Epidemiology and Clinical Trials Unit

Kharghar, India

Epidemiology and Clinical Trials Unit

Kharghar, India
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Murthy V.,Tata Memorial Center | Gurram L.,Tata Memorial Center | Kannan S.,Epidemiology and Clinical Trials Unit | Gandhi M.,Epidemiology and Clinical Trials Unit | And 4 more authors.
Advances in Radiation Oncology | Year: 2017

Purpose: The main objective of this study was to evaluate appropriate doses for elective nodal irradiation (ENI) in head and neck squamous cell carcinoma (HNSCC) patients to optimize the therapeutic ratio. Methods and materials: A matched pair analysis of 2 similar cohorts of HNSCC treated with intensity modulated radiation therapy with different dose prescriptions to the elective nodal regions was conducted. One group received 60 Gy, whereas the other received 50 Gy (ENI60 and ENI50 groups, respectively). Isolated regional recurrences (IRR) and locoregional control were evaluated. Doses received by the parotid and thyroid glands were compared among both groups and were clinically correlated with the trend of salivary function recovery and incidence of hypothyroidism. Results: Of the 110 patients studied, 97 were eligible for analysis after matching based on propensity scores. The 3-year locoregional control rate was similar in ENI60 and ENI50 (78.7% and 77%, respectively; P = .93). There were no IRR in ENI regions in either group. The mean ipsilateral parotid dose in ENI60 was significantly higher compared with ENI50 (42 vs 35.7 Gy, P = .03). There was no significant difference in the mean contralateral parotid doses (32.5 vs 31.7 Gy, P = .6). The mean thyroid doses were high in ENI60 compared with ENI50 (54.7 vs 43.3 Gy, P < .001). A significant difference in ipsilateral parotid salivary excretory fraction ratio at 1 year (P = .03) was observed with quicker recovery of salivary function. The salivary excretory fractions were poorer in the ENI60 group with higher mean parotid doses (P = .009). At 2 years, 26 patients (54%) in the ENI60 group and 13 patients (26.5%) in the ENI50 group developed biochemical hypothyroidism (P = .007). Conclusions: Doses of 50 Gy equivalent are sufficient to sterilize the uninvolved nodal regions because the rates of IRR are extremely low. Using ENI50 results in clinically meaningful reduction in salivary and thyroid toxicity in HNSCC. © 2017 The Authors.


Chinnachamy A.N.,Tata Memorial Hospital | Krishnatry R.,Tata Memorial Hospital | Kannan S.,Epidemiology and Clinical Trials Unit | Mahantshetty U.,Tata Memorial Hospital | And 2 more authors.
Japanese Journal of Clinical Oncology | Year: 2013

Background: Lack of agreement and inconsistency in capturing late bowel toxicity may be a source of error while reporting trials with toxicity endpoints. Documenting baseline inconsistency while scoring toxicity questionnaires (RTOG/EORTC and CTCAE) may be worthwhile. The present study was conducted as a quality assurance measure prior to initiating a randomized trial (PARCER; NCT01279135) that evaluates the impact of image-guided radiation on bowel toxicity. Methods: From August 2010 to July 2011, patients with cervical cancer who underwent pelvic chemoradiation >6 months ago, with controlled disease and any bowel symptom at follow-up, were included. RTOG and CTCAE questionnaires were filled by two blinded observers. Interscale (RTOG vs CTCAE) and interobserver (observer A and B) agreement were evaluated with Spearman's correlation and kappa statistic. Results: Fifty-five patients were included. Twelve patients with symptoms could not be graded by the RTOG scale. Of those graded as asymptomatic on RTOG, distension, vomiting, pain and nausea were identified as the most common symptoms. Amongst these, grade 1, 2 and 3 toxicity was observed in 6, 5 and 1 patient, respectively. The interscale correlation was moderate (Spearman's correlation ρ = 0.56; P = 0.001). High interobserver agreement (92%) was observed within the RTOG scale [kappa (κ) -0.94; 95% CI 0.77-1]. All disagreements were observed while scoring grade 1-2 toxicity. Among CTCAE, agreement was lower with modules such as distension, anorexia, nausea and constipation. Conclusions: High interobserver agreement was observed for both RTOG and most CTCAE subscales; most disagreements were for grade 1-2. Interscale agreement (RTOG and CTCAE) was moderate. Detailed patient interrogation or use of patient-reported-outcome scores while documenting the aforesaid subscales may be worthwhile. © The Author 2013. Published by Oxford University Press. All rights reserved.


Joshi N.N.,Cancer Research Institute | Bhat S.,Cancer Research Institute | Hake S.,Cancer Research Institute | Kale M.,Cancer Research Institute | Kannan S.,Epidemiology and Clinical Trials Unit
International Journal of Immunogenetics | Year: 2014

In an earlier study, the genotypes associated with higher level of transforming growth factor-β1 (TGF-β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro- and anti-inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single-nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL-4 (IL-4 C-590T; rs2243250), IFN-γ (IFN-G A + 874T; rs2430561) and MCP-1 (MCP-1 A-2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL-4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37-0.98) was seen similar to that seen in TGF-B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP-1 or IFN-γ. In individuals positive for three or more alleles associated with higher levels of either pro- or anti-inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF-B1 & IL-4, OR = 0.33, 95% CI 0.12-0.87; for IFN-G & MCP-1, OR = 2.29, 95% CI 0.95-5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti-inflammatory genotypes in the modulation of risk for breast cancer in western Indian women. © 2013 John Wiley & Sons Ltd.


Joshi N.,Cancer Research Institute | Kannan S.,Epidemiology and Clinical Trials Unit | Kotian N.,Cancer Research Institute | Bhat S.,Cancer Research Institute | And 2 more authors.
Human Immunology | Year: 2014

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) -174G>C polymorphism in this cohort (patients. = 182; controls. = 236) suggested a protective role for IL-6 -174C allele associated with the lower expression of the cytokine (OR. = 0.54; 95% CI 0.32-0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) -174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR. = 1.07; 95% CI 1.00-1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR. = 0.73; 95% CI 0.55-0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR. = 0.51; 95% CI. = 0.37-0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR. = 2.51; 95% CI 1.59-3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 -174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians. © 2014 American Society for Histocompatibility and Immunogenetics.


Chopra S.,Advanced Center for Treatment | Krishnatry R.,Tata Memorial Hospital | Dora T.,Advanced Center for Treatment | Kannan S.,Epidemiology and Clinical Trials Unit | And 7 more authors.
British Journal of Radiology | Year: 2015

Objective: This study investigates the correlation between dose-volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer. Methods: From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS® v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL). Results: On univariate analysis, V30 PC$900cm3 (p50.01), V40 PC$750cm3 (p50.03) and V40 TB$280cm3 (p50.03) and use of concurrent chemotherapy (p50.03) predicted grade $II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1-11.1, p50.03] and V30 PC$900cm3 (OR 2.3, 95% CI 1-5.5, p50.05) predicted acute grade $II toxicity. On univariate analysis for late toxicity, SB (V30$190cm3, p50.009; V40$150cm3, p50.03), LB (V15$250cm3, p50.04), V40 PC (V40$750cm3, p50.001) and presence of acute grade $III toxicity (p50.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p50.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index $25 kgm22 (OR 7.3, 95% CI 1.6-31.6, p50.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4-18.1, p50.007). Conclusion: V30 PC$900cm3 and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade $III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities. Advances in knowledge: Study establishes PC thresholds that can minimize both acute and late bowel toxicities. © 2015 The Authors. Published by the British Institute of Radiology.


PubMed | Tata Memorial Center, The Surgical Center, Narayana Health and Epidemiology and Clinical Trials Unit
Type: | Journal: Asia-Pacific journal of clinical oncology | Year: 2016

Surgery is the only modality that offers cure for periampullary adenocarcinoma. However, surgery alone results in failure in 60% of patients. Studies have shown some benefits of chemotherapy in node positive and higher tumor stage patients. We sought to determine the role of adjuvant chemotherapy in early tumors with uninvolved nodes.A retrospective analysis of a prospectively maintained database of patients resected of periampullary tumors from 2007 to 2014 was performed. Patients were studied for adverse risk factors, adjuvant therapy received and the survival.Of 105 patients, 14 patients received adjuvant chemotherapy and 85 were observed. After a median follow-up of over 36 months, the overall 3-year survival was 94.2% in the observed group and 100% in the group that received chemotherapy (P = 0.33), with the 3-year disease-free survival being 81.9% and 90.9%, respectively, (P = 0.477). Serum CA 19-9 levels above 100 U/mL were a poor prognostic factor.This study did not find a benefit with the use of adjuvant chemotherapy, but chemotherapy might improve survival. The benefit for adjuvant chemotherapy needs further confirmation in prospective trials.


Alam H.,Cancer Research Institute CRI | Gangadaran P.,Cancer Research Institute CRI | Bhate A.V.,Cancer Research Institute CRI | Chaukar D.A.,Tata Memorial Hospital TMH | And 9 more authors.
PLoS ONE | Year: 2011

Background: Keratins are cytoplasmic intermediate filament proteins expressed in tissue specific and differentiation dependent manner. Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression, invasion and poor prognosis in human oral squamous cell carcinomas (OSCCs). K8 and K18 undergo several post-translational modifications including phosphorylation, which are known to regulate their functions in various cellular processes. Although, K8 and K18 phosphorylation is known to regulate cell cycle, cell growth and apoptosis, its significance in cell migration and/or neoplastic progression is largely unknown. In the present study we have investigated the role of K8 phosphorylation in cell migration and/or neoplastic progression in OSCC. Methodology and Principal Findings: To understand the role of K8 phosphorylation in neoplastic progression of OSCC, shRNA-resistant K8 phospho-mutants of Ser73 and Ser431 were overexpressed in K8-knockdown human AW13516 cells (derived from SCC of tongue; generated previously). Wound healing assays and tumor growth in NOD-SCID mice were performed to analyze the cell motility and tumorigenicity respectively in overexpressed clones. The overexpressed K8 phospho-mutants clones showed significant increase in cell migration and tumorigenicity as compared with K8 wild type clones. Furthermore, loss of K8 Ser73 and Ser431 phosphorylation was also observed in human OSCC tissues analyzed by immunohistochemistry, where their dephosphorylation significantly correlated with size, lymph node metastasis and stage of the tumor. Conclusion and Significance: Our results provide first evidence of a potential role of K8 phosphorylation in cell migration and/or tumorigenicity in OSCC. Moreover, correlation studies of K8 dephosphorylation with clinico-pathological parameters of OSCC patients also suggest its possible use in prognostication of human OSCC. © 2011 Alam et al.


Chopra S.,Advanced Center for Treatment Research and Education in Cancer | Dora T.,Advanced Center for Treatment Research and Education in Cancer | Chinnachamy A.N.,Tata Memorial Hospital | Thomas B.,Advanced Center for Treatment Research and Education in Cancer | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose The present study investigates relationship between dose-volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. Methods and Materials From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. Results The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. Conclusions V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%. © 2014 Elsevier Inc.


PubMed | Advanced Center for Treatment Research and Education in Cancer, Tata Memorial Hospital and Epidemiology and Clinical Trials Unit
Type: Journal Article | Journal: Brachytherapy | Year: 2015

To investigate the correlation of rectal dose volume metrics with late rectal toxicity after high-dose-rate pelvic interstitial brachytherapy.From October 2009 to November 2012, 50 patients with residual or recurrent cervical cancer were included. Patients received external radiation 50 Gy in 25 fractions over 5 weeks with weekly cisplatin. Rectum and rectal mucosal (RM) contours were delineated retrospectively. RM was defined as the outer surface of the flatus tube inserted at brachytherapy. The dose received by 0.1, 1, 2, 5 cc of rectum, RM, and sigmoid was recorded. Cumulative equivalent dose in 2 Gy (EQD2) for organs at risk was calculated assuming / of 3. Univariate analysis was performed to identify predictors of rectal toxicity.At a median follow-up of 34 months (12-51 months), Grade II and III late rectal toxicity was observed in 9 (18%) and 2 (4%) patients, respectively. On univariate analysis, rectal doses were not significant predictors; however, D 0.1-cc RM dose >72 Gy (p = 0.04), D 1-cc RM dose >65 Gy (p = 0.004), D 2-cc RM dose >62.3 Gy (p = 0.004), and D 5-cc RM dose >60 Gy (p = 0.007) correlated with Grade II toxicity. On probit analysis, the estimated dose in EQD2 for a 10% and 20% risk of rectal toxicity was D 2-cc rectum of 55 and 66 Gy, and RM <55 and 63 Gy, respectively.Limiting 2-cc RM and rectal doses within the proposed thresholds can minimize Grade II toxicity for gynecologic high-dose-rate interstitial brachytherapy.


PubMed | Advanced Center for Treatment Research and Education in Cancer, Tata Memorial Hospital and Epidemiology and Clinical Trials Unit
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2014

The present study investigates relationship between dose-volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer.From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15.The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant.V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%.

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