Researcharticle Open Access
Researcharticle Open Access
Researcharticle Open Access
RESEARCH ARTICLE
Open Access
Abstract
Background: Combined radiotherapy and chemotherapy is considered the standard of care for locally advanced
nasopharyngeal carcinoma (LA-NPC) in Epstein-Barr virus infection endemic area. This study compared the long-term
outcomes between LA-NPC patients treated with neoadjuvant chemotherapy followed by radiotherapy (NACT) and
those treated with concurrent chemoradiotherapy (CCRT).
Methods: From 2003 to 2007, a total of 128 histopathologically proven LA-NPC patients receiving either NACT or CCRT
were consecutively enrolled at the National Cheng Kung University Hospital in Taiwan. NACT consisted of 3-week cycles
of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL) or weekly alternated
cisplatin on day 1 and fluorouracil and leucovorin on day 8 (P-FL). CCRT comprised 3-week cycles of cisplatin (Cis 100)
or 4-week cycles of cisplatin and fluorouracil (PF4). The first failure site, disease free survival (DFS), overall survival (OS),
and other prognostic factors were analyzed.
Results: Thirty-eight patients (30%) received NACT. Median follow-up duration was 53 months. More patients with
advanced nodal disease (N2-N3) (86.8% vs 67.8%, p =0.029) and advanced clinical stage (stage IVA-IVB) enrolled in the
NACT group (55.2% vs 26.7%, p =0.002). For NACT, both MEPFL and P-FL had similar 5-year DFS and OS (52.9% vs 50%,
p =0.860 and 73.5% vs 62.5%, p =0.342, respectively). For CCRT, both PF4 and Cis 100 had similar 5-year DFS and OS
(62.8% vs 69.6%, p =0.49 and 72.9% vs 73.9%, p =0.72, respectively). Compared to CCRT, NACT had similar 5-year DFS
and OS (51.5% vs 65.1%, p =0.28 and 71.7% vs 74.3%, p =0.91, respectively). Among patients who were recurrence-free
in the first 2 years after treatment, those treated with NACT experienced poorer locoregional control compared to those
treated with CCRT (Hazard ratio =2.57, 95% confidence interval: 1.02 to 6.47, p =0.046).
(Continued on next page)
* Correspondence: yencj@mail.ncku.edu.tw
Equal contributors
1
Division of Hematology/Oncology, Department of Internal Medicine,
National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan
Full list of author information is available at the end of the article
2014 Wu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Page 2 of 10
Conclusions: For LA-NPC, both CCRT and NACT were similarly efficacious treatment strategies in terms of long-term
disease control and survival probability. Close locoregional follow-up is recommended for patients receiving NACT,
because these patients are more prone to develop locoregional failure than patients receiving CCRT.
Keywords: Neoadjuvant chemotherapy, Concurrent chemoradiation, Nasopharyngeal carcinoma, Outcome
Background
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr
virus-associated cancer with a high incidence in Southeast
Asia, including Taiwan. The majority of NPC cases in
Southeast Asia are classified as WHO undifferentiated
type III [1], which differs from the WHO type I NPC commonly seen in the Western counties and is relatively sensitive to radiotherapy (RT) and chemotherapy [2,3]. For
early stage disease, RT is the mainstay treatment modality
with a 5-year overall survival of 75-90% [1,4]. For locally
advanced NPC, combined chemotherapy with RT may
prolong overall survival with an absolute 5-year survival
benefit of 4% [5-7].
In a recent meta-analysis, Langendijk et al. showed
that the most efficacious way to introduce chemotherapy
was concurrently with radiotherapy and this approach
resulted in an absolute 5-year survival benefit of 20% [5].
But Zhang et al. reported that the relative benefit of this
approach might be less in NPC-endemic area than that
in non-NPC-endemic area [8] and Lee et al. reported
after median follow-up 5.9 years, the administration of
cisplatin plus adjuvant cisplatin-fluorouracil concurrent
with radiotherapy showed a better 5-year progression
free survival but also greater incidence of acute toxicity
and no 5-year overall survival difference compared with
radiotherapy alone [9]. In addition, the pivotal INT-0099
trial showed that 37% of patients in the concurrent chemoradiotherapy arm prematurely terminated the treatment because of excess toxicity [10].
Neoadjuvant (induction) chemotherapy before radiotherapy may significantly reduce the risk of locoregional
recurrence and distant metastases and may improve disease specific survival in locally advanced NPC [11]. This
approach may eradicate micrometastases, facilitate the
planning of radiotherapy, and improve local disease control by reducing the tumor volume prior to RT [12].
Two studies conducted in NPC-endemic area by Hong
et al. [13] and Lin et al. [14] reported that after neoadjuvant chemotherapy over 90% of NPC patients were able
to complete definitive radiotherapy, which is considered
the mainstay treatment in NPC. Therefore, for patients
with locally advanced NPC in NPC-endemic area, the
best timing to incorporate chemotherapy with radiotherapy is still an unresolved issue [8]. Despite the proven
advantage of neoadjuvant or concurrent chemotherapy
with radiotherapy over the radiation alone, the direct
Methods
Between 2003 and 2007, patients with pathologically
confirmed, previously untreated stage IIB to stage IVB
NPC according to the 2002 American Joint Committee
on Staging of Cancer classification [15], who received
study-defined neoadjuvant chemotherapy as well as who
received concurrent chemoradiotherapy in the National
Cheng Kung University Hospital (NCKUH) in Tainan,
Taiwan were consecutively enrolled. Treatment decisions
were made by an institutional tumor board consisted of
otolaryngologists, medical oncologists and radiation oncologists. Either NACT or CCRT was an accepted treatment option during that period.
Pretreatment evaluation for eligible subjects included
a general physical examination, fiberoptic endoscopy,
contrast-enhanced computed tomography (CT) and/or
magnetic resonance imaging (MRI) of the nasopharynx
and neck, chest x-ray, hepatic ultrasonography, and radionuclide bone scan.
In general, we followed the criteria reported by Lin
et al. [14] to select patient to receive NACT: (1) neck
nodal size >6 cm; (2) supraclavicular node metastasis;
(3) skull base destruction/intracranial invasion, and
(4) multiple neck nodes metastasis with one of nodal
size >4 cm. In addition, if a patient could not accept a delay
in radiation simulation, we also assigned him/her to receive
NACT.
To be eligible, all patients had to receive study-defined
chemotherapy regimen with no distant metastasis and
no concurrent malignancies. Patients who had no subsequent clinical follow-up data, did not receive tumor
board-defined treatment options or died during chemotherapy and/or radiotherapy treatment period were excluded from the current study.
The study was approved by the Institutional Review
Board of National Cheng Kung University Hospital and
preceded according to the Helsinki Declaration.
Treatment
For patients receiving NACT, the study-defined neoadjuvant chemotherapy consisted of MEPFL regimen (mitomycin 8 mg/m2, epirubicin 60 mg/m2, and cisplatin
60 mg/m2 on day 1 and 5-fluorouracil [5-FU] 450 mg/m2
plus leucovorin 30 mg/m2 on day 8, 3-week cycle for
3 cycles) or weekly P-FL regimen (cisplatin 60 mg/m2 3-h
infusion alternating with 5-FU 2500 mg/m2 plus leucovorin 250 mg/m2 continuous infusion for 24 h weekly for a
total of 10 weeks) then followed by radiotherapy alone as
defined by previous studies [13,14].
For patients receiving CCRT, we followed the protocol
of Lin et al. (cisplatin 20 mg/m2/day plus fluorouracil 400 mg/m2/day by 96-hour continuous infusion
during weeks 1 and 5 of radiotherapy; PF4 regimen)
or AI-Sarraf M et al. (cisplatin 100 mg/m2 on day 1, 22,
and 43 during radiotherapy; Cis 100 regimen) [10,16].
Chemotherapy modification was permitted at the discretion of the primary treating physician when patients
experienced grade 3 toxicity and the modification was
guided by the designs of the original trials.
Radiotherapy
Intensity Modulated Radiotherapy (IMRT; Clinac iX accelerator, Varian) was equipped in our hospital in 2006.
All patients treated after May 2006 used IMRT technique
except one patient who received radiosurgery boost.
In the 2D method, we used bilaterally opposed fields
with a matched lower anterior neck field first. The bilateral opposing fields were then coned down to the highrisk regions that included nasopharynx after 43.2 Gy to
avoid spinal cord damage. The posterior neck node regions were boosted with 9-12 MeV electron beam. Nasopharyngeal tumor and gross nodes were boosted by 3D
conformal RT or a frameless stereotactic body radiation
therapy (SBRT; Cyberknife) to the planned dose [17].
Among patients receiving IMRT, the inverse planning
software (Eclipse treatment planning system, Varian) was
used. The high-risk clinical target volume (CTV) covered the entire nasopharynx, tumor invasion areas, and
gross nodes. The intermediate-CTV included the suspected nodes plus the involving neck levels. The lowrisk CTV included other lower risk lymphatic regions
for occult micrometastases. The low neck lymphatic regions were treated with the same IMRT plan. Planning
target volumes (PTVs) were created by automated expansion of 3 to 5 mm of all CTVs to account for setup
error. Normal structures, including the parotid glands,
spinal cord, brain stem, optic nerves, and optic chiasm
were also contoured on the treatment plan.
Page 3 of 10
Results
Patient characteristics
All patients had regular follow-up with radiation oncologists at the outpatient clinic. Patients received regular
In the NACT group, six of eight patients (75%) completed the planned three-cycle MEPFL and twenty-nine
Page 4 of 10
No.
No.
Age, years
15.7 - 81.5
22.9 - 73.0
Median
48.2
48.2
Mean
47.9
47.8
CCRT group
(n = 90)
NACT group
(n = 38)
RT Technique
0.95
Range
P-value
NACT group
(n = 38)
P-value
0.667
2D, n (%)
44 (48.9)
17 (44.7)
IMRT, n (%)
46 (51.1)
21 (55.3)
RT Compliance
Gender
0.347
Male
73
81.1 28
73.7
Female
17
18.9 10
26.3
WHO Classification
57 (48 - 81)
0.772
0.941
Type I
4.4
Type II
31
34.4 12
31.6
5.3
Type III
55
61.1 24
63.2
T stage
0.200
T1 to T2
56
62.2 19
50
T3 to T4
34
37.8 19
50
N0 to N1
29
32.2 5
13.2
N2 to N3
61
67.8 33
86.8
N stage
0.029
Overall Stage
0.002
IIB-III
66
73.3 17
44.8
IVA-IVB
24
26.7 21
55.2
NACT group
(n = 38)
No.
No.
Locoregional
12
13.3
23.7
Distant
14a
15.6
21.1
Lung
Bone
Liver
Others
2b
1c
8.3
Re-irradiation
8.3
66.7
33.3
Re-CCRT
41.7
Chemotherapy
41.7
a
One patient had bone and lung metastases concurrently and the other one
had bone, liver and lung metastases simultaneously bone patient developed
mediastinal lymph node metastases and the other one developed para-aortic
lymph node metastases cthe subject developed axillary lymph node metastases.
Page 5 of 10
after treatment (Figure 1A). According to past experience, most NPC patients suffered from disease recurrence in the first 2-3 years while completing radical
therapy for advanced disease control [13,18]. When we
only considered patients who remained disease-free in
the first 2 years for further analysis, compared to those
who received CCRT, patients who received NACT had a
higher risk for recurrence (HR = 2.57, 95% CI:1.02 to
6.47, p =0.046) (Figure 1C). No other clinical parameters, such as gender (p =0.26), histology classification
(p =0.23), clinical T stage (p =0.07), clinical nodal stage
(p =0.44) and clinical stage (p =0.49), had a significant
influence on late disease recurrence.
The 5-year TTLF rate was 85.2% for CCRT and 74.5%
for NACT (p =0.20) and the 5-year TTDF rate was 83.1%
for CCRT and 76.4% for NACT (p =0.56). The KaplanMeier curve did not separate till 2 years in TTLF analysis
(Figure 2A) but not in TTDF analysis (Figure 2B). When
we re-analyzed patients who remained disease-free in first
2 years, patients who received NACT had a higher risk for
developing locoregional failure (HR =6.31, 95% CI: 1.22 to
32.59, p =0.03) but not distant failure (HR =1.87, 95% CI:
0.50 to 6.96, p =0.35). No other clinical parameters, such
as gender, histology classification, clinical T stage, clinical
nodal stage and clinical stage had a significant influence on
late locoregional failure or distant failure (Table 6).
Table 4 Univariate Cox regression analysis for disease free survival and overall survival
DFS
Event
OS
HR
95% CI
P-value
Event
33
1.00
0.32-1.47
0.33
0.35
1.00
HR
95% CI
P-value
0.11-1.14
0.08
Gender
Male (n = 101)
41
1.00
Female (n = 27)
0.69
1.00
WHO Classification
Type I (n = 6)
Type II (n = 43)
17
0.63
0.18-2.14
0.46
12
1.59
0.21-12.22
0.66
29
0.61
0.19-2.02
0.42
23
1.68
0.23-12.47
0.61
T1-2 (n = 75)
21
1.00
13
1.00
T3-4 (n = 53)
28
2.19
23
2.9
1.47-5.73
0.002
N0-1 (n = 34)
11
1.00
10
1.00
N2-3 (n = 94)
38
1.38
26
1.06
0.49-2.13
0.95
IIB/III (n = 83)
23
1.00
15
1.00
IVA/IVB (n = 45)
26
2.70
21
3.00
1.54-5.83
0.001
31
1.00
25
1.00
18
1.38
11
1.04
0.51-2.12
0.91
cT
1.24-3.85
0.007
0.70-2.70
0.35
cN
Stage
1.54-4.74
0.0006
0.77-2.46
0.28
Treatment
DFS, disease free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval.
Page 6 of 10
Table 5 Univariate Cox regression analysis for locoregional failure and distant failure
Locoregional failure
Event
HR
Distant failure
95% CI
P-value
Event
20
1.00
0.41-3.04
0.83
0.36
1.00
HR
95% CI
P-value
0.08-1.53
0.16
Gender
Male (n = 101)
16
1.00
Female (n = 27)
1.11
Type I (n = 6)
1.00
Type II (n = 43)
0.98
0.12-7.82
0.98
0.75
0.09-6.21
0.79
12
0.83
0.11-6.39
0.86
15
1.05
0.14-7.94
0.96
T1-2 (n = 75)
1.00
10
1.00
T3-4 (n = 53)
12
2.11
12
1.90
0.82-4.39
0.14
1.00
19
2.43
0.72-8.24
0.15
10
1.00
12
2.62
1.13-6.08
0.02
14
1.00
1.29
0.54-3.08
0.56
WHO Classification
cT
0.89-5.02
0.09
0.44-3.29
0.72
cN
N0-1 (n = 34)
1.00
N2-3 (n = 94)
16
1.20
IIB/III (n = 83)
1.00
IVA/IVB (n = 45)
12
2.84
12
1.00
1.75
Stage
1.19-6.77
0.02
0.74-4.16
0.20
Treatment
Discussion
For locally advanced NPC, the present study demonstrated that both NACT and CCRT resulted in similar
outcomes in terms of 5-year DFS and OS, despite that
more patients with advanced nodal disease (N2-N3,
86.8% vs 67.8%, p =0.029) and advanced overall clinical
stage (stage IVA-IVB, 55.2% vs 26.7%, p =0.002) enrolled
in NACT group. In addition, our study also showed that
for patients who were disease-free in the first two years
after the completion of treatment, those who received
NACT experienced poorer late locoregional control
Page 7 of 10
Figure 1 Kaplan-Meier curves of disease free survival and overall survival. Kaplan-Meier curves of disease free survival (A) and overall survival
(B) for patients in NACT group (red) in comparison with CCRT group (black). Patients without recurrence or death in first 2 years were further
analyzed and disease free survival (C) and overall survival (D) curve as illustrated.
Figure 2 Kaplan-Meier curves of time to locoregional failure and time to distant failure. Kaplan-Meier curves of time to locoregional failure
(A) and time to distant failure (B) for patients in NACT group (red) in comparison with CCRT group (black). Patients without recurrence or death
in first 2 years were further analyzed and time to locoregional failure (C) and time to distant failure (D) curve as illustrated.
Page 8 of 10
Table 6 Univariate Cox regression analysis for locoregional failure and distant failure for subjects without recurrence
or death in the first two years
Locoregional failure
Event
HR
Distant failure
95% CI
P Value
Event
HR
1.00
0.27-7.29
0.68
1.00
95% CI
P Value
Gender
Male (n = 76)
1.00
Female (n = 21)
1.41
1.00
Type II (n = 35)
4.39
0.85-22.62
0.08
0.83
0.21-3.33
0.79
Type I (n = 3)
T1-2 (n = 62)
1.00
1.00
T3-4 (n = 35)
2.47
2.25
0.61-8.41
0.22
N0-1 (n = 27)
1.00
1.00
N2-3 (n = 70)
2.64
1.49
0.31-7.19
0.62
IIB/III (n = 72)
1.00
1.00
IVA/IVB (n = 25)
2.31
0.79
0.16-3.82
0.77
1.00
1.00
6.31
1.87
0.50-6.96
0.35
WHO Classification
cT
0.55-11.05
0.24
0.32-22.02
0.37
cN
Stage
0.52-10.35
0.27
1.22-32.59
0.03
Treatment
Conclusions
In conclusion, our study demonstrated that both CCRT
and NACT are similarly efficacious treatment strategies
in terms of long-term DFS and OS for locally advanced
NPC in Taiwan and possibly in the other Epstein-Barr
viral infection endemic areas. For patients receiving
NACT, a long-term follow-up is recommended because
these patients are more prone to develop locoregional
failure than patients receiving CCRT. It seems that neoadjuvant chemotherapy followed by concurrent chemoradiation therapy can provide the best survival benefit
for LA-NPC but several studies have generated conflicting results and this issue needs further investigation with
a proper study design and patient selection [20,24,25].
The long-term follow-up result from the phase III study
of Xu et al. [22] will provide more direct evidence and
knowledge about the role of NACT for LA-NPC in
NPC-endemic area.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
CJY conceived and designed the study. MWY, WTH, STT, KYC, JRH contributed
materials. CJY, YHW, SYW performed the experiment. JSC, SYW, CJY analyzed
and interpreted the data. SYW, YHW, JSC wrote the manuscript. All authors
read and approved the final manuscript.
Acknowledgement
We thank all physicians who participated in the institutional head and neck
cancer tumor board for their dedication in patient care and Ms. Chen-Lin Lin,
the head and neck cancer case manager of Cancer Center, National Cheng
Kung University Hospital, for her assistance in patient data collection.
Author details
1
Division of Hematology/Oncology, Department of Internal Medicine,
National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. 2Department
of Radiation Oncology, National Cheng Kung University Hospital, College of
Page 9 of 10
Reference
1. Wei WI, Sham JST: Nasopharyngeal carcinoma. Lancet 2005,
365(9476):20412054.
2. Rottey S, Madani I, Deron P, Van Belle S: Modern treatment for
nasopharyngeal carcinoma: current status and prospects. Curr Opin
Oncol 2011, 23(3):254258.
3. Nicholls J: Nasopharyngeal carcinoma: classification and histological
appearance. Adv Anat Path 1997, 4:7184.
4. Geara FB, Sanguineti G, Tucker SL, Garden AS, Ang KK, Morrison WH,
Peters LJ: Carcinoma of the nasopharynx treated by radiotherapy
alone: determinants of distant metastasis and survival. Radiother
Oncol 1997, 43(1):5361.
5. Langendijk JA, Leemans CR, Buter J, Berkhof J, Slotman BJ: The additional
value of chemotherapy to radiotherapy in locally advanced nasopharyngeal
carcinoma: a meta-analysis of the published literature. J Clin Oncol 2004,
22(22):46044612.
6. O'Sullivan B: Nasopharynx cancer: therapeutic value of chemoradiotherapy.
Int J Radiat Oncol Biol Phys 2007, 69(2 Suppl):S118121.
7. Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M,
Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP, MAC-NPC
Collaborative Group: Chemotherapy in locally advanced nasopharyngeal
carcinoma: an individual patient data meta-analysis of eight
randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 2006,
64(1):4756.
8. Zhang L, Zhao C, Ghimire B, Hong MH, Liu Q, Zhang Y, Guo Y, Huang YJ,
Guan ZZ: The role of concurrent chemoradiotherapy in the treatment of
locoregionally advanced nasopharyngeal carcinoma among endemic
population: a meta-analysis of the phase III randomized trials. BMC Cancer
2010, 10:558.
9. Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R, Siu L, Ng WT,
Sze WK, Au GK, Law SC, O'Sullivan B, Yau TK, Leung TW, Au JS, Sze WM,
Choi CW, Fung KK, Lau JT, Lau WH: Randomized trial of radiotherapy
plus concurrent-adjuvant chemotherapy vs radiotherapy alone for
regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst
2010, 102(15):11881198.
10. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA,
Adams G, Sakr WA, Schuller DE, Ensley JF: Chemoradiotherapy versus
radiotherapy in patients with advanced nasopharyngeal cancer: phase III
randomized Intergroup study 0099. J Clin Oncol 1998, 16(4):13101317.
11. Chua DTT, Ma J, Sham JST, Mai HQ, Choy DTK, Hong MH, Lu TX, Min HQ:
Long-term survival after cisplatin-based induction chemotherapy and
radiotherapy for nasopharyngeal carcinoma: A pooled data analysis of
two phase III trials. J Clin Oncol 2005, 23(6):11181124.
12. Ma BB, Chan AT: Recent perspectives in the role of chemotherapy in the
management of advanced nasopharyngeal carcinoma. Cancer 2005,
103(1):2231.
13. Hong RL, Ting LL, Ko JY, Hsu MM, Sheen TS, Lou PJ, Wang CC, Chung NN,
Lui LT: Induction chemotherapy with mitomycin, epirubicin, cisplatin,
fluorouracil, and leucovorin followed by radiotherapy in the treatment
of locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001,
19(23):43054313.
14. Lin JC, Jan JS, Hsu CY, Jiang RS, Wang WY: Outpatient weekly neoadjuvant
chemotherapy followed by radiotherapy for advanced nasopharyngeal
carcinoma: high complete response and low toxicity rates. Br J Cancer
2003, 88(2):187194.
15. Greene F, Page D, Fleming I, Fritz A, Balch CM, Haller DG, Morrow M: AJCC
Cancer Staging Manual. 6th edition. Berlin, Heidelberg, New York, London,
Paris, Tokyo and Hong Kong: Springer-Verlag; 2002.
16. Lin JC: Phase III study of concurrent chemoradiotherapy versus
radiotherapy alone for advanced nasopharyngeal carcinoma:
positive effect on overall and progression-free survival. J Clin Oncol
2003, 21(4):631637.
Page 10 of 10
17. Chen HH, Tsai ST, Wang MS, Wu YH, Hsueh WT, Yang MW, Yeh IC, Lin JC:
Experience in fractionated stereotactic body radiation therapy boost for
newly diagnosed nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys
2006, 66(5):14081414.
18. Lee AW, Foo W, Law SC, Poon YF, Sze WM, O SK, Tung SY, Chappell R,
Lau WH, Ho JH: Recurrent nasopharyngeal carcinoma: the puzzles of
long latency. Int J Radiat Oncol Biol Phys 1999, 44(1):149156.
19. Chan AT, Gregoire V, Lefebvre JL, Licitra L, Felip E, Group E-E-EGW:
Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for
diagnosis, treatment and follow-up. Ann Oncol 2010, 21(Suppl 5):v187189.
20. Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, Yu BK, Chiu SK, Kwan
WH, Ho R, Chan I, Ahuja AT, Zee BC, Chan AT: Randomized phase II trial of
concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel
and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol 2009,
27(2):242249.
21. Komatsu M, Tsukuda M, Matsuda H, Horiuchi C, Taguch T, Takahashi M,
Nishimura G, Mori M, Niho T, Ishitoya J, Sakuma Y, Hirama M, Shiono O:
Comparison of concurrent chemoradiotherapy versus induction
chemotherapy followed by radiation in patients with nasopharyngeal
carcinoma. Anticancer Res 2012, 32(2):681686.
22. Xu T, Hu C, Zhu G, He X, Wu Y, Ying H: Preliminary results of a phase III
randomized study comparing chemotherapy neoadjuvantly or
concurrently with radiotherapy for locoregionally advanced
nasopharyngeal carcinoma. Med Oncol 2012, 29(1):272278.
23. Kwong DL, Nicholls J, Wei WI, Chua DT, Sham JS, Yuen PW, Cheng AC,
Wan KY, Kwong PW, Choy DT: The time course of histologic remission
after treatment of patients with nasopharyngeal carcinoma. Cancer 1999,
85(7):14461453.
24. Fountzilas G, Ciuleanu E, Bobos M, Kalogera-Fountzila A, Eleftheraki AG,
Karayannopoulou G, Zaramboukas T, Nikolaou A, Markou K, Resiga L,
Dionysopoulos D, Samantas E, Athanassiou H, Misailidou D, Skarlos D,
Ciuleanu T: Induction chemotherapy followed by concomitant radiotherapy
and weekly cisplatin versus the same concomitant chemoradiotherapy in
patients with nasopharyngeal carcinoma: a randomized phase II
study conducted by the Hellenic Cooperative Oncology Group
(HeCOG) with biomarker evaluation. Ann Oncol 2012, 23(2):427435.
25. Huang PY, Cao KJ, Guo X, Mo HY, Guo L, Xiang YQ, Deng MQ, Qiu F,
Cao SM, Guo Y, Zhang L, Li NW, Sun R, Chen QY, Luo DH, Hua YJ,
Mai HQ, Hong MH: A randomized trial of induction chemotherapy
plus concurrent chemoradiotherapy versus induction chemotherapy
plus radiotherapy for locoregionally advanced nasopharyngeal
carcinoma. Oral Oncol 2012, 48(10):10381044.
doi:10.1186/1471-2407-14-787
Cite this article as: Wu et al.: Comparison of concurrent
chemoradiotherapy versus neoadjuvant chemotherapy followed
by radiation in patients with advanced nasopharyngeal carcinoma in
endemic area: experience of 128 consecutive cases with
5 year follow-up. BMC Cancer 2014 14:787.