family and Staff Educational
Needs at Major Referral Pediatric Oncology
Hospitals: A Qualitative Study in EL Salvador,
Guatemala and Mexico
E. Atwood1 , F. Antillon2 , S. Fuentes Alabi3 , L. Vega-Vega4 , I.
Albanti5
1 Harvard
T.H. Chan School of Public Health, Global Health & Population,
Boston, USA; 2 Unidad Nacional de Oncologia Pediatrica, Pediatric
Oncology, Guatemala City, Guatemala; 3 Benjamin Bloom National
Children's Hospital, Centro Medico Ayudame a Vivir, San Salvador, El
Salvador; 4 Hospital Infantil Teleton de Oncologia, Pediatric Oncology,
Queretaro, Mexico; 5 Dana Farber/Boston Children's Cancer and Blood
Disorders Center, Global Health Institute, Boston, USA
Background/Objectives: Best practices for identifying and
matching the informational needs of parents at the time of
their child's diagnosis with cancer are currently unknown, and
research in low- and middle-income countries is even more
limited. There is also little guidance about how to deliver
information to parents and in what setting. Aspects to consider when developing the information include the socioeconomic level of parents, cultural or language barriers, and the
availability of qualified personnel or resources to create educational materials. This study assessed how families receive
information and explored further needs regarding the most
important topics and the desired method of communication.
Design/Methods: A qualitative study was designed and over
50 in-person interviews were conducted in English and Spanish using a structured guide. Key informants included parents, physicians, nurses, psychosocial staff, administrative
SIOP ABSTRACTS
S482 of S518
and foundation leadership, volunteers, communication and
government professionals. The study sites included Unidad
Oncología Pediátrica in Guatemala, Benjamin Bloom Hospital in El Salvador, and Hospital Infantil Teletón de Oncología
in Mexico. NVivo was used for thematic analysis.
Results: Across all sites, the most common questions were:
Why my child? What is cancer? How do I discuss this with my
other children? The educational needs included explaining the
origin of cancer and addressing perceptions of guilt and myths
about cancer, how to care for the child at home and adherence
to treatment. The preferred communication medium was an
audiovisual tool such as a video, with internet and radio as
secondary options.
Conclusions: This study demonstrates that educational needs
of parents differ despite geographic proximity and shared
language. Developing an educational program in resourcelimited settings can be challenging, but it is crucial to maintain family participation. This study can be used as a guide
for other programs wanting to develop educational materials.
Further research could evaluate the effectiveness of the information in educating parents.
PO-100 The Effect of Sexual Health on Body
Image and Self Esteem Among Adolescents and
Young Adults with Cancer
Y. Ben-Gal1
1 Schneider
Children's Medical Center of Israel, Pediatric
Hematology-oncology, Petach-Tikva, Israel
Background/Objectives: During adolescence hormonal,
physical and mental changes occur. These changes effect body
image, self esteem and sexual health,and are more complex
in teenager cancer patients. The disease and therapies, effect
negatively on their body image and self esteem.
Objectives - identify the variables affecting self esteem, body
image and sexuality among teenagers cancer patients
Design/Methods: During 4 years, data was collected via
interviews with 26 adolescent cancer patients that treated
in the Department of Pediatric Hematology Oncology of
SCMCI.
Results: Fourteen adolescent boys and 12 girls participated.
Average age was 16.46 years, Female adolescent possessed a
lower self-image and body image than their male counterparts
(p < 0.0025). A decrease was found in body image among
male adolescents who underwent fertility preservation procedure, (3.1) compared to those who had not (3.6) (p < 0.001).
Female teenagers with GnRH antagonist treatment reported a
significantly higher self-image and body image compared to
those not treated (p < 0.014).
Adolescents who engaged in their sexuality prior to their illness experienced a decrease in self-image and body image.
Pearson test showed positive correlation (0.67) (p < 0.00)
between body image and self-image, and negative correlation
(-0.57) (p < 0.001) between body image and side effects.
Regression analysis of demographic data and sexually related
variants found higher satisfaction with body image (p < 0.00),
intimate behavior prior to illness (p < 0.001) and parental marital status (married) are predictive of higher self-esteem during treatment.
Conclusions: Self-esteem and body image are negatively
affected by side-effects of cancer treatment. As the perception of the side effects by the teenagers is greater, there is a
decrease in body-image and self-esteem. There is a need for a
comprehensive preparation prior to fertility preservation procedures and medical treatment with explanations and emotional support for adolescents. Preparing such an intervention,
further study on the effect of fertility preserving procedures on
body-image and self-esteem are needed.
PO-101 Health Related Quality of Life During
Treatment in Adolescents Aged 12-18 Years with
Cancer
M. Bult-Mulder1 , S. Sasja1,2,3 , K. Van Bindsbergen1 , H. de
Ridder-Sluiter1 , V. Chris4 , V.L. Raphaela5 , M. Hans2 , V.N. Max1 ,
G. Martha1,2
1 Prinsess
Máxima Center, Psychosocial Research & Healthcare Innovation,
Utrecht, The Netherlands; 2 Emma Children's Hospital- AMC, Pediatric
Oncology, Amsterdam, The Netherlands; 3 St. Jude Children's Research
Hospital, Psychology, Memphis, USA; 4 Amalia Children's HospitalRadboud University Medical Center, Medical Psychology, Nijmegen, The
Netherlands; 5 VU Medical Center, Pediatric Hematology/Oncology,
Amsterdam, The Netherlands
Background/Objectives: A cancer diagnosis influences
health related quality of life (HRQOL). The objectives for this
study are: 1) to describe the HRQOL of adolescents aged 1218 years in active treatment for cancer and compare them to
their healthy peers, 2 ) to get insight in the oncology specific
HRQOL during treatment.
Design/Methods: HRQOL was measured using the PedsQL (Pediatric Quality of Life Inventory) 4.0. Mean scale
scores were compared between adolescents with cancer
(N=73, Mage=14.71, SD=1.85) and a healthy reference group
(N=268, Mage=14.23, SD=1.51) using MANOVA analysis.
To measure Cancer-specific HRQOL, the PedsQL Cancer
Module 3.0 was used. Scores were dichotomized as absence
of problems (‘never-almost never’) and prevalence of problems (‘sometimes- often, almost often). Percentages were calculated to determine the proportion of adolescents reporting
problems on the PedsQL Cancer module 3.0.
SIOP ABSTRACTS
S483 of S518
Results: Adolescents under active cancer treatment reported
significantly lower physical (Mcancer 57.11, Mcontrol 85.58),
emotional (Mcancer 72.05, Mcontrol 76.36), social (Mcancer
78.56, Mcontrol 88.84), school (Mcancer 57.67,Mcontrol 75.47),
psychosocial (Mcancer 69.43, Mcontrol 80.22), and total HRQOL
scores (Mcancer 65.14, Mcontrol 82.09), all ps<.05, effect sizes
were small to large (ɳ2= .10 to .44). Prevalence of cancer
specific HRQOL problems was highest for items on pain
(hurt in joint or muscle, 42.9%), nausea (nausea during
treatment 47.1%, food doesn't taste good 54.3%, nausea when
smelling food 61.4%), worry (about relapse 45.7%, about side
effects 52,9%), cognitive (problems paying attention 47.1%)
and physical appearance (not looking good 47.1%) domains.
Conclusions: Lower HRQOL and Cancer specific problems
are experienced on both physical and psychosocial domains.
Monitoring of HRQOL is of utmost importance to adequately
support adolescents. Interventions should focus on physical
aspects of relieving pain and nausea but also on information
about treatment to decrease worrying, help with schoolwork
and support for dealing with body image.
PO-102 Preliminary Feasibility and Acceptability
of Light Therapy to Increase Energy in Adolescents
and Young Adults Newly Diagnosed with Solid
Tumors
V. Crabtree1 , H. Zhang2 , J. Brigden1 , L.A. Christy1 , M. Wilson3 , A.
Pappo4
1 St
2 St
Jude Children's Research Hospital, Psychology, Memphis, USA;
Jude Children's Research Hospital, Biostatistics, Memphis, USA;
3 University of Tennessee Health Science Center, Ophthalmology, Memphis,
USA; 4 St Jude Children's Research Hospital, Oncology, Memphis, USA
Background/Objectives: Fatigue is one of the most consistent, distressing symptoms reported by pediatric oncology patients. Bright white light has been shown to prevent
increases in fatigue in adult breast cancer patients and reduce
fatigue in adult cancer survivors. However, no definitive intervention to reduce fatigue has been developed for pediatric
oncology patients. The current study was designed to estimate
the feasibility and acceptability of bright white light as an
intervention to decrease fatigue in adolescents/young adults
(AYA) who are newly diagnosed and receiving treatment for
solid tumors, including lymphoma.
Design/Methods: Twenty-nine AYA (ages 12-22) diagnosed
with a solid malignancy, including lymphoma, in the past
30 days who have begun cancer-directed therapy have been
approached to participate. Participants were randomized to
receive dim red light (DRL, n = 12) or bright white light
(BWL, n = 11) for 30 minutes upon awakening daily for eight
weeks. Side effects are assessed weekly via modified Systematic Assessment for Treatment Emergent Effects (SAFTEE).
Results: Feasibility of the intervention was a priori defined as
at least 65% of participants consenting to participate. At preliminary data check, 79.3% of approached participants (n=23)
consented, demonstrating initial evidence of feasibility. To
determine acceptability, a stopping rule was developed to
evaluate side effects of extreme headache or eye strain after
the first 15 participants completed intervention. Preliminary
findings demonstrate that no DRL patients reported extreme
headaches or eye strain. One BWL patient reported extreme
blurred vision during week 2, and no BWL patients reported
extreme headache.
Conclusions: Preliminary findings of this feasibility and
acceptability trial of bright white light to reduce fatigue in
AYA newly diagnosed with solid tumors demonstrate that use
of light therapy is both feasible and acceptable. Measures of
fatigue, mood, and adherence continue to be collected and
should provide additional information regarding potential efficacy of this promising intervention.
PO-103 Managing Your Health: Development of
a Self-Management Skills Intervention to Overcome
Barriers to Transition Readiness Among Adolescent
and Young Adult (AYA) Cancer Survivors
A. Viola1 , M. Masterson2 , D. Carey2 , S. Stephens2 , S. Manne1 , K.
Devine1
1 Rutgers-
Cancer Institute of New Jersey, Medicine/Population Science,
New Brunswick, USA; 2 Rutgers- Cancer Institute of New Jersey, Medicine,
New Brunswick, USA
Background/Objectives: Childhood cancer survivors are
a growing population who are at risk for adverse late
effects from treatment. Survivors require lifelong “risk-based”
follow-up care; however, less than 1 in 5 survivors obtain the
necessary care. Many survivors are lost to follow-up in the
transition from pediatric to adult follow-up care, partially due
to low “transition readiness” or having the skills, motivation,
and resources to make the transition. Few interventions have
been developed to improve transition readiness among adolescents and young adults (AYAs) with cancer. This study aimed
to identify the content of the self-management intervention for
AYA survivors.
Design/Methods: Initial interviews with 19 AYA survivors
of pediatric cancer identified barriers and facilitators to riskbased care. Next, we conducted interviews with 5 AYA
survivors (ages 18-25, 3 female), 1 parent and 3 medical providers to identify essential components of a selfmanagement intervention. Informed by these interviews and
the Social-Ecological Model of Readiness to Transition, the
basic content of the intervention was developed. Three AYA
survivors gave feedback on intervention modules. Thematic
SIOP ABSTRACTS
S484 of S518
content analysis by two independent raters was used to identify targets for the intervention.
ily members affects medical care providers’ attention, availability and energy as well.
Results: The major themes for the self-management modules included: understanding treatment and the survivorship
care plan, the logistics of managing health care and insurance, negotiating family involvement in care, dealing with
emotions, and staying healthy in the context of life transitions.
Initial feedback from the AYA survivors indicated that the
content was relevant, but should include interactive elements
(narrated presentations, videos, tailored feedback) to make the
intervention more engaging.
Conclusions: Childhood cancer is a complicated problem
in Syria. Unsafe hospital locations and difficulties of transport during wartime and other problems create challenge in
childhood cancer management and increase the psychological burdens facing patients, their families and health care
providers.
Conclusions: Incorporating AYA survivors, parents, and
providers in the design phase has been essential to
content development for the self-management program.
We are currently refining the content to be used in a
randomized controlled trial with AYA childhood cancer
survivors.
PO-104 Psychological Challenges Faced When
Fighting Childhood Cancer During Wartime in
Syria
O. Fawaz1 , A. F PATENAUDE2
1 al
bairouni university hospital for cancer, pediatric department, damascus,
Syria; 2 Dana-Farber Cancer Institute, Center for Cancer Genetics and
Prevention, Boston, USA
Background/Objectives: Childhood cancer is a challenge for
the child, his/her parents and medical care providers in limited resource countries. When war conditions and violence are
present, treatment is much harder, physically and emotionally
for all involved.
Design/Methods: From observations and discussions with
colleagues, patients and parents during the 7 years in which
much of Syria has experienced war, we report on ways in
which occurrence of war and associated hardships adds multiple burdens and challenges, threatening the psychological equilibrium and coping efforts of patients, parents and
providers. Observations occurred at the Department of Pediatric Oncology at Al Bairouni Hospital in Damascus, one of
3 Syrian hospitals offering specialized pediatric cancer treatment
Results: Disempowerment was the major psychological burden. Fear, anxiety and loss of hope were also difficult. Psychological challenges faced when treating cancer during wartime
include: changing the life priority of the child and his/her
family, lack of medication availability and increased costs,
difficulties and dangers of transport of patients to and from
the hospital location, and the heavy, resulting psychological
impacts on patient, parents and medical care providers. Exposure to war and worry about the safety of near and distant fam-
PO-105 A Service Evaluation Comparing the
Need for Psychology Input Between Paediatric
Neuro-Oncology Patients and Paediatric Oncology
Patients Within the Leeds Teaching Hospitals Trust
Between 2005-2009
S. Haley1 , E. Hirst1 , S. Wilkins2 , K. Shimmon2 , R. Donaldson2
1 University
of Leeds, School of Medicine, LEEDS, United Kingdom; 2 Leeds
Teaching Hospitals Trust, Paediaric Oncology, Leeds, United Kingdom
Background/Objectives: Children with brain cancer are
known to be more likely to suffer from suicidal ideation
and depression than their other oncology counterparts. We
hypothesised the need for psychological input would be higher
in paediatric neuro-oncology patients compared to other paediatric oncology patients. We aimed to assess the need for
psychological services within the paediatric oncology department and alter services to meet demand.
Design/Methods: Patient data were collated from the
database within the paediatric oncology department at LTHT
from a five year period. We collected information on the
patients’ age at diagnosis, gender, tumour type and treatment
received, including number of psychology referrals made and
reasons for referral. Treatments types and combinations were
coded for interpretation.
Results: Data was collected for 556 patients, and of these, 102
were referred to clinical psychology services within LTHT.
Nearly 45% of the neuro-oncology patients were referred to
psychology compared to 12% in the other oncology group.
There were no significant differences for gender or age. The
most common treatment for a significant majority(?) of referrals was chemotherapy only – potentially due to long hospital
stays and the disruption to daily life.
Conclusions: The results are consistent with existing research
strengthening further the argument for targeted specialised
psychological support in this group. Clinical implications for
the service are discussed.
PO-106 Survivorship Identity in Childhood
Cancer Survivors and their Parents: Results from
Project Reach
SIOP ABSTRACTS
C. Hungr1 , L.B. Kenney1 , C.J. Recklitis1
1 Dana
Farber Cancer Institute, Pediatric Oncology, Boston, USA
Background/Objectives: Health implications of “Survivor”
and “Victim” identity have been described in adult cancer survivors, but little is known about identity in childhood cancer
survivors (CCS). This study investigated CCS and their parents’ views on the child's survivorship identity, and the association of identity with the child's functioning.
Design/Methods: Fifty-nine CCS (34% female, Mean
age=16.7) from a prospective cohort study rated their identification with “Survivor” and “Victim” identity on a five-point
scale, perceived impact of cancer on their identity, and
frequency of thought about their cancer. Parents completed
parallel ratings on perception of their child's identity, impact
of cancer on their child, and frequency of their own thoughts
about their child's cancer. Identity terms were dichotomized
into high and low (cutoff ≥3). Current functioning was
assessed by the PedsQL.
Results: Overall, few CCS (3.5%) or parents (5.2%) endorsed
“Victim” identity, while a majority of CCS (78%) and parents (86%) endorsed “Survivor” identity. PedsQL scores were
not associated with parent or child ratings of either identity.
Within parent-child dyads, a significant number of parents
(16/59) thought about the cancer more frequently than their
child did (Kappa=0.19). Also, dyads disagreed significantly
on endorsement of “Survivor” identity, where 19 of 59 dyads
gave discrepant ratings (K=-0.09). Of these 19, 12 resulted
from parents endorsing their child as “Survivor” while their
child did not. Dyads agreed significantly on the impact cancer
had on child's identity (K=0.24).
Conclusions: Few CCS or parents identify with the term
“Victim,” though they commonly identify with the term “Survivor.” Although parent-child dyads agreed on the impact cancer had on CCS identity, parents overall thought about the
cancer more frequently, and were more likely than their child
to see their CCS as a “Survivor.” Notably, CCS identity was
not related to quality-of-life. Future study could explore longterm functional implications of survivorship identity.
S485 of S518
Background/Objectives: Facilities and programs targeting
adolescents and young adults (AYAs; aged 15-39) are now
emerging within community cancer centers in the United
States. We describe the formation and first meeting of a community AYA stakeholder council and report the discussion
themes and priorities of this group.
Design/Methods: We created a stakeholder council to identify the healthcare needs and preferences of AYAs treated at
community cancer centers. The group, which included nine
patients/survivors, two parents, one spouse, one sibling, two
researchers, and an AYA-focused child life specialist, convened at a one-day workshop moderated by CanTeen Australia. Participants shared and compared their healthcare experiences and identified unmet needs. Workshop notes were analyzed using inductive content analysis to identify themes. The
group also prioritized topics for future discussion and action.
Results: The experiences of AYAs treated at community
centers varied widely, but the majority reported satisfaction
with their cancer treatment experience. Experience, identity,
expression, and advocacy were the major themes of discussion.
The group was enthusiastic about sharing stories and advocating for others. They identified topics for future discussion by identifying and ranking the greatest healthcare-related
needs of AYAs at community medical centers. Peer connection was identified as the most pressing need, followed by
government advocacy to improve programming and financial
support, complementary medicine, research & clinical trials,
staff education, choice & voice in decision-making, fertility,
survivorship, and mental health services.
Conclusions: Most AYAs reported positive treatment experiences at community medical centers. They desire more peer
connection, financial support and empowerment in healthcare
decision-making.
PO-108 Development of the First Psychosocial
Oncology Program in Armenia
A. Kamalyan1 , Y. Asribabayan1 , J. Fernandez2 , B. Delaney2 , I.
Albanti3 , L. Lehmann4 , L. Sargsyan1 , A. Avagyan1 , L. Safaryan1 ,
G. Tamamyan1
PO-107 Putting Ayas in a Room Together:
Launching an Adolescent and Young Adult
Oncology Council
R. Johnson1 , B. Pflugeisen2 , P. Patterson3 , C.F. Macpherson2 , B.
Ray2 , J. Rebecca2
1 Mary
Bridge Children's Hospital/MultiCare Health System, Pediatric
Hematology/Oncology, Tacoma, USA; 2 Mary Bridge Children's
Hospital/MultiCare Health System, MultiCare Institute for Research and
Innovation, Tacoma, USA; 3 CanTeen Australia, CanTeen Australia, SydneyNSW, Australia
1 Muratsan
Hospital Complex of Yerevan State Medical University, Clinic of
Chemotherapy, Yerevan, Armenia; 2 Dana-Farber/Boston Children's Cancer
and Blood Disorders Center, Department of Psychosocial Oncology and
Palliative Care, Boston, USA; 3 Dana-Farber/Boston Children's Cancer and
Blood Disorders Center, Global Health Initiative, Boston, USA;
4 Dana-Farber/Boston Children's Cancer and Blood Disorders Center,
Pediatric Stem Cell Transplant Center, Boston, USA
Background/Objectives: Historically in Armenia, cancer
has been viewed exclusively as a medical issue and there were
no comprehensive psychosocial services offered to patients. In
an effort to integrate psychologic care into multidisciplinary
SIOP ABSTRACTS
S486 of S518
cancer care we developed a psychosocial oncology program.
The aim was to provide support to pediatric and adult cancer
patients and their families beginning at the time of diagnosis
and continuing throughout the course of treatment.
Thus, in March 2016 at the Clinic of Chemotherapy of Muratsan Hospital Complex of Yerevan State Medical University,
with the support of Dana-Farber/Boston Children's Cancer
and Blood Disorders Center Global Health Initiative (DF/BC
GHI) and City of Smile Foundation, the first psychosocial
oncology program in Armenia was established. The program
is staffed by two psychologists (part-time).
Design/Methods: Program development has included the
review and analysis of examples of psycho-oncology delivery
of care in high, low– and middle-income countries (LMIC),
design of a psychosocial model of care, creation of a needs
assessment tool and format for clinical progress notes, translation of psycho-educational materials for patients, families,
providers, and development of mechanisms for involving volunteers into the service. These activities and others have been
carried out in ongoing consultation with the specialists of
DF/BC GHI.
Results: As a result of the program development the following services are now available to patients and families: psychosocial assessment, individual psychotherapy for patients
and their families, group counselling for children and parents,
bereavement support, psychoeducation, organized sociocultural activities. During the first year 22 children and their parents (100% of pediatric patients, 176 discrete visits) and 58
adult patients and their relatives (48% of adult patients, 194
visits) received psychosocial support.
Conclusions: Psychosocial programs for oncology patients
can be successfully implemented in LMIC. Our program can
serve as a model for other cancer delivery programs in Armenia and can be replicated in other LMIC.
1
1,2
1
Results: The children were diagnosed as ALL, AML, or neuroblastoma etc. at the age of 0 to 15. Four families have experienced the disease before the disaster. At the beginning of
the hospitalization, almost all the children missed families and
schoolmates. Some mothers suppressed their fear for the prognosis, and faced their children's disease optimistically. Fathers
tended to give priority to work, but fathers’ emotional support
encouraged mothers. If parents needed the other family members’ assistance (i.e. healthy siblings’ or grandparents’), they
shared the diagnosis with them. Some sibling somatized psychological distress during prolonged hospitalization, when no
one played mother's role at home. The impacts of the disaster
varied according to causes (earthquake, tsunami, or radioactive contamination) and degree of the damages they received.
Some families had increased cohesiveness through facing the
disease, and overcame the disaster. In the opposite direction,
some families gained strength by overcoming the disaster,
and struggled with the disease constructively. A survivor in
their young adulthood reaffirmed that happiness means living
a normal life.
Conclusions: Although the families had experienced two big
trauma, they were able to struggle with the second one in
mighty heart in the case families had increased cohesiveness
by the first one. We will analyze their longitudinal narratives
to clarify challenges, because there might be long-run biopsycho-social effects of both trauma on the families.
M.F.M. Manhaes1 , C.D. Bergerot1
1 Universidade
1
K. Kamibeppu , K. Kurihara , M. Ikeda , I. Sato , T. Soejima , R.
Kikuchi1,3 , S. Suzuki1 , Y. Nagoya4 , Y. Yamane4 , M. Takahashi4 , H.
Hayasaka4 , R. Tsuda4 , M. Imaizumi5 , A. Sato5 , H. Shiwaku6 , Y.
Suzuki6 , Y. Inoue6 , Y. Sasahara6 , T. Rikiishi6
1 The
Design/Methods: This study is a part of an ongoing longitudinal study started in April 2015. We conducted a semistructured interview every 6 months for 3 years for 7 families
who experienced childhood cancer and the earthquake. We
analyzed the first interviews of the families by content analysis.
PO-110 Distress and Biopsychosocial Needs of
Brazilian Adolescent and Young Adults Patients
with Cancer
PO-109 The Struggle of Families Who
Experienced Childhood Cancer and Great East
Japan Earthquake Disaster
1
Background/Objectives: To clarify the struggle of families
who experienced two big trauma such as childhood cancer and
the Great East Japan Earthquake Disaster.
Universty of Tokyo, Department of Family Nursing- Graduate School
of Medicine, Tokyo, Japan; 2 Tokyo Women's Medical University, School of
Nursing, Tokyo, Japan; 3 Osaka University, Division of Health SciencesGraduate School of Medicine, Osaka, Japan; 4 Miyagi Children's Hospital,
Nursing Department, Miyagi, Japan; 5 Miyagi Children's Hospital,
Department of Hematology/Oncology, Miyagi, Japan; 6 Tohoku University,
Graduate School of Medicine, Miyagi, Japan
Federal de São Paulo, Departament of clinical and
experimental oncology, São Paulo, Brazil
Background/Objectives: A cancer diagnosis can negatively
affect the biopsychosocial functioning of adolescents and
young adults (AYA).This study aims to describe levels of, and
relationships between, distress and biopsychosocial unmet
needs in a sample of Brazilian AYA patients with cancer.
Design/Methods: A study was conducted among 122 AYA
patients with cancer aged 18 to 35 years, treated at a Brazilian public hospital. They were assessed using the Distress
SIOP ABSTRACTS
Thermometer, the Hospital Anxiety and Depression Scale
and the Functional Assessment of Cancer Therapy - General.
Descriptive statistics were obtained for all measures, itemlevel frequencies were examined to identify common unmet
needs and relationships between distress and unmet needs
were explored.
Results: AYA patients were mostly were male (50.8%), single (54.1%), white (52.5%), diagnosed with, central nervous
system (31.1%), hematologic (23%) or genitourinary (15.6%)
cancers, at an advanced disease stage (41.8%). AYA reported
greater distress (50%), being commonly related to practical (60.7%), emotional (73.8%) and physical (86.1%) problems. Financial (32%), worry (56.6%), nervousness (50%),
sadness (31.1%), pain (47.5%), fatigue (39.3%), memory concentration (35.2%), and sleep (32%)were the highest scored.
However, 25.4% reported clinical symptoms of anxiety and
9.8% of depression. AYA patients reported poor levels of
quality of life that is at 50th percentile of the US norm.
Distress, symptoms of anxiety/depression and quality of life
were significantly associated with biopsychosocial problems
reported (p<.001). Higher levels of distress was predicted by
symptoms of anxiety (B=0.2; p<.001), depression (B=0.2;
p<.001), emotional (B=0.8; p<.001) and physical (B=0.3;
p<.01) problems.
Conclusions: Brazilian AYA patients reported high levels
and numbers of unmet needs and substantial distress. Strong
associations were found between increased distress and more
unmet needs. Findings suggest the need for psychosocial intervention for Brazilian cancer patients that target helping them
cope with biopsychosocial distress. Further, this preliminary
data highlight opportunities to re-orientate services to better
meet AYA needs.
PO-111 Reflective Practice and Leadership in
Global Pediatric Hematology/Oncology
P. Mehta1 , J. Slone1 , K. Chinyundo1 , E. Ishigami2 , P. Wasswa1 , A.
Anderson1 , D. Niremberg1 , M. Noli1 , S. Kahan1 , J. Lubega1 , G.
Airewele1 , E. Fruge1
1 Baylor
College of Medicine, Pediatrics, Houston, USA; 2 Texas Children's
Hospital, Cancer and Hematology Centers, Houston, USA
Background/Objectives: TXCH Global HOPE operates
projects in sub-Saharan Africa (SSA). Placement in leadership positions in such settings can present significant challenges beyond the scope of pre-service orientation. We have
expanded our evidence-based Reflective Practice & Leadership Seminar (RP&L) methods to provide ongoing leadership education for team members in SSA and fellows in
the East African Pediatric Hematology-Oncology Fellowship
Program.
S487 of S518
Design/Methods: One hour teleconference seminars are routinely conducted with faculty, staff and fellows in 4 sites
in Sub-Saharan Africa. Seminar participants present current
challenges and seasoned faculty guide the discussion through
a disciplined, step-wise analysis including a “diagnosis” of the
situation and a plan for strategic action – the leadership dimension of a health care professional's role.
Results: Topics covered in the seminar included the challenges of introducing a new sub-specialty into a country,
bringing new staff members onto a team, negotiating care
delivered by an ancillary in-country service, petitioning for
resources within the context of a larger local organization,
negotiating for the change of medical personnel provided
through a separate institution, and negotiating change within
an external institution that directly affects program function.
Self-report post-seminar questionnaires indicated participants
strongly agreed (5 on 1-5 scale) with the following statements:
the seminar improved their ability to 1) analyze complicated
clinical service situations 2) navigate inter-institutional politics, and 3) effectively build cross-service relationships to
improve patient care.
Conclusions: This Global Leadership Seminar has demonstrated success in helping our SSA staff and trainees improve
leadership capacity and negotiate change effectively.
PO-112 Health-Related Quality of Life in
Mothers with Children with Cancer: A Systematic
Review
C. Nicolaou1
1 Cyprus
University of Technology, Nursing, Limassol, Cyprus
Background/Objectives: Studies among parents of children
with cancer have focused on anxiety, depression, or posttraumatic stress, and less so on overall measures, such as
Health-Related Quality of Life (HRQoL).
Design/Methods: Literature review in Scopus and Cinahl
with terms: mothers OR carers etc AND child* OR adolesc*
etc AND cancer or oncolog* etc AND quality of life OR
HRQoL etc, in 65 combinations. Selection criteria: mothers
(or predominately in mixed samples), children aged<18 in
active treatment (no palliative), quantitative, some measure of
quality of life, comparative (e.g. population norms, or control
group) or correlational, or baseline in interventions, English
language, prior 2016.
Results: Of 237 studies reviewed in full-text among 2184,
10 fulfilled all criteria: 6 mothers only, 4 mixed with separate results for mothers, and additional 10 with sample of predominately mothers. With the exception of a series of studies
from Canada (N>400), most studies had small sample sizes
(N<150). European studies originated from limited number of
settings. There were single-sample correlational studies (e.g.
SIOP ABSTRACTS
S488 of S518
coping, anxiety, depression, sleep quality), internal comparisons (e.g. single- vs two-parent families, time since diagnosis, or same group longitudinal, etc) or external (i.e. mothers
of healthy children, or other diagnosis, or population norms).
SF-36 was commonly used. In studies with external comparison, quality of life was significantly reduced amongst mothers (or parents) of children with cancer. Despite cross-national
heterogeneity, in studies that the SF-36 commonly effect sizes
were in the range of 0.5-1 SD for mental health and ∼0.5 SD
for physical health dimension.
Conclusions: Physical health as well as mental health aspects
of the quality of life appear affected in this vulnerable group,
highlighting the need to monitor and incorporate QoL as an
outcome measure in assessing the effectiveness of psychosocial intervention programs.The main message is: The Quality
of life is compromised in mothers of children with cancer.
PO-113 Integrating Young Adult Feedback into
the Cross-Cultural Adaptation of an Advance Care
Planning Guide for Brazilian Youth Living with
Cancer
M. N. F. Arruda-Colli1,2 , M. A. Santos1 , S. Z. Bedoya2 , É. A.
Oliveira-Cardoso1 , L. Wiener2
1 University
of Sao Paulo, Faculty of Philosophy- Sciences- and Letters at
Ribeirao Preto, Ribeirao Preto, Brazil; 2 National Cancer Institute,
Pediatric Oncology Branch, Bethesda, USA
Background/Objectives: Given the importance of having
culturally appropriate tools to initiate advance care planning
conversations with young adults, a cross-cultural adaptation
of Voicing My CHOiCESTM (VMC) in Brazil is underway.
Design/Methods: VMC was translated to Portuguese by 2
bilingual translators. A synthesis version was defined and submitted for semantic validation by experts. Patients aged 18-39
undergoing cancer treatment were then invited to evaluate the
modified version in terms of clarity, cultural and age appropriateness, helpfulness and stressfulness. The revised version
was back-translated to English by 2 bilingual translators and
discussed with VMC's authors to refine the final Portuguese
version. Quantitative data were analyzed by descriptive analysis, while qualitative data were evaluated by thematic content
analysis.
Results: Nine experts and 15 patients were enrolled. Overall, experts evaluated the tool as “totally adequate” or “adequate” in regards to document structure, relevance of topics
covered and adequacy of use across settings with the targetpopulation. Suggestions for adaptation focused on cultural,
legal and linguistic aspects. The document was revised and
then introduced to patients. Over 80% of the patients considered all topics covered to be age and culturally appropriate. Similarly, over 80% of the participants found all the top-
ics to be “very helpful” or “helpful” except for the section
that addresses funeral planning, which only 53% described
as “helpful” and endorsed as being “very stressful”. Patients’
feedback focused on cultural aspects and how to incorporate
the tool into the treatment trajectory.
Conclusions: Obtaining the target-population feedback during the semantic validation was essential to ensure appropriate linguistic and cultural adaptations. Further study with the
adapted version of VMC in Portuguese will be implemented
to evaluate the tool's feasibility and to identify potential burdens and benefits of its use.
Acknowledgement: This study is supported by grant
#2016/15269-3, Sao Paulo Research Foundation (FAPESP)
and in part by the NIH Intramural Research Program.
PO-114 A Mixed-Method Study Conducted in
Parents and Professionals to Improve the Concept
and Tools of a Psychosocial Intervention to Support
Parents in Pediatric Oncology
D. Ogez1 , C.J. Bourque1 , K. Péloquin2 , R. Ribeiro2 , D. Curnier3 , V.
Marcil4 , D. Sinnett1 , S. Sultan2
1 CHU
Sainte-Justine, Research center, Montreal, Canada; 2 Université de
Montréal, Psychology, Montreal, Canada; 3 Université de Montréal,
Kinesiology, Montreal, Canada; 4 Université de Montréal, Dietetic,
Montreal, Canada
Background/Objectives: Only two manualized intervention
programs have been effective to reduce parental distress when
the child is being treated for cancer: Bright Ideas and SCCIP.
These programs bear some limitations related to dissemination, focus on the individual vs the family, etc., which we
wanted to deal with in a new integrative program, taking the
best of what is currently available. The aim of this preliminary study was to refine the design of an integrative program
“Regain control together” a 6-session face-to-face intervention to support parents.
Design/Methods: This sequential mixed-method study called
for two steps: (1) parents were invited to an information session on the intervention project and completed a questionnaire on objectives, procedure, manuals and tools; (2) after the
descriptive analysis of the questionnaire responses, areas for
improvement were discussed in a focus group of parents. The
process was repeated with professionals. Descriptive analyses
of questionnaire responses and a computerized thematic analysis (NVIVO) allowed for organizing different categories of
recommendations for program refinement.
Results: Six parents and six professionals participated in the
study. The results showed the strengths of the program: pertinence for solving problem practical approach and couple
intervention. The main areas of improvement were the accessibility of the language for the manuals and the adaptation of
SIOP ABSTRACTS
the program to different cultures. We discuss the program,
recommendations of participants and changes made accordingly. A final version available for a formal Phase II pilot-test
is available and its core features will be presented.
Conclusions: This study illustrates that it is necessary to
include parents and final users in the elaboration of such intervention programs. The final version will now be available for
gradual implementation and testing (feasibility, acceptability,
and effects).
S489 of S518
Conclusions: These findings suggest that pediatric cancer is a
significant stressor for both children and their mothers. Clinicians should be aware of psychiatric symptoms of children
who underwent such a life-threatening condition.
PO-116 Quality of Life in Survivors of Bone
Tumours at Hospital Infantil De Mexico
M.A. Palomo Colli1 , J.Z. Lugo Juárez1 , L.E. Juárez Villegas1 , J.
Mier Cabrera2 , J.F. Gaytan Morales1 , M. Mier Cabrera3 , L.
Barcenas Bobadilla4 , S. Sadowinski Pine5
PO-115 Anxiety, Depression, Burn Out and Post
Traumatic Stress Disorders in Children with
Cancer and Their Mothers
A. Okur1 , E.O. Ozmen1 , E. Güney2 , F.G. Pinarli1 , E.G. Saripinar2 ,
C. Karadeniz1
1 Gazi
University, Pediatric Oncology, Ankara, Turkey; 2 Gazi University,
Pediatric Psychiatry, Ankara, Turkey
Background/Objectives: The aim of this prospective study is
to investigate the prevalence of anxiety, depression, burnout
and posttraumatic stress disorder in pediatric oncology
patients and their mothers.
Design/Methods: Children and adolescents (n=60) aged 8-18
years who were actively treated or followed-up in remission
at Gazi University Pediatric Oncology Department and their
mothers were recruited as the study group. The control group
for anxiety, depression and burnout (n=30) consisted of children without chronic disease who were admitted to General
Pediatric Clinic as outpatients and their mothers. Self-report
questionnaires measuring anxiety and depression were administered to the children and mothers. Post-traumatic stress disorder (PTSD) scale for children and mothers were performed
as face-to-face surveys in the presence of the clinician. The
control group for PTSD (n=15) consisted of children and their
mothers who experiered a serious traumatic event such as traffic accident, earthquake and close relative's death.
Results: There was no significant difference with regard to
anxiety, depression and burn out in terms of any scale score
between children in remission and children under treatment.
The mothers of children under treatment were significantly
more traumatized and more anxious than those of children
in remission. However there was no significant difference in
burnout symptoms between mothers of children under treatment and mothers of children in remission. Children with cancer were more depressed and worried than control groups.
Mothers of healthy children were significantly less depressed
and anxious than mothers of children under treatment and in
remission. We found that there were significantly more PTSD
symptoms in patients both under treatment and in remission
children and mothers of patients than the PTSD control group.
1 Hospital
Infantil de México Federico Gómez, Oncology, México, Mexico;
Nacional de Perinatologia “Isidro Espinoza de los Reyes”,
Subdireccion investigacion en intervenciones comunitarias, México,
Mexico; 3 Hospital Regional Alta Especialidad Ixtapaluca, Pediatrics,
Ixtapaluca, Mexico; 4 Hospital Infantil de México Federico Gómez, Nursing,
México, Mexico; 5 Hospital Infantil de México Federico Gómez, Pathology,
México, Mexico
2 Instituto
Background/Objectives: Patients with bone tumours (BT)
undergo extensive and aggressive chemotherapy treatment
and surgery, which can have significant acute and longterm effects on patients. Considering the high survival rates
of childhood cancer, physical and psychosocial long-term
effects, as well as assessment of health-related quality of
life (HRQoL), are becoming new focus of clinical research.
Patients with these diagnoses are at high risk of poor HRQoL
compared to other childhood cancer survivors.
Assesment the Quality of life in survivors childhood with BT.
Design/Methods: Descriptive and observational study conducted at Hospital Infantil de Mexico “Federico Gómez”. Eligible study participants were enrolled between August 2015
and July 2016. Participants completed a self-administered
questionnaire (KIDSCREEN-52). The instrument measures
ten dimensions: physical well-being, psychological wellbeing, moods and emotions, self-perception, autonomy, parent relations and home life, social support and peers, school
environment, social acceptance (Bullying), and financial
resources. Test items are rated on a 100-point Likert-type
scale. High scores indicate good quality of life
Results: Thirteen BT survivors between 8 and 18 years old,
who were followed at least one year after complete treatment,
participated in this study. Twelve patients with osteosarcoma
and one with Ewing Sarcoma. Seven were male. Four (30%)
had metastasis at diagnosis. Seven (53.8%) had undergone
amputation KIDSCREEN-52 scores were 64 points for physical well-being, 75 for psychological, 76 for autonomy, 79
for school environment and social support and 95 for social
acceptance.
Conclusions: Although many BT survivors report excellent
functional and HRQoL outcomes, a significant number report
long-term disability and impairments. Further follow-up of
this cohort, including reassessment to observe changes in
SIOP ABSTRACTS
S490 of S518
scores and perceived disability over time, is clearly warranted.
We hope this study will help provide patients and families
with needed information about anticipated long-term outcomes and how to maximize function and RHQoL
PO-117 School Performance of Childhood
Cancer Survivors in Korea: A Multi-Institutional
Study on Behalf of Korean Society of Pediatric
Hematology and Oncology (KSPHO)
tumors (52.6% vs. 31.8%, p=0.04). Survivors reported that
they missed school due to physical illness or fatigue (58.0%),
medical care (19.0%), and parents’ concern (19.0%). Approximately 41% of children reported learning difficulty, mainly
due to the difficulty in understanding the materials (58.0%)
or concentration in classes (28.7%). Children who received
hospital school support during cancer treatment repeated less
often than children who did not (8.3% vs. 17.2%, p=0.05). The
school marks in Korean language (p=0.03), English (p=0.04),
and physical education (p=0.04) was worse for the children
with brain tumors than for the children with other tumors.
M. Park1 , J.M. Lee2 , H.J. Park3 , H.Y. Ju3 , B.K. Park3 , J.Y. Kim4 ,
S.K. Park5 , Y.H. Lee6 , Y.J. Shim7 , H.S. Kim7 , J.A. Lee8 , Y.J. Lim9 ,
H.W. Cheuh10 , J.K. Park11 , M.J. Lee12 , S.K. Kim13 , H.S. Choi14 ,
H.J. Kang15 , K.D. Park15 , H.Y. Shin15
Conclusions: This study demonstrated that survivors of cancers require special care and attention when they return to
school. Those treated for brain tumor remain particularly vulnerable.
1 Chungbuk
National University College of Medicine, Pediatrics, Cheongju,
Republic of Korea; 2 Yeungnam University College of Medicine, Pediatrics,
Daegu, Republic of Korea; 3 National Cancer Center, Pediatric Oncology,
Goyang, Republic of Korea; 4 Kyungpook National University School of
Medicine, Pediatrics, Daegu, Republic of Korea; 5 Ulsan University
Hospital- University of Ulsan College of Medicine, Pediatrics, Ulsan,
Republic of Korea; 6 Hanyang University College of Medicine, Pediatrics,
Seoul, Republic of Korea; 7 Keimyung University College of Medicine,
Pediatrics, Daegu, Republic of Korea; 8 Korea Cancer Center Hospital,
Pediatrics, Seoul, Republic of Korea; 9 Chungnam National University
College of Medicine, Pediatrics, Daejon, Republic of Korea; 10 Dong-A
University College of Medicine, Pediatrics, Busan, Republic of Korea;
11 Inje University Busan Paik Hospital, Pediatrics, Busan, Republic of
Korea; 12 Dankook University College of Medicine, Pediatrics, Cheonan,
Republic of Korea; 13 Inha University College of Medicine, Pediatrics,
Incheon, Republic of Korea; 14 Seoul National University Bundang Hospital,
Pediatrics, Seongnam, Republic of Korea; 15 Cancer Research InstituteSeoul National University College of Medicine, Pediatrics, Seoul, Republic
of Korea
PO-118 An Examination of Barriers to Care and
Illness Uncertainty in Parents of Children Newly
Diagnosed with Cancer
M. Perez1 , C. Sharkey1 , D. Bakula1 , A. Mullins1 , S. Mayes2 , R.
McNall-Knapp2 , L. Mullins1
1 Oklahoma
State University, Psychology, Stillwater, USA; 2 University of
Oklahoma Health Sciences Center, Pediatric Hematology Oncology,
Oklahoma City, USA
Background/Objectives: Successful return to school after
cancer diagnosis is important to facilitate the child's normal learning and attainment of academic skills. Absenteeism
in vulnerable cancer survivors might exacerbate treatmentrelated learning challenges. In this study, we addressed the
issue of peer relationship, school attendance and academic
achievement.
Background/Objectives: A subset of caregivers of children
newly diagnosed with cancer are at risk for psychological
distress. Both parental illness uncertainty (IU) and barriers to care have been linked to parental distress. Our previous research indicates that IU may mediate the relationship
between barriers to care and distress. To further evaluate the
pathways by which barriers to care may impact IU, the present
study assessed the relationships between distinct barriers to
care (i.e., pragmatics, skills, expectations, marginalization,
knowledge/beliefs) and specific components of IU (i.e., ambiguity, lack of clarity, lack of information).
Design/Methods: Between July 2015 and December 2016,
15 institutions in Korea participated in this study on behalf
of Korean Society of Pediatric Hematology and Oncology
(KSPHO). We studied 241 children treated for cancer who, at
the time of study, were older than 9 years. The self-reported
paper-and-pencil questionnaire was used in this study.
Design/Methods: Caregivers (N=52) of children newly diagnosed with cancer (MDays =91.1, SDDays =52.3) were recruited
at a Midwest medical center, and completed the Barriers
to Care Questionnaire (BCQ) and the Parent Perception of
Uncertainty Scale (PPUS) as part of a larger study on parental
adaptation to the pediatric cancer diagnosis.
Results: Approximately 21% of the survivors suffered from
lack of friends. Bullying was reported by 29.4% of survivors.
There was no difference in experiencing bullying according
to disease categories. However, survivors who returned to
primary school reported higher incidence of bullying compared to survivors who returned to middle or high school
(22.9%, 10.6% and 6.1%, p=0.03). The percentage of children who missed classes more than 4 days in a month was
higher in survivors with brain tumor than those with other
Results: Expectations significantly predicted ambiguity
(p=0.003), lack of clarity (p<0.001), and lack of information
(p=0.002). Marginalization significantly predicted ambiguity
(p=0.006), lack of clarity (p=0.001), and lack of information
(p=0.012). Skills significantly predicted ambiguity (p=0.013)
and lack of information (p=0.010). Knowledge/beliefs significantly predicted ambiguity (p=0.043) and lack of clarity (p=0.041). Pragmatics significantly predicted ambiguity
(p=0.036).
SIOP ABSTRACTS
Conclusions: Caregivers who perceived low quality of care
or personalized the negative experiences of their child's care
experienced higher ambiguity and deficits in clarity and information concerning the illness. Parents who reported lower
confidence in ability to manage their child's medical care,
experienced ambiguity and lack of information regarding illness and treatment. Lastly, parents who disagreed with medical professionals about care reported increased ambiguity and
lack of clarity. The results suggest that parents perceiving care
as being of low quality or parents disagreeing with medical
treatments are experiencing higher IU. Improvements in communication and relationships between caregivers and the clinical team may reduce barriers and IU, and potentially attenuate
distress.
S491 of S518
between parent psychological distress and child HRQL (b=
-.64, p=.04).
Conclusions: Higher levels of treatment intensity for cancer
put children at risk for poor HRQL, which in turn has implications for long-term social and mental health outcomes. In the
current study, a resiliency effect was observed, where children with a history of high levels of treatment intensity were
buffered from experiencing poor quality of life if they had low
psychosocial family risk.
PO-120 Decision-Making in Pediatric Oncology:
Needs, Preferences and Experiences of Families
E.G. Robertson1,2 , J. Fardell1,2 , R. Cohn1,2,3 , C. Wakefield1,2
1 Sydney
Children's Hospital, Behavioural Sciences Unit- Kids Cancer
Centre, Randwick, Australia
2 UNSW
PO-119 Treatment Intensity and Health-Related
Quality of Life in Pediatric Cancer Survivors: The
Role of Psychosocial Family Functioning
N. Racine1 , B. Russell2 , M. Khu3 , K. Reynolds4 , G. Guilcher3 , F.
Schulte5
1 University
of Calgary, Psychology, Calgary, Canada; 2 Alberta Children's
Hospital, Hematology- Oncology- and Transplant Program, Calgayar,
Canada; 3 Alberta Children's Hospital, Hematology- Oncology- and
Transplant Program, Calgary, Canada; 4 Alberta Children's Hospital, Long
Term Survivor Clinic, Calgary, Canada; 5 Alberta Children's Hospital,
Hematology- Oncology- Transplant Program, Calgary, Canada
Background/Objectives: With increased survival of children
treated for pediatric cancer, attention has turned to their longterm health and well-being. The aim of the current study was
to examine treatment intensity as a risk factor for poor HRQL
(Health-Related Quality of Life) in pediatric cancer survivors.
It was hypothesized that higher treatment intensity would be
associated with lower HRQL. However, it was also hypothesized that family psychosocial functioning (including family
cohesion, social support, and availability of resources) would
buffer survivors from the deleterious consequences of high
treatment intensities.
Design/Methods: Fifty-two pediatric cancer survivors (mean
age=11.92 yrs, Range= 6-17 yrs) and their parents were
recruited during routine follow-up appointments at a hospitalbased long-term survivor clinic and completed questionnaires
addressing HRQL (PedsQL 4.0) and family psychosocial
risk (PAT 2.0). Intensity of treatment was determined via a
standardized tool (Intensity of Treatment Rating Scale) and
was independently rated by two health care providers.
Results: Multiple regression analyses revealed that after controlling for age, sex, and parent psychological distress, treatment intensity (b= -.23, p = .04) and psychosocial family risk
(b= -.61, p<.001) negatively predicted parent-proxy reported
HRQL. Psychosocial family risk moderated the association
Medicine- The University of New South Wales, Discipline of
Paediatrics- School of Women's and Children's Health, Randwick,
Australia; 3 Sydney Children's Hospital, Kids Cancer Centre, Randwick,
Australia
Background/Objectives: Families of children diagnosed
with cancer are faced with difficult treatment decisions,
including radiation therapy, fertility preservation, and
enrolling in research studies. Many patients and parents find
it difficult to understand the rationale and implications of
treatment options. They may also be at risk of experiencing
decisional anxiety and conflict, uncertainty, and distress. We
aimed to qualitatively explore the decision-making process
of parents and young people when faced with a treatment
decision, as well as any information needs and preferences.
Design/Methods: We conducted semi-structured interviews
with recently diagnosed adolescents and parents. Interviews
were audio recorded, transcribed verbatim and analysed via
content analysis using NVivo. To date, 3 adolescents (mean
age=14y) and 8 parents (mean age of child=8y) have completed the interview. The study is still recruiting; anticipated
study close is Mar-17.
Results: To date, 3 adolescents (mean age=14y) and 8 parents (mean age of child=8y) have completed the interview.
Early findings suggest families often engage in parent-driven
or parent-child shared decision-making, with the relationship
with their clinician a major influence in the decision process. Parents tend not to include their child in major decisions (e.g. clinical trial enrolment) due to the age of their
child, however acknowledge the importance for children to
be involved in day-to-day decisions (e.g. pain relief). Some
parents express dissatisfaction with their level of decisionalinvolvement. Barriers to involvement include feeling distressed and overwhelmed with information.
Conclusions: Decision-making in pediatric oncology is complex. Families require clearer information provided in multiple modalities, more guidance to engage in shared decision-
SIOP ABSTRACTS
S492 of S518
making, and more emotional support throughout the decision
process. These findings have contributed to the development
of Delta – an online decision-aid supporting families deciding
whether to enrol in a pediatric oncology clinical trial.
PO-122 Long Term Positive and Negative
Psychological Late Effects for Parents of Childhood
Cancer Survivors: An Updated Systematic Review
K. Shimmon1 , B. Phillips2 , P. Siddell1
1 leeds
teaching hospitals, Paediatric Psychology, leeds, United Kingdom;
of York, Centre for Reviews and Dissemination, York, United
Kingdom
2 University
PO-121 Returning Research Results Caregivers’
Reactions Following Computerized Cognitive
Training Among Childhood Cancer Survivors
S. Scott1 , J. Ashford1 , K. Clark1 , K. Martin-Elbahesh1 , H. Conklin1
1 St.
Jude Children's Research Hospital, Psychology, Memphis, USA
Background/Objectives: Few researchers routinely disseminate results following participation in a study; however,
there is increasing acknowledgment that benefits of returning results far outweigh potential risks. Some researchers
endorse returning research results as another component of
ethical research. Among a pediatric population, specifically,
it is important to determine the preference in which families would like to receive research results and guidelines for
developing a clear summary of results. The current study
explores the practice of returning results to families of childhood cancer survivors following participation in a computerized cognitive training program using Children's Oncology
Group (COG) guidelines.
Design/Methods: In a previous study, survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor
(BT; N = 68) with identified cognitive deficits were randomly
assigned to participate in a computerized cognitive intervention or assigned to a wait-list. Following conclusion of the
previous study, participants’ families were contacted by postal
letter, phone call, and/or patient approach and provided with a
summary of results from the computerized cognitive training
study and a survey gauging their interpretation of the summary, reaction to the results, and preference regarding the
return of results.
Results: Forty-three participants returned the survey and
caregivers indicated they perceived the results as important
(93.0%), helpful (93.0%), relevant to their child (90.7%), and
easy to understand (97.7%). The results provided in the summary were mostly interpreted in a positive manner, with many
endorsing satisfaction (83.8%) and/or relief (41.9%). Further,
many caregivers preferred receiving research results through
postal letter (88.4%) or email (46.5%).
Conclusions: In summary, the benefits of returning research
results regarding the effects of computerized training on childhood cancer survivors far outweigh the perceived risks. The
practice of regularly returning research results can directly
benefit families when making future healthcare-related decisions, in addition to disseminating accurate, nuanced research
results.
Background/Objectives: The long term psychological
effects of childhood cancer upon parents has been studied
extensively, yet uncertainty remains about the degree and
nature of any positive or negative psychological sequelae.
This paper updates and expands upon a review assessing the
literature published between 1988 and 2010 on the positive
and negative long term psychological late effects for parents
of childhood cancer survivors (CCS) reported at least five
years after the child's diagnosis and/or two years after the end
of the child's treatment.
Design/Methods: Standard systematic review methods were
employed. Two independent reviewers conducted searches in
the databases CINAHL, EMBASE, PsychINFO and PubMed,
performing quality appraisal using the QUALSYST tool and
extracting data. Ninety-one possible papers were reviewed, 19
assessed in full-text and 10 added, with a total of 25 finally
included. Synthesis of the data was undertaken using a narrative framework, as heterogeneity of the underlying data collection precluded quantitative meta-analysis.
Results: A total of 10 new studies including 880 parents were
added. Overall, the majority of studies report no differences in
levels of psychological distress for parents of survivors compared to norms, with a small subset reporting elevated levels of Post Traumatic Stress Symptoms (PTSS). Two additional studies found lower PTSS and/or higher Post Traumatic
Growth (PG). Factors associated with negative long term late
effects included: more avoidant coping styles, age of parent,
caregiver strain and conflictive family functioning.
Conclusions: There is little evidence to suggest that having
a child with cancer results in general with increased levels
of psychological distress for parents in the long term; some
opportunities for personal growth may be experienced, but for
others the events trigger PTSS. The clinical implications of
these findings argue for awareness and specific referrals when
required.
PO-123 Depressive Symptomathology in 100 AYA
Cancer Survivors: A Significant Predictive Model
M. Tremolada1 , S. Bonichini1 , G. Scarzello2 , G. Basso3 , M. Pillon3
1 University
of Psychology, Department of development and social
psychology, PADOVA, Italy; 2 Istituto Oncologico Veneto, Pediatric
Radiotherapy Unit, Padua, Italy; 3 University Hospital of Padua,
SIOP ABSTRACTS
Department of Child and Woman's Health- Oncology Hematology Division,
Padua, Italy
Background/Objectives: Due to advances in chemotherapy
and supportive care in the last years, the number of childhood cancer survivors has fortunately increased. Unfortunately, they could self-report several negative psycho-social
effects linked to the cancer treatment. A few studies adopted
a mixed-method approach crossing narrative data with those
coming from self-report questionnaires to identify the possible significant predictors of psychopathologic symptoms in
their quality of daily life and in their relationships’ characteristics. The aim of this study is to assess quality of daily life,
family and social relationships in pediatric cancer survivors,
adopting the mixed method to identify the possible psychosocial factors impacting on their depressive symptomatology.
Design/Methods: Participants consists in 100 north-east Italian AYA cancer survivors, mean age at diagnosis of 9.26
years (SD=4.29), 51 treated for haematologic disease and
49 for solid tumours, off-therapy from a mean of 8.19 years
(SD=2.62). The Ecocultural Family Interview (Tremolada
et al., 2013). new version AYA cancer survivors - took place
in the DH of the Onco-hematology clinic during their medical controls. This interview resulted psychometrically reliable and solid with the extraction of 12 good internal consistence general dimensions from 102 items. Self-report questionnaires measuring feelings and emotions (CCSS) and the
Brief Cope were administered as well.
Results: A hierarchical regression analysis showed that
depressive symptoms (R2 = 0.36; F = 7.14 p = 0.0001) were
predicted by Age at diagnosis (beta = -0.41; p = 0.03), by
Relationships with parents (beta = -0.22; p = 0.01) and by
Self-blame coping strategy (beta = 0.41; p = 0.0001). Medical
and sociodemographic variables didn't impact significantly.
Conclusions: A good relationship with parents and older
age at the diagnosis were identified as protective factors for
depressive symptomatology, while self-blame coping strategy
represented a risk factor. These empirical data should lead to
focused interventions.
PO-124 Child and Family Perspectives of
Pediatric Hematopoietic Stem Cell Transplant: A
Retrospective Pilot Study
C. West1 , D. Dusome2 , L. Rallison3 , J. Winsor1
1 University
of Manitoba, College of Nursing, Winnipeg, Canada; 2 Brandon
University, Faculty of Health Studies, Winnipeg, Canada; 3 University of
Calgary, Faculty of Nursing, Calgary, Canada
Background/Objectives: Pediatric hematopoietic stem cell
transplant (HSCT) is a highly intensive treatment. Children
and family members experience significant illness distress,
including anxiety, depression, and post-traumatic stress symp-
S493 of S518
toms. The distress of family members plays a pivotal role in
the level of distress experienced by ill children during HSCT.
The key limitation of existing research is the “family” has primarily been studied from the perspective of individual family members, not the family unit. This study used a family
systems-expressive arts framework to identify the main factors that influence the family transition through HSCT, as well
as specific family needs and outcomes.
Design/Methods: A retrospective pilot study was conducted
using constructivist grounded theory. Fifteen family members
(9 parents/primary caregivers, 3 recipients, 3 siblings) from
six families participated in two qualitative interviews. During
the second interview, participants drew an image of how they
experienced HSCT treatment. The researchers guided family
members through a “dialoguing with images” process: each
family member asked the image questions, and then answered
those questions as if they were the image.
Results: An inductively derived theory of the family transition through HSCT was developed:the pre-HSCT trajectory,
including the relationship dynamics within the family and
those with the health care team, were powerful modulators of
this transition. A highly tenuous process of family fragmentation occurred during hospitalization. Experiences of trauma
occurred, particularly for ‘parent caregivers’ who lived in the
transplant room 24 hours/day, sustaining the ill child. During
hospitalization, family members experienced one of two dominant patterns of interaction with health care professionals:
expression-support (5 families) or conflict-withdrawal (1 family). Following discharge, families struggled to reintegrate,
holding unvoiced experiences of trauma, which differed for
each family member.
Conclusions: We identified a crucial need for targeted family systems-expressive arts intervention during the transition into HSCT and post-hospitalization. Acknowledgments:
Children's Hospital Research Institute of Manitoba Operating
Grant.
PO-125 Validating the Patient-Reported
Outcomes Measurement Information System
(PROMIS-25) to Measure Health-Related Quality
of Life in Pediatric Lymphoma Patients in Malawi
K. Westmoreland1,2 , T. van der Gronde3 , A. Amuquandoh3 , S.
Itimu3 , A. Salima3 , C. Stanley3 , M. Chikasema3 , P. Ward3 , S.
Gopal4,5,6 , B. Reeve7
1 UNC
Project-Malawi, Pediatric Hematology Oncology, Lilongwe,
Malawi; 2 University of North Carolina, Pediatric Hematology Oncology,
Chapel Hill, USA; 3 UNC Project-Malawi, Oncology, Lilongwe, Malawi;
4 UNC Project-Malawi, Cancer Program Director, Lilongwe, Malawi;
5 University of Malawi School of Medicine, Oncology and Infectious
Disease, Lilongwe, Malawi; 6 University of North Carolina, Oncology and
Infectious Disease, Chapel Hill, USA; 7 University of North Carolina,
Health Policy and Management, Chapel Hill, USA
SIOP ABSTRACTS
S494 of S518
Background/Objectives: Measuring health-related quality
of life (HRQoL) among cancer patients is important to comprehensively and holistically assess outcomes. Internationally
validated tools to measure patient-reported HRQoL are available, but efforts to translate and culturally validate such tools
in sub-Saharan Africa (SSA) have been scarce.
Design/Methods: The Patient-Reported Outcomes Measurement Information System 25-item short form (PROMIS-25)
assesses six HRQoL domains: mobility, anxiety, depression,
fatigue, peer relationships, and pain interference by asking
four questions per domain. A single-item pain intensity question is also included. The PROMIS-25 instrument was translated into Chichewa: two forward independent translations,
reconciliation, back translation, three independent reviews,
finalization, and harmonization. Cultural validation was conducted through five semi-structured cognitive interviews.
Baseline questionnaires were collected for children enrolled
in an ongoing prospective lymphoma cohort at Kamuzu Central Hospital in Lilongwe. Psychometric validity was assessed
using Spearman's correlation among items within and across
domains, Cronbach's alpha for internal consistency reliability
within each domain, and t-test for known group validity.
Results: The interviews discovered that the translation of
being able to walk ‘one block’ was not culturally applicable; therefore, this item was changed to ‘the length of one
soccer pitch’. Thirty-two lymphoma patients completed the
PROMISE-25 questionnaire. Items within each domain were
more correlated than with items outside the domain supporting structural validity. Reliability of each scale was satisfactory (range alpha= 0.68-0.91). Children with a hemoglobin
<9.0 g/dL had worse fatigue HRQoL than those with
hemoglobin ≥9.0 g/dL (p=0.048). Children with a Lansky
performance status (LPS) ≤70 had a worse mobility HRQoL
than those with LPS >70 (p=0.002).
Conclusions: Translation and cultural validation of the
PROMIS-25 into Chichewa for Malawi was successful. As
pediatric cancer care and research programs expand in SSA, it
will be vital to incorporate assessment of HRQoL using selfreported instruments validated within the local context.
that sibling donors are at risk for depression, anxiety, withdrawal, behavioral problems, and lowered self-esteem. Even
after donation procedures are explained, siblings have been
found to have difficulty understanding the information and
to experience anxiety. No prospective studies examining educational tools and transplant knowledge in sibling stem cell
donors are currently available.
Design/Methods: A study was designed to assess donor comprehension of donation procedures and to compare knowledge and anxiety prior to and post educational interventions.
Participants include siblings of pediatric patients, ages 1026. Assessment of baseline knowledge and state anxiety is
obtained before and after the consent/assent meeting with the
medical team. Donors are then stratified into 2 groups by age.
Donors’ ages 10 to 15 play an adapted version of ShopTalk and
donors’ ages 16 to 25 are provided a workbook designed for
sibling stem cell donors. Knowledge and anxiety is reassessed
24 hours following the intervention and again 1 month later.
Results: 16 sibling donors enrolled, 7 completed all time
points. Knowledge about how stem cells can help a cancer patient was very good at baseline. Areas lacking include
how stem cells are collected and possible complications post
donation and transplant. A trend for increased knowledge and
reduced anxiety has been found post intervention. Enrollment
is ongoing.
Conclusions: Preliminary results suggest that education that
provides information via a game or workbook increases
knowledge and may reduce anxiety in sibling donors. Providing detailed information about donation and discussion of procedures should be tailed to the individual learning style and
supplemented with additional visual information.
PO-127 Advantages, Challenges and
Opportunities in Working with Participatory Visual
Approaches in Qualitative Research Involving
Children and Youth in the Context of Cancer
Research
R. Woodgate1 , P. Tennent1 , M. Zurba1
PO-126 Educational Interventions with Pediatric
Sibling Hematopoietic Stem Cell Donors to Increase
Knowledge of Donation and Reduce Anxiety: A
Pilot Study
L. Wiener1
1 NCI,
Pediatric Oncology Branch, Bethesda, USA
Background/Objectives: Siblings are most often selected as
a donor match for patients with malignant and nonmalignant hematologic diseases. Research on preparing siblings
donors for stem cell donation is limited. Current data suggests
1 University
of Manitoba, Rady Faculty of Health Sciences- College of
Nursing, Winnipeg, Canada
Background/Objectives: Since the mid-1990s, participatory
visual approaches in qualitative research have grown in popularity. Such creative approaches work towards facilitating
the authentic expression of the complex realities of people
engaged in research, as well as the more affective connections
between people, their environments and life situations. The
purpose of this presentation is to describe the use of participatory visual approaches including the advantages, challenges
and opportunities in research that seeks to advance our under-
SIOP ABSTRACTS
standing of children and youth's perspectives of cancer and
cancer prevention.
Design/Methods: The advantages, challenges and opportunities in working with participatory visual approaches including drawing and photovoice in qualitative research are gleaned
from the literature and research conducted by the first author.
Results: Participatory visual approaches such as drawing and
photography enable children and youth in qualitative research
to have a conversation with themselves by thinking through
how they wanted to represent their own perspectives and experiences. Through participatory visual methods, they are able
to produce powerful metaphors or literal depictions of their
lived realities. Nonetheless, procedural, ethical and relational
challenges in working with participatory visual approaches
at various stages from activation to interpretation and dissemination can result including issues with data validity and
authenticity.
Conclusions: The insights derived from the literature and
through the research provide standards for the advancement
of participatory visual approaches in qualitative research that
seeks to advance our understanding of children and youth's
perspectives of cancer and cancer prevention. Enhancements
to the didactic quality of the research, and considerations for
extending participatory visual approaches into care following the completion of research are two areas where these
approaches could be developed with great promise.
PO-128 Navigating Ethical Challenges in
Qualitative Research with Children and Youth
Living with Cancer and Other Complex
Conditions: Sustaining Mindful Presence
R. Woodgate1 , P. Tennent1 , M. Zurba1
1 University
of Manitoba, Rady Faculty of Health Sciences- College of
Nursing, Winnipeg, Canada
Background/Objectives: A number of ethical challenges
can emerge when engaging children and youth in qualitative
research. The purpose of this presentation is to discuss how to
mitigate ethical challenges in research that seeks to advance
our understanding of children and youth living with cancer
and other complex conditions.
Design/Methods: Ethical challenges in qualitative research
are explored by bringing forward examples from the first
author's research program that is focused on the significance
of multiple perspectives and the value of gauging the needs
of young people living with cancer and other complex conditions. The studies address what children and youth think about
their illness and contribute to building insights into their lived
experience of illness.
S495 of S518
Results: In addition to highlighting the ethical challenges
in working with children and youth in research, a case that
ethical considerations need to extend beyond research ethics
boards protocols is made. “Sustaining mindful presence” is
proposed as a novel and inclusive framework through which
researchers can navigate ethical challenges in research and
involves moving through the research field with careful forethought, attentive pace and receptive attention to and awareness of what is taking place with the potential for the authentic expression of participants. Sustaining mindful presence
includes the following characteristics that can become highly
developed within a researcher: (i) openness and curiosity, (ii)
empathy and acceptance, (iii) receptive attention and deep listening, (iv) relationally engagement, (v) flexibility and reflexivity, (vi) self-awareness and self-regulation, and (vii) being
nonjudgmental and respectful.
Conclusions: Through sustaining mindful presence,
researchers are more able to provide a safe and comfortable
research environment, consider the young person's physical
and psychological state and avoid placing demands on the
young people that could cause harm to them physically or
psychologically, and make careful preparations for exiting
from the field.
PO-129 Who do Young Adults Talk to and What
do they Talk About Regarding their End-of-Life
(EOL) Care Preferences
S. Zadeh Bedoya1 , H. Battles1 , M. Lyon2 , A. Gross3 , S. Jacobs4 , K.
Zabokrtsky5 , L. Paredes5 , K. Fasciano6 , P. Malinowski6 , C. Heath7 ,
A. Hoeft7 , L. Wiener1
1 National
Cancer Institute, Pediatric Oncology Branch, Bethesda, USA;
National Medical Center, Center for Translational Research,
Washington, USA; 3 Children's National Medical Center, Pediatric
Hematology/Oncology, Washington, USA; 4 Children's National Medical
Center, Center for Cancer and Blood Disorders, Washington, USA;
5 Children's Hospital of Orange County, Hyundai Cancer Institute, Orange,
USA; 6 Dana-Farber Cancer Institute, Young Adult Program, Boston, USA;
7 Cook Children's Medical Center, AYA Oncology Program, Fort Worth,
USA
2 Children's
Background/Objectives: About 9,000 young adults (YA) die
from cancer each year, making it the 4th leading cause of
death in this age group (ACS, 2015). Advance care planning (ACP) documents provide patients an opportunity to
express their preferences for care and make informed decisions. Both family and providers describe discomfort with
initiating these conversations with AYA. This study aims to
understand whether AYA are having ACP conversations with
family members, friends or health care providers and if not,
what barriers they perceive in doing so.
Design/Methods: Participants, aged 18-39, with cancer or
other life threatening illnesses were administered a questionnaire to determine whether they had engaged in commu-
SIOP ABSTRACTS
S496 of S518
nication with family, friends, and/or health care providers
about preferences for care if they were to become seriously
ill. Perceived barriers to having these conversations was also
assessed. The study is open at 5 cancer centers.
Results: Fifty-three AYA completed the questionnaire. Fiftyone percent of participants indicated having had an EoL planning conversation with a family member, while only 30% had
spoken with a friend and 17% with a health care provider. Perceived barriers to communication include upsetting family, a
desire to maintain normal life with friends, and not feeling
comfortable initiating discussion about ACP with their health
care providers.
Conclusions: Most particpants have not had communication
regarding their EoL preferences with either family, friends,
or health care providers. Given the importance of end-of-life
planning and challenges in ensuring these conversations occur
with the medical team, interventions are being developed to
enhance provider comfort with initiating these discussions
and helping helping patients communicate with their family
and friends about what is most important to them when their
EoL is near.
EPIDEMIOLOGY - PATHWAY OF
CA R E
Design/Methods: Descriptive, retrospective study including
406 patients from 0-15 years old. Inclusion criteria was, age
between 9years11months and 14years11months old, and diagnostic of CNS cancer confirmed by Radiology or Pathology
area.
Results: Only 8.6% (n = 35)children from a total of 406
patients were diagnosed with CNS Tumor. Most of cases were
found in males and mean age of diagnosis was ten years
old(32%). Fifty-seven percent corresponded to posterior fosa
but globally most common type was Astrocytoma(43%) and
least was Ependimoma(3%). Results are similar to previously
findings in England and US, only population admitted in this
pediatric hospital was enrolled causing selection Bias.
Conclusions: Cancer treatment in Adolescents is still being
a challenge because poor improvement in survival rates seen
despite of changes in management. This study shows that incidence of CNS cancer in adolescents between 10-15 years old
is similar to distribution in children described in previous
studies. Therefore, other causes rather than distribution should
be related to survival outcomes. New factors need to be investigated.
PO-131 New Patient Process Documentation at
Children's Cancer Hospital Egypt (CCHE) and
Recommendations for Improvement
O. Elmadhoun1 , N. Ugonabo1 , I. Albanti2
PO-130 Incidence of CNS Tumors in Adolescents
at a Children Hospital in Ecuador
A. Borja1 , M.J. Pesantez1 , D. Franco2
1 Hospital
Axxis, Oncología Pediatrica, Quito, Ecuador; 2 Hospital
Metropolitano, Patología, Quito, Ecuador
Background/Objectives: According to literature about 25%
of all tumors in children between 0–14 years old involve CNS.
However this percentage decrease at the end of adolescence(25% in adults). Most CNS tumors in childhood are located
in posterior fossa but the most common type are astrocytomas. Due to differences in epidemiology and management
the APP and NCI recommend that children seek diagnose and
treatment at specialized pediatric centers for cancer. According to studies, children receiving care in those institutions
show 20-40% higher survival rates. However, survival outcomes in adolescents with CNS tumors have not shown an
improvance. This dispartity shows adolescents have a higher
mortality, hence, understanding of distribution of CNS cancer in this group will contribute to better, individualized treatments.
Objetive: Determine incidence of CNS tumors in adolescents
at Children Hospital in Ecuador from January 2007 to August
2013.
1 Harvard
T.H. Chan School of Public Health, Health Policy and
Management, Boston, USA; 2 Dana Farber/Boston Children's Hospital, The
Global Health Initiative, Boston, USA
Background/Objectives: This project at the Children's Cancer Hospital of Egypt-57357 (CCHE) aimed to define the new
patient process for solid tumor patients, study the patient flow
and analyze the process to be able to identify root causes
and suggest actionable recommendations for improvement.
CCHE is the largest specialized children's cancer hospital in
the world and is located in Cairo, Egypt. Being the only hospital offering high quality pediatric oncology care completely
free of charge, 57357 experiences a very high demand which
necessitates continuous improvement in the handling of new
patients in order to make the process efficient and enhance the
patient experience.
Design/Methods: Our project aimed to apply Lean Management – Six Sigma tools to define the new patient process, collect data on the new patient process, study the patient flow and
identify root causes. We also used and incorporated the Dana
Farber/Boston Children's Quality Improvement policies and
toolkits.
Results: The key findings of this project include a full process
map of the New Patient Solid Tumor Process at both 57357
and Dana Farber/ Boston Children's as well other visual tools
SIOP ABSTRACTS
utilized in LEAN/Six Sigma. In addition, we drafted a list of
ten preliminary recommendations for improvement which we
presented to the 57357 team.
Conclusions: Those recommendations laid the groundwork
for the establishment of a new patient clinic to meet the high
patient volumes and enhance the patient experience.
S497 of S518
PO-133 Children's Cancer in Morocco: An
11-Year Retrospective Study
A. Haimer1 , F. Habib2 , A. Soulaymani1 , A. Mokhtari1 , H. Hami1
1 Laboratory
of Genetics and Biometry- Faculty of Science, Ibn Tofail
University, Kenitra, Morocco; 2 Al Azhar Oncology Center, Rabat, Morocco
Background/Objectives: This study was conducted to determine the epidemiological characteristics of childhood cancer
in Morocco.
PO-132 Early Diagnostic of Cancer Children and
Adolescents Program in South of Brazil, 8 Years of
Activities
C. Fiori1 , A. Carla Rosa1 , C. Santos1 , S. Buettner1 , M.I. Melo1 , F.
Neves1
1 Hospital
do Câncer de Cascavel-UOPECCAN, Pediatric Oncology,
Cascavel, Brazil
Background/Objectives: Introduction: In developed countries the cure rate of cancer children exceeds 75%. This reality is far from being achieved in Brazil and the main reason is
the difficulty that health professionals have to diagnose the
disease early. The Cancer Hospital of Cascavel - UOPECCAN - in partnership with the Ronald McDonald Institute,
through the Early Diagnosis of Cancer Children and Adolescents Program, trains professionals of health and pediatrics of
the municipalities of Parana-Brazil.
Objective: Trainning professionals of health and pediatricians
in order to contribute to the early identification of cancer in
children and adolescents, reducing the time between the onset
of signs and symptoms and diagnosis in a specialized center.
Design/Methods: Methodology: Health professionals from
several cities of Parana were trained from April / 2008 to
December /2016. They received basic information about children cancer and adolescents (Epidemiology; signs and symptoms of suspicion; care needed for the attention to children
and adolescents with cancer). The groups were formed with
40 professionals, 16 hours / course.
Results: Results There were trained 1805 professionals, 125
doctors, 193 nurses, 305 technicians / nursing assistants, 836
community health agents, 184 upper level and 162 mediumlevel professionals or auxiliary.
Conclusions: Comments: Among the diagnosed cases of cancer in children in Brazil, many are referred to treatment centers with the disease at an advanced stage. One goal of the
campaign is to encourage educational and preventive actions,
spreading knowledge for more people about the disease. We
observed in the last three years, a cha nge in staging diagnosis
of patients who are coming to the reference center. Children
are coming up with more localized disease. Shortening the
time between the suspicion of cancer and early diagnosis and
treatment will certainly contribute to the increasing expectations of cure in developing countries.
Design/Methods: This is a descriptive retrospective analysis
of childhood cancer cases, diagnosed and treated at Al Azhar
Oncology Center in Rabat during a period of 11 years (20052015).
Results: During the study period, 115 children under the
age of 15 were diagnosed with cancer at Al Azhar Oncology Center, accounting for 1.05% of all new cancer cases
reported during this period. Nearly two-thirds were boys with
a male-female ratio of 1.94. The average age at diagnosis was
8.45±3.99 years. More than a quarter of the reported cases
were diagnosed during the first five years of life, while the
highest rate for children was noted between 10 and 14 years
of age. Brain tumors were the most common childhood cancer
(15%), followed by cavum cancer (13%). Among all detected
cases, 2.6% were diagnosed with metastatic disease and 13.9%
died during the study period.
Conclusions: Although rare, cancer in children has a substantial impact on public health in Morocco. A national cancer
registry will assist in better planning, resource allocation and
management including psychosocial support to improve the
quality of life of childhood cancer survivors and their families.
PO-134 Financial Planning of Pediatric Cancer
Hospitals in Low-and-Middle-Income Countries:
The Unidad Nacional de Oncologia Pediatrica's
Experience
N. Shrivastava1 , F. Antillón2 , G. De Dios3 , I. Albanti4
1 Harvard
T.H. Chan School of Public Health, Health Policy and
Management, Boston, USA; 2 Unidad Nacional de Oncología Pediátrica,
Pediatric Oncology, Guatemala City, Guatemala; 3 Fundación Ayúdame a
Vivir, Pediatric Oncology, Guatemala City, Guatemala;
4 Dana-Farber/Boston Children's Cancer and Blood Disorders Center,
Pediatric Oncology, Boston, USA
Background/Objectives: While financial planning resources
for the establishment of new pediatric oncology facilities in low-and-middle-income countries (LMICs) are limited, Unidad Nacional de Oncología Pediátrica (UNOP),
Guatemala's national pediatric cancer hospital, in partnership with its foundation, Ayúdame a Vivir (AYUVI), has sustainably operated for more than 15 years and has recently
expanded to a new clinical site. This study aims to examine
SIOP ABSTRACTS
S498 of S518
financial planning practices at UNOP and AYUVI, highlight
important lessons learned, and assess the impact of effective
budgeting on improving outcomes for children with cancer in
Guatemala.
Design/Methods: Semi-structured face-to-face key informant
interviews were conducted with 9 staff members (physicians,
administrators, accountants, and staff in volunteering and
fundraising) in English or Spanish at UNOP and AYUVI.
Interview content was transcribed and analyzed to identify
recurring themes. Informants also provided relevant financial
planning documentation.
Results: Interviewees emphasized the importance of having
diverse funding sources including the government, corporate
sponsorships, and both local and international fundraising to
prevent reliance on a sole funder. For budgeting, respondents
highlighted the importance of gathering local epidemiological data to forecast disease burden and patient demand. These
data are used to determine required number of patient beds,
necessary quantities of equipment, and required clinical staff,
which directly influence the construction, start-up, and operational budgets. Informants noted several costs unique to pediatric cancer hospitals including the increased need of isolation
areas and infectious disease care for immunocompromised
patients, and the need to plan for lodging for parents from faraway locations to stay during longer treatments.
Conclusions: UNOP's ability to increase Guatemala's overall survival rate from pediatric cancer from 20% to 70% over
15 years has been made possible in part due to strategic and
effective financial management. This institution's continued
success highlights the feasibility of providing cost-effective
access to care for children living with cancer in resourcelimited settings.
LATE EFFECTS
PO-135 Rendering of Rehabilitation Help to the
Russian Children with Oncohematological Disordes
E. Zhukovskaya1 , A. Rumyantsev2 , V. Kasatkin1 , A. Karelin1 , L.
Sidorenko1
1 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Rehabilitation Centre “Russkoe Pole”, Moscow, Russia;
2 Federal
Research Center of Pediatric Hematology - Oncology Immunology, Administration, Moscow, Russia
Background/Objectives: The long-term consequences of
chemoradiotherapy are preserved until 3-10 years or more
after completion of treatment in children and adolescents.
The aim of the research is analysis of the rehabilitation care
for children and adolescents in Russian Federation cured of
malignant neoplasms.
Design/Methods: The rehabilitation care to patients with
oncohematological pathology in 24 centers and clinics in Russian Federation were studied within the framework of the multicenter study. The sources of the data were official statistical reports and a questionnaire for physicians, including 22
parameters studied, 2,320 parents were interviewed with a
prepared questionnaire.
Results: Rehabilitation of patients cured of malignant neoplasms is carried out in rehabilitation departments of 3
regional hospitals, 3 specialized rehabilitation centers, in 14
cities, children receive rehabilitation courses during special
shifts in children's sanatoriums, dispensaries. “National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology named after. Dmitry Rogachev» is a
methodical center for the delivery and testing of rehabilitation
technologies. Only 20% of survivors received rehabilitation
courses in connection with insufficient number of the rehabilitation wards. The late effects of antitumor therapy were registered in 68.7% of patients aimed at rehabilitation had organic
and functional health disorders, manifestations of deprivation
and desocialisation, which caused the need to develop technologies for drug, nutritional, neurocognitive, physical and
psychological and social rehabilitation of recovered patients.
The parents’ survey revealed the interest of families of patients
in expanding rehabilitation opportunities; they prefer rehabilitating in the conditions of specialized centers.
Conclusions: The doctors emphasize the lack of trained personnel in the field of restorative medicine,absence of the evidence based criterias of the causal patterns of the development revealed symptomatology, premorbid/comorbid conditions that limit the effectiveness of rehabilitation programs
for patients with oncohematological diseases.The expense
of compulsory medical insurance, social protection system
ensures accessibility for families with children cured of malignant tumors.
Pediatric
Blood &
Cancer
A U T H O R /A B S T R A C T I N D E X
A
A. Oliveira-Cardoso, É., PO-113
A. Santos, M., PO-113
Aalfs, C., P-523
Abate, C., P-486
Abbas, A., P-168
Abbott, I., P-224
Abboud, M., PD-002
Abdallah, D., P-122
Abdel Alim, M., P-027
Abdel Hamid, S., O-112, P-209
Abdel Khalek, E.R., P-395, P-557
Abdel Monem, M., P-557
Abdel Rahman Sayed, H., O-112
Abdelbaki, M., P-542
Abdelfattah, A., P-580
Abdelrahman, H., PD-016
Abdelrazig, N., P-401, PO-079
Abdessalam, S., P-336
Abe, K., P-380, P-205, PD-027
Abe, Y., P-345
Abel, B., P-494
Abel, L., P-212
Abeling, N., O-052, P-157
Abeln, V., PO-093
Abosoudah, I., P-168
Abouelnaga, S., O-041, O-057, P-542
Abraham, C., P-134
Abramowitz, L., O-196
Abramowski, P., O-094
Abramson, D.H., O-041
Abriata, G., PD-092
Abruquah, A.A., P-450
Abu Tair, T., PD-056
Abugideiri, M., P-110
Acha, T., O-075
Acharya, S., AW-07
Achbergerova, M., P-065
Acosta, S., P-289
Acosta, S.M., P-148
Acquah, G., P-450
Adachi, M., P-514
Adachi, S., P-074, PD-036, PD-037
Adaletli, I., P-177, P-427
Adam, L., P-401, PO-079
Adam, R., O-083
Adamczewska, K., P-011
Adamkiewicz-Drożyńska, E., P-266, P-579
Adams, M., O-085
Adamski, J., O-047
Adan Pedroso, R., P-304, P-526, PO-015, PO-056
Adhikari, N., P-207
Adly, M.H., P-574
Ådnanes, M., PD-070
Adrianowska, N., P-524
Adu-Gyamfi, L., P-450
Aerts, I., P-307, P-384
af Sandeberg, M., P-487
Affinita, M.C., O-085
Afify, Z., P-079
Afungchwi, G., P-532, O-196
AGARWAL, B., P-039, O-193
Agarwal, R., PD-034
Agarwala, S., O-174, P-337
Agrali, N., P-279
Agrawal, A., P-452
Agrawal, V., O-029
Agresta, F., O-102
Aguiar, S., P-328
Aguiar, T., P-250, P-254, P-256
Aguilar de la Red, Y., P-455, PO-077
Aguilar, D., PD-053
Agulnik, A., O-064, O-035, P-411
Ahad, A., P-001
Ahern, V., P-342
Ahlhelm, F., P-361
Ahmad, A., P-396, P-533, PD-012, PO-021, P-168
Ahmad, F., P-459
Ahmad, N., P-401, PO-079
Ahmad, S., PO-050
Ahmed, A., P-066
Ahmed, B., PO-014, PD-078
Ahmed, N., PO-006
Ahmed, S., P-210, P-261, PD-026
Ahuja, A., P-582
Aiba, H., P-205, P-380, PD-027
Aimsirirak, P., P-498
Airewele, G., P-541, P-588, P-591, PO-111
Aizenshtein, A., P-302
AJLOUNI, F., P-186
Akbar, S.A., P-338
Akçay, A., P-270
Akdemir, U.Ö., P-527
Akdeniz Odemis, D., P-235
Akgoz, A., P-248
Akhtar, T., P-454
Akhter, F., P-308
Akici, F., P-270, P-177, PO-029, PO-084
Akiko, I., P-495
Aksoylar, S., P-562, PO-060
Aktas, S., P-123, P-192, P-124, P-516, PO-024,
PO-025
Akyüz, C., P-169, P-248, P-198, P-276, PO-016
Al- Nassan, A., P-397
Alabi, S., PD-014
Alaggio, R., O-087
alahmari, A., P-002
Alapetite, C., P-365
Al-Aridi, C., PD-002
Alattas, M., P-580
Albanti, I., P-545, P-580, P-586, PO-099, PO-108,
PO-131, PO-134
Albeltagi, D., P-068
Albert, K., P-388
Alberti, D., O-166, P-339
Alberto Scrideli, C., P-392
Albihani, S., PD-051
Alcasabas, A.P., P-228, PD-033, P-167
Alcasabas, P., P-548
Alderfer, M., PO-098, P-491, PD-067
Alderliesten, T., P-367
Aldiss, S., O-177
Aldrink, J.H., PO-066
Alebouyeh, M., P-314, PO-036
Alencastro Veiga Cruzeiro, G., P-327
Alers, W.C., O-212
Alexander, N., P-587
Alexis, C., PD-091
alexopoulou, K., P-363
Alfaar, A., P-574
Alfaro, E., P-044
AlFawaz, I., P-168, P-297, PO-044
Al-Hameed, M., PO-018
Al-Hamid, H., PO-018
Alhmouz, A.S., PO-044
AlHussain, T., P-168
Ali, A., P-003, P-168, P-297, P-459, PO-044
Ali, F., PD-090, PO-046
ali, K., P-476
Ali, M., P-574
Ali, N., P-295
Alkan, M., P-278
Al-Karmi, S., P-296
Alkofide, A., PO-044, P-297, P-168
Allen, C., P-541, P-549
Allen, U., PD-091
Alles, L., AW-08, O-066
Alles, L.A., O-071
Allingham, C., O-210
Allinson, K., PO-057
Alma, B., P-559
Almalky, M., P-395, P-557
Almazan, B., PO-032
Almazan-García, B., P-555
Almeida Silva, L.C., P-445
Almeida, C., P-453
Almeida, J., P-515
Almeida, R.S., P-004
AlMesfer, S., PO-044
Al-Nassan, A., P-581
ALONSO, C., P-044, P-130
Alonso, C.N., P-015
Alpakra, M., PO-006
Alpaslan Pinarli, F., P-318
The American Society of
Pediatric Hematology/Oncology
Alpaslan Pinarli, F., P-095
AlQaisi, M., P-168
Al-Saadi, R., O-002, O-074, O-077
Alseraihy, A., P-002
Alsheshtawi, K., PO-089
al-sweedan, S., P-002, P-003
altaf, S., PO-041
Altun, Z., P-124, P-123, P-516
Álvarez Guisasola, F.J., P-028
Alvarez, C., P-239, P-309
Alves Corrêa, C., P-327
Alvi, F., O-063
Alzahrani, Z., PO-006
amal, A., P-003
Amayiri, N., P-125
AMDEKAR, Y.K., O-193
Ames, B., P-568
Amichetti, M., P-375, P-376
Amiel, J., P-212
Amoroso, L., P-155
Amos, L., P-102
Amthauer, H., P-137
Amuquandoh, A., P-489, PD-075, PO-125
Anacak, Y., P-080, P-368, PO-060
Anatoliy, K., P-185
Anaya, S., P-319
ANCONA-LOPEZ, F., P-410
Ande, S., P-489
Andersen, K.V., PD-066
Andersen, L.B., P-448
Anderson, A., P-541, PO-111
Anderson, J., O-077, O-094, P-173, PD-050
Anderson, J.R., O-073
Anderson, L., PD-098
Anderson, P., O-161
Anderson, R., O-152
Andrade, A.F., P-286, P-327, P-328, P-390
Andrade, F., O-050
André, N., P-307, P-384
Andrea, B., O-091
Andreev, E., P-126, P-141
Andrews, T., PD-095
Angelica, Z., O-084
Angelico, R., P-339
Angelini, M.C., P-282
Angelini, P., O-090, P-298
Anis, H., P-558
Anisimov, V., P-301, P-322
Ankit, P., P-041, PO-012
Anna, K., P-007
Annamalai, A., O-108, P-070, P-071
Anne-Sophie, D., P-208
Ansari, F., P-111
Ansari, S.H., P-112
Anthracycline Cardiotoxicity Working Group, O.B.O.T.,
O-079
Antillón, F., PO-099, PO-134
Antillon-Klussmann, F., O-064
Antonenko, F., P-324
Antonini, S.R.R., P-286
Antunes Correia, D., P-226
Antunes Moreno, D., P-327
Anwar, S., P-005, P-172
Anwarali, S., PD-078
Aoi, S., O-173
Aoki, Y., O-126
Aparisi, M.J., P-383
Apkon, D., P-479
Appiah, R., PD-079, P-450
Aquilina, K., P-326
arafa, O., P-437
Arafah, O., P-436, P-261, PO-050
Arakawa, Y., O-129
Araki, Y., P-205, P-380, PD-027
Arango, R.H., O-064
Araújo, F.S., P-004
Arcangeli, S., O-093
Archana, S., P-041, PO-012
Ares, G., P-343
Arevian, M., P-481
Ariga, T., P-129
Armstrong, G., O-106
SIOP ABSTRACTS
S500 of S518
Arora, B., O-022, O-061, P-040, P-052, P-054, P-460,
P-583, PD-015
Arora, R., P-592
Arora, R.S., O-181
Arreguin, F., P-559, P-319, PO-032
Arreguín-González, F., P-555
Arsenian Henriksson, M., P-127
Arshad, A.A., P-203, P-204
Arshad, M., P-175
Arthurs, O., PD-021
Arul, S., PD-107, P-213, PO-073
Arvidson, J., P-425
Aschero, A., P-384
Asghar, N., PD-012
Ash, S., PD-018
Ashford, J., PO-121
Ashraf, N., P-338
Asiamah, C., P-450
Asribabayan, Y., PO-108
Assanasen, C., PO-086
Astigarraga Aguirre, I., P-526, PO-015, PO-056
Astigarraga, I., P-020, P-518
Atabay, B., P-080
Ataseven, E., P-080, P-090
Atay Kapucu, O., P-527
Atay, G., P-092
Atenafu, E., O-099, O-100
Athale, U., P-008
Athanasiadou, A., P-180, P-315
Athanasopoulos, E., P-051, PO-009
Atkin, K., P-443
Atra, A., P-352
Attia, I., O-121
Attri, S., O-111, P-428
Atwood, E., PO-099
Audry, G., PD-106
Aune, G., PD-095
Aurélie, D., P-140
Aurora, B., P-013
Aurtenetxe Saez, O., P-304, PO-056
Avagyan, A., PO-108
Avanoglu, A., P-368
Avdonina, M., PD-057
Avgerinou, G., P-031
Avila, J., O-207
Avila, J.M., P-167
Ayan, I., P-235
Ayas, M., P-168, P-297, PO-044
Ayçiçek, A., PO-029, PO-084
Aydin, B., P-169
Aydın, B., P-198, PO-016
Aydın, M., P-123
Aydogan, G., P-177, P-270, PO-084
Aydos, U., P-527
Ayla, M., P-124
Ayoroa, A., O-117
Aytaç, S., P-077
Azevedo, R.M., P-521
Aziz, A.A., O-016
Azizi, A.A., P-323
Azuma, H., PO-013
B
Baba, M., P-508
Babelyan, S., P-310, P-311
Bachir, J., P-362, P-387
Bacus, E., PD-053
Badowska, W., P-053
Badrinath, Y., P-013, P-052, P-100
Baedorf-Kassis, S., P-366
Baez, F., PD-014
Bagai, P., O-134, O-136, O-144, P-582
Bagga, D., PD-108
Baggott Do not use, C., P-496
Bahl, P., P-583
Bahrani, S., PO-018
Bai, J., O-178, PD-080, P-511
Baialardo, E., P-015, P-044
Bailey, C., O-001
Bailey, S., O-015
Bajaj, M., P-214, P-280
Bajaj, M.S., P-264, P-265
Bajin, I., P-248, PO-016
Bajpai, J., P-220, PD-028
Bajpai, M., PD-108
Bajwa, C., P-055
Bak, E., P-233, PD-035
Baker, D., O-152
Bakhshi, S., O-030, O-062, O-174, O-181, P-207,
P-280, P-293, P-337, PD-003
bakliwal, A., P-120
Bakshi, A., AW-01
Bakula, D., PO-118
Bakula, D.M., O-179
Bala, S., PO-001
Balasa, V., PO-018
Balcarcel, T., P-540
Balceiro, R., P-356
Balcerska, A., P-579
Balfour, A., P-462, P-463
Balgobind, B., P-367
Balistreri, K., PD-058, PD-062
Baltazar, W., P-167
Balwierz, W., P-012, P-042, P-067
Banavali, S., O-022, O-058, O-061, P-013, P-052,
P-054, P-460, P-563, P-583, PD-015, PD-065
Banavali, S.D., P-040, P-100
Banerjee, A., O-041
Banerjee, J., P-026
Banerjee, P., O-104
Baños, E., PO-032
banovic, P., P-363
Bansal, D., O-111, O-120, P-032, P-055, P-428
banthia, P., P-120
Baqari, S.A.S., P-204
Baraka, A., P-027
Barakat, L., P-492, PD-063
Barakat, L.P., P-465, PD-073
Baran Aksakal, N., P-095
Baran, J., P-492, PD-063
Barcenas Bobadilla, L., PO-116
Barese, C., P-385, PD-051
Barking, C., P-113
Barnabas, M., P-081
Barnett, M., O-142
Barnhart, D., O-154
Barone, A., P-381
Baroni, M., P-327, P-328
Barr, R., P-560, P-473, PD-093
Barrantes-Zamora, J.C., PO-075
Barrera, M., O-100, PD-058, PD-061, PD-062
Barret, E., O-043
Barrett, D.M., O-123
Barrett, J., PD-051
Barretta, F., PD-038
Barria, G., PO-044
Barros, J., P-256
Bartels, U., O-047, P-312, PD-061
Barth, M., P-525
Bartholdson, C., O-180
Bartholomew, J., P-497
Barton, C., PD-059, PO-078
Baruchel, S., P-134
Barwick, M., O-146
Bassioli, C., O-116
Basso, G., P-093, P-118, PO-123
Basu, S., PD-001
Bate-Eya, L.T., O-071
Bates, J., P-211
Batista, C., O-142
Batra, A., O-062, O-030, P-293
Battles, H., PO-129
Bauer, A., P-492
Baumann, F.T., P-571, PD-056
Baumbusch, L.O., P-149
Baumhoer, D., O-056
Bauters, T., P-398, PD-081
Bautista, F., O-032
Bay Buyukkapu, S., P-235
Bay, S., P-177
Bayliss, J., O-187
Bayram, C., PO-029, PO-084
Bean, A., P-164
Beaumont, L., P-560
Bechtel, A., PD-030
Becking, A., P-367
Becmeur, F., O-169
Bedard, P., P-312
Bedos, N., P-366
Beeby, T., AW-06
Beeput, S., PD-091
Begum, F., P-045, P-237
Begum, M., P-045
Behan, J., O-181
Behera, M., PD-080
Beiske, K., P-149
Bekele, W., P-553
Bel, A., P-367
Belderson, K., O-207
Belen, F.B., P-080
Belinda, M., O-194
Bellavance, F., P-587
Bellido, R., P-319
Bellini, G., PD-025
Belogurova, M., P-303, P-577
Belohlavek, O., P-274
Belokon, O., PO-049
Ben Ami, T., PD-039
Ben-Arush, M., O-084
Bendel, A., O-044
Benedicenti, F., O-091
Ben-Gal, Y., PO-100
Benito, A., PO-032
Benito-Resendiz, A., P-555
Bennett, K., P-534
Benoit, L., P-140
benquan, Q., O-031
Bergamaschi, L., O-025
Berger, L., P-523
Bergeron, C., O-086, AW-03, O-075, O-084, P-208,
PD-031
Bergerot, C.D., PO-110
Beringer, N., P-534
Berk, B., P-062, P-083, P-332, PO-034, PO-037,
PO-052
Berlanga, P., P-383, P-402
Berman, J.N., PD-010
Bermúdez Cortés, M.D.M., P-116
Bernhardt, M.B., O-125
Bernier, V., P-364
BERNIER-CHASTAGNER, V., O-081
Berrevoets, M., O-023
Berthier, A., P-441
Berthold, F., O-053, O-055
Bertocchini, A., PO-067
Bertout, L., PD-060
Bertozzi, V., P-470
Beshlawi, I., O-016
Besli, L.U., P-527
Best, K., PD-107
Betonte, P., P-375
Beukhof, A., O-182
Bezerra Salomão, K., P-327
Bhakta, N., O-064, P-581
Bhalla, R., P-582
Bhanushali, K., P-583
Bharat, A., P-041, PO-012
Bharathi, V., P-070
Bharathy, N., O-003
Bhasker, S., P-374
Bhat, K., P-543
Bhatia, K., P-334
Bhatia, P., P-032
Bhatnagar, S., P-340, PD-113
Bhatnagar, V., O-174, P-337
Bhattacharjee, B., O-181
Bhattacharya, A., O-120
Bhattacharya, K., P-558
Bhattacharya, M., P-464
Bhattacharya, S., P-399
Bhattacharyya, A., P-399
Bhatt-Carreño, S., P-238
Bhuta, R., P-006, PD-109
Biagi, E., O-091, O-093, O-092
Biasoni, D., PD-038
Biassoni last author, L., PD-021
Biassoni, V., O-025
Bielack, S., O-056
Bielack, S.S., P-223
Bien, E., PD-039
Bilal, D., O-113
Bilbao Salcines, N., P-304, PO-056
Bilgic, B., P-177
Billett, A., P-586
Billmire, D., O-038
Billups, C., O-014, O-044, PD-099
Bilska, K., P-266
Bindal, A., P-561, P-369
Bingen, K., P-490
Biondi, A., O-092, O-093
Bird, J., PD-091
Bird, N., O-137, P-389
Birnie, K.A., PD-085
Bisharat, M., O-164
Bishop, H., P-401, PO-079
Bisht, S., P-229
Bisogno, G., O-084, PD-039, O-085, O-087, O-089,
O-162, O-166, PD-038
Bisoi, A.K., O-174
Biswas, A., P-207
Biswas, B., P-293
Biswas, S., P-460
Bjork, M., P-477
Blanca, A.G., P-559
Blanche, S., P-212
Blanchette, V., PD-091
SIOP ABSTRACTS
Blanco, E., P-193
Blanco, J., PD-014
Blanco, S., O-142
Blanquer Blanquer, M., P-116
Blatt, J., P-511
Bleeker, F., P-523
Bloch, W., P-571, PD-056
Blom, T., O-054
Blomgren, K., O-188
Bloyd, J., O-132
Boaro, M.P., P-093
Boccieri, E., P-043
Böckenhauer, D., O-077
Bode, U., P-572, PD-045
BODHANWALA, M., O-193
Bodkyn, C., PD-091
Boekhoff, S., P-316, PD-044
Bohnenkamp, B., P-113
Bohrer, S., PO-053
Bojaxhiu, B., P-361
Boldrini, E., P-520
Boldrini, R., PD-038
Bollag, D., P-019
Bollard, C., P-385, PD-051
Bolle, S., O-059, P-364, P-365
Bolsi, A., P-226, P-361, P-371
Bomfim, G., P-400
Bonaventure, A., O-006
Bonazza, C., P-375
Bond, G., P-099
Bondiau, P.Y., O-059
Bonichini, S., PO-123
Bonilla, M., P-553
Bora, H., PO-061
Borcek, A., PO-061
Bordbar, M., P-382
Borges, R., P-250
Borja, A., P-535, PO-130
Borkens, S., P-378
Borkhardt, A., O-042, PD-088
Bornfeld, N., P-243
Borodina, I., P-301, P-303, P-320
Borowitz, M., O-018, O-020
Borowski, M., P-243
Borrelli, A., P-009
Boscarelli, A., PD-103
Bosi, J., O-194
Botafogo, V., P-515
Bouchabki, G., P-473
Bouffet, E., O-014, O-047, O-090, P-125, P-296, P-312
Bourdeaut, F., O-115
Bourne, H., O-102
Bourque, C.J., PO-114
Boutroux, H., O-010
Bowers, D., O-044
Bowman, C., P-194
Bowman, P., O-018
Boyle, H., P-404
Boyle, R., PD-091
Brackett, J., O-125, P-536, PD-094
brandal, P., P-363
Brandalise, S.R., P-286, P-328
Brandi, S., P-400
Brannigan, R., P-433
Brauer, N., P-394
Braunstein, S., P-145
Brennan, A., P-564
Brennan, B., O-087, O-089
Brenner, W., P-137
Breunis, W.B., PD-031
Brichard, B., P-330
Bride, K.L., O-123
Brigand, C., O-169
Brigden, J., PO-102
Brinkman, T.M., O-104
Brisse, H., P-208
Broas, J., P-553
Brodsky, C., PD-063
Broekmans, M., P-158
Brok, J., AW-03, O-039, P-170, O-074, O-076, O-077,
PD-024
Broniszczak, D., P-252
Bronsema, A., O-090
Brouwer- van de Poll, M.A., O-212
Brouwers-Vos, A., P-047, P-076
Brown, A., P-536, PD-094
Brown, A.L., O-114
Brown, P., O-049
Brown, V., O-020
Brozou, T., PD-088
Brozyna, A., P-252
Brugières, L., O-008, O-115, O-159
S501 of S518
Bruins, W.C., O-069
Bruneau, J., P-212
Bruner, D., PD-080
Brzezinski, J., P-587
Bu, F., P-194
Bubanká, E., P-057
Bubanská, E., P-065, P-546
Buchhalter, I., O-044
Buchholz, J., PD-045
Buchsbaum, J., O-041
Buckland, T., PD-093
Budi, T., P-273, PO-070
Buettner, S., PO-132
Buffardi, S., P-022
Bui, L., PO-026
Buidenok, Y., O-080
Bukowska-Strakova, K., P-007, P-042
Buletov, D., PO-039, PO-038
Bull, K., P-299
Bullock, R., P-589
Bulsa, J., P-053
Bult-Mulder, M., PO-101
Bulut, I., P-467
Burak, Z., P-562
Burchill, S., O-068
Burdach, S., O-056
Burger, P., O-013, O-045
Burke, M., O-019
Burns, J., PO-073
Burns, L., P-414
Burns, W., PD-060
Bushnak, D., P-168
Butia Mutai, M., O-065
Butia, M., P-073, P-489, PD-075
Butia-Mutai, M., P-412
Butker, C., P-110
Butker, E., P-110
Butler, E., P-465
Butler, M., AW-06
Butler, T., P-208
Buyukpamukcu, M., P-169, PO-016
Buyukunal, C., P-177
Buzzaccarini, M.S., P-093
Byung-Kiu, P., P-215
C
C, V., AW-01
Cabrera, M.L., P-238
Cacchione, A., P-376
CACCIAVILLANO, W., P-130
Cacciotti, C., P-008
Cadigan, C., PD-068
Cahlon, O., P-366
Cai, J., O-167, P-259
Cai, M., PD-013
Cai, S., P-283
Caires, L., P-254
Cakmakci, S., P-421
Calabria, I., P-383
Calaminus, G., P-394, PD-044
Calciano, L., PD-024
Calley, J., P-401, PO-079
Calore, E., P-118
Caloretti, V., P-253
Caltabellotta, N., O-213
Caltabellotta, N.M., O-211
Cameron, A., P-362
Camitta, B., O-018
Campagna, G., P-151
Campbell, F., O-146, P-435
Campbell, M., P-334
Campillo Marquina, J.A., P-116
Caneba, J.P., P-167
Canellas, M.C., P-515
Cañete, A., O-068, P-383, P-402
Cangelosi, D., O-068
Caniza, M., P-403, P-444
Cantez, S., P-092
Cao, C., P-292
Cao, L.Z., PD-049
Capkova, L., P-335
Capolino, P., O-043
Cappellano, A., O-116
Cappuzzello, C., O-091, O-093
Caraglia, M., P-010
Carai, A., P-376
Caran, E., O-116
Caran, E.M.M., P-405, P-406, PO-081
Carbone-baneres, A., P-020
Cardellicchio, S., P-267
Cardenas, M., PD-082
Cárdenas-Cardós, R., P-555
Carey, D., PO-103
Cargill, J., P-454
Carla Rosa, A., P-539, PO-132
Carlini, B., O-068
Carlotti, C.G., P-328, P-390
Carlsson, I.M., P-513
Carmo, D., P-453
Carnevale, F., O-181
Caron, H., P-157
Caron, H.N., AW-08, O-066, O-069, O-071
Carpenter, A., P-491
Carpenter, K., O-119
Carranza, M., P-540
Carranza-Castañón, A., P-058
Carraro, D., P-256
Carraro, D.M., P-250, P-254
Carraro, E., P-093
Carrasquillo, J., O-088
Carretier, J., P-404
carrie, C., P-363
Carroll, A., O-020
Carroll, W., O-018, O-019, O-020
Carroll, W.L., O-021
Carr-Wilkinson, J., P-565
Carton, M., O-131
Carvalho, R., P-174
Casale, F., P-009, P-010, P-043, PD-025
Casanova, J.L.(.,4.,8.,9.,1.e., P-212
Casanova, M., O-025, O-087, P-362
Casas, J., O-065
Casey, D., P-381
Cassar, O., P-212
Cassidy, R., P-110
Cast, A., O-128, P-251, P-258
Castel, D., O-043
Castel, V., O-068, P-383, P-402
Castellano, A., O-068, PO-067
Castellanos, A., P-182
Castellanos, M.E., PD-014
Castex, M.P., P-208
Castor, C., O-183
Castorena Villa, I., P-202
Castro, L., P-515
Caswell, D.M., PO-078
Catangui, A., P-167
Cataudella, D., PD-061
Cattelan, C., P-118
Cave, H., O-115
Cazzaniga, G., O-092
Ceccanti, S., O-155, PD-103
Cecchetto, G., O-162, O-166, PD-038, PD-106
Cecchi, C., P-267, P-470
Cecen, E., P-516
Cecen, R.E., PO-024, PO-025
Cecil, K., P-573
Cecile, D., P-208
Cecinati, V., O-166
Cela de Julian, E., PO-077
Celik, A., P-177, P-368
Celkan, T., P-177, P-427
Cellier, C., O-159
Cermak, M., P-065
Cernaianu, G., PD-104
Ceroni, F., O-074
Cervellone, A., O-155
Cervera, J., P-383
Cesaro, S., O-166
Cesen, M., PD-039
Çetin, M., P-056, P-077
Cetingoz, R., PO-024, PO-025, PO-042, PO-058
Çetingül, N., P-368, PO-060, P-562
Çetinkaya, D., P-077
Cezar, I., O-050
Chadha, J., P-583
Chadha, R., P-348
Chagtai, M., O-074
Chagtai, T., O-002
chai, X., P-128
Chai, Y., PD-005
Chakiba, C., O-089
Challinor, J., O-196, O-207, P-553
Chambers, C., O-146
Chambon, F., PO-053
Chamorro, M., P-482
Chamouine, A., PO-053
Chan, M.Y., O-157, PO-045
Chanapai, J., P-498
Chaney, J.M., O-179
Chang, A., P-366, PD-087
Chang, J., P-165
Chang, K.T.E., O-157
Chang, Y.C., PO-080
SIOP ABSTRACTS
S502 of S518
Chantada, G., AW-02
Chantada, G.L., O-041
Chapple, C.L., P-438
Chard, J., P-342
Chargari, C., P-350
Chasela, M., O-065, P-073, P-412
CHASTAGNER, P., O-131, P-307, P-384, O-081
Chaterjee, G., P-052
Chatterjee, G., P-013, P-100
Chau Van, H., P-447
Chaudhari, S., P-369
Chaudhary, S., P-561
Chavez, L., O-046
Chavez, S., P-206, P-253, P-585
Chávez-Zuñiga, M., P-058
Chawla, A., PD-109
Chawla, B., PD-034, P-234, P-245
Chawla, K., P-582
Cheah, S.M., P-349
Chełmecka-Wiktorczyk, L., P-266
Chemaitilly, W., O-026
Chen, G.H., PD-049
Chen, H.Q., PD-049
Chen, J., P-190
Chen, K., P-494
Chen, M.H., PO-080
Chen, Q., P-377
Chen, S., O-019, O-021
Chen, W.H., PD-020
Chen, X., O-167, P-259
chen, Y., P-128
Chena-Sánchez, A., P-471
Cheng, D., P-086
Cheng, H.Y., P-171
Cheng, S., P-312
Chennamaneni, R., PO-001
Cherian, A., PD-024
Cheriyalinkal Parambil, B., O-061
Cheshier, S., PD-041
Cheuh, H.W., PO-117
Cheung, C., PD-077
Cheung, N.K., O-088
Cheung, Y.T., O-104
Chi, Y.Y., O-072, O-073, P-173
Chiangthong, K., PO-062
Chiaravalli, S., O-025, O-090
Chiba, K., P-029
Chibon, F., O-089
Chiengthong, K., P-050, P-294
Chikasema, M., PO-125
Chin, F.K.C., O-157
Chinnaswami, G., P-369
Chinnaswamy, G., P-563, O-058, P-184, P-220, P-460,
P-561, P-583, PD-015, PD-028, PD-065, PD-111
Chintagumpala, M., PD-096
Chintagumpala, M.M., O-041
Chinyundo, K., PO-111
Chiraporn, P., P-498
Chisholm, J., O-086, P-362, P-367
Chisholm, J.C., PD-031
Cho, C.S., P-233, PD-035
Cho, H., P-150
Cho, J., O-045
Cho, Y., P-129
Choi, E., PO-007
Choi, H.S., PO-117
Choi, I., PD-035
Choi, S.H., PD-084
Choi, Y.B., PD-017
Chong, C.Y., P-349
Chopra, A., O-030, P-337, PD-003
Chopra, M., PD-021
Choudhary, A., PD-107
choudhary, D., P-120
Choudhury, S., O-135
Choudhury, T., PD-024
Choufani, S., P-565
Chowdhury, T., O-077
Chris, V., PO-101
Christensen, A.B., P-502
Christensen, J.F., P-448
Christy, L.A., PO-102
Chrousos, G., P-180, P-315
Chrzanowska, K., P-329
Chu, A., PD-067
Chu, C., P-590
Chufal, K., P-277
Chui, C.H., PD-102
Chung, J., PD-061
Cicala, D., PO-002
Cicero Oneto, C., P-202
Cieslik, K., P-236
CIMOLAI, M., P-130
Cintra, C., P-400
Cipolla, C., PD-092
Claren, A., O-059
Clark, C., O-152
Clark, H., O-102
Clark, K., PO-121
Clarke, G., O-102
Clarke, S., P-438
Classen, C.F., P-300
CLAUDE, L., O-059, O-081
Claudia, G., P-540
Clavel, J., O-008
Cleve, G., P-487
Clifford, S., O-015
Coakley, B., O-161
Cobat, A., P-212
Cobellis, G., O-165
Coelho Soares Lima, S., P-183
Coelho, S., P-025, P-174, P-272
Cohn, R., O-103, O-105, PO-120
Cohn, R.J., P-466
Coish, K., P-499
Colafati, G.S., P-376
Cole, K., O-090
Cole, K.A., PD-042
Cole, P., P-006
Coleman, L., P-334
Collazos Zabala, L., P-304
Colli, S., P-148
Collin, M., O-158, P-341, P-342, PD-105
Collini, P., PD-038
Colliver, D., O-156
Colmenero, I., P-290
Colombet, M., P-546
Coltin, H., PD-089
Comes, G.T., P-282
Commander, S., P-151
Compas, B., PD-058
Conard, K., PD-030
Concha, M.E., PD-053
Conklin, H., O-017, PO-121
Consarino, C., P-155
Constine, L., P-569
Conte, M., P-154, P-155, PD-038
Cooke, A., P-291
Cooke, R., P-454
Cooper, B., P-194
Copáková, L., P-065, P-057
Copeland Wahlo, Y., PO-076
Copland, C., O-143, P-584
Corkum, K., P-343
Corradini, N., O-059, O-089, O-169, P-307, P-384
Correa, C., O-168
Corrêa, C.A.P., P-328, P-286
Correcher, M., P-402
Correia, D.G., P-371
Corrias, M.V., O-068
Cortes, D., P-319
Costa, C., P-256
Costa, C.M.L., P-254
Costa, D., O-140
Costa, S., P-256
Costa, S.S., P-254
Côté, J., P-355
Coulomb, A., P-208
Coutinho, L.L., P-004
Covens, A., O-038
Cox, M.C., P-388
Coyne, K., P-432, P-433
Cozic, N., P-208
Cozzi, D., O-155, PD-103
Cozzi, F., O-155, PD-103
Cozzolino, T., P-339
Crabtree, V., PO-102
Crandell, J., P-511
Cranston, A., P-560
Crawford, J., O-044
Cresswell, G., O-002
Crocoli, A., O-166, PO-067
Crosier, S., O-015
Crowley, M.J., PO-078
Cruickshank, S., P-388
Cruz, C.R., P-385
Cruz, E., P-257
Cruz, R., PD-051
Cruzeiro, G.A.V., P-328
Csoka, M., PO-070
Cui, L., PD-005
Cui, Y., PD-005
Cullinan, N., PD-089
Cunliffe, N., P-454
Cunningham, L., P-145
Cupino, N., P-167
Curiel, L., P-134
Curnier, D., O-096, PO-114
Curtis, E., PD-099
Cypriano, M., O-116, P-250, P-254, P-256
Cyprova, S., P-325
Czech, T., P-323
Czogala, M., P-067
Czogala, W., P-114
D
D'Angelo, V., P-043
D, K.T., PO-045
D, L., PO-014
da Costa, C.M.L., P-250
da Costa, S.S., P-250
da Cunha, I.W., P-250, P-254
DA SILVA, K.N., P-409
Dababo, A., P-297
Dabas, S., P-592
Däggelmann, J., P-571
Daley, J., PD-109
Dallapicola Brisson, G., P-069, PD-007, PD-008
Dall'Igna, P., O-166
daly, P., P-363
D'Amico, M.R., P-022
Dang, J., P-312
D'Angelo, P., P-155, PD-038
D'Angelo, V., P-009, P-010
Danysh, H., P-536
Darendeliler, E., P-177, P-235, P-270
Das Thakur, M., P-393
Das, A., O-120, P-399
Das, S., P-147
Dasgupta, R., O-154
Datchary, J., P-365
Daubenbüchel, A., P-316
David, E., PO-008
Davidoff, A.M., O-026, PD-032
Davies, B., O-156
Davies, E., P-463
Davies, J., O-151
Davilla Fajardo, R., P-367
Daw, N., O-073, P-173
Day, S., O-196, O-206
Daylidite, V., P-310, P-311
D'cruz, C., PD-093
de Alarcon, P., PD-014
De Andrade, P.V., P-390
De Bernardi, B., PD-018
De Camargo, B., AW-03, P-183, O-075, P-521
De Dios, G., PO-134
De Jonge, R., O-023
De Lambert, G., P-350
De Lucio, A., PO-082
De Matteo, E., P-281
De Munter, J., PD-081
de Oliveira, E., P-515
De Pasquale, M.D., O-166, PD-038
De Pedro Olabarri, J.M., P-526, PO-015
de Ridder-Sluiter, H., PO-101
de Ridder-Sluiter, J.G., O-212
De Salvo, G.L., O-087, O-084, O-089, O-162
de Souza, J.E.S., P-250
de Toledo, S.R.C., P-250, P-254
de Vathaire, F., O-024
De Wilde, B., O-051, P-144
Deasy, R., O-016
Debatin, K.M., O-124, PD-006
Debiec-Rychter, M., P-216
Debily, M.A., O-043
Dębski, R., P-266
Decarolis, B., O-053
DEEBAJAH, R., P-249, P-186
Dehner, L., PD-030
Del Pozo Carlavilla, M., P-116
Delafoy, M., P-181
Delaney, B., PO-108
Delgado-Avendaño, M., PO-075
Delphine, H., P-584
Deluca, B., P-384
Dembowska - Bagińska, B., P-570
Dembowska-Bagińska, B., P-236, P-252, P-266, P-305,
P-329
Demir, S., O-124, P-103, PD-006
Demiral, A., PO-024, PO-025, PO-042, PO-058
Demirkaya, M., P-552
Demirkiran, D., P-192
Demoor-Goldschmidt, C., P-363
Demuynck, R., O-051
Den Hoed, M., O-023
SIOP ABSTRACTS
DeNardo, B., P-006, PD-109
Depani, S., O-036
Depreitere, B., P-330
Deprez, S., P-578
Derême, J., P-330
Derks, Y., PD-022
Derpoorter, C., O-051, P-144
Derwich, K., P-011, P-012, P-053
Desai, S., P-460
Desandes, E., O-008
Deshpande, N., P-013, P-100
Desjardins, L., PD-061
Detassis, M., P-375
Devalck, C., PD-031, PD-039
Devasenathipathy, K., O-174
Devidas, M., O-018, O-019, O-021
Devine, K., PO-103
Dewalt, D., O-011
Dhakal, S., P-569
Dhaliwal, A., P-558
Dhaliwal, D., P-013, P-100
Dhamankar, V., P-563
Dharshika, I., P-046
Dhawan, D., O-062
Dhingra, N., P-014, P-024
Dhooge, C., P-398, PD-081
Dhua, A., O-174
Dhungel, B., O-060
Di Cataldo, A., P-155
Di Florio, N., P-118
Di Lallo, T., O-133
Di Martino, M., P-009, PD-025
Di Massa, L., P-009
Di Palma, A., P-375
Di Pinto, D., P-010, PD-025, PD-038
Diachinsky, M., PO-094
Diallo, I., O-024
Diaz, N., P-482
Diaz, R., P-206, P-253, P-585
Dickinson, F., O-156
Dieckmann, K., P-363, P-323
dieter-kortmann, R., P-363
Diez-Fraile, A., P-144
Digiorge, J.A., P-015
Digout, C., P-429, PD-055, PD-093
Dijkstra Pinto Leite, J.E., O-212
Dijkstra, S., P-136
Dikme, G., P-427
Diletto, B., O-025
Dilley, R.L., PD-042
Dillon, S., P-407
Dilloo, D., P-394
Dimaras, H., P-230, P-232
Dinand, V., O-110, P-417, P-418, P-424
Dincaslan, H., P-467, PO-047
Ding, L., P-131
DiNofia, A., P-016
Dirks, P., O-047
Dirksen, W., P-408
Diskin, S., O-067
Dittmer, D., O-060
Dix, D., O-072, O-154
Dluzniewska, A., P-114
Dogbe, J., P-450, P-483
Dogru, O., P-062, P-083, P-332, PO-034, PO-037,
PO-052
Dolendo, M., PD-033
dolendo, M.C., PD-053
Dolgopolov, I., P-310, P-311
Dolgushin, B., P-244
Dolman, E., O-071
Dolz, S., P-383
Dome, G., PD-071
Dome, J., O-001, O-072, O-073, O-154, P-173
Domingo, E., P-228, PD-033
Dommering, C., P-523
Donadi, E.A., P-004
Donadieu, J., O-159
Donaldson, R., PO-105
Dong, K., P-132, P-344, P-191
Dong, R., P-132
Doolan, E., O-103, O-105
Dorascenzi Magri Teles, N., PO-083
Doronina, I., P-577
Dory-Lautrec, P., P-307
dos Santos Maia Lemos, P., PO-083
dos Santos, F.A., P-250
doval, D., P-120
Downie, P., O-102
Doyen, J., O-059
Doyle, T., P-426
Dr, G.H., PD-072
S503 of S518
Dr, L.E., PD-072
Dr., J.B., PD-072
Drake, E.K., O-146
Dran, G., O-117
Dray, E., P-411
Dreneva, A., P-301, P-302
Drenyova, A., P-322
Drinkard, B., P-494
Drogosiewicz, M., P-252, P-329
Drouin, S., PD-060
Druley, T.E., PD-010
Druy, A., P-133, P-303
dsa, S., P-543
D'Souza, A., P-251
Duan, C., P-128, PO-040
Duarte, A., O-140
Dubashi, B., PO-033, P-091
Dübbers, M., PD-104
DuBois, S., O-067
DuBois, S.G., P-388
Ducassou, A., P-364
Ducassou, S., O-032
Dufour, C., O-032, O-043, O-078, P-181
Dugas, M., PD-088
Dumoucel, S., O-131
Duncan, C., O-077, PD-024
Dunkel, I.J., O-041
Dupuis, L.L., P-435
Duran Leite, N., P-475
Dusome, D., PO-124
Dusza, A., P-064
Dvorak, C., P-145
Dvorakova, P., P-335
Dwyer, E., P-016
Dye, K., P-566
Dzieran, J., P-127
Dzierma, Y., P-370
E
Earle, C., O-083
Eaton, B., P-110, PD-032
Ebeid, E., P-066, P-295
Eberhart, C., O-014
Ebinger, M., O-153
Ebus, M., PD-019
Ebus, M.E., AW-08, O-066
Echebarría Barona, A., P-304, P-526, PO-056, PO-015
Echebarria-Barona, A., P-518
Eckert, C., O-124
Eckert, K., P-571
Eduardo, B.R., P-559
Edwards, L., O-101
Edwinson Månsson, M., O-185, O-186
Egan, D.A., O-071
Egeland, S.E., O-184
Eggert, A., O-053, O-055, O-068, P-137, P-243
Ehlert, K., P-113
Ehrlich, P., O-154, O-072, O-073, P-173
Ehsani, M., P-017
Ehsani, M.A., PO-036
Eikemo, T.A., PD-070
Eissa, S., P-068, P-082
Eissler, N., P-386
Eker, N., P-083, PO-034, P-062, P-332, PO-037,
PO-052
Ekinci, S., P-169
Ektova, A., P-320, P-577
El Gebaly, H., O-112
El Malki, K., PD-056
El nemer, D., P-063
El Shafie, A., P-574
El Tabech, D., PD-002
Elbourne, C., O-151
Eleveld, T.E., O-071
Eleveld, T.F., AW-08, O-066
El-Fayech, C., O-024
Elgalaly, D., P-210, P-261, PO-050
Elgendy, A., O-171
Elguindy, N., PD-009
Elhaddad, A., P-082, P-210, P-580
El-Haj, N., P-084
elhemaly, A., P-135
Elias, B.C., PO-083
Elias, D., O-169
El-Khatib, G., P-481
Elkholy, E., P-209
Elkinaai, N., P-261, PO-050, P-209
Ellerkamp, V., PD-101
Ellison, D., O-044
Elmadhoun, O., PO-131
elmahalawy, H., P-437
El-Mahalawy, H., P-436
Elmalik, K., O-156
El-Mallawany Kim, N., PD-075
El-Mallawany, N., P-268, P-269, P-412, P-489, P-541
El-Mallawany, N.K., O-065
elmenawi, S., P-135
Elmeniawy, S., P-580
Elmont, G., O-082
Elnadi, E., P-209
Elsayed, A., O-121
Elshafiey, M., P-210
Elshahoubi, A., P-125
Elshail, E., P-297
El-Sheikh, A., P-413
Elsherif, M., P-210
El-Solh, H., PD-002
Elwakeel, M., P-210, P-261, PO-050
Elze, M., P-362
Emad, R., P-295
Embry, L., P-564
Emery, J., P-466
Emmanuele, C., PD-087
English, R., P-016
Entz-Werle, N., P-384, P-307
Erbay, A., P-103, PO-095
Ercetin, P., P-123, P-124, P-192
Erdag, T., P-279, PO-042
Erdem, M., P-090, P-279, PO-024, PO-025, PO-042,
PO-058
Erdmann, F., P-537
Erega, E., P-320, P-577
Ergun, O., P-368
Eric, G., O-072
Eric, M., O-059
Eric, S., O-125
Eriksson, C., PD-076
Erkoc, E., P-279
Erminio, G., P-155
Ermoian, R., P-366
Ersoy, G., PO-029, P-270, PO-084
Ertekin, M., P-552
Escobar, P., P-383
Eshiashvili, N., PD-032
Esiashvili, N., P-110
Esparza, R., PD-041
Espeleta, H.C., O-179
Esquembre, C., P-383
Essa, I., P-462
Essam, M., PO-050, P-261
Eun-Suk, K., PD-017
Evangelista dos Santos, A.C., P-241
Evans, G., O-016
Eveslage, M., PD-044
Evin, H., P-516
Eweida, W., O-057
Ewert, P., P-575
Eyiah-Mensah, W., P-469
Eyrich, M., P-572
Ezer, S., PO-095
F
F PATENAUDE, A., PO-104
Faber, J., P-571, PD-056
Faber, M., P-448, PD-066
Fábri, O., P-065, P-057
Fadel, S., O-171, P-122
Fadoo, Z., PO-041
Faheem, M., P-543
Fahy, A., P-134
Fairclough, D., PD-058, PD-061
Faizan, M., P-172, P-005
Fajardo, P., P-167, P-228, PD-033
Falcone, M.P., O-074, O-077
Falconi, I., O-155, PD-103
Faldum, R., PD-045
Fang, J.P., PD-049
fang, L., O-031
Fang, X., P-190
Fang, Y., P-431
Farace, P., P-376
Faranoush, M., PO-036, P-314
Fardell, J., O-105, PO-120
Fardell, J.E., P-466
Fares, S., P-481
Farghaly, H., P-459
Faria Andrade, A., P-392
Faria Domingues de Lima, M.A., P-241
Faria, C., O-042
Faria, P., P-183, P-272
Faria, P.A., P-521
Farinha, N.J., PD-039
Farncombe, T., P-560
Farooqi, M., O-049
SIOP ABSTRACTS
S504 of S518
Farrag, A., P-538, PD-090
Farrow, E., O-049
Fasciano, K., PO-129
Fateha Noor, S., P-045
Faure Conter, C., O-038
Favre, C., P-470
Fawaz, O., PO-104
Fawzy, M., P-135, PO-006
Fawzy, N., P-395
Fazio, G., O-092
Fechina, L., P-133
Feddersen, I., P-394
Federico, A., O-192
Federico, S., P-145
Federman, N., P-388
Fedoriw, G., O-060
Fedorov, D., PO-049
Felice, M., P-044
Felice, M.S., P-015
Felsberg, J., O-042
Feltbower, R., P-566
Fendler, W., P-333
Feng, X.Q., PD-049
Feoktistova, E., P-141
Ferman, S., P-174, P-272
Fernandez, C., O-072, O-073, O-146, O-154, P-173
Fernandez, J., PO-108
Fernandez-Pineda, I., O-026
Ferner, R.E., O-016
Feroz, A., PO-085
Ferrante, A., O-213
Ferrante, A.C., O-211
Ferrão, P., P-515
Ferrari, A., O-025, O-084, O-086, O-087, O-089, O-166
Ferreira-Facio, C., P-515
Ferretti, R.L., P-405, P-406, PO-081
Ferri, C., P-010
Ferris, M., P-110
Fervers, B., P-404
Fesenko, D., PD-057
Field, A., PD-030
Figarella-Branger, D., O-045
fikry, S., O-121
Filander, A., P-487
Filippidou, M., P-031
Filippidou, M.C.S., P-550
Finlay, J., P-319
Fiocco, M., O-148, P-157
Fiori, C., P-539, PO-132
Fischer, M., P-394
Fish, J., PO-022
Fisher, A., P-457
Fisher, J., O-094
Fisher, M.J., O-016
Fisher, P., O-044
Fisher, R., O-156
FitzGerald, T., P-377
Flaherty, T., P-016
Flanders, A., PD-093
Flatt, T., P-500
Fleischhack, G., P-378, P-572, PD-045
Flerlage, J., P-096
Flower, E., P-342
Flowers, S., P-488
Flynn, P., P-444
Fonseca, A., P-271, P-296
Font de Mora, J., O-068, P-383
Font-Gonzalez, A., P-435
Ford, D., P-213
Forrest, H., P-403
Forrest, S., O-199
Forster, V., P-565
Fort, C., P-441
Foster Akard, T., PD-058
Foster, R., O-106
Foudaneel, M., P-297, PO-044
Fouladi, M., O-014
Foulkes, W., PD-089
Fouquet, C., O-115
Fraga Piovacari, S.M., P-445
Frahsek, S., P-572
Francine, K., P-532
Francisca, P., O-201
Francisco, F., O-140
Franck, L., O-200
Franco, D., P-535, PO-130
Francotte, N., O-087
Fransson, S., P-143
Frappaz, D., P-393
Frazier, L., O-037, O-038, P-540
Freccero, P., P-414
frediani, S., O-155, PD-103
Freha, M., P-497
Freling, N., P-367
Fremerey, J., PD-088
Fréneaux, P., O-131
Fresneau, B., O-024, O-038
Friderici, J., P-084
Friedrich, C., P-572
Friedrich, P., P-548, P-586
Friend, A.J., P-566
Froňková, E., P-057
Fruci, D., O-068
Fruge, E., P-541, P-588, P-591, PO-111
Fu, L., O-142
Fu, Y., P-101
Fuchimoto, Y., P-345, P-391
Fuchs, J., O-153, O-160, O-175, P-223, PD-101,
PD-106
Fuentes Alabi, S., P-540, P-444, PO-099
Fuentes-Alabi, S., AW-02
Fujii, Y., P-029
Fujimura, J., O-126
Fujino, A., PO-068
Fujisaki, H., P-161
Fujiwara, T., PO-043
Fukuda, K., P-391, PO-013
Fukuoka, K., P-317
Fukushima, H., P-317
Fuller, T., O-123
Fumino, S., O-173
Furman, W., P-145
Fürst-Recktenwald, S., P-362, P-387
Furth, C., P-137
Furtwängler, R., AW-03, P-370
Furukawa, T., O-173
Fuster Soler, J.L., P-116
G
G. Andrade, F., P-036
Gaber, M., PO-089
Gabra, H., P-346
Gagniere, J., O-169
Gaipa, G., O-091
Gajjar, A., O-013, O-014, O-044
Galbarriatu Gutierrez, L., P-304, PO-056
Galea, N., O-074
Galera Miñarro, A.M., P-116
Galezowska, G., P-524
Gallego, S., O-084, O-086, PD-031
Gallie, B., P-231
Gallotto, S., P-366
Galmiche, L., P-208
Galmiche-Rolland, L., O-115
Gamboa, Y., PD-014
Gamboa-Chaves, Y., PO-075
Gamwell, K.L., O-179
Gandola, L., O-025
Gandolfo, C., PD-018
Ganesan, V., O-157
Gao, J., PD-005
Gao, Y., P-260, PD-005
Gao, Y.J., P-085
Garami, M., P-273
Garavelli, L., PO-059
Garaventa, A., O-068, P-154, P-155
García de Andoin, N., P-020, P-518
Garcia Lombardi, M., P-148, P-281, P-289
Garcia Rives, A., P-304
Garcia, A., P-319
Garcia, J.L., P-021
García, L., O-117
Garcia, N., P-319
García-Ariza, M., P-020, P-304, PO-056, P-526,
PO-015, P-518
García-Jiménez, E., P-058
Garcia-Orad, A., P-020, P-518
Gardling, J., O-185, O-186
Gardner, M., P-488
Gargallo, P., P-383, P-402
Garming-Legert, K., P-425
GAROFOLO, A., P-410, P-517
Garrè, M.L., P-155
Garrido Colino, C., P-455
Garrido, C., AW-02
Garrote Molpeceres, R., P-028
Gaspar, N., O-059, O-159
Gaspard, J., PD-091
Gastier-Foster, J., O-020, O-072
Gattuso, J., O-194
Gaudet, D., P-366
Gavens, E., O-156
Gavrylyuk, Y., P-231
Gaytan Morales, J.F., P-202, PO-116
Gaze, M., P-362, P-367, PD-024
Gaze, M.N., PD-031
Gazzola, L., P-375
Geat, M., P-375
Gedleh, A., P-230
Geel, J., P-534, P-554
Geller, J., P-173, O-072, O-073, O-154
Geller, J.I., P-170
Genere, L., PO-090
Gentet, J.C., P-208, P-307, P-384, P-484
Geoerger, B., P-362, P-387, P-393
George, B., O-090
George, C., PD-091
Georgiou, G., O-105
Gepte, B., P-228
Geraci, M.W., O-033
Gerhardt, C., O-211, O-213, P-491, PD-058, PD-062
Geron, L., P-327
Geronimo, J., P-206
Gerrard, C., P-454
Gershenson, D., O-038
Gerstle, J.T., P-134
Gessain, A., P-212
Gessi, M., O-045
Geyer, J.R., O-013
ghandoUr, K., P-186
Ghanem, K., PD-002
Ghemlaz, I., P-002
Ghogale, S., P-013, P-100
Gholamin, S., PD-041
Ghzally, M.H., P-538
Giagnuolo, G., P-022, PO-002
Gian Luca, D.S., O-086
Giangaspero, F., O-045
Gianni, B., O-086
Gibbs, C.P., P-211
Gibson, D., PD-091
Gibson, F., O-187, O-177
Gibson, M., O-049
Gibson, T., O-106, PD-091
Giglio, S., P-267
Gil, O., O-168
Gilberto Carlotti, C., P-392
Gill, A.N., P-501
Gill, J., P-224
Gill, R.N., P-501
Gillam, L., O-102, O-210
Gilliland, T., P-556
Gilmer, M.J., PD-058
Gioia, A., PD-071
giralt, J., P-363
Gisselsson, D., AW-05
Gissler, M., PD-097
Glade Bender, J., P-387
Glaser, A., P-419, P-420, P-566
Glasgow, K., PD-091
Glehen, O., O-169
Gleissman, H., P-386
Glick, R., O-154
Glosli, H., O-084, O-086, PD-031
Goddard, K., P-312, PD-048
Godzinski, J., PD-106
Goedkoop, D., P-158
Goel, G., P-399
Goerike, S., P-243
Goghale, S., P-052
Goh, B., PD-105
Gojo, J., P-323
Gökşen, D., P-562
Gold, S., P-511
Goldish on behalf of SPARCCC & Summit participants,
M., PO-098
Goldsby, R., O-200, P-145
Goleta-Dy, A., P-228
Goma, G., O-078, P-181
Gombert, M., PD-088
Gomes Andrade, F., P-069, PD-007, PD-008
Gomez-Garcia, W., AW-02
Gonçalves, F.F., O-198, PO-072
Gonzaga Tone, L., P-327, P-392
Gonzaga, L.G., P-076
Gonzalez Camacho, U., P-526, PO-015
Gonzalez Cerdeira, Y., O-142
González García, H., P-028
Gonzalez, M., PO-082, P-403
Gonzalez, R., P-319
Gonzalo Pascual, H., P-455
Gook, D., O-102
Goorden, S., P-157
Gopakumar, V., P-461
Gopal, S., P-489, PD-075, PO-125
Gorbatykh, S., P-320
SIOP ABSTRACTS
Gorbunova, T., PO-038, PO-039
Gorczynska, E., P-012
Gordon, L., P-143
Gore, L., O-019
Gorelyshev, S., P-310, P-311
Gorgun, O., P-235
Gorlick, R., P-194
Gorovets, D., P-194
Gorovtsova, O., P-244
Goseingfiao, Y., P-432
Gosheger, G., O-056
Gosiengfiao, Y., P-433
Goto, H., O-032, O-040, P-195, PO-013
Goto, S., PO-013
Gottardo, N., P-334
Gottchalk, S., PD-051
Goudie, C., PD-089
Goudjil, F., P-364
Goulart, E., P-254
Goumenrova, L., P-542
Govindaranjan, K.K., PO-071
Gow, K., O-073, O-154, P-173
Gowdy, C., P-438
Gozdzik, J., P-114
Grabois, M., P-174
Grabois, M.F., P-025
Grabowski, D., P-067
Graf, N., AW-03, O-075, P-370, P-394, PD-106
Grajkowska, W., P-305, P-252, P-329, PO-065
Grandér, D., PD-047
Granger, M., O-041
Granhagen Jungner, J., O-188
Grant, M., PD-051
Grant, R., P-271
Gratias, E., O-154, P-173
Gratias, E.J., O-073
Gravestock, H., P-457
Gray, J., P-291
Green, D., O-106
Green, D.M., O-026
Green, K., P-086
Greenberg, M., PD-093
Greenberg, R.A., PD-042
Greensher, J., PO-022
Grewal, S., P-084
Griffin, M., PD-098
Grigorian, M., PO-049
Grill, J., O-043, O-016, P-387
Grimaldi, C., PO-067, O-166, P-339
Grimes, A., P-564
Grimshaw, S., P-415
Grinenko, A., PO-049
Grishina, E., P-577
Groll, A.H., P-113
Grootenhuis, M.A., O-098, O-107, O-202, O-212
Gross, A., PO-129
Grosshans, D., PD-096
Grundy, P., O-073, P-173, PD-093
Grupp, S.A., O-123
Gruszka, R., P-333
Gruzdev, V., PD-100
Grynszpancholc, E., O-117
Guan, J., P-143
Guaraldi, A.L.D.M., P-025
GUEDES, K.J.T., P-405, P-406, PO-081, P-517
Guérin, F., O-162, P-350
Guerra, J.V.S., P-521
Guest, E., O-049
Guilcher, G., PO-119
Guillen Burrieza, G., O-162
Guimier, A., P-212
Guinipero, T., O-032
Guitter, M., P-015, P-044
Gujral, S., O-022, P-013, P-040, P-054, P-100
Guleryuz, H., P-090, PO-024, PO-025, PO-042, PO-058
Gulia, A., O-058
Gumbatova, E., PO-030
Gumley, D., P-298
Gümrük, F., P-056, P-077
Gun Soysal, F., P-177
Gunasekaran, V., O-110
Gundersen, L.W., PD-066
Gundeti, S., PO-001
Gunduz, K., PO-047
Güneş, B., P-080
Güney, E., PO-115
Guo, R., P-164
Guo, X., P-085, P-190
Gupta, A., P-258, P-271, P-456
Gupta, B., P-023, P-035
Gupta, C., P-220
Gupta, C.L., P-413
S505 of S518
Gupta, H., O-134
Gupta, J., PD-065
Gupta, N., P-024, P-014, P-264, P-265
Gupta, S., O-028, O-083, P-306, PD-003, PD-091,
P-581, PD-093
Gupta, S.K., P-087
Gupta, V., O-029, P-087
Gupta, Y., P-089, P-088
Guram, S., P-416, PO-057
Guru, V., P-245
Gururangan, S., P-387
Gusev, A., PO-049
Gutiérrez Meléndez, P., P-028
Gutierrez, F.N., P-025, P-174, P-272
Gutierrez, M.F., P-289, P-148
Gutierrez-Camino, Á., P-020, P-518
GUZMAN, E., PO-064
H
H N, R., P-417, P-418
Haapa Hybinette, H., PO-076
Haberler, C., O-045, P-323
Habib, F., PO-133
Habib, Z., P-168
Habrand, J.L., P-365
Hadad, A., P-068
Haddad, A., PD-009
Haddy, N., O-024
Hadj, T., PO-014
Haers, M., P-331
Hafez, A., O-118
Hafez, H., P-436, O-113, P-209
Hafiz, H., P-437
Hagan, M., PD-062, PD-058
Hager, A., P-575
Hahn, S.M., P-033
Haie-Meder, C., P-350
Hailu, D., P-553
Haimer, A., PO-133
Hajime, H., P-138
Hakim, H., P-444
Hakim, S., P-164, PD-052
Hakkert, A., PD-019
HALALSHEH, H., P-125, P-186
Hale, J., O-036
Halepota, H., P-175
Haley, S., PO-105
Haliloğlu, M., P-276
Hall, S., O-187
Hallberg, B., P-143
Hallström, I., O-183, O-185, O-186, P-477
Halpern-Felsher, B., O-200
Halvorsen, J.F., PD-070
Hama, A., P-074
Hamada, K., PO-043
Hamanoue, S., PO-013
Hamdy, A., P-580
Hami, H., PO-133
Hamid, M., O-135
Hamilton, T., O-154
Hammad, M., P-068, PD-009
Hammarlund, K., P-477
Hammond, C., PD-093
Hammond, P., O-152
Hamoda, A., P-135
Hamouda, A., O-121
Han, J., P-494
Han, J.W., P-033
han, W., PO-048
Hanafy, E., PO-006
Hanafy, H., P-542
Hancerli, S., P-092
Hancock, K., O-099, O-100, PD-061
Hand, M., O-210
Handgretinger, R., O-175
handoo, A., P-120
Hangard, G., P-364
Hanley, P., P-385, PD-051
Hans, M., PO-101
Hansen, M., O-054
Hansen-Moore, J., P-488
Hansford, J.R., P-334
Hansson, H., P-502, O-183
Hansson, M., P-143
Haq, A., P-297
Hara, J., P-161, P-163, P-317
Hardy, K., O-106, PD-071
Hargrave, D., O-016, P-326, P-387, PD-043
Hargreave, M., O-005
Harila Saari, A., PO-076
Harila-Saari, A., P-026
Harm, V.T., AW-03
Harper, F.W.K., O-178
Hartsell, W., P-366
Harvey-Wood, K., P-462, P-463
Hasan, F., PD-034
Hasan, H., PD-048
Hasbay, B., P-103, PO-095
Hasegawa, D., P-029, P-074
Hashem, M., P-063
Hashii, Y., PO-043
Hasle, H., PD-066
Haslund, H., O-190
Hassaan, A., PD-026
Hassall, T., O-044
Hassan, B., P-193
Hassan, H., P-419, P-420
Hassan, N., O-112
Hassan, S., O-112
Hassan, T., P-027
Hassonah, M., P-297
Hata, K., O-048, O-129
Haupt, R., PD-018
Hauser, P., O-045, P-273
Hautz, W., P-236
Haverman, L., O-202
Havitcioglu, H., P-192
hawazen, A., P-003
Hawkins, C., O-014, O-045, O-047
Hawkins, D.S., P-388
Hayasaka, H., PO-109
Hayashi, K., P-205, P-380, PD-027
Hayashi, R., O-106
Hayashi, Y., O-048, O-129
Hayashibe, A., P-451
Hayati, H., P-017
Hayden, R., P-444
Hayes, L., O-013
Hayes-Jordan, A., O-161
Hays, A., P-102
He, J., P-159
He, L., P-308
He, M., P-503, O-167, O-208, P-259, PD-083
Head, H., P-528
Heath, C., PO-129
Heather, G., O-011
Heaton, T., O-088
Hecht, J., P-329
Hecker-Nolting, S., O-056
Hed Myrberg, I., PD-047
Hedayati Asl, A.A., P-314, PO-036
Heerema, N., O-020
Heier, L., O-014
Heij, H., O-148, PO-069
Heike, T., PD-036
Heil, S., O-023
Heilman, C., PD-066
Heinävaara, S., PD-097
Hekimci Ozdemir, H., PO-060
Helfre, S., P-364, P-365
Helleday, T., PD-047
Helms, A.S., PD-066
Heloury, Y., O-102, O-210
Hendershot, E., PD-098
Heng-Maillard, M.A., P-307, P-384
Hennekam, R., P-523
Henniger, N., PD-056
Henry-Moss, D., P-465
Henter, J.I., PD-047
Herman, N., P-398
Hermiston, M.L., O-123
Hernaiz Driever, P., O-016
Hernández San Pelayo, T., P-455
Hernández, D., P-257
Hernandez, E., P-585
Hernychova, L., P-335
Hero, B., O-055, O-053, P-394, PD-104, PO-093
Herold, N., PD-047
Herraiz Cristobal, R., P-028
Herrero, M.J., P-402
Hertle, S., O-032
Herzog, C., O-161
Hesham, M., P-063
Hess, C., P-366
Hesseling, P., P-532
Hetherington, M., P-102
Heyman, M., PO-076
Heyn, H., PD-019
Hezam, I., O-078, P-181
Hibi, T., P-345
Hicks, D., O-015
Higashi, M., O-173
Highberger, M., P-510
Higuchi, T., P-205, P-380, PD-027
SIOP ABSTRACTS
S506 of S518
Hijiya, N., O-032
Hilden, J., O-019
Hill, D.A., PD-030
Hill, J., P-230
Hill, R., O-015, P-438
Hiller, T., PD-087
Hill-Kayser, C., P-366
Hilton, M., P-387
Hind AlHindi, H.A., P-297
Hindle, A., PD-020, P-150
HInds, P., O-011
Hirabayashi, S., P-029
Hiramatsu, H., PD-036, PD-037
HIrano, S., O-004
hirata, M., P-514
Hirst, E., PO-105
Hishiki, T., PO-068, O-126, O-163
Hislop, C., P-422
Hitoshi, S., P-512
Hitzler, J., PD-010
Hiyama, E., O-004, O-126, O-163, P-567, P-547
Hizhnikov, A., PO-023
Hjemdal, O., PD-070
Ho, C., O-102
Hoag, J., P-490
Hoang, T., PO-026
Hobin, D., P-088, P-089, PO-073
Hockenberry, M., P-536, PD-094
Hockenberry, M.J., O-114, O-189
Hocking, M., PD-063
Hodgson, D., P-312
Hoeft, A., P-528, PO-129
Hoffer, F., O-073, P-173
Hoffmann, A., P-316, PD-044
Hofheinz, F., P-137
Hogan, A., P-219
Hol, J., O-075, P-188
Hol, M.L., P-367
Holguín, A., O-168
Hollis, R., O-196
Holm, S., P-478
Homsi, M., P-403
Honda, S., O-126, O-163
Hong Hoe, K., PD-017
Hong, S., PD-084
Honoré, S., P-307
Hoogerbrugge, P., P-136
Hooke, C., PD-094
Hooke, M.C., O-189, O-114, P-536
Hooper, E., P-018
Hoover, J., P-385, PD-051
Hopman, S., P-523
Hopper, E., P-019
Hoq, F., P-385, PD-051
Horbinski, C., O-014
Horibe, K., P-547
Horikoshi, Y., P-379
Hörl, R., PD-006
Hornsey, S., P-299
Horton, S., P-581
Hoshino, K., O-126, O-163, P-345
Hoshino, N., O-129
Hosoi, H., O-173, PD-029
Hosszu, E., P-273
Hough, R., P-457
Hougham, K., P-232, P-230
Houghham, K., P-231
Houghtelin, A., P-385
Houlahan, K., P-542, P-586
Howard, F., PD-048
Howell, R., O-106
Hroch, P., PD-085
Hsu, C.Y., PD-032
Hu, D., P-190
Hu, Q., P-131, P-431
Hu, S., P-431, PD-005
Hu, W., P-260
Hu, W.Y., PO-080
Hua, C.H., O-017
Huang, A., P-271, P-296
huang, C., P-128
Huang, D., PO-028
Huang, L.B., PD-004, PO-010
Huang-, L.H., PO-080
Hudson, M.M., O-026, O-104
Huerta Aragonés, J., PO-077
Hughes, D., O-156
Hughes, E., P-566
Huh, W., O-161
Huitrón-Hernández, M., P-472
Hui-Zhen, T., PD-004
Hukin, J., P-312
Hum, V., PD-085
Humphries, P., PD-021
Hundsdoerfer, P., P-137
Hung, P.H., PO-003
Hunger, S., O-018, O-019, O-020
Hunger, S.P., O-021, P-016
Hungr, C., PO-106
Hurteau, J., O-038
Huybrechts, S., O-043, O-131
Huynh, R., PO-086
Hyakuna, N., P-029
Hyeon Jin, P., P-215
Hyun Guy, K., P-215
I
Iannotta, A., P-009, P-010
Ibragimova, S., PO-004
ibrahim, G., P-003
Ichimura, K., P-317
Ida, K., O-126
Iehara, T., O-126, P-138, O-173, PD-029
Iguchi, A., P-129
Ijaz, H., PD-042
Ijovskyi, A., PO-049
Ikeda, A., P-272
Ikeda, M., PO-109
Ilari, M., O-165
Ilhan, İ., P-421, P-197
Im, L., O-123
Imade, S., PD-065
Imaizumi, M., PO-109
Imam, U., PO-046
Imamura, T., O-048
Imyanitov, E., P-275
İNCE, D., P-090, PO-024, PO-025, P-279, PO-042,
PO-058
Indelicato, D., P-211, O-017, P-366
Indini, A., O-025
Indolfi, P., P-009, P-010
Indranee, J., P-117
Inglis, V., P-422
Inomistova, M., P-139
Inoue, M., O-173
Inoue, T., P-317
Inoue, Y., PO-109
Inserra, A., O-166, PD-038, PO-067
Inyushkina, E., P-320
Iovino, N., P-211
Irıbas, A., P-177
Irisuna, F., O-004
Irnich, M., P-394
Irtan, S., O-159, O-039, PD-106
Irwin, K., O-146
Ishak, M., P-574
Ishida, Y., P-379
Ishigami, E., P-588, P-590, P-541, P-589, P-591,
PO-111
Ishutina, J., PD-112
Islam, A., P-045
Islam, J., P-237
ISMAEEL, T., P-186
Ismail, H., P-252
Ismail, M., PD-051
Ismayilzade, R.S., P-474
Isobe, T., O-048, O-129
Isohashi, F., PO-043
Italiano, A., O-131
Itimu, S., O-060, P-489, PD-075, PO-125
Ito, Y., O-006
Ittmann, M., P-164
Ivankovich-Escoto, G., PO-075
Ivanova, N., P-244, PD-112
Ivanova, S., P-109, P-105, P-106, P-107
Ivanovski, A., PO-059
Ivanovski, I., PO-059
Ivanovski, P., PO-059
Iwamoto, S., P-074
Iwasaki, F., PO-013
Iyer, N., O-108, P-070, P-071
Iyer, V.K., P-337
Izu, A., O-109, P-446
Iżycka-Świeszewska, E., P-266
J
Jaboma, I., P-423
Jackson, A., O-024
Jackson, C., P-212
Jackson, T., P-194
Jacobs, S., O-011, P-330, P-331, P-578, PO-129
Jacques, T., O-045
Jacques, T.S., O-015, P-326
Jadhav, N., P-091
Jafa, E., P-091
Jaffri, R., P-002
Jain, P., O-110, P-424
Jain, R., O-111, O-120, P-428
Jain, S., O-150, O-157, P-351, P-592, PD-011, PD-054
Jakab, Z., PD-039
Jamal, C.Y., P-030, P-045
Jamal, M., P-068
Jana, M., O-174, P-061
Jankowska, A., PD-064
Jannier, S., P-140
Jans, M., O-148, PO-069
Janssens, G., P-363
Jansson, C., AW-05
Janu, A., O-058
Jarfelt, M., PD-086
jarusevicius, L., P-363
Jarzembowski, J., PD-030
Jaspan, T., O-016
Jatia, S., PD-065, P-583
Javakhadze, T., PO-011
Javed Khan, S., P-203, P-204
Javed, R., P-308
Javed, S., P-121
Jayabose, S., P-071, O-108, P-070
Jayasinghe, Y., O-102, O-210
Jayasuriya, S., O-102, O-210
Jeanne, A., O-115
Jefffrey, I., O-164
Jehanne, M., PO-053
Jenney, M., O-084, O-085, O-086, PD-031
Jenovari, Z., P-273, PO-070
Jensberg, H., PD-070
Jeppesen, M.D., O-190
Jester, I., PD-107
Jezierska, M., P-266
Jezova, M., P-335
Ji Won, L., PD-017
Jiang, H., P-078, P-085, P-431, P-431
jiayuan, Z., O-031
Jibb, L., PD-085, O-146
Jimenez, M., O-159
Jin, H., P-190
Jin, M., P-128, PO-027, PO-040
Jin, R., P-431, PD-005
Jin, R.M., P-085
Jindal, B., PO-071
Jingyan, T., O-122
Jo, D.H., P-233, PD-035
Jo, T.K., PO-087
Jocham, S., P-113
Johannes, S., P-243
Johansen, C., PD-066
Johassson, H., P-127
John, R., P-176
Johnsen, J.I., P-143, P-386
Johnson, E., P-433
Johnson, I., O-034
Johnson, K., PD-076
Johnson, P., P-505, O-204
Johnson, R., PO-107
Johnston, J., O-049
Johnston, M., P-387
Jonathan, K., P-194
Jones, D.T.W., O-046
Jones, J.M., P-466
Jones, R., PD-051
Jones, V., O-187
Jong Hyung, Y., P-215
Jongmans, M., P-523
Jorgensen, M., P-326
Jose, W., P-321
Joseph, S., O-169
Joshi, A., O-015
Joshi, N., O-144
Jouin, A., O-059
Jouve, E., P-384
Jozala, D.R., P-282
Ju, H.Y., P-215, PO-117
Ju, X., P-431
Ju, X.L., P-085
Juárez Villegas, L.E., PO-116
Jubran, R.F., O-041
Judkins, A., O-013
Juergen, S., O-153
Juhnke, B.O., P-572, PD-045
Julia, C., O-084
Julieron, M., O-131
Julieta, R.C., P-559
Juma, N., PD-085
Jun, H.O., P-233, PD-035
Jun, M., P-465
SIOP ABSTRACTS
June Hyuk, K., P-215
Junior, R.H., P-025
Jurkiewicz, E., P-236, P-305
Justin, L., P-231
Jüttner, M., O-070
K
K P, H., P-306
K, J., P-543
Kaah, J., P-532
Kabickova, E., P-274, P-325
Kabiru, J., P-230
Kabra, S., P-001, P-061
Kachanov, D., P-141, P-142, P-275, PD-018
Kadioglu, B., P-368
Kager, L., O-056
Kagoro, N., P-591, P-541, P-588, P-589, P-590
Kahalley, L., PD-096
Kahan, S., PO-111
kai, C., P-072
Kairalla, J., O-020
Kaiserová, E., P-065, P-546
Kakkar, N., O-120
Kalapurakal, J., O-072, O-154, P-173
Kalapurakal, J.A., O-073
Kalashnikova, I., P-147
Kalay, G., P-552
Kaliciński, P., P-252
Kalinova, M., P-274
Kalkan, N., P-276
Källstrand Eriksson, J., P-513
Kalra, M., AW-01
Kalyoncu Uçar, A., P-427
Kamal, N., PD-026
Kamalyan, A., PO-108
Kamath, N., P-543
Kamel, A., P-066
Kamer, S., P-080, P-368
Kamibeppu, K., P-504, PO-109, P-495
Kamijo, T., P-138
Kamikubo, Y., PD-036
Kamiyama, M., P-163
Kamiyango, W., P-268, P-269
Kamman, R.L., O-212
Kampani, C., O-060
Kampouraki, E., P-051
Kamsvåg Magnusson, T., P-425
Kamwagha, J., P-268
Kanakkande Kandy, Z., PO-005
Kanamori, Y., PO-068
Kandeel, E., P-066
Kang, G., O-013, P-145
Kang, H.J., O-032, PO-117
Kang, M., P-150
Kansiime, R., P-588
Kantar, M., PO-060, P-368, P-562
Kapoor, G., PD-054, O-150, P-351, P-592, PD-011
Kapoor, R., O-120
Karabacak, I.N., P-527
Karachunskiy, A., P-303
Karadeniz, C., P-095, P-318, P-527, PO-061, PO-115
Karady, Z., P-273, PO-070
Karagenc, A., P-092
Karajannis, M., P-194
Karajannis, M.A., O-046
Karakas, Z., P-092, O-032, P-177
Karaman, S., P-092
Karelin, A., P-320, PD-057, PO-135
karim, S., P-237
Karimi, M., P-382
Karitskiy, A., P-107
Karitsky, A., P-109
Karlsson, J., AW-05
Karns, R., P-251
Karolczyk, G., P-053, P-266
Karpelowsky, J., O-158, P-341, P-342, PD-105
Karpińska-Derda, I., P-067, P-266
Kasatkin, V., P-301, P-302, P-322, PO-135
Kashyap, S., P-234, P-207, P-214, P-246, P-247, P-264,
P-265, P-280
Kaspers, G.J., P-157
Kaspers, G.J.L., O-098, O-107
Kassam, A., O-083
Katan, H., PO-044
Katanoda, K., O-006
Kataoka, K., P-029
Katewa, S., P-217, PO-020
Kato, H., P-379
Kato, I., PD-036, PD-037
Kato, M., P-029, PO-068
Katsibardi, K., P-031
Kattamis, A., P-031, P-550
S507 of S518
Katzenstein, H.M., O-127
Katzilakis, N., P-051, PO-009
Kavan, P., PD-093
Kavlak Akar, D., PO-047
Kawaguchi, K., P-379, PD-037
Kawai, T., O-048, O-129
Kawakubo, N., P-359
Kawasaki, H., P-010
Kawashima, M., O-004, O-163, P-567
Kayal, S., P-091, PO-033
Kazak, A., PD-063, PD-067
Kazakova, A., P-141, P-142, P-275
Kazama, T., O-126, O-163
Kazancev, A., PO-023, O-172, P-347, P-357
Kazanowska, B., P-223, P-266
Kazantsev, A., PD-100
Kazembe, P., O-065, P-268, P-269, P-412, P-489,
PD-075
Kazi, M.Y., P-533
Kazuyo, W., P-447
Kearns, J., P-426
Kearns, P., P-213
KebriaeeZadeh, A., P-017
Kebudi, R., P-177, P-235, P-427
Kedia, S., P-013
Kelkar, R., P-460
Kelley, L., O-056
Kelley, S., O-049
Kellick, M., O-041
Kellie, S., O-013
Kelly, K., O-191, P-096, P-525
Kelsey, A., O-074, O-084, O-087, O-089, O-162,
PD-031
Kembhavi, S., P-369, P-561, PD-111
Kemertzis, M., O-102, O-210
Kennedy, C., P-299
Kennedy, S., O-137
Kennedy, T., PD-071
Kenney, L.B., P-568, PO-106
Keon Hee, Y., PD-017
Kerimov, P., O-172, P-347, P-357, PD-100, PO-023
Kerr, C., P-364
Kerre, T., PD-081
Kerstjens, M., O-071
Kessel, S., P-377
Keuleva, S., P-108
Kevric, M., O-056
Khafagh, Y., P-297, PO-044
Khaiman, C., PO-062
Khaing, A.A., P-414
Khalaf, M., O-121, P-209
Khaled, E., P-209, P-210
Khalifa, N., P-027, P-557
Khan, F., P-569
Khan, F.S., PD-012, PO-021
Khan, H., P-501
Khan, R., PD-099
Khan, S., P-175, P-168
Khan, S.J., P-121
khandelwal, V., P-120
Khanna, G., O-072, O-154
Khanna, K., PD-108
Khanna, N., PD-028, O-058, P-184, P-220, P-369,
P-561, PD-111
Khanna, V., P-348, PD-108
Khattab, E., P-125
Khattab, T., PO-006
Khedr, R., O-121, P-542
Khera, S., P-032, P-428
Kheradpour, A., O-032
Khochenkov, D., P-199, P-310, P-311, PO-035
Khranovska, N., P-139
Khu, M., PO-119
Khullar, P., P-277
Khurana, M., O-144
Khvedelidze, M., PO-011
Ki Woong, S., PD-017
Kibria, C.S.H., P-045
Kieran, M., P-542
Kihira, K., O-126
Kikuchi, K., PD-029
Kikuchi, R., PO-109
Kikuta, A., P-138
Kilic, S.S., P-278
Kill Suazo, V., P-392
Killela, M., P-506
Kim, D.S., P-034
Kim, E., P-151
Kim, H.S., PO-117
Kim, J., PO-007, PO-007
Kim, J.H., P-233, P-233, PD-035, PD-035
KIM, J.Y., PO-117, PO-087
Kim, M.K., P-033
Kim, S.K., PO-117
Kim, Y., O-073
Kimani, K., P-230
Kimikazu, M., P-512
Kimura, S., O-048, P-029
Kinoshita, Y., P-359
Kinsey, S., P-419, P-420
Kiratli, H., P-248
Kirby, J., P-403
Kisby, N., PO-088
Kishore, M., P-543
Kitagawa, N., P-195, O-040
Kitagawa, Y., P-345, P-391
Kitago, M., P-345
Kitamura, M., PO-068
Kitazawa, H., P-379
Kiyokawa, N., O-048, P-029
Kiyotani, C., P-161, PO-068
Kızılocak, H., P-427
Kizmazoglu, D., P-279, P-090, PO-024, PO-025,
PO-042, PO-058
Kizyma, R., P-178
Kizyma, Z., P-178
Kjaer, S.K., O-005
Kliebsch, U., P-226, P-361
Klingebiel, T., O-160, P-223
Klosky, J.L., O-026
Klymniuk, G., P-139
Klymnyuk, G., PO-049
Knight, P., P-224
Knox, L., O-137, P-389, P-422
Kobayashi, M., O-048
Kobys, V., P-196
Kobyzeva, D., P-303, P-320
Koç, B., PO-084, PO-029
Koçak, Ü., P-527, P-427
Kodet, R., P-274
Koerner, K.M., O-189
Koga, Y., P-359
Kogner, P., P-143, P-386, PD-047, PO-076
Koh, K., O-048, O-129
Kohashi, K., P-359
Kohli, S., PO-019
Kohno, T., P-317
Köhrer, S., PD-006
Kok, N., O-182
Kokkinou, E., P-550
Kolatan, E., P-192, P-516
Kolenová, A., P-065, PD-039, P-057, P-546
Kolodziejczyk-Gietka, A., P-236
Koltan, A., P-053
Komoravolu, P., P-461
Koneru, B., P-150, PD-020
Koneru, S., PD-054
Konovalenko, V., P-196
Konovalov, D., P-141, P-275, P-303
Kontny, U., P-394
Koo, H.H., P-034
Kool, M., O-044, O-045
Koopmans, B., O-071
Koptyra, M.P., PD-042
Korneeva, A., PD-112
Korones, D., P-553
Korshak, A., PO-049
Korshunov, A., O-045, P-320
Kortlandt, M., P-156
Kortmann, R.D., P-572, PD-045
Korzeniewska, J., P-570
Koscielniak, E., O-160, P-223, PD-039
Kosiak, M., P-579
Kostadinov, R., O-049
Kostantinov, D., PD-039
Koster, J., AW-08, O-066, O-071, P-158, PD-019
Kotenko, O., PO-049
Kotlovsky, A., P-358, PD-112
Kotne, S., P-321
Kotsay, B., P-178
Kotulska, K., P-305
Kovalenko, S., P-221, P-303
Kowalczyk, J., P-053
Kowgier, M., P-393
Kraal, K., O-052, P-136, PD-018
Kraal, K.C.J.P., P-156
Krailo, M., O-036, O-037, O-038
Krailo, M.D., O-041, O-127
Krajinovic, M., P-486, PD-060
Krallis, N., P-031
Kramer, A., P-494
Kramp, V., P-571
Krasin, M., P-145, PD-032
Krasin, M.J., O-026, O-104
SIOP ABSTRACTS
S508 of S518
Krasowska-Kwiecien, A., P-114
Krauel Gimenez Salinas, L., P-355
Krauss, J., P-572
Krawczuk-Rybak, M., P-012
Kreiger, P., PD-030
Kremer, A., P-113
Kremer, L.C.M., O-079, P-435
Kremer, V., P-356, O-170, O-198, P-282, P-353,
PO-072
Krepischi, A., P-254, P-250, P-256
Krishnan, V., P-041
Krista, R., PD-055
Krskova, L., P-274, P-325
Krüger, P.C., P-137
Krull, K., O-106
Krull, K.R., O-104
Ksiazek, T., P-067
Kudo, M., P-508
Kuehl†, J., P-572
Kuhlen, M., PD-088
Kühn, A., P-575
Kühne, T., O-056
Kuick, C.H., O-157
Kuiper, R., AW-06
Kuleva, S., P-107, P-105
Kulis, J., P-053
Kulkarni, K., P-429, PD-055, P-426
Kulyova, S., P-106, P-109
Kumar, A., P-023, O-030, O-136, P-035, P-013, P-060
kumar, B., PO-031, PO-051
Kumar, C., P-582
Kumar, R., P-337, PD-003
kumar, S., PO-031, PO-051
Kumari, M., O-062
Kumirova, E., P-303, P-320, P-577
Kumura, S., P-567
Kumwenda, I., P-073
Kunkel, R., P-554
Kurch, L., P-096
Kurdyak, P., O-028
Kürekçi, E., P-427
Kuriahra, S., P-567
Kurian, J., P-176
Kurihara, K., PO-109
Kurihara, S., O-004, O-163
Kurkure, P., P-369, P-561, P-563
Kuroda, T., P-345, P-391
Kuroglu, S., P-177
Kurucu, N., P-197, PO-016, P-169, P-198, P-276
Kuruoglu, S., P-427
Kurylak, A., P-579
Kuşkonmaz, B., P-077
Kutluk, T., P-198, P-169, PO-016
Kutzner, J., PD-047
Kuzyk, A., P-178
Kwan, A., P-393
Kwiecien, R., PD-045
Kyncl, M., P-274, P-325
Kyr, M., P-335
L
L.A, K., PO-014
Laack, N., P-366
Labarque, V., P-578
Lacour, B., O-008, P-208
Ladanyi, M., P-194
Ladas, E., P-473
Ladenstein, R., P-223
Laengler, A., P-394
Laetsch, T.W., P-388
Lafay-Cousin, L., O-014
Lagarda, S., P-319
Lagiou, P., AW-07, PD-046
Lähteenmäki, P.M., O-027
Lai, C., P-189, PD-023
Lakhoo, K., O-151
Lam, A., P-334
Lam, C., P-548, PD-033, PD-053
Lam, C.M.J., PO-045
Lam, J.C.M., P-349
Lam, K.W.K., P-430
Lamba, M., P-573
Lambrinos, E., O-192
Lammens, T., O-051, P-144
Lanaspeze, C., P-364
Landgren, K., O-183
Lane, S., O-151
Lang, H., PD-051
Langevin, A.M., P-393
Langham Jr, M.R., O-127
Langini, M., O-042
Laohasurayothin, S.L., PO-062
Laperriere, N., O-047, P-312
Lapierre, V., O-078, P-181
Laprie, A., O-059, P-364
LaQuaglia, M.P., O-088
Larios, T., P-319
Larouche, V., O-090
Larroquet, M., O-159
Larsen, E., O-018, O-019, O-021
Larsen, H.B., PD-066, P-448
Laselva de Sá, B., P-445
Lashkari, H., P-543
Laskar, S., P-369, O-058, P-220, P-561, PD-028,
PD-111
Lassaletta, A., O-047
lassen, Y., P-363
Łastowska, M., O-045, P-329
Latanov, A., P-322
Lau, B., P-084
Laughlin, S., O-047
Lauhasurayotin, S., P-050
Laurence, B., O-169
Laureys, G., O-051, P-144, P-398, PD-081
Laurie, F., P-377
Lautz, T., P-343, P-432, P-433
Laverdière, C., P-486, PD-060
Lawes, T., P-401, PO-079
Lazo-Páez, G., PO-075
Le Deley, M.C., O-043, O-059
Le Dret, L., O-043
Le Tourneau, C., O-131
Le, C., PO-026
Le, H., PO-026
Le, N., PO-026
Leal, C., P-240, P-319
Leal, L.F., P-286
Leandre-Broome, V., PD-091
Leblond, P., P-307, P-384
Lecciones, J., P-228, PD-033
Leclair, M.D., O-169
Lecomte, D., P-365
Lee, A., P-230
Lee, B., P-479, P-545
Lee, J.A., PO-117
Lee, J.M., PO-117
Lee, K., PO-007
Lee, K.S., PO-087
Lee, M.J., PO-117
Lee, M.L., O-116
Lee, M.R., P-033
Lee, M.W., P-034
Lee, S., P-493, PD-035
Lee, V., P-349
Lee, Y.H., PO-117
Lee, Y.L., PO-080
LEE, Y.T., PD-110, O-157, P-349, P-360
Leen, R., P-158
Lefèvre-Utile, A., P-212
Lehmann, L., P-542, P-586, PO-108
Lehmann, V., O-211, O-213, P-491
Lehtio, J., P-127
Leisenring, W., O-106
Leitnerova, M., P-065
Lelieveld, D., O-071
Lemelle, L., O-131
Lemiere, J., P-331, P-578
León, A., P-257
leon, E., P-309
Leontina Couto, L., P-241
Leseur, J., P-364
Lesperance, J., P-164, PD-052
Leszczyńska, E., P-266
Letai, A., PD-006
Letteboer, T., P-523
Letyagin, I., O-080
Leuschner, I., P-223
Levashov, A., P-310, P-311, P-199, PO-035
Levchenko, E., PO-030
Leverger, G., O-010, O-131
Levine, J., O-142
Levitt, M.A., PO-066
Levy, A., P-224
Lewis, J., O-088
Lewis, K., P-251
Lezama-del Valle, P., O-176
Li, A., PD-087
Li, C., PD-005, P-160, P-431
Li, C.G., PD-049
Li, C.K., P-431
Li, H.C.W., P-430
Li, K., P-191
Li, M., O-167, P-189, P-259
LI, M.J., PD-023
Li, S., P-128, P-098, PO-027
Li, T., P-537
Li, X., P-159
Li, Y., PD-063
Li, Z., PD-005
Lian, D.W.Q., O-157
Liang, C., P-431, PO-010
Liberski, P.P., P-333, PO-065
Libes, J., P-554
Libura, M., PD-064
Lie C, H., O-184
Likar, Y., P-141, P-142
Lim, B.L.K., PD-110
Lim, J., P-033
Lim, Y.J., PO-117
Lim, Y.T., P-034
Lima, F., P-174, P-272
Lima, F.F., P-025
Lima, L., O-198
Lima, V., P-241
Lin, P., PD-001, P-018
Lin, Y.D., PD-049
Lindhorst, S., O-090
Lindsey, J., O-015
Linke, G., P-336
Linnea, L., O-164
Lion, A., P-404
Lira, R.C.P., P-286
Lisitsa, T., PD-057
Litchvan, L., P-453
Litsenburg, R.R.L., O-098, O-107
Liu, A., P-131
Liu, A.G., P-085
Liu, J., O-012, O-016
Liu, R.Y., PD-049
Liu, W., O-106
Liu, X., P-132, P-238, P-308, P-308
Liu, X.J., PO-010
Liu, Y., O-001, O-001, O-083, P-131, P-519
Liyanarachchi, S., P-046
Lizano-Contreras, A., PO-075
Ljungblad, L., P-386, PD-047
Ljungman, G., P-425
Llanas, D., O-024
Llavador, M., P-383
Llinares Riestra, M.E., P-116
Lo, A., P-312
Locatelli, F., P-393
Lock, R., O-105
Lockart, B., P-432, P-433
Lode, H., O-070, O-055, P-137
Loeffen, E.A.H., O-079, P-434, P-435
Loffredo, G., P-022
LOH, A.H.P., O-157, P-349, P-360
Loh, H.P.A., PD-110
Loh, M., O-019, O-020, O-021
Lohmann, D., P-243
Loibner, H., O-070
Loka, T., PD-043
Loke, B.N., O-157
Lomax, A., P-226
Lombardi, A., P-010
Long, A., O-097
Long, K., P-491, PD-067
Lopes, E., P-272
Lopes, E.C., P-025
Lopes, J., P-213
Lopes, L., P-356
Lopes, L.F., P-520
Lopez Almaraz, R., PD-039
LOPEZ HERNANDEZ, G., P-115
Lopez, A., P-319
Lopez, M., AW-03, O-075, PD-106
Lopez, V., O-064
Lopez-Almaraz, R., P-526, PO-015, P-304, PO-056
López-Facundo, N.A., P-555
Lopez-Terrada, D., P-164
Lorentini, S., P-376
Loret De Mola, R., PD-076
Loria, D., PD-092
Louie, J., PO-022
Lourençao, P.L.T.A., P-282
Lu, H., O-203, O-208
Lu, J., P-085
Lu, L., O-026
Lu, Z., P-146, P-160
Lubega, J., P-544, P-541, P-588, P-591, PO-111
LUC, A., O-081
Luc, M., P-140
Lucas Jr., J., P-145
Lucas Jr., J.T., AW-07, PD-032, PD-046
Lucas, I., P-441
SIOP ABSTRACTS
Lucena-Silva, N., P-004
Lucio, F., P-445
Ludwinski, D., O-137, P-389, P-422
Luengas, J.P., O-168
Lugo Juárez, J.Z., PO-116
Luisi, F., O-116
Lukavetskyi, I., P-178
Luksch, R., O-025, O-068
Luna-Fineman, S., PD-014
Luna-Gierke, R., AW-04, PD-094
Lund, B., PD-070
Luo, X.Q., PD-049, PO-010
Lupo, P., AW-04, P-536, P-549, PD-094
Lupo, P.J., O-114
Lurvey, M., O-196
Luscombe, N.M., O-002
Luta, G., P-537
Luty, J., P-084
Lv, L., P-160
Lyon, M., PO-129
Lysa, Z., P-065
Lyu, C.J., P-033
M
M, B., PO-014
Ma, X., P-128, P-283, PO-027, PO-040
Maal, T., P-367
Mabbott, D., O-047
MacDonald, T., P-429, PD-055
Macedo, C., O-116
Machida, J., P-195
Macias, G., PD-092
Maciej, S., P-007
Macigova, P., P-287, P-522
Mack, R., P-411
MacKinnon, D., O-109, P-446
MacLean, J., P-429, PD-055
Macpherson, C.F., PO-107
Madanat-Harjuoja, L., O-027, PD-097, O-007
Madasamy, P., P-091
maddali, L., PO-001
Madden, N., P-110
Madhi, S.A., O-109, P-446
Madney, Y., P-437, PO-089, P-436
Madni, M., P-290
Madsen, M., P-502, PD-066
Maendley, C., P-482
Mafwimbo, J., O-063
Magadi, W., O-006
Magnani, C.F., O-091, O-092, O-093
Mahajan, A., O-193, AW-01, O-134, P-366, PD-096
Mahajan, J.K., P-263
Mahakal, N., P-583
Mahapatra, M., P-014, P-024
Mahmoud, G., PO-006
Mahmoud, S., PD-009, PO-089
Mahmoud, T., PO-014
Mahon, C., PD-043
Mahone, E.M., P-573
mahoney, A., P-499
Mahoney, D., O-065
MAIA-LEMOS, P., P-517
MAIA-LEMOS, P.D.S., P-409
MAIA-LEMOS, P.S., P-405, P-406, PO-081, P-410
Mainardi, C., P-118
Maisto, G., P-022, PO-002
Makena, M., P-150, PD-020
Makka, F., P-545
Makohusová, M., P-065, P-546, P-057
Malan, V., P-212
Malbari, F., P-224
Malbora, B., P-080
Malik, R., P-352
Malila, N., O-007, O-027, PD-097
Malinowska, I., P-053
Malinowski, P., PO-129
Malkin, D., PD-089
Mallebranche, C., O-085
Malogolowkin, M., O-127
malone, S., P-499
Maloof, T., PO-066
Mamontov, O., PO-030
Mamtaz, B., P-237
Manabe, A., O-048, P-029
Manca, R., P-009
Mancini, A., P-009
Manda, A., P-489
Mandeville, H., O-162, P-367
Mandhani, G., AW-01
Mangona, V., P-366
Manhaes, M.F.M., PO-110
Manley, P., P-568
S509 of S518
Manlokiya, B., P-450
Mannaerts, A., P-398, PD-081
Manne, S., PO-103
Manning, I., O-187
Mansour, A., P-581
Mansuy, L., P-208
Manthalu, O., PD-075
Mantovani, A., PD-024
Manzitti, C., P-154, P-155
Manzo, I., P-043, PD-025
Manzoli, B., P-473
Mao, J., O-167, P-259
Mara Fernandez, C., PO-077
Maradiegue, E., P-253
Marcil, V., O-096, PO-114
Marciniak-Stępak, P., P-012, P-011
Marco, A., P-383, P-402
MARÇON, C.F., P-409
Marcus, K., P-479
Marec Berard, P., PO-090
Marec-Bérard, P., P-441, O-081, O-059, P-404
Margraf, L., P-528
Mariam, N., O-195
Marie, L., P-140
Maris, J., O-067
Marjerrison, S., PD-098
Markaki, E.A., P-051
Markiewicz, M., P-252
Marks, S., PD-024
Maron, G., P-444
Marquardt, V., O-042
Marques, L.V.C., P-036
Marques, R.G., P-282
Marr, K., PD-093
Marra, N., PO-002
Marriott, C., P-560
Marroquin, F., P-444
Marshall, K., O-105
Marsland, A., P-491
Marta, M., P-007
Martelli, H., O-084, O-162, P-208, P-350
Martha, D.M., P-559
Martha, G., PO-101
Martimianaki, G., P-051
Martin Guerrero, I., P-304, PO-056
Martin Manso, M., PD-051
Martin, P., O-018
Martin, S., P-494
Martin-Elbahesh, K., PO-121
Martinez Gonzalez, M.J., P-304
Martinez Sánchez, M.V., P-116
Martinez, R., AW-02, O-142
Martin-guerrero, I., P-020
Martino, A., O-165
Martins, A., O-177
Martins, C.A.S., P-025
Martinsson, T., P-143
Martynov, L., PD-100, O-080
Maru, B., O-099
Marven, S., O-156
Marx, P.D.A., O-095
Mary, N., P-200
Marzollo, A., P-118
Masako, T., P-439
Masalu, N., O-063, P-464
Mascarenhas, L., P-388
Maschan, A., O-032
Maschietto, M., P-520, P-521, P-183, P-254
Mashalli, N., P-122
Masjosthusmann, K., P-113
Mason, C., PD-068
Mason, G., O-090
Mason, J.L., PD-042
Massano, D., P-093
Massimino, M., O-025
Mastellaro, M.J., P-286
Masterson, M., PO-103
Mastronuzzi, A., P-376
Mata Fernández, C., P-455
Mathew, L.G., P-176
Matinyan, N., O-080, PD-100
Matle, M., O-160
Matook, K., P-006
Matsubara, K., P-345
Matsuda, T., O-006
Matsumoto, K., P-547, O-126, P-161, PO-068
Matsusaka, Y., P-317
Mattano, L.A., O-021
Matthay, K., O-067, P-145
Matus-Obregón, D., PO-075
Matysiak, M., P-266
Maude, S.L., O-123
Maurice-Stam, H., O-202
Mauz-Koerholz, C., P-096
Mavinkurve-Groothuis, A.M.C., O-212
Max, V.N., PO-101
Mayes, S., PO-118
Mayr, L., P-323
Maza, I., P-206, P-585
Mazar, J., P-147
Mazariegos, G., P-099
Mazewski, C., O-013
McAtee, C., O-125
McBride, M., PD-093
McCarten, K., P-096
McCarthy, A., P-440
McCarthy, L., P-213
McCarthy, M., O-210
McClain, K., P-549
McCurdy, S., PD-051
McDonald, L., P-438
McDowell, D., O-158, PD-105
McGuirk, S., PO-073
McHugh, K., O-085, PD-018, PD-024, PD-031
Mckillop, S., PO-094
McLaughlin, L., P-385
McLean, S., PD-091
McLoone, J.K., P-466
McNall-Knapp, R., PO-118
Meadows, E., PD-062
Meany, H., P-385
Meazza, C., O-025
Medhi, S., P-184, PD-028
Medi, K., P-277
Medin, M., P-281
MEDINA, A., P-015, P-130
Medina-Paez, J.P., O-142, P-238
Medina-Sanson, A., P-238
Meel, R., P-265, P-280, P-207, P-214, P-234, P-264
Meenakshi, D., O-020
Mehmood, T., P-179, P-313, PO-063
Mehrvar, A., P-017, P-314, PO-036
Mehrvar, N., P-314, PO-036
Mehta, P., PO-111, O-065, P-242, P-268, P-269, P-412,
P-541, P-556, P-588, P-591
Mehta, P.S., O-119
Mehyar, M., P-249
meijinders, P., P-363
Meinsma, R., P-158
Mejia, B., O-142
Melchionda, F., PD-038
Melchior, P., P-370
Melchor Vidal, Y., P-115
Melicharkova, K., P-287, P-522
Melin, B., AW-04
Melin, J., PD-097
Mellgren, K., P-425
Melo, M.I., PO-132
Melosi, F., P-470
Mendes, W., O-032
Mendonça, V., P-241
Meneghello, L., P-375
Menna, G., P-022, PO-002
Menon, D., P-321
Mentkevich, G., P-075, P-310, P-311
Mercado, G., P-228, PD-033
Merchant, T., O-017, O-020, O-044
Merchant, T.E., AW-07, O-041, PD-046
Merks, H., P-157, P-523
Merks, J., P-367
Merks, J.H., O-084
Merks, J.H.M., O-085, O-086, P-362, P-387, PD-031
Merkulov, N., P-141
Merkulov, O., PO-038, PO-039
Messahel, B., P-416, PO-057
Messina, C., P-118
Messinger, Y., PD-030
Metzger, M., AW-02, P-096, PD-014
Metzger, M.L., O-026
Metzguer, M., P-540
Meyer, F., O-042
Meyer, L., O-124
Meyer, L.H., PD-006
Meyers, R.L., O-127
Mi, Q., O-122
Michalski, A., P-298
Michaud, A., PD-068, P-568
Michaux, K., P-441
Michel, G., P-466
Michel, J.L., PO-053
Michiels, E., O-082
Michlitsch, J., P-452
Michon, J., P-393
Michon, O., P-064
SIOP ABSTRACTS
S510 of S518
Middelbeek, J., PD-022
Mielcarek-Siedziuk, M., P-012
Mier Cabrera, J., PO-116
Mier Cabrera, M., PO-116
Mier-Cabrera, M., P-202
Mifsud, W., O-002, O-074, O-077, PD-024
Mikasch, R., P-378, PD-045
Mikhail, R., P-185
Mikroutsikos, L., P-361
Milanaccio, C., P-155
Milaschenko, N., O-080
Millan, N., P-044
Miller, N., O-049
Million, L., P-377
Millot, F., O-131
Millson, S., P-008
Mimi, K., P-215
min, R., O-031
Min, S.Y., PO-087
Minagawa, H., PO-043
Minard Colin, V., O-084
Minard, C., PD-096
Minard-Colin, V., O-086, O-089, O-162, P-208, P-350,
PD-031
Minguela Puras, A., P-116
Mintz, E., PD-051
Miraglia, R., P-339
Mishra, A., P-582
Mishra, P., P-014, P-024
Mishra, S., O-150, P-351, P-592
MISRA, R., PO-019
Mitby, P., O-189
Mitchell, A., P-291
MITCHELL, R., P-130
Mitiushkina, N., P-275
Mitra, S., PD-041
Mittal, B., O-120
Miyagawa, N., PO-013
Miyamura, T., PO-043, P-074
Miyano, S., O-048, O-129, P-029
Miyashiro, I., O-006
Miyazaki, O., PO-068
Mizia-Malarz, A., P-049, P-064, P-266
Mizrahy, S., O-020
Mlynarski, W., P-064
MM, H., P-543
Mochizuki, K., P-195
Modaboyina, S., P-264, P-265
Modak, S., O-088
Mogeniene, G., P-370
Mogensen, P., P-037
Mohamed S Zaghlol, M., P-209
Mohamed, M., P-458
Mohamed, R., P-459
Mohammad Wali, R., P-204, P-203
Mohammad, S., P-168
Mohammed, V., P-168
Mohan Sobhanna, N., P-392
Mohanti, B., P-207
Mohapatra, S., O-120
Mohey, R., PD-016
Mohrmann, C., O-106
Mohsen, E., P-210
Mokhtari, A., PO-133
Molenaar, J., O-052, PD-019
Molenaar, J.J., AW-08, O-066, O-071
Molenda, K., P-011
Monção Damasceno, C., P-392
Monção, C.C.D., P-390
Monnereau, A., O-008
Monsereenusorn, C., P-548
Monserrat Coll, J., P-116
Montalvao-de-Azevedo, R., P-183
Montgomery, N., O-060
Monti, L., PO-067
Montini, E., O-091
Montoya Vasquez, J.E., P-038
Montoya, J., P-225
Moore, I., O-189, P-536, PD-094
Moore, I.M., O-114
Moore, L., O-138, O-139, P-442
Mora, A.M., P-537
Morach, P., P-361
Moraes Moreira, M.A., P-241
Moraleda Jiménez, J.M., P-116
Moran, E., O-064
Morana, G., P-154
Morand, K., O-010
Morano, K., P-377
Mørch, L.S., O-005
Moreira, L.B.P., P-048
Moreno, A., P-167
Moreno, F., PD-092, P-540
Morgan, J., P-443
Morgenstern last author, D., PD-021
MOri, M., O-126, P-514
Moriarty, D.P., P-440
Morin, L., P-590
Morini da Silva, S.R., P-520
Morini, M., O-068
Morita, K., PD-036
Morosi, C., O-025
Moroz, V., O-074
Morris, C., P-211, P-299
Morris, L., O-156
Morris, N., PD-069
Morrison, C., P-525
Morrissey, L., O-196, O-192, P-586
Morsy, A., P-458, P-459
Moschovi, M., P-180, P-315
Moses, C., P-232
Mosse, Y., O-067
Mosseri, V., O-089
Mostoufi-Moab, S., P-492
Mouffak, S., O-010
Mousa, A., P-297
moussa, E., P-135
Mozzilli, S., O-140
Mpasa, A., P-073, O-065, P-412, P-489, PD-075
Ms, C.L., PD-072
MS, E.D., PD-072
Msika, S., O-169
Mtete Kumwenda, I., O-065
Mtete, I., P-489, PD-075
Mtete-Kumwenda, I., P-412
Mtunda, M., P-412
Muckaden, M.A., P-369, P-561
Mudaliar, S., P-039
Mudry, P., P-287, P-522
Muffazzal, R., P-348
Mujagic-Cammett, D., O-141
Mukesh, D., P-041, PO-012
Mukherji, A., PO-033
Mukhtar, Z., O-164
Mukkada, S., P-444
Mulder, R.L., O-079, P-435
Mullassery, D., P-352
Mullen, E., O-072, O-073, O-154, P-173
Müller, H.L., P-316, P-387, PD-044
Müller, J., P-575
Mullins, A., PO-118
Mullins, L., PO-118
Mullins, L.L., O-179
Mulrooney, D.A., O-104
Mulyowa, I., P-480
Muñoz Pérez, J.P., P-116
Munro, F., O-152
Münter, M., P-223
Muracciole, X., P-364
Murayama, S., P-379
Muriel, A.C., PD-067
Murphy, E.S., AW-07, PD-046
Murray, F., P-226
Murray, J., P-528
Murray, M., O-038
Murthy Chennapragada, S., O-158
Mushtaq, I., PD-024
Mushtaq, N., PO-041
Musioł, K., P-049
Musiwa, P., O-065
Mustafa Ali, M., P-397
Mustafa, A., P-295
Muszynska-Roslan, K., P-053, P-067
Mutafoglu, K., P-090, P-279, PO-024, PO-025, PO-042,
PO-058
Mutch, M., P-341
Muwakkit, S., PD-002
Mycko, K., P-067
Mycroft, J., O-034
Myint, H.H., P-040
Mynarek, M., O-045, P-572, PD-045
N
N, B., PO-014
N. F. Arruda-Colli, M., PO-113
N. Olgun, P-090, PO-024
N. Olgun, P-279, PO-025, PO-058
N. Olgun, PO-042
Naafs-Wilstra, M.C., O-212
Nabarrete, J., P-445
Nachman, A., O-028
Nadeem, A., P-168
Naderi, A., P-314
Nagar, G., O-136
Nagasubramanian, R., P-388
Nagoya, Y., PO-109
Nagtegaal, M., O-052
Naguib, H., P-063
Naguib, S., O-121
Nahata, L., O-211, O-213
Naidu, G., O-109, P-446
Naifeh Khoury, M., P-481
Naik-Mathuria, B., P-151
Najam-ud-din, P., P-172
Naka, N., PO-043
Nakagaki, N., P-507
Nakagawa, N., PD-029, PO-043
Nakagawara, A., P-138
Nakahata, T., PD-036
Nakamura, K., PD-029
Nakamura, T., P-163
Nakano, Y., P-317
Nakaoka, T., P-163
Nakashima, K., P-074
Nakata, K., O-006, O-074, O-077
Nakazawa, A., P-138
Nakjang, S., P-565
Nakvijit, P., P-498
Namata, A., PD-051
Nana, M.E., P-281
Nana, P., P-532
Nandaula, S., PO-096
Nantron, M., P-155
Narciso, A., O-166
Naredi, B.K., PO-071
Narendran, G., P-493
Narula, G., O-022, O-061, P-013, P-040, P-052, P-054,
P-100, P-460, P-563, PD-015, PD-065
Nascimento, V., P-272
Nasedkina, T., PD-057
Naseer, M., P-041, PO-012
Nassogne, M.C., P-330
Natacha, E.W., P-140
Natalie, O., P-465
Nathan, P., O-028, O-099, O-100, O-146
Nathrath, M., O-056
Navajas Gutierrez, A., P-304
Navajas, A., P-020, P-518, PO-056
Navarro Diaz, D., O-207
Navid, F., P-387
Nawaiseh, I., P-249
Nayak, A., PD-028
Nayak, S., P-543
Neal, C., P-147
Nechesnyuk, A., P-141, P-142, P-303, P-320
Nekulova, M., P-335
Nelson, K., O-083
Nelson, M., O-001
Nemirovchenko, V., P-075
Neradil, J., P-522, P-287
Nersting, J., P-448
Ness, K.K., O-026, O-104
Nesterova, J., PD-112
Neto Rafael, M., P-473
Neu, M., P-571
Neu, M.A., PD-056
Neumann, E., PO-091
Neves, F., PO-132
Neville, H., P-219
Newman, A., O-197
NG, M.H.L., PD-005
Ngo, N., PO-026
Nguyen Thi Kim, H., P-447
Nguyen, H., PO-026
Nguyen, N., PO-026
Nguyen, T., P-292, PO-054, P-150, PD-020
Nguyen, T.T., P-262
Nguyen, V., PO-026
Nguyen, V.S., PO-086
Nicastro, M., P-445
Nicholls, E., O-164
Nichols, K., O-194
Nicholson, J., O-036, O-038
Nicklaus-Wollenteit, I., PO-073
Nicolaou, C., PO-112
Nicolau Neto, P., P-183
Nicolin, G., P-291
Niedzielska, E., P-053
Niedzwiecki, M., P-053
Niehues, T., P-394
Nielsen, M.H., PD-066
Nielsen, M.K.F., P-448, PD-066
Nieves, R., PD-014
Niggli, F., P-223
Niinimaki, R., P-026
Nikas, I., P-180, P-315, P-550
SIOP ABSTRACTS
Nikfar, S., P-017
Nikolaou, M., P-315
Nino, F., O-165
Nirali, P., P-465
Niremberg, D., PO-111
Nishimoto, S., P-163
Nishonov, D., PD-112
Nitani, C., P-161
Nitin, S., P-041, PO-012
NIVARGI, S., PO-019
Njambi, L., P-230
Njamnshi, V., P-532
Njere, I., O-164
Nøddeboe, M., P-502
Nodomi, S., PD-036, PD-037
Nogueira, S., P-174
Noh, O.K., PO-055
Noli, M., PO-111
Nonaka, J., P-449, PO-092, P-514
Noronha Barrére, A.P., P-445
Northcott, P., O-044
Nour, S., O-156
Novak, E., P-256
Novichkova, G., P-303
Novikov, S., P-105
Novikov-, S., P-108
Nowosławska, E., PO-065
Nozawa, K., P-195
Ntoulia, A., P-529
Nuchtern, J., P-151
Nunes, J.A., P-328
Nursal, G.N., P-103
Nurzyńska-Flak, J., P-266
Nwatah, V., PO-008
Nyarko, E., P-187
Nygren, J., P-513
Nysom, K., O-043
O
Oara, A., P-547
Obara, H., P-345
Obeng, P., P-450
Oberhoffer, R., P-575
Oberlin, O., P-362, PD-031
Oberoi, J., P-417, P-418
Obu, S., PD-036
Ociepa, T., P-053
Oda, Y., P-359
Odalı, P., P-092
Odaman Al, I., PO-029
Odone Filho, V., P-445, P-473
Odone, V., P-250
Odone-Filho, V., P-256
O'Driscoll, K., O-199
Oeffinger, K., O-106
Ogasawara, M., P-451
Ogawa, E., PD-036, PD-037
Ogawa, J., P-508, P-514
Ogawa, S., O-048, O-129, P-029
Ogez, D., PO-114, O-096
Ogg, S., O-194
Ogura, T., P-379
O'Halloran, K., P-201
Ohara, A., O-048
Ohara, Y., P-508, P-514
O'Hare, P., PD-043
Ohga, S., P-359
Ohno, M., PO-068
Ohshima, J., P-129
Ojinaga Niño, I., P-304, PO-056
Oka, S., P-449, PO-092
Okada, K., P-161
Okajima, H., PD-036, PD-037
Okamoto, S., PD-036, PD-037
Okcu, M.F., PD-096
Oki, K., O-048
Okita, H., P-391
Okoye, B., O-164, P-352, PD-106
Okur, A., PO-115, P-095, P-318, P-527, PO-061
Okur, V., P-077
Okuyama, H., P-354
OLAYA VARGAS, A., P-115
Olderode-Berends, M., P-523
Oldridge, D., O-067
Oldrieve, N., O-187
Olechowski, A., P-236
Olgun, N., P-123, P-124, P-192
Olgun, Y., PO-042
Olguner, M., PO-024, PO-025
Oliveira Jr, W., P-356
Oliveira Júnior, W.E., P-282, PO-072, O-170, O-198,
P-353
S511 of S518
Oliveira, A.C., P-473
Oliveira, J., P-272
Oliveira, J.T.D.S.D., P-025
Oliveira, V., P-473
Oliynyk, G., P-127
Oller, A., P-148, P-289
Ollett, L., O-199
Olsen, O., AW-03, O-039, PD-024
Olshanskaya, Y., P-133, P-141, P-142, P-275, P-303
Olson, T., O-037, PD-030
Olsson, M., PD-086
Onal, H.C., P-103
Onar, A., O-014, O-044
Onay, H., P-562
Önder Siviş, Z., P-562
ondrova, B., P-363
O'Neil, B., PD-087
O'Neill, A., O-127
Onesi, L., O-142
Ong, C.P.C., PD-110
Onitake, Y., P-567
Oniyangi, O., PO-008
Öniz, H., P-080
Onofre Vidal, D., P-520
Oosterom, N., O-023
Opocher, E., O-016, O-090
Øra, I., PO-076
Oral, A., P-562
Oranges, K., P-016
Oravkinová, I., P-065, P-057, P-546
Orbach, D., O-089, O-085, O-087, O-131, O-169,
P-208, PD-031, PD-039
Oren, M., O-090
Oreste, M., P-009, P-043
Orfao, A., P-515
Orhan, D., P-276
Orjuela-Grimm, M., O-142, P-238
Orme, L., O-102, O-210
Orobio, J., PD-096
Orr, B., O-044, O-045
Ortiz, D., P-319
Ortiz, R., AW-02, P-482
Ortolan, E.V.P., P-282
Orwig, K., P-433
Osawa, E., P-195
Osborn, M., O-090
Oscanoa, M., P-094, P-206, P-585
Osei-Nkrumah, A., P-450
Osei-Tutu, L., P-483, P-450
Ospa, K., P-064
Osterlundh, G., PD-039
Osumi, T., PO-068
Ottensmeier, H., P-572
Otto, H., PD-056
Oubouzar, Y., O-078
Oue, T., P-255, P-354
Oulton, K., O-187
Oussama, A., PD-085
Owczarzak, A., P-524
Owens, C., PD-018
Owoc-Lempach, J., P-012
Oyesakin, A., PO-008
Ozawa, M., O-147
Özbek, N.Y., P-427
Özçelik, M., P-527
Ozdemir, G.N., PO-029, PO-084
Ozdemir, I., P-095
Ozden, O., P-278
Özen, S., P-562
Ozer, E., PO-024, PO-025, PO-042
Ozerov, S., P-142, P-303, P-320, P-577
Özkınay, F., P-562
Ozmen, E.O., PO-115
Ozono, K., PO-043
Özyurt, J., P-316
P
P. Noronha, E., P-036
Pachl, M., P-213, PD-107, PO-073
Pacquement, H., O-024, O-159
Paczesny, S., O-033
Padovani, L., P-364
Pain in Children with Cancer, O.B.O.T.G.W.G., P-435
Paintsi, V., P-081
Paintsil, V., P-450, P-483
Pakakasama, S., P-498
Palacios, J., P-257
Palamar, M., P-368
Palaniappan, A., O-108
Pałgan, I., PD-064
Pallotti, F., O-025
Palma Matta, B., P-241
Palma, J., O-035
Palmer, J., O-199
Palmer, R.H., P-143
Palmer-Mitchell, N., PD-091
Palomo Colli, M.A., P-202, PO-116
Palumbo, M., PD-093
Pamukoglu, A., P-124
Pan, C., P-260
Pan, K., P-431
Pan, W., O-114, O-189
Pandit, U., PD-065
Pandit-Taskar, N., O-088
Panduro, N., O-190
Pant, G., P-023, P-035
Panzoldo, L., O-140
Pao, M., O-209
Paolo, D., P-339
Papanicolau-Sengos, A., P-525
Papp, S., P-134
Pappo, A., O-037, PD-032, PO-102
Pappo, A.S., P-388
Papusha, L., P-303, P-320
Papworth, K., AW-04
Paramanandhan, M., P-091
Parashar, K., P-213
Parasole, R., PO-002, P-022
paredes, G., P-239
paredes, G.G., PO-064
Paredes, L., PO-129
Paret, C., PD-056
Pariseau, E., PD-067
Pariury, H., P-452
Park, B.K., PO-117
Park, H.J., P-034, PO-117
Park, H.R., PD-084
Park, J.E., PO-055
Park, J.K., PO-117
Park, K.D., PD-035, PO-117
Park, M., PO-117
Park, S.K., PO-117
Park, Y.J., P-034, PD-035
Parker, J., O-146
Parry, R., O-151
Pashankar, F., O-037, O-038
Pasik, U., P-236
Pasqualini, C., O-078, P-181
Passariello, A., P-339
Passot, G., O-169
Patel, A., PD-050
Patenaude, A., O-103, O-105, PD-062
Pathy, S., P-245, PD-034
Pati, H.P., P-014, P-024
PATIN, R.V., P-409
Patıroğlu, T., P-427
Patkar, N., O-022, P-052, P-100
Patrus, N., P-121, P-501
Patte, C., O-038
Patterson, P., PO-107
patteson, B., P-499
Pattnaik, J., P-091
Pauck, D., O-042
Paul, R., O-062
Paulino, A., P-173, P-366, PD-096
Paulino, A.D.C., O-073
Paulussen, M., P-394
Pavelka, Z., P-335
Pavithran, K., P-321
Pavlovskaya, A., P-244
Pavlyk, S., P-139
Pawińska-Wąsikowska, K., P-067, P-042, P-007
Peate, M., O-102, O-210
Peckham-Gregory, E., P-549
Pecori, E., O-025
Pedich, M., P-236
Pedrola, L., P-383
Pedrotti, D., P-375
Peeraully, M., O-156
Peixoto Lira, R.C., P-327
Péloquin, K., O-096, PD-060, PO-114
Peña, A., PD-014
Pena, H., P-182, P-240
Pena-Hernandez, A., AW-02
Peñaloza-González, J., P-058, P-059, P-471, P-472
Peng, X., P-283
Penner, L., O-178
Peregud-Pogorzelski, J., P-266
Pereira Noronha, E., P-069, PD-007, PD-008
Pereira, B., P-183
Perek-Polnik, M., P-329
Perel, Y., O-115
Perez Bañuelos, A., P-202
Perez Garcia, M., P-115
Perez, A., P-240
SIOP ABSTRACTS
S512 of S518
Perez, C., P-225
Perez, E., O-130, P-218, P-219, P-319
Perez, M., PO-118
Perez, M.N., O-179
Pergert, P., O-188
Periera, N., P-460
Perkins, S., P-366
Perlman, E., O-072, O-073, P-173
Perna, E., P-048
Perrotta, S., P-010, PD-025
Persson, U., P-487
Pesantez, M.J., P-535, PO-130
Peters, N., P-263
Peters, S., P-378
Petersen, C., PO-076
Petersen, G., P-502
Peterson, C., PD-069, PD-074
Petit, A., O-010
Petit, P., P-384
PETRILLI, A.S., P-410
Petrilli, S., O-116
Petrone, A., P-375
Petruzziello, F., P-022, PO-002
Petterson, T., O-034, P-117
Pettersson, L., P-487
Petts, H., P-509
Peyrl, A., P-323
Pezet, D., O-169
Pezzolo, A., O-068
Pfaff, E., O-046
Pfister, S., O-044, PD-045
Pfister, S.M., O-045, O-046
Pflugeisen, B., PO-107
Pham, H., PO-026
Phan, A., P-292, PO-054
Philip, A., P-321
Philip, D., PD-015
Philippe-Chomette, P., O-169
Phillips, B., P-419, P-420, PO-122
Phillips, P., PD-063
Phillips, R., O-009, P-443
Phipps, K., P-298, P-326
Phipps, S., O-097
Phung, L., PO-026
Pianovski, M., P-453
Piazza, M., P-339
Pica, A., P-009, P-371
Picado, O., O-130, P-218
Picard, D., O-042
Piccardo, A., P-154
Pichardo, S., P-134
Piché, N., P-355
Pickles, J., P-326
Pickova, J., P-386
PICNICC, C., O-009
Picot, S., O-043
Piekutowska- Abramczuk, D., P-329
Pierron, G., O-131, P-208
Pierzyna, M., P-053
Pieters, B., P-367
Pieters, R., O-023
Pietsch, T., O-045, PD-045
Pilato, M., P-339
Pillai, R., P-321
Pillon, M., P-093, P-118, PO-123
Pilotto, C., O-012, O-016
Pimenov, R., PO-023
Pinarli, F.G., P-095, P-318, P-527, PO-061, PO-115
Pineda, E., P-444
Pinho, F., P-414
Pino Vázquez, M.A., P-028
Pinto Nasr, B., P-241
Pinto, V., O-117
Piorkowska, K., P-134
Piperno-Neuman, S., O-159
Pires, A., O-116
Pissaloux, D., O-089
Pitkäniemi, J., O-007, O-027
Pizer, B., P-454
Pizza, J., P-492
Placidi, L., P-361, P-371
Plantaz, D., O-131, PD-018
Plass, C., P-378
Platschek, A.M., PO-093
Plaza Fornieres, M., P-116
Plessier, A., O-043
Płoski, R., P-329
Pluijm, S., O-023, O-052
Podda, M., O-025
Pohorecka, J., P-067
Pokka, T., P-026
Polad, K., P-185
Połczyńska, K., P-266
Pole, J., O-028, O-083, PD-093
Pollack, I., O-013
Pollio, M.L., P-009
Polushkina, O., PD-112
Polyakov, V., O-080, P-244, P-551, PO-038, PO-039
Pombo-de-Oliveira, M., O-050
Pombo-de-Oliveira, M.S., P-069, PD-007, PD-008
Ponce Salas, B., P-455, PO-077
Ponce-Castañeda, V., P-238
Ponce-Cruz, J., P-058
Pons, R., P-550
Pons, S., P-541
Pooniya, V., P-060
Popa, A., P-075
Poplack, D., P-541
Popov, A., PO-049
Porreca, A., P-118
Positano, K., PD-085
Postell, E., P-499
Postema, F., P-523
Pota, E., P-010, P-043, PD-025
Potet, H., P-364
Potter, E., O-205
Pourtsidis, A., PD-039
Powell, S., P-016
Powers, K., P-510
Powis, M., PD-106
Poyiadjis, S., O-109, P-446
Poyraz, A., PO-061
Pozzo, E., P-216
Prabhu, S., P-543
Pradhan, N., PD-015
Pramanik, R., O-030
Prasad, M., O-022, O-058, O-061, P-040, P-054, P-460,
P-563, P-583, PD-015, PD-028, PD-065, PD-111
Pratap, S., P-193
Premachandra, K., P-046
Pritchard-Jones, K., O-076, O-077, AW-03, O-002,
O-006, O-039, O-074, O-075, P-170, PD-024
Prityko, A., P-358, PD-112
Priya, P., P-456
Prof, S.M., PD-072
Prokop, A., P-394
Prokopp, T., P-273
Pruden, P., P-542
Przybyla, W., P-149
Przybyszewski, B., P-067
Pshonkin, A., P-577
Psihogios, A., P-492
Puget, S., O-043
Pugh, G., P-457
Pui, C.H., O-026
Pule, M., PD-050
Pullen, J., O-018
Pulsipher, M., O-020
Puma, N., O-025
Punjwani, R., PD-078
Punnett, A., P-096, P-587
Punzo, F., P-043
Puppa, G., P-148
Purandare, N., O-058
Puri, A., O-058, P-348
Purva, K., P-041, PO-012
Pushker, N., P-214, P-264, P-234, P-247, P-265, P-280
Puškáčová, J., P-065, P-546
Pyke-Grimm, K., O-200
Pyzlak, M., P-252
Q
Qaddoumi, I., P-314, PD-099
Qayed, M., O-127
Qazi, A.Q., P-338
Qian, X., P-101
Qin, M., PO-027
Quah, B.L., PO-045
Quast, L., PD-063
Qudsia, Z.F., P-338
Queiróz, R.D.P., P-048
Queiroz, R.G.P., P-390
Quenet, S., O-032
Quinn, V., O-105
Quintero Escobar, M., P-520
Quispe, C.D., P-044
Qureshi, S., PD-111, P-184, P-220, P-369, P-561,
PD-028
R
Rachet, B., O-006
Racine, N., PO-119
Radhakrishnan, N., P-418, O-110, P-417, P-424
Rae, C., PD-093
Raeke, L., P-366
Raetz, E., O-019, O-020, O-021
RAFAT, J., P-003
Rafiee, G., O-015
Raghavan, A., O-156
Raghubar, K., P-573
Raghubar, K.P., O-114
Rahman, A.A., P-045
Raible, A.S., O-175
Raj, A., P-293
Rajagopal, R., P-334
Rajotiya, M., P-100
Raju, M., P-438
Rajwanshi, A., O-120
Raletshegwana, M., P-556
Rallison, L., PO-124
Ramadwar, M., P-184, O-058, P-369, P-561, PD-028
Ramadwar-, M., PD-111
Ramaglia, M., P-009, P-010
Ramaiah, V.K., P-372, P-373, P-374
Ramamoorthy, J., O-120
Ramamswamy, V., O-044
Raman, P., PD-042
Ramanathan, S., O-058
Ramanujachar, R., P-291
Ramaswamy, V., O-047
Ramirez Uribe, N., P-115
Ramirez, R., P-148, P-289
Ramírez-Ortiz, M., P-238
Ramos Elbal, E., P-116
Ramos, R., O-207
Ramzan, M., P-217, PO-020
Ranasinghe, J., P-046
Ranasinghe, N., P-554
Ranchère -Vince, D., O-086
Ranchère-Vince, D., O-089, P-208
Ranganathan, S., P-099
Rantanen, M., O-007, O-027
Rao, A., P-377
Rao, B.N., O-026
Rao, K., P-218, P-219, O-130
rao, R.N., PO-031, PO-051
Rao, S., P-543
Rąpała, M., P-266
Raphaela, V.L., PO-101
Rascon, J., PD-039
Rashed, W., P-261, PO-050
Rashed, W.M., P-574
Rassidakis, G., PD-047
RASTOGI, N., PO-019
Ratajczyk, J., P-524
Rathnam, K., P-070
Rathnayaka, W., P-046
Rattina, V., P-212
Rawat, A., P-055
Ray, B., PO-107
Reaman, G., P-381
Rebecca, J., PO-107
Rebelo, F., P-174
Rechl, H., O-056
Recht, M., PD-076
Reck, C., PO-066
Recklitis, C., PD-068
Recklitis, C.J., PO-106
reda, H., P-135
Reddy, A., O-013
Reece-Mills, M., PD-091
Reed, H., P-242
Reeve, B., PD-075, PO-125
Regla Vargas, F., P-241
Reguerre, Y., PO-053
Rehana, P., O-196
Rehm, R., O-200
Reichardt, P., O-056
Reichek, J., P-343
Reifenberger, G., O-042
Reilly, A., P-016
Reimann, M., P-432, P-433
Reiner, B., P-575
Reinfjell, T., PD-070
Reinhardt, D., P-378, P-394
Reisinger, D., P-323
Rekhi, B., P-220, O-058, P-184, PD-028
Rellensmann, G., P-113
Remke, M., O-042
Renard, M., P-216
Rensen, N., O-098
Resch, A., P-572
Reschke, M., P-243
Resham, S., PO-041
Resnick, A.C., PD-042
Revon-Riviere, G., P-484
Rex, D., O-164
SIOP ABSTRACTS
Reyes, E., P-319
Reynolds, C.P., P-150, PD-020
Reynolds, K., PO-119
Reynolds, M., P-432
Rezk, M.A., P-574
Rheingold, S., P-016
Rho, Y.S., PD-093
Riad, K., P-458, P-459
Ribeiro, A., O-198
Ribeiro, R., P-356, O-096, PO-114
Ribeiro, R.C., O-170, O-198, P-353, AW-02, P-282,
PO-072
ricardi, U., P-363
Richards, E., P-416
Richards, S., P-389, O-137, P-422
Richardson, M., P-084
Richardson, S., O-015
Rickett, A., O-156
Ricondo De Diego, A., P-304, PO-056
Ridgway, K., P-499
Rieger-Fackeldey, E., P-113
Rigby, K., P-429
Riikonen, P., P-026
Rikiishi, T., PO-109
Rinaldo, C., PO-076
Rincón López, E., P-455
Rinku, S., O-083
Rios, L., P-225
Ripaldi, M., P-022
Ris, M.D., P-573, PD-096
Ritthisong, S., P-498
Rivas, M., P-256
Rivas, M.P., P-254
Rivera, G., O-206
Rivera, R., P-319
Rivera-Luna, R., P-319, P-555
Rizhova, M., P-577
Rizvi, A.R., PO-041
Rizvi, M.A., P-246
Rizzari, C., O-032
Robb, A., P-213
Robertson, E.G., PO-120
Robinson, G., O-044, O-014, O-045
Robison, L., O-106
Robison, L.L., O-026, O-104
Robles, J., PO-032
Robson, K., O-015
Rodgers, C., P-510, O-189, O-191
Rodgers, C.C., O-114
Rodrigues Bonvicino, C., P-241
Rodrigues, A.M., P-282
Rodrigues, P., P-013
Rodrigues, T., P-250
Rodriguez Inchausti, T., P-526
Rodríguez Inchausti-, T., PO-015
Rodriguez, A., P-444
Rodriguez, B., P-150
Rodríguez, R., P-257
Rodriguez-Galindo, C., O-037, O-041, O-064, P-411,
P-540, P-548, P-553, P-586, PD-033
Rodziewicz, A., P-067
Roellecke, K., P-394
Roganovic, J., PD-039
Rogasch, J., P-137
Rogers, J., O-137, P-389
Rogers, P., PD-093
Rogers, T., O-086
Rogers, T.N., O-162
Roh, D.E., PO-087
ROHA Network, ., PD-092
Rojas Vasquez, M., PO-094
Rojas, L., O-201
Roka, K., P-550, P-031
Rokhoev, M., P-358
Roland, P., P-502, PD-066
Rolink, A., O-092
Romaniuk, M., PO-094
Romanyshyn, B., P-178
Rombi, B., P-375, P-376
Romero-Rendón, J., P-238
Rompola, M., P-419, P-420
Rondeau, É., PD-060
Rosa, C., P-470
Rosado, A., P-147
Rosanna, W., P-565
Roschin, V., P-141, P-142, P-275
Rosenberg, C., P-250, P-254, P-256
Rosenfeld, E., P-151
Rosengard, S., PO-030
Rosenthal, J., PO-018
Rossato, G., P-393
Rossi, E., PD-014
S513 of S518
Rossi, F., P-010, P-043, PD-025
ROSSI, J., P-015, P-044, P-130
Rossi, L., O-140
Rossi, V., O-092
Rössig, C., O-056
Rostovtsev, N., P-221
Roszkowski, M., P-305
Roth, M., P-224
Rotiroti, M.C., O-093
Rouaida, M., PO-014
ROUSSET-JABLONSKI, C., O-081
Rowan, C.M., O-033
Rowe, B., O-109, P-446
Rowell, E., P-343, P-432, P-433
Rowntree, C., PD-001
Roy Choudhury, S., P-348
Roy Moulik, N., O-034, P-117
Rubanskaya, M., O-172, P-185
Rübe, C., P-370
Ruben, S.B., P-559
Rubino, C., O-024
RUBIO, P., P-015, P-130
Ruckert, M., P-047, P-076
Rudd, S., PD-047
Rudneva, A., P-577
Rudneva, V., O-044
Ruiz de Gopegui Ruiz, E., P-304, PO-056
Ruiz Perez, M.V., P-127
Ruiz, A., P-238
Ruiz, E., P-253
Rumyantsev, A., PO-135, P-303, P-303, P-320
Russ, D., O-067
Russell, B., P-493, PO-119
Russell, C., P-488
Russell, K., O-097
Rustler, V., P-571
Rutenberg, M., P-211
Rutkowski, S., P-572, PD-045
Rutynowska-Pronicka, O., P-236
Ruud, E., O-184
Ryabova, A., P-302
Ryan, J., PD-006
Ryan, T., O-123
Rybakova, D., P-357, PO-074, O-172, P-347
Rykov, M., P-551
Ryzhova, M., P-310, P-311, P-320
S
S. Pombo-de-Oliveira, M., P-036
Saab, R., PD-002
Saad, M., P-210
Saad-eldin Sadek, Y., P-284
Saakyan, S., P-285
Saat, H., P-318
Sabel, M., O-090
Sabha, M., P-397
Sabin, N.D., O-104
Sachdeva, A., O-110, P-417, P-418, P-424
Sadighi, Z., PD-099
Sadiq, M., P-533
Sadowinski Pine, S., PO-116
Saeed, H., P-121, P-203, P-204
Saeed, P., P-367
Saez, S., O-035
Safarinejad, M.R., P-152, P-153
Safaryan, L., PO-108
Saffari, S.E., P-349
Saffioti, M.C., P-339
Saha, V., PD-001
Sahin, A., PO-060
Saida, S., PD-036, PD-037
Saito, A., P-547
Saito, S., P-451
Sajaroff, E., P-015
Sakai, K., O-173
Sakai, T., PD-029
Sakamoto, H., P-317
Saklani, A., PD-028
Sakuta, K., P-508
Salama, A., P-082, PO-089
Salazar, C., P-482
Salceda-rivera, V., P-319
Salcioglu, Z., PO-084, P-270
Saleem, M., P-172
Saleh, A., PD-061
Saleh, S., P-482
Salem, S., PD-009, PD-016
Salem, S.I., P-068
Sali, A., P-184
Salifu, N., P-460
Salima, A., O-060, PD-075, PO-125
Sallai, A., P-273
Salnikova, E., P-320
Salzer, W., O-019
Samaranayaka, L., P-046
Samargandi, O., PD-048
Samarin, A., P-303, P-320
Sambandan, K., PO-071
Samir, S., PO-089
Samsudin, H., PD-110
Samuel, D., O-090
Sanada, M., O-048, O-129
Sanchez La Rosa, C., P-044
Sánchez Salinas, A., P-116
Sánchez-Montenegro, C., PO-075
Sánchez-Salazar, M., PO-075
Sander, S., P-270
Sanders, M., O-060
Sangeeta, M., P-041, PO-012
Sanjiv, K., PD-047
Sankar, J., P-456
Sankaran, H., P-321, P-461
sanli, K., PO-084
Santacroce, S., P-511, P-506
Santana, V., P-145
Santiago García, B., P-455
Santo, K., P-163
Santos Murra, M., P-475
Santos, C., PO-132
Santos, C.S.D., P-025
Santos, E., P-400
Santos, V.D.N., P-025
Sanyal, M., P-013
Sapra, S., P-245, P-576
Sarashina, T., PO-013
Sardou Cezar, I., P-069, PD-007, PD-008
Sarfo Frimpong, E., P-483
Sargsyan, L., PO-108
Sari, N., P-421
Sarı, N., P-197
Sarialioglu, F., P-103, PO-095
Sariban, E., P-330
Saripinar, E.G., PO-115
Sarnacki, S., O-169, O-115, O-159
Sarnecka-Paruch, A., P-114
Sarper, N., P-427
Sarpong, A., PO-097
sarrawi, T., P-186
Sasahara, Y., PO-109
Sasaki, T., P-255, P-354
Sasja, S., PO-101
Sassi, E., O-140
Sastre, A., P-020, P-518
Sastry, J., O-118, P-462, P-463
Sath, S., O-204
Satish, G., O-060
Sato, A., PO-109
Sato, I., PO-109
Satwani, P., O-142
Sauerwein, W., P-243
Saveliev, L., P-133
Savlaev, K., PD-112
Sawhney, K., O-134, O-136
Sawi, H., PO-006
Sawicka-Zukowska, M., P-524
Saxena, R., P-014, P-024
Saxton, A., P-464
Sayaka, G., P-512
Sayed, H., P-222
Scaccia, V., P-432, P-433
Scalabre, A., O-169
Scalini, P., P-267
Scanlan, P., P-544
Scarborough, M., P-211
Scarzello, G., P-093, PO-123
Schacter, B., PD-093
Schaller, T., PD-047
Schatka, I., P-137
Scheer, M., P-223
Scheffold, A., PD-006
Schelstraete, P., P-398
Schembri, A., P-494
Schepers, S., O-097, O-202
Scheurer, M., AW-04, P-268, P-536, P-549, P-556,
PD-094
Scheurer, M.E., O-114, O-119, O-189
Schiavello, E., O-025
Schifflers, S., P-330
Schild, L., AW-08, O-066, O-071
Schlegel, M., O-056
Schlegel, P.G., P-572
Schleiermacher, G., O-068
Schmid, E., O-175, PD-101
Schmid, I., P-575
SIOP ABSTRACTS
S514 of S518
Schmidt, A., O-153
Schmidt, M., O-053
Schmiegelow, K., O-005, P-448, PD-066
Schneider, D., P-394
Schneider, R., P-226, P-361
Schneller, N., O-125
Schroeder, K., O-063, P-464
Schubert, N.A., O-071
Schulte, F., P-493, PO-119, O-099, O-100
Schultz, K., O-020, PD-105
Schultz, K.A., PD-030
Schuringa, J.J., P-047, P-076
Schürmann, E., P-378
Schüz, J., P-537
Schwalbe, E., O-015
Schwartz, L., P-465, PD-073
Sciot, R., P-216
Scobie, N., O-143, P-584
Scott, S., PO-121
Scrideli, C.A., P-048, P-286, P-390, P-327,
P-328
Seal, S., P-147
Sebastian Viapiano, M., P-392
Sebire, N., PD-021, PD-024
Sedek, L., P-053
Seelisch, J., P-096
Segalerba, D., O-068
Segers, H., P-216
Segovia Weber, L., O-206, O-207
Segovia, L., O-201
Sehested, A.M., O-016
Seils, A., O-095
Seitz, G., O-160, P-223
Seki, M., O-048, O-129, P-029
Sekiguchi, M., O-129
Seksarn, P., P-050, PO-062
Sekula, N., P-064
Selivanova, G., O-124
Semary, S., P-068, P-082
Sementa, A.R., O-068
Semeraro, M., O-115
Semetsa, P., P-556
Semiglazova, T., P-105, P-108
Semmel, E., PD-062
Sen, S., P-176, P-207, P-214, P-234, P-246, P-247,
P-264, P-265, P-280
Senay, E., P-062, P-083, P-332, PO-034
Senay, R.E., PO-037, PO-052
Sencer, S., P-235
Senzhapova, E., P-199, PO-035
Seo, J., PO-007
Seo, J.J., P-097
Seog Yun, P., P-215
Seregni, E., O-025
Serinan, E., P-123, P-516, PO-024
Serov, Y., P-244
Serra, A., PO-067
Serra, K., PO-060
Serrano, J., P-194
Servaes, S., P-529
Servaes, S.E.N., O-154
Sètchéou Allodji, R., O-024
Seth, R., P-245, P-576, P-001, P-061, P-456,
PD-034
Seth, S., P-576
Seth, T., P-014, P-024
setia, R., P-120
Sevinir, B., P-552
Seyfried, F., PD-006
Sfiridaki, A., PO-009
Shaaban, K., P-068, PD-009
Shad, A., P-553
Shah, A., PD-028
Shah, S., P-369, P-561, PD-028
Shahgholi, E., P-017
Shahryari, M., P-382
Shaikh, F., O-038
Shalaby, L., P-437, O-113, P-436, PO-089
Shalkow, J., P-257
Shamanskaya, T., P-142, P-275, P-126, P-141
shan, W., P-162
Shao, J., P-146
Shapochnik, A., P-303, P-320
Sharapova, G., P-303
Sharkey, C., PD-071, PO-118
Sharkey, C.M., O-179
Sharma, A., P-023, O-144, P-035
Sharma, S., P-120, P-582, PD-034
Sharoev, T., P-358, PD-112
Shashni, A., P-264, P-265
Shats, L., P-577
Shaw, D., O-013
Shaw, F., P-454
Shaw, N., PO-088
Shay, A., P-564
Shcherbenko, O., P-320
Shchurovska, I., P-178
Shelmerdine, S., O-039
Shen, H., P-098
Shen, N., O-203, O-208, P-503, PD-083
Shen, S., P-431
Shengelaia, A., PO-011
Shenoy, R., P-543
Shepherd, J., P-299
Shereck, E., PD-076
Sherief, L., P-557
Sherif, L.M., P-395
Shetty, D., O-022, P-054
Shevtsov, D., P-141
Shi, X., PD-005
Shim, Y.J., PO-117
Shimada, H., O-032
Shimamura, A., P-056
Shimizu, T., P-391
Shimmon, K., PO-122, PO-105
Shimojima, N., P-345
Shin, H.Y., PO-117
Shin, S., P-258
Shinkai, M., O-040, P-195
Shinoda, M., P-345
Shioda, Y., P-161, PO-068
Shiomi, M., PO-013
Shipman, P., P-334
Shipway, L., O-187
Shirai, F., P-514
Shiraishi, Y., O-129, P-029
Shiwaku, H., PO-109
Shorikov, E., P-133
Shraddha, C., P-041, PO-012
Shrivastava, N., PO-134
Shroff, R., PD-024
Shu, Q., P-519, O-167, P-098, P-189, P-259, P-288,
PD-023
Shu, Y., P-519
Shuangshot, S., P-294
Shuangshoti, S., PO-062
shuchun, W., O-031
Shuo, T., P-029
Shurupova, M., P-322
Siaw, J., P-143
Siddell, P., PO-122
Siddiqui Khawar, S.K., PO-044
Siddiqui, K., P-002, P-003, P-297
Side, L., O-077
Sidorenko, L., PO-135
Siebert, N., O-070
Siegler, N., P-378, PD-045
Sieswerda, I., O-212
Signorelli, C., P-466, O-103, O-105
Sikorska-Fic, B., P-067
Silva de Miranda Gomes, M.C., P-241
Silva Silveira, V., P-327
Silva, M., O-116
Silva, N., O-116
Silveira, V.S., P-047, P-076
Silverman, L., O-020
Sim, S.W., O-157
Simmons, I., O-016
Simon, C., P-319
Simon, T., O-053, O-055, P-394, PD-104, PO-093
Simonin, M., O-010
Simon-Keller, K., O-095
Sinatora, F., P-118
Sindhi, R., P-099
Singh Yadav, P., P-348
Singh, A., P-061, P-245, P-576
Singh, J., P-091
Singh, L., P-246, P-234
Singh, M., P-032, P-234
Singh, M.K., P-247
Singh, N., P-119
Singh, S., P-351
Singh, S.K., O-029
Singh, T.B., O-029, P-087
Sinha, C., O-164
Sinha, D.I., PO-078
Sinnett, D., O-096, P-486, PD-060, PO-114
SinQuee-Brown, C., PD-091
Sint Nicolaas, S.M., O-202
Siracusa, F., PD-038
Sirnivas, M., O-174
Siviş, Z., P-080
Sjöberg, C., P-513
Skachkova, O., P-139
Skalska- Sadowska, J., PD-064
Skalska-Sadowska, J., P-067
Skinner, R., P-438
Sklar, C.A., O-026
Skoczen, S., P-114
Slaby, O., P-287, P-335
Slager, T.J., O-069
Slater, O., P-367
Slavc, I., P-323
Slayton, W., O-020
Sleurs, C., P-578, P-331
Slobina, E., P-324
Slone, A., P-556
Slone, A.K., O-119
Slone, J., P-554, P-242, P-541, P-556, P-588, P-591,
PO-111
Slone, J.S., O-119
Sloof, N., PD-098
Smeele, L., P-367
Smeulders, N., PD-024
Smith, A., O-015
Smith, E., O-154
Smith, K., P-432, P-494
Smith, L., O-156
Smith, S., O-106, P-388
Sniderman, E., O-204
Snuderl, M., O-046, P-194
Soanes, L., O-205
Soberanis Vasquez, D.J., O-064
Soberanis, D., O-035, P-411
Sobhy, M., P-574
Sobieralska- Michalak, K., PD-064
Sobko, R., P-178
Sobol-Milejska, G., P-049, P-053, P-266
Sobral da Costa, E., P-515
Sobral, J., P-250
Soejima, T., PO-109
Soh, S.Y., O-157, PO-045
Sola, J., O-130, P-218, P-219
solak mekic, M., P-363
Soledad, P.C., P-559
Soler, C., O-169
Soliaman, R., O-113
Soliman, R., O-057, PD-026
Soliman, S., P-231, PD-009
Solórzano, S., P-257
Soltys, K., P-099
Somers, G., P-134
Sonaglio, V., O-140
Sonmez, C., P-197, P-421
Sonoda, M., PD-036
Sonowal, R., P-087
Sonsala, A., P-053
Söntgerath, R., P-571
Sophie, D., P-208
Sorg, C., PD-101
Sorrentino, S., P-154, P-155, PD-018
Sosothikul, D., P-050, O-032, P-294, PO-062
Sotnikov, A., O-080, PD-100
Soulaymani, A., PO-133
Sousa, A.V., O-116
Souweidane, M., O-014
Souzaki, R., P-359, O-129
Sovinz - Ritter, P., P-243
Spada, M., O-166, P-339
Sparber-Sauer, M., P-223, O-160
Specht, K., O-056
Speleman, F., PD-019
Spiegel, A., O-131
Spiers, D.L., P-440
Spira, M., P-224
Spreafico, F., AW-03, P-170, PD-038
Spreafio, F., O-025
Spunt, S., P-377
Sramek, M., P-287, P-522
Sredni, S., O-140
Srikanthan, A., PD-093
Srinivasan, R., O-120
Srivastava, D., O-104
Srivastava, D.K., O-026, O-106
Stachowicz-Stencel, T., P-524
Stagno, M.J., O-175
Stam, R.W., O-071
Stancel, H., PD-096
Stančoková, T., P-546
Stanek, J., PO-066
Stanley, C., P-489, PO-125
Stanley, K., P-099
States, L., P-529
Stawiski, K., P-333
Stearns, D., O-090
Steendam, L., PD-081
SIOP ABSTRACTS
Stefan, D., P-365
Stefanaki, K., P-180, P-550
Stefanowicz, J., P-266, P-579
Stefanski, A., O-042
Stegenga, K., O-191
Steliarova-Foucher, E., P-546
Stenman, J., P-143
Stephens, S., PO-103
Sterba, J., P-287, P-335, P-522
Stern, E., O-011
Stern, K., O-102
Stern, M., PD-072
Steur, L.M.H., O-098, O-107
Stevens, E., PD-073
Stevens, M.C.G., PD-031
Stewart, L., O-009, P-443
Stewart, R., O-156
Stezhka, M., PO-049
Stiakaki, E., P-051, PO-009
Stilgenbauer, S., O-124, PD-006
Stiller, C., O-006, O-074
Stinson, J., O-146, PD-085
Stisen, L., PD-066
Stolfi, A., P-413
Stoneham, S., O-036, O-038
Stork, L., PD-076
Stössel, S., PD-056, P-571
Straathof, K., PD-050
Strandvik, B., P-386
Stratigaki, M., P-051, PO-009
Stroganova, A., P-310, P-311
Strother, D., O-014
Strüder, H.K., PO-093
Stühler, K., O-042
Sturm, D., O-045
Suazo, V.K., P-048
Subbotina, N., P-310, P-311
Subramanian, P., P-052, O-022, P-013, P-040
Subramanian, P.G., P-100
Subramanium, P., P-054
Subramonian, D., P-164, PD-052
Sudjoko, A.U., O-145
Suenobu, S.I., P-439
Sugandhi, N., PD-108
Sugiyama, M., P-129
Suh, H.R., PO-087
Suh, J.K., PO-087
Suksalee, S., P-498
Suleymanova, A., P-275
Sullivan, C., O-206, O-207, O-196
Sullivan, J., P-016
Sullivan, M., O-102, O-210, P-334
SULTAN, I., P-581, P-249, P-397, P-186
Sultan, S., O-096, P-486, PD-060, PO-114
Sumerauer, D., P-325, O-045, P-274
Sun, J., O-208, O-203, P-131, P-503
Sun, L., P-431
Sun, Q., O-124
Sun, Z., P-190
Sunaert, S., P-578
Sund, A.M., PD-070
Sundler Johansson, A., P-477
Sung, K.W., P-034
Sunkara, A., P-145
Super, L., O-102
Supiot, S., P-364
Surman, M., P-042
Suththanantha, J., PO-057
Sutradhar, R., O-028
Suzana, K., PD-041
Suzuki, H., O-048
Suzuki, S., PO-109
Suzuki, Y., PO-109
Svanberg, A., P-425
Švec, P., P-065, P-057
Svedberg, P., P-513
Svenberg, P., P-143
Svensson, P.J., P-143
Swami, A., P-039
Swieszkowska, E., P-252
Swigonski, N., O-033
Switcheko, J., P-110
Syed, A.S.B., P-203
Synakiewicz, A., P-524
Synyuta, A., P-178
Szczepański, T., P-012, P-053
Szłapińska, A., P-011
Szwajcer, D., PD-093
Szychot, E., PD-021
T
T. G. Pina, E., P-036
Tabone, M.D., O-159
S515 of S518
Tabori, U., O-047, O-090
Tacyildiz, N., P-467, PO-047
Taga, T., P-074
Tagarelli, A., PD-039
Tagen, M., P-393
Tagoe, L.G., P-187
Taguchi, T., O-126, O-129, O-163, P-359
Taha, G., P-209, P-210, P-261, PO-050
Taha, H., O-121, P-210
Tahara, K., PO-068
Tahira, N., P-533
Tajiri, T., O-173, P-138, PD-029
Takahashi, I., P-379
Takahashi, M., PO-109
Takahashi, N., P-345
Takahashi, Y., P-514
Takama, Y., O-163
Takegawa, B.K., P-282
Takemoto, J., P-359
Takenaka, S., PO-043
Takenouchi, N., P-514
Takeuchi, A., P-205, P-380, PD-027
Takeuchi, S., P-514
Takezoe, T., PO-068
Takimoto, T., P-138, P-547
Takita, J., O-048, O-129, P-029
Talaat, S., PD-016
Talat, N., P-172
Taluja, A., O-134
Talypov, S., P-141, P-275
Tamamyan, G., PO-108
Tamburini, A., P-267
Tan, A.M., O-157, PO-045
Tan, C.B., P-349
Tan, E., P-326
Tanaka, H., P-029
Tanaka, M., O-040, P-195, P-445
Tanaka, N., P-255, P-354
Tanaka, T., PD-029
Tanaka, Y., O-040, O-126, O-129, P-195
Tandon, S., P-054, P-040
Tanenbaum, D., P-110
Tang, D.X., PD-023
Tang, H.F., PD-023
Tang, J., P-260, P-431
Tang, J.Y., P-085
TANG, P.H., PD-110, P-360
Tang, W., P-344
Tang, Y.L., PO-010
Taniguchi, Y., P-205, P-380, PD-027
Tanner, L., P-468
Tantawy, M., PD-016
Tarar, M.A., P-338
Tarek, N., PD-002
Tarrillo, F., P-206
Tas, M., O-052
Tashiro, J., O-130, P-219
Tashvighi, M., P-314, P-017, PO-036
Taskinen, M., O-007
Tausch, E., O-124
Tavelin, B., AW-04
Tawng, K.D., O-157
Taylor, M., O-044
Taylor, O., PD-094, O-189, P-536
Taylor, O.A., O-114
Tbakhi, A., P-249
te Kronnie, G., O-124
te Loo, D.W.M.W., O-098, O-107
Teachey, D.T., O-123
Techavichit, P., P-294, P-050, PO-062
Tedroff, K., P-386
Teerapakpinyo, C., P-294
Teinturier, C., O-024
Teisseyre, J., P-252
Teixeira, S., P-392
Teixeira, S.A., P-390
Tejocote, I., P-319
Tejocote-Romero, I., P-555
Tembere, P., P-054
Tembhare, P., O-022, P-013, P-040, P-052, P-100
Temiz, A., P-103
Temming, P., P-243
Tennent, P., PO-127, PO-128
Teramukai, S., P-138
Terashima, K., PO-068
Terashita, Y., P-129
Terenziani, M., PD-038
Teresa, S.S., PD-039
Tereschenko, G., P-141, P-142
Terezakis, S., P-377
Terra-Granado, E., P-069, PD-007, PD-008
Terras, E., O-051
Terui, K., P-074
Terwisscha Van Scheltinga, S., O-148, P-188, PO-069,
O-162
Tesfaye, M., P-464
Tessier, D., PD-109
Tettamanti, S., O-091, O-093
THAKKAR, D., PO-019
Thakwani, A., P-277
Themistocleous, M., P-550
Thevanesan, C., PD-050
Thomas, G., O-090
Thomas, K., P-194
Thorner, P., P-294
Thorsteinsson, T., P-448, PD-066
Thulkar, S., O-174
Thurairasa, D., O-164
Tian, X., P-431
tianfeng, L., O-031
Tieku-Ward, B., P-469
Tiitinen, A., PD-097
Tijtgat, G.A., AW-08, O-066
Timchenko, N., P-258, O-128, P-251
Timmermann, B., P-378
TIP, S.W.M., P-360
Tippelt, S., PD-045, P-378
Tiselius, E., O-188
Tissing, W., O-023
Tissing, W.J.E., O-079, O-098, O-107, P-434, P-435
Tjaden, K., P-316, PD-044
Tochner, Z., O-073, P-173
Tojal, I., P-250
Tokuc, A.G., PO-037, PO-052
Tokuc, G., P-062, P-083, P-177, P-332, PO-034
Tolbert, V., P-145
Toledo, S., P-256
Toledo-Tamula, M.A., P-494
Tolkkinen, A., O-007
Tomaszewska, R., P-067
Tomboc, P., O-090
Tomfohr, L., P-493
Tomiyama, A., P-317
Tomizawa, D., P-074, PO-068
Tomoka, T., O-060
Tondo, A., P-470
Tone, L.G., P-328, P-047, P-048, P-286, P-390
Tong, R.S., PD-010
Tony, L., P-361
Toporski, J., P-425
Torbecke, M., P-408
Torelli, A., O-201
Torino, G., O-165
Tormen, T., P-453
Törnqvist, E., O-185, O-186
Torrens, L., P-463
Torres, T., P-500
Tórtola, A., P-402
Tortora, C., P-043, PD-025
Tourkantoni, N., P-031
Tracey, J., P-465
Trager, C., PD-018
Trahair, T., PD-018
Tran, D., P-292
Traverso, A., P-118
Trebichavsky, J., P-355
Treger, T., O-002
Treger, T.D., AW-03
Trehan, A., P-055, O-111, O-120, P-032, P-428
Treis, D., P-143
Trelinska, J., P-053
Tremolada, M., PO-123, P-118
Trevisan, F., P-470
Trippett, T., P-393
Trnka, J., P-057
Trøen, G., P-149
Trofimov, I., O-080, P-244
Troschke-Meurer, S., O-070
Trubicka, J., P-329, P-305
Truc, G., P-364
Truillet, R., P-307
Truong, B., O-067
Truong, T., P-231
Tsang, D.S., AW-07, PD-046
Tsaur, G., P-133
Tsimicalis, A., O-181
Tsipi, M., P-550
Tsipou, H., P-031
Tsuchiya, H., PD-027, P-205, P-380
Tsuda, R., PO-109
Tsukazaki, Y., P-163
Tsyrlina, E., P-105, P-108
Tucker, K., O-103, O-105
Tuğcu, D., P-092, P-177, P-270, P-427, PO-029
SIOP ABSTRACTS
S516 of S518
Tugnait, S., O-074, O-077
Tumino, M., P-118
Tuncer, B., P-235
Tuncer, S., P-235
Tunn, P.U., O-056
Tupper, B., P-388
Turazzi, N., O-092
Turhan, T., P-368, PO-060
Türker, M., P-080
Turpin, B., P-388
Turpin, K.H., P-466
Tutelman, P., O-146
Twardoch, M., P-053
Tweddle, D., P-565
Tyagi, A., O-030
Tyagi, S., P-014, P-024
Tyldesley, S., P-312
Tytgat, G., O-052, O-148, P-157, P-158, PO-069
Tytgat, G.A.M., O-069
Tytgat, L., O-054, P-136
Tzetis, M., P-550
U
Uchida, M., P-514, PO-092
Uddin, N., PD-012, PO-021
Ueda, Y., O-004, O-163, P-567
Uemoto, S., PD-036, PD-037
Ueno, H., O-048
Ugaz Olivares, C., P-225
Ugonabo, N., PO-131
Uitdehaag, S.J., O-212
Ukpai, N., PO-008
Ullrich, N., P-568
Umeda, K., PD-037, PD-036
Umerez, M., P-518
Unal Cabi, E., PO-047
Unal, E., P-427, P-467
Ünal, Ş., P-056, P-077
Üner, A., P-276, PO-016
upadhyaya, V., PO-031
upadhyaya, V.D., PO-051
Uparkar, U., P-291
Urbaneja Rodríguez, E., P-028
Urbanska-Rakus, J., P-064
Urbieta, M., P-148, P-289
Urey, C., O-142
Urushihara, N., P-379
Ushakova, T., O-080, P-244
Usui, H., P-195
Usui, N., P-354
Uyar Gocun, P., P-095
Uysalol, E., P-427, PO-084
Uyttebroeck, A., P-216, P-331, P-578
V
Vaarwerk, B., O-085, PD-031
Vadeboncouer, C., O-083
Vahidifar, M., P-382
Vaidya, S., O-034, P-117
Vaishnavi, K., O-111
Vaksman, Z., O-067
Valadares, E., P-250
Valanejad Keifer, L., P-251
Valanejad Kiefer, L., O-128
Valanejad, L., P-258
Valdez, J., O-194
Valdivieso, B., P-402
VALDUGA, J., O-081
Valduvieco, I., P-304
Valind, A., AW-05
Valle, L., P-375
Valli, H., P-433
Valteau-Couanet, D., O-078, P-181
Valverde-Rojas, B., PO-075
Van Amstel, J., O-082
van Baren, R., O-148
Van Bindsbergen, K., PO-101
Van Bruggen, L., O-034
Van Dalen, E.C., O-079
Van Damme, A., P-330
Van Damme, N., P-330
van de Veen, K.P., PD-106
van de Ven, C., O-148, P-188, PO-069
van de Wetering, M., O-182
Van de Wetering, M.D., O-079, P-435
Van Delft, F., P-565
van den Bergh, E.M.M., O-212
van den Bos, C., O-098, O-107
Van den Heuvel-Eibrink, M., P-188, O-023, O-075
van den Heuvel-Eibrink, M.M., AW-03, O-212
Van den Wyngaert, L., P-331
van der Galiën, H.T., P-434
van der Gronde, T., O-060, P-489, PD-075, PO-125
van der Lee, J.H., PD-031
van der Meer, L., AW-06
van der Schoot, C.E., O-069
Van der Schoot, E., O-054
van der Sluis, I.M., O-098, O-107
van der Veen, M.E., O-212
van Eijkelenburg, N.K.A., O-098, O-107
van Groningen, T., P-158
Van Grotel, M., P-188, O-075
van Grotel, M.P., P-156
van Helvoort Lengert, A., P-520
Van Ingen Schenau, D., PD-022
Van Kuilenburg, A., P-157, P-158, O-054
Van Lancker, S., PD-081
Van Leeuwen, F., AW-06, PD-022
Van Loon, F., O-082
van Nes, J., P-158
Van Noesel, M., O-087, O-052, P-157, P-136
van Noesel, M.M., O-069
van Noesel, M.M.P., P-156
Van Paemel, R., O-051
van Peer, S., P-188
van Rijn, R.R., O-085, PD-031
van Rooijen, A., P-156
Van Roy, N., P-144
van Sluis, P., AW-08, O-066
Van Tinteren, H., O-075
van Wezel, E., O-069
van Wijk, J., O-069
van Zogchel, L., O-069
Vanackova, J., P-287
Vanan, M., O-090
Vandemeulebroecke, K., P-144
Vandenabeele, K., P-331
Vandenwyngaert, L., P-578
Vandepoele, K., P-144
Vannatta, K., PD-058, PD-062
Varan, A., P-248, P-169, P-198, PO-016
Varesio, L., O-068
Varfolomeeva, S., P-141, P-142, P-275
Varga, E., P-273, PO-070
Varlet, P., O-043
Varma, N., P-032
Varone, A., PO-002
Varshney, A., P-337
Vaská, A., P-057
Vasquez, L., P-206, P-585, P-225, P-309
Vasquez, R.F., P-444
Vassal, G., O-043
Vasudevan, S., P-151
Vaz, F., P-157
Vega-Salas, S., PO-075
Vega-Vega, L., PO-099
Veintemilla, G., O-168
Velangi, M., P-290
Velasco-Hidalgo, L., P-555
Velazquez-Aviña, M., P-059, P-471, P-472, P-058
Velázquez-Martin, B.M., PD-073
Velleuer, E., PD-088
Venkatramani, R., O-073
Vennarini, S., P-376, P-375
Vercruysse, G., P-331, P-578
Veres, C., O-024
Vergara, P., O-035
Verhaak, C.M., O-202
Vérité, C., O-059, P-208
Verlekar, D., P-150
Verlooy, J., P-330
Verly, I., P-157, P-158, O-069
Verma, N., P-023, P-060, P-035
Verschuur, A., P-307, P-384, AW-03
Versteeg, R., AW-08, O-066, P-158, PD-019
Veselska, R., P-287, P-522
Vetsch, J., O-103
Vettenranta, K., O-027
Viani, K., P-473
Vianna, R., P-025, P-272
Vicente dos Santos Bueno, F., P-069, PD-007, PD-008
Vieira-Lopes, D., P-515
Viet, T., P-231
Vigholm, J., PO-076
Vigneron, C., P-364
Vijaysekharan, K., O-058
Vilanova Sanchez, A., PO-066
Villafuerte III, C.V., P-167
Villalobos-Ortiz, M., PD-006
Villani, A., PD-089
Villiera, J., P-269, P-268
Vincent, S., O-024
Vincent, T., O-123
Viola, A., PO-103
Viprey, V.F., O-068
Virgone, C., O-166
Viscardi, E., P-155
Vishnu, S., P-001
Vishwanath, L., P-373
Viswanathan, G.K., P-100
Viswanathan, K., O-108, P-070, P-071
Viveros Lamas, P., O-206, O-207
Vizhlukova, O., P-577
vizkeleti, J., P-363
Voigt, K., P-510
Vojtesek, B., P-335
Vokuhl, C., P-223
Volckmann, R., AW-08, O-066
Vollbrechthaussen, L., P-115
von Bueren, A., P-572
von Essen, L., P-425
von Hoff, K., O-045, P-572, PD-045
von Kalle, T., O-056, P-223
von Luettichau, I., O-056
von Schweinitiz, D., PD-106
vonAhlefeld, T., P-336
Vora, T., O-058, P-184, P-220, P-369, P-460, P-561,
P-563, PD-015, PD-028, PD-065, PD-111
Voss, S., P-096
VP, K., PO-012
Vrenken, K., PD-022
Vu Thi, H., PO-003
Vu, Q., PO-026
Vu-Bezin, G., O-024
Vujanic, G., O-074
Vural, S., P-177
VYAS, C., PD-011
W
Waack, K., P-394
Waanders, A.J., PD-042
Wachepa, S., O-065, P-073, P-412, P-489, PD-075
Wachowiak, J., P-011, P-012
Wachowiak-Szajdak, K., P-266
Wachtel, A., P-253
Wada, K., P-449
Waespe, N., P-587
Wagner, A., P-523
Wainwright, R., O-109, P-446
Wakama, T., PO-008
Wakefield, C., O-103, O-105, PO-120
Wakefield, C.E., P-466
Wakefield, D.V., PD-032
Walenciak, J., P-064
Walentyna, B., P-007
Wali, R., P-121
Walker, B., O-194
Walker, D.A., O-012, O-016
Walker, J., O-156
Wallace, H., O-152
Wallace, V., P-440
Walser, M., P-226, P-361
Walsh, K., PD-071
Walter, C., PD-088
Walwyn, T., P-334
Wan, W.Q., PD-049
Wanaguru, D., PO-073
Wang, B., PO-027
Wang, H., O-149, P-101
Wang, J., O-167, P-259, P-485, O-011, P-159, P-189,
P-190, P-288
Wang, J.H., PD-023
Wang, M., O-106
Wang, N., P-431
Wang, R., P-349
Wang, S., P-160, P-194
Wang, T., P-260, PD-005
Wang, X., P-128, PO-027, PO-040
Wang, Y., O-001
Ward, D., O-073, P-173
Ward, P., O-065, P-073, PD-075, PO-125
Warmann, S., PD-106
Warmann, S.W., O-153, O-175
Warmuth-Metz, M., P-316, P-572, PD-044, PD-045
Warwick, A., O-073, P-173
Waspe, A., P-134
Wasswa, P., P-073, O-065, P-412, P-489, P-541,
PD-075, PO-111
Watanabe, K., P-379, O-126, O-129, PD-037
Watanabe, T., P-508, PO-068
Wataya, T., P-379
Watson, T., PD-024
Weaver, L., PO-066
Weaver, P., PD-074
Weber, D.C., P-226, P-371, P-361
Wedel, F., P-137
SIOP ABSTRACTS
Weil, J., P-575
Weiner, D., P-569
Weinstein, J., O-041
Weinstein, R., P-541
Weirauch, M., O-128
Weissman, I., PD-041
Weitz, J., P-407
Weitzman, S., P-553, PD-091
Welch, J., P-006
Welch, K., P-299
Wenyu, Y., O-031
Werneck, I., P-256
Werner, M., O-056
Wessman, S., P-143
West, C., PO-124
West, T., PO-088
Westmoreland, K., O-060, PD-075, PO-125, P-489
Westmoreland, T., P-147
Weyman, E., P-366
Wharton, S., O-015
Whitehead, W., PD-096
Whitehouse, W.P., O-012
Whiteside, S., O-213
whitfield, G., P-363
Wickström, M., P-386
Widger, K., O-083
Wiecha, O., P-114
Wiecrorek, A., PD-018
Wieczorek, D., PD-088
Wiener, L., O-209, PO-126, PO-113, PO-129
Wiersma, J., P-367
Wiersma, Y., O-212
Wiesmüller, L., O-124
Wijatyk, A., P-019
Wijnen, M., O-148, P-136, PO-069
Wilde, J., PO-069
Wilhelm, M., PD-030
Wilkes, J., P-016
Wilkins, S., PO-105
Willems, L., P-330
Willhoite, J., P-452
Williams, A., P-569
Williams, D., P-568
Williams, E., PD-051
Williams, G., PD-030
Williams, K., PD-051
Williams, M.H., PD-042
Williams, R., O-002, O-074, O-077
Wilson, C., PD-087
Wilson, C.L., O-026
Wilson, M., PO-102
Wilson, S., P-193
Wilson-Lewis, K., P-541, P-589, P-588, P-590,
P-591
Wiltsie, L., P-525
Windhager, R., O-056
Wingerter, A., PD-056
Winiarski, J., P-425
Winick, N., O-018, O-019, O-020, O-021
Winsnes, K., PD-076
Winsor, J., PO-124
Winther, J.F., O-005
Wisidagamage Don, N.D., O-094
Withycombe, J., O-191
Witkowski, L., PD-089
Witt, O., PD-045
Witteman, H., O-146
Wolfe, J., O-083, P-479
Wolff, J.E., P-572
Wollman, M.R., P-201
Wolters, P., P-494
Wong, C., P-586
Wong, L., P-336
Wong, M.K., O-157
Wong, W.H., PD-010
Wongsingrad, N., P-498
Wood, B., O-020
Wood, B.L., O-123
Wood, N., P-102
Wood, R.J., PO-066
Woodfield, S., P-164
Woodgate, R., PO-127, PO-128
Woszczyk, M., P-053
Wozniak, M., P-114
Wright, M., O-128, P-251, P-258
Wu, M., PD-005
Wu, P., P-194
Wu, S., O-017
Wulff, B., P-394
Wyka, K., P-064
Wysocki, M., PD-064
X
S517 of S518
Xalafova, L., P-474
Xavier Del Rio, L., P-475
Xess, I., P-061
Xia, C., O-036, O-038, O-127
Xiao, L., O-161
Xiao, X., P-191, P-344
xiaofan, Z., O-031
xiaojuan, C., O-031
Xiao-li, Z., PD-004
xiaoming, L., O-031
Xie, M., P-085
xing, T., P-128
Xingdi Hu, X., P-018
Xu, S., PD-023
xue-qun, L., PD-004
Y
Yabu, G., O-140
Yadav, J., P-061
YADAV, S., PO-019
Yagci, A., P-368
Yagi, H., P-345
Yagyu, S., PD-029
Yakemchuk, V., P-560
Yalcin, B., P-169, PO-016
Yalçın, B., P-198
yali, H., P-227
Yamada, Y., P-345
Yamagishi, M., O-173
Yamamoto, N., P-205, P-380, PD-027
Yaman Agaoglu, F., P-235
Yaman Bajin, İ., P-077
Yamane, Y., PO-109
Yamasaki, K., P-161, P-317
Yamashita, K., O-147
Yamazaki, F., P-161
Yamazaki, M., P-449, PO-092
Yamoah, P., P-450
Yan, J., P-085
Yanez, Y., O-068
Yang, C., P-162, P-160
Yang, J., P-078
Yang, L.H., PD-049
Yang, X., P-288, P-159
Yang, Y., P-131
Yano, M., O-126
Yao Zou, Z., O-031
Yao, K.P., PO-080
Yao, W., P-191
Yaralı, N., P-427
Yarovaya, V., P-244
Yarovoy, A., P-244
Yasin, S., P-326
Yasko, L., P-303
Yassin, D., P-068
Yavuz, G., P-467, PO-047
Yazıcı, H., P-235
Yazici, N., P-103, PO-095
Ye, G., O-031
Ye, J., P-159, P-288
Ye, Q., P-260
Yeager, N., O-213
Yeamin, M.B., P-030
Yeap, B., P-366
Yeates, K., P-573
Yelton, L.L., P-413
Yenigurbuz, F., P-090
Yijin, G., P-227, O-122
Yıldırım, M., P-197
Yildirimoglu, C., P-318
Yilmaz, B., P-062, P-332, PO-037, PO-052
Yılmaz, B., P-083, PO-034
Yılmaz, E., PO-084
Yilmaz, O., P-192
Yılmaz, O., P-516
Yilmaz, S., P-177
Yock, T., P-366
Yokoi, A., O-163
Yokosuka, T., PO-013
Yokota, I., P-138
Yonayama, M., P-449, PO-092
Yoneda, A., P-163, P-138, P-354
Yoo, B., O-049
Yoo, K.H., O-032, P-034
Yoon, S.R., PD-035
Yoshida, A., P-317
Yoshida, H., PO-043
Yoshida, K., O-048, O-129, P-029
Yoshida, M., O-040, O-129
Yoshizawa, A., PD-036, PD-037
Yoshizawa, K., P-195
Younes, A., P-209
Young, A.L., PD-010
Young-Saleme, T., P-488, PD-058
Younis, A., O-171
Yousef, Y., P-249
Yturralde, E., P-167
Yu, J., P-159, AW-06, P-288, P-431, PD-005
Yu, Y., P-151
Yuan, X.J., P-085
Yue, Z., P-128, PO-027
Yumei, C., O-031
Yunes, J.A., P-286
Yupensuk, N., P-050
Yurikusa, S., P-379
Z
Z. Bedoya, S., PO-113
Zabokrtsky, K., PO-129
Zabrowski, J., PD-099
Zacharin, M., O-102, O-210
Zadeh Bedoya, S., O-209, PO-129
Zage, P., P-164, PD-052
zaghloul, M., O-121
Zahran, A., P-222
Zakaria, M., P-063
Zakaria, O., P-104, P-530, P-531
Zakharus, M., P-178
zaki, I., P-436
Zakrzewska, M., P-333, PO-065
Zakrzewski, K., PO-065, P-333
Zaky, I., P-437, O-171
Zaldumbide Dueñas, L., P-304, PO-056
Zalewska-Szewczyk, B., P-064
Zamecnik, J., P-325
Zampogiannis, A., P-180
Zamzam, M., O-057, PD-026, P-542, P-580
Zanato, S., P-118
Zanella, A., P-093
Zanetti, I., O-084, O-087
Zangari, A., O-165
Zanzonico, P., O-088
Zapata, A., P-206
Zapata-Tarrés, M., P-555
Zapotocky, M., O-047
Zappeij-Kannegieter, L., O-069
Zareifar, S., P-382
Zaychikov, A., P-133, P-303
Zbigniew, R., P-290
Zebrack, B., PD-077
Zekavat, O., P-382
Zelcer, S., O-083
Zelinskaya, N., P-324
Zeltzer, L., PD-070
Żemojtel, T., P-329
Zengin, E., P-427
Zenitani, M., P-255, P-354
Zhai, X., P-101, P-431
Zhang, B., PD-083, PD-042
Zhang, C., PO-017, P-231
Zhang, D., P-128, PO-027, PO-040
Zhang, H., PO-102
Zhang, L., O-031, P-134, PD-005
Zhang, R., PD-005
Zhang, W., PO-028
Zhang, Y., PO-028
Zhang, Y.T., P-165
Zhao, Q., P-128, P-166, PO-040
Zhao, W., P-128, PO-027, PO-040
Zhao, Z., P-160
Zheludkova, O., P-320, P-324, P-577
Zheng, H., PD-005
Zheng, S., P-191
Zhi-Yong, K., PD-004
Zhong, X.D., P-165
Zhou, C., PD-005
Zhou, J., P-308
Zhou, M., P-260
Zhu, C., P-224
Zhu, G., PO-027
Zhu, J., P-078
Zhu, L., P-258
Zhu, X., P-431, PD-005
Zhu, Y., P-431, PD-042
Zhu, Z., PD-040
Zhukova, N., P-334
Zhukovskaya, E., PD-057, PO-135
Ziegler, D., O-090
Zielezinska, K., P-067
Zimmer, P., PD-056
Zinngrebe, J., PD-006
Zirath, H., P-127
Zitterbart, K., P-335
Zlotecki, R., P-211
SIOP ABSTRACTS
S518 of S518
Zobeck, M., P-556, P-554
Zöllner, S., P-113
Zou, Y., PD-005
Zou, Y.H., O-157
ZUBIZARRETA, P., P-130
Zubizzareta, P., P-044
Zucchetta, P., P-093
Zulfikar, B., P-177
Zumpe, M., O-070
Zuna, J., P-057
Zuñiga, Á., P-383
Zurba, M., PO-127, PO-128
Zuzak, T., P-394
Zvyagintseva, D., P-105, P-106, P-108, P-107,
P-109
Zwaan, M., O-052, O-082, P-157
Zwaveling, S., O-148
Zwijnenburg, D.A., AW-08, O-066