Papers by Balakrishnan Rajan
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The British Journal of Radiology, 1997
Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local co... more Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.
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Indian Journal of Medical and Paediatric Oncology, 2014
This consensus statement was produced along with the gastric cancer discussions as stomach is the... more This consensus statement was produced along with the gastric cancer discussions as stomach is the most common site for gastrointestinal stromal tumor (GIST). The recommendations apply to treatment of GIST.Evaluation of a patient with newly diagnosed GIST should include essential tests: A standard white light endoscopy with 6-8 biopsies (c-KIT testing on immunohistochemistry) from the tumor for confirmation of the diagnosis, a computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal function tests and liver function tests. Endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI)/positron emission tomography (PET)-CT are not recommended for all patients.For localized and resectable disease, surgery is recommended. The need for adjuvant treatment with imatinib would be guided by the risk stratification on the histopathological analysis of the resected specimen.For localized but borderline resectable tumors, upfront surgery may be considered only if complications due to the tumor are present such as major bleeding or gastric outlet obstruction. In all other patients, neoadjuvant imatinib should be considered to downstage the disease followed by surgery (with a curative intent, if feasible) in those with stable or partial response. This may be followed by adjuvant imatinib. In those patients with a poor response, further imatinib with dose escalation or sunitinib may be considered.Patients with metastatic disease must be assessed for treatment with imatinib as first-line therapy followed by sunitinib as second-line therapy versus best supportive care on an individual basis.
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Physica Medica, 2011
To start total body irradiation (TBI) treatments, physical parameters are measured for a magna fi... more To start total body irradiation (TBI) treatments, physical parameters are measured for a magna field irradiation. 6 MV photon beam from Clinac 600 CD linear accelerator (Varian, USA) with fully opened collimator at 45° and gantry at 270° provided a diamond shaped magna field with diagonal dimension 224 cm at 4.0 m source skin distance (SSD). The flatness of the radiation field was measured in the presence of locally designed acrylic beam spoiler and beam flatness filter. Central Axis Depth dose data (CADD), tissue maximum ratios and entrance dose pattern are measured using large phantoms. Methods for clinical dose estimation using semi-conductor diodes and TLD were standardized. PVC beam flattener at the shielding tray position and the presence of acrylic beam spoiler in the radiation field provided a flatness of 100.15% ± 0.44% compared to open beam flatness 101.6 ± 1.5%. A reduction of 2% in percentage depth dose was observed at 10 cm depth in the presence of 15 mm acrylic beam spoiler. However, no changes are observed in the TMRs with presence of beam spoiler. The measured ionization ratios clearly showed change of beam quality with the introduction of beam spoiler. The presence of 15 mm beam spoiler ensured entrance dose 100% at skin and remaining unchanged within 1% upto a depth of 10 mm. Phantom measurements show good agreement between calculated and measured doses. The paper recommends use of modified CADD parameters for treatment planning, if calibration of output is carried out in the presence of beam spoiler.
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Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
Metabolic activation and inactivation of potential genotoxic agents occur by Phase I and Phase II... more Metabolic activation and inactivation of potential genotoxic agents occur by Phase I and Phase II enzymes in multiple interactions. An expanding body of literature demonstrates that ethnic differences in breast cancer incidence may be partly caused by host genetic factors particularly genetic polymorphisms of these carcinogen-metabolizing enzymes. The present case-control study aimed at identification of such low penetrance breast cancer susceptibility genes in 224 Indian women and to investigate the potential effects of their polymorphisms on sporadic breast cancer risk. The main objective of the study was to evaluate the effects of genetic polymorphisms of the xenobiotic metabolizing genes CYP1A1, GSTM1 and GSTT1 on breast cancer risk by PCR-RFLP and DNA sequencing. Our results showed a significant association between CYP1A1 m1, m2 polymorphisms and breast cancer risk; however there was a lack of association between GSTM1 null deletion and breast cancer. The associations of CYP1A1, GSTM1 and GSTT1 genotypes with breast cancer risk were more pronounced among the pre-menopausal patients. Combined genotype analysis revealed the CYP1A1 m2 ValVal-GSTM1 homozygous null deletion genotype combinations to be associated with the highest risk of breast cancer (OR=10.3, 95% CI=1.2-86.1). Correlations with clinicopathological factors and treatment outcome were also analyzed for predicting disease free survival by univariate and multivariate analysis. Significant differences in disease free survival between the wild and polymorphic genotypes were observed only for CYP1A1 m2, GSTT1 genotypes. Our results based on the analysis of functionally relevant polymorphisms in these low penetrance genes may provide a better model that would exhibit additive effects on individual susceptibility to breast cancer. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening and therapeutic intervention in breast cancer. Hence, the present study may provide strong supportive evidence for genetic interactions in the etiology of breast cancer.
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International Journal of Radiation Oncology*Biology*Physics, 1999
To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high g... more To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.
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International Journal of Radiation Oncology*Biology*Physics, 1997
To assess the frequency, mode of presentation, treatment, and outcome of acute complications in p... more To assess the frequency, mode of presentation, treatment, and outcome of acute complications in patients with craniopharyngioma around the time of radiotherapy. A review was made of 188 patients with craniopharyngioma treated with conservative surgery and external beam radiotherapy at the Royal Marsden Hospital between 1950 and 1992. Twenty six (14%) (95% confidence interval: 9-19%) patients with craniopharyngioma developed acute deterioration immediately before, during and 2 months after radiotherapy with visual deterioration (19 patients), hydrocephalus (7 patients), and global deficit (7 patients). Cystic enlargement with or without hydrocephalus was the most common cause of deterioration. No patient or disease characteristics were predictive of deterioration on univariate or multivariate analysis. Eighteen patients had surgical intervention at the time of deterioration and survived the immediate period. Six of seven patients who did not have surgical intervention died. All patients who survived the postcomplication period completed the full course of external beam radiotherapy. The 10-year progression-free survival of 162 patients without deterioration was 86%, and of 18 patients with acute deterioration who recovered after surgery, 77%. Patients with craniopharyngioma develop acute deterioration around the time of radiotherapy owing to cystic enlargement and/or hydrocephalus which does not represent tumor progression. Early recognition and appropriate surgical treatment followed by conventional full-dose radiotherapy are associated with good long-term outcome.
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International Journal of Cancer, 2009
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International Journal of Cancer, 2008
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Health Physics, 2009
The coastal belt of Karunagappally, Kerala, India, is known for high background radiation (HBR) f... more The coastal belt of Karunagappally, Kerala, India, is known for high background radiation (HBR) from thorium-containing monazite sand. In coastal panchayats, median outdoor radiation levels are more than 4 mGy y-1 and, in certain locations on the coast, it is as high as 70 mGy y-1. Although HBR has been repeatedly shown to increase the frequency of chromosome aberrations in the circulating lymphocytes of exposed persons, its carcinogenic effect is still unproven. A cohort of all 385,103 residents in Karunagappally was established in the 1990's to evaluate health effects of HBR. Based on radiation level measurements, a radiation subcohort consisting of 173,067 residents was chosen. Cancer incidence in this subcohort aged 30-84 y (N = 69,958) was analyzed. Cumulative radiation dose for each individual was estimated based on outdoor and indoor dosimetry of each household, taking into account sex- and age-specific house occupancy factors. Following 69,958 residents for 10.5 years on average, 736,586 person-years of observation were accumulated and 1,379 cancer cases including 30 cases of leukemia were identified by the end of 2005. Poisson regression analysis of cohort data, stratified by sex, attained age, follow-up interval, socio-demographic factors and bidi smoking, showed no excess cancer risk from exposure to terrestrial gamma radiation. The excess relative risk of cancer excluding leukemia was estimated to be -0.13 Gy-1 (95% CI: -0.58, 0.46). In site-specific analysis, no cancer site was significantly related to cumulative radiation dose. Leukemia was not significantly related to HBR, either. Although the statistical power of the study might not be adequate due to the low dose, our cancer incidence study, together with previously reported cancer mortality studies in the HBR area of Yangjiang, China, suggests it is unlikely that estimates of risk at low doses are substantially greater than currently believed.
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Breast Cancer, 2003
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Clinical Oncology, 1992
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Papers by Balakrishnan Rajan