Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Initial Experience of Head and Neck Cancer Patients Treated in an Oncologist Led Palliative Cancer Care Clinic at a Tertiary Cancer Care Center in Uttar Pradesh: Is the Initiative of a Full-fledged Palliative Care for Cancer Patients Justified.

INTRODUCTION: Poor socioeconomic status and illiteracy attribute to the advanced presentation of head and neck cancer (HNC) patients in India and are candidates for palliation in our setup. We set up a palliative cancer care clinic (PCCC), and an audit of initial 153 HNC patients is presented. AIMS AND OBJECTIVES: To assess the impact of palliative cancer care services. METHODOLOGY: Data of advanced HNC patients suited for palliation were collected to document demography, symptomatology, cancer treatment, and supportive care. RESULTS: One hundred and fifty-three patients were seen during January 2013 to March 2015 in the PCCC. Seventy-two (47%) referral cases were due to disease progression and 81 (53%) due to de novo advanced cases. Median follow-up for this group was 5.3 months. Ninety (59%) cases needed some degree of assistance for their normal activities. Sixty-seven (44%) patients belonged to poor socioeconomic status and 65 (43%) were educated up to equivalent of high school. One hundred and thirty-five (88%) patients had an adequate family support. Pain was the most common presenting symptom in 134 (87%) cases with adequate relief in 112 (84%) patients with another 13 (09%) could not be assessed. Overall median duration of symptoms was 6 months. Cancer-directed therapy was used in 143 (93%) patients. Near the end of life in 47 (73%) out of 63 documented cases, caregivers were psychologically prepared for the inevitable. CONCLUSION: The role of palliative care team in alleviating physical, psychosocial, and emotional issues of patient and family members was significant. PCCC seems to be a feasible working model in our setup.

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population.

Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo-tagging SNP rs7922612 may modify survival outcome of ESCC patients.

Salivary gland tumors: an audit from a tertiary care centre in Northern India.

Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology. Patients underwent surgery, with some receiving adjuvant treatment. Demographic information, treatment interventions, and survival outcomes were analyzed using SPSS software. A total 89 as malignant salivart gland tumours were audited Malignant tumors were predominantly found in the parotid gland, with fewer cases in the minor salivary gland and submandibular gland.The median age of presentation was 47 years, and the majority of patients were male. The study examined various pathological and clinical factors, including tumor stage, nodal status, and the presence of facial palsy. Surgical procedures and histological types of tumors were documented. Adverse histological features like positive margins, lymph node positivity, lympho-vascular invasion, extracapsular spread, and perineural invasion were noted. POSTOP RT was administered to high-risk patients. Most malignant salivary gland tumors were found in the parotid gland, while minor salivary gland tumors were underrepresented in the audit. Surgical practices were diverse. Radiotherapy protocols were relatively standardized. The study found that certain histological features, such as lymph node positivity, margin positivity, lympho-vascular invasion, perineural invasion, and extracapsular spread, were associated with adverse effects on DFS and OS. The findings suggest that specific histological features, including LVI and ECE have emerged as independent prognostic factors for DFS and OS.

Evaluation of common genetic variants in pre-microRNA in susceptibility and prognosis of esophageal cancer.

Genetic variants in micro-RNAs (miRNA) have been shown to affect progression, diagnosis, and prognosis of various malignancies; however, their role in esophageal squamous cell carcinoma (ESCC) susceptibility is controversial. Therefore, we aimed to determine role of common genetic variants in cancer related pre-miRNA in susceptibility and survival outcome of north Indian ESCC patients. We genotyped four common polymorphisms in pre-miRNA: mir-196a-2C>T, mir-146aG>C, mir-499T>C, and mir-423C>A in 289 incident ESCC cases (including 153 follow-up cases) and 309 controls using PCR/PCR RFLP-based methods. Binary logistic regression was applied for risk estimation, while Kaplan-Meier and Cox Regression tests were performed for survival analysis. We observed that none of the pre-miRNA genetic variants were associated with ESCC or its clinical phenotypes independently, however, combined risk genotypes of four pre-miRNA polymorphisms increased risk of ESCC in dose-response manner (Ptrend = 0.011). Specifically, patients with 2-4 risk genotypes of pre-miRNA polymorphisms had 1.4-fold higher risk of ESCC compared to patients with 0-1 risk genotypes (OR = 1.43, 95% CI = 1.02-1.09, P-value = 0.037). The risk was more pronounced in ESCC cases with upper-third esophageal tumors. Moreover, cumulative but not independent effect of risk genotypes of pre-miRNA polymorphisms was observed on survival outcome of ESCC patients. Cases with 2-4 risk genotypes had significantly lower median survival (11.60 vs. 30.2 months) and 2.3-fold greater hazard of death compared to patients with 0-1 risk genotypes. In conclusion, the four studied common pre-miRNA polymorphisms cumulatively affect susceptibility and survival of ESCC patients in north Indian population. © 2012 Wiley Periodicals, Inc.

Modification of risk, but not survival of esophageal cancer patients by esophageal cancer-related gene 1 Arg290Gln polymorphism: a case-control study and meta-analysis.

BACKGROUND AND AIM: Esophageal cancer-related gene 1 (ECRG1) is a novel tumor suppressor gene known to affect matrix remodeling, cell growth, and differentiation. Previous studies in high incidence geographical regions of esophageal cancer (EC) have shown association of ECRG1 Arg290Gln polymorphism with risk of esophageal squamous cell carcinoma (ESCC); however, role of this variant in low incidence region is missing. So, we aimed to evaluate association of ECRG1 Arg290Gln with susceptibility and prognosis of EC patients in low-risk north Indian population. METHODS: The genotyping of ECRG1 Arg290Gln polymorphism was done in 310 incident EC cases (including 179 follow up cases) and 310 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis applied were binary logistic regression for risk estimation and Kaplan-Meier/log-rank test for survival analysis. Meta-analysis of published studies, exploring role of ECRG1 polymorphism in ESCC risk, was carried out using MIX 2.0 software. RESULTS: ECRG1 Arg290Gln polymorphism significantly conferred 1.8-fold increased risk of EC in dominant model (odds ratio = 1.78, 95% confidence interval = 1.27-2.49, P = 0.001). Stratification based on clinical phenotypes showed pronounced risk in cases with ESCC histopathology and middle/lower third tumor locations. No significant interaction with environmental risk factors was observed. Meta-analysis also showed significant association of ECRG1 Arg290Gln polymorphism with risk of ESCC. Kaplan-Meier and Cox regression tests suggested that ECRG1 polymorphism did not modulate survival outcome of ESCC patients. CONCLUSIONS: ECRG1 Arg290Gln polymorphism significantly affects the susceptibility but not the prognosis of ESCC patients in low-risk north Indian population.

Performance evaluation of respiratory motion-synchronized dynamic IMRT delivery.

The purpose of this study was to evaluate the capabilities of DMLC to deliver the respiratory motion-synchronized dynamic IMRT (MS-IMRT) treatments under various dose rates. In order to create MS-IMRT plans, the DMLC leaf motions in dynamic IMRT plans of eight lung patients were synchronized with the respiratory motion of breathing period 4 sec and amplitude 2 cm (peak to peak) using an in-house developed leaf position modification program. The MS-IMRT plans were generated for the dose rates of 100 MU/min, 400 MU/min, and 600 MU/min. All the MS-IMRT plans were delivered in a medical linear accelerator, and the fluences were measured using a 2D ion chamber array, placed over a moving platform. The accuracy of MS-IMRT deliveries was evaluated with respect to static deliveries (no compensation for target motion) using gamma test. In addition, the fluences of gated delivery of 30% duty cycle and non- MS-IMRT deliveries were also measured and compared with static deliveries. The MS-IMRT was better in terms of dosimetric accuracy, compared to gated and non-MS-IMRT deliveries. The dosimetric accuracy was observed to be significantly better for 100 MU/min MS-IMRT. However, the use of high-dose rate in a MS-IMRT delivery introduced dose-rate modulation/beam hold-offs that affected the synchronization between the DMLC leaf motion and target motion. This resulted in more dose deviations in MS-IMRT deliveries at the dose rate of 600 MU/min.

A dose escalated fiducial marker-based image guided radical radiotherapy in locally advanced prostate cancers: A single institute experience from India.

Purpose: Image guided radiotherapy (IGRT) is one of the most commonly used treatment in LAPC. Dose escalation >74 Gy has shown to improve the biochemical control and freedom from failure rate in LAPC.We started treating LAPC patients with dose escalated IGRT in our institute since 2008. We did a retrospective analysis to see the biochemical relapse-free survival, cancer-specific survival, and bladder and rectal toxicity. Methods: A total of 50 consecutive prostate cancer patients were treated with dose escalated IGRT between January 2008 to Dec 2013. Out of these, 37 patients of LAPC were analyzed and their medical records were retrieved. All were biopsy proven adenocarcinoma of prostate with D'Amico high risk category (PSA >20 ng/mL or Gleason score (GS) >7 or T2c-T4). Three gold fiducial markers were placed in the prostate. Patients were immobilized in supine position with either ankle or knee rest. Partial bladder filling and rectum emptying protocol was followed. Clinical target volume (CTV) segmentation was done according to EORTC recommendation. Population based PTV expansion from CTV of 10 mm (cranio-caudal), 10 mm (medio-lateral), 10 mm (anterior) and 5 mm (posterior) was given. In patients with radiologically enlarged pelvic lymph node, whole pelvis intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy/28# followed by prostatic boost 26Gy/13# by IMRT using image guidance. Rest of the patients received prostate only RT to a dose of 76Gy/38# by IGRT. Daily On board KV images were taken and 2D-2D fiducial marker matching was done and shifts were applied on machine before treatment. Biochemical relapse was defined as per Phoenix definition (nadir + 2 ng/mL). Radiation Therapy Oncology Group (RTOG) toxicity grading system was used to document acute and late toxicity. Results: Median age of patients was 66 years. Median pre-treatment PSA was 22 ng/mL. Thirty patients (81%) had T3/T4 lesions and nodal metastasis was seen in 11 (30%). Median GS was 8. Median radiotherapy dose was 76 Gy. Imaging before radiation delivery was done in 19(51%) patients and 100% in 14 (38%) patients. With a median follow up of 6.5 years, 5-year biochemical relapse-free survival (bRFS) and cancer-specific survival (CSS) was 66% and 79% respectively. Mean bRFS and CSS were 71 months and 83 months however Median bRFS and CSS were not reached. Distant metastasis was seen in 8 (22%). RTOG grade III bladder and rectal toxicity was seen in 2 (6%) and 2 (6%) patients respectively. Conclusion: Dose escalated IGRT with fiducial marker positional verification for LAPC is doable in Indian setup provided more emphasis given on daily on-board imaging with rigorous bladder filling and rectal emptying protocol. Long term follow up is needed to assess the effect on distant disease-free survival and CSS.

Role of p53 and p73 genes polymorphisms in susceptibility to esophageal cancer: a case control study in a northern Indian population.

Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16-2.60, P = 0.007) in an allele dose-dependent manner (P(trend) = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18-2.67, P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18-2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04-3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary, p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population.

Dynamic contrast-enhanced magnetic resonance imaging-derived kep as a potential biomarker of matrix metalloproteinase 9 expression in patients with glioblastoma multiforme: a pilot study.

OBJECTIVE: To look for the association of tissue matrix metalloproteinase 9 (MMP-9) expression with dynamic contrast-enhanced magnetic resonance imaging and to see whether these can prognosticate patients with glioblastoma multiforme (GBM). METHODS: Forty-seven patients with GBM underwent dynamic contrast-enhanced magnetic resonance imaging to look for association of its indices with tissue MMP-9 expression using Pearson correlation. Kaplan-Meier survival analysis was performed to study the survival pattern for low-, medium-, and high-tissue MMP-9 expression and kep values. RESULTS: Among perfusion indices, kep, k, and ve significantly correlated with MMP-9 expression. Matrix metalloproteinase 9 expression was found to be best estimated by kep using a quadratic model. The 1-year survival in low-, medium-, and high-tissue MMP-9 and kep groups were 59%, 45%, and 7%, and 59%, 33%, and 15%, respectively. CONCLUSION: The association of kep and MMP-9 expression with survival suggests that kep may be used as imaging biomarker of GBM progression and its prognostication.

Pediatric glioblastoma: clinico-radiological profile and factors affecting the outcome.

BACKGROUND AND PURPOSE: Glioblastoma in the pediatric age group is relatively rare. As a result, it has been difficult to deduce any consistent clinico-radiological and pathological profiles on these patients. Also, the prognostic factors affecting the survival in pediatric glioblastoma are not as well defined as in adults. PATIENTS AND METHODS: In this retrospective series, 65 pediatric patients (age ≤ 18 years) from January 1995 to December 2011 with histopathologically proven diagnosis of intracranial glioblastoma were studied. Clinico-radiological, pathological, treatment, and follow-up data were collected. Progression-free and overall survivals were assessed using the Kaplan-Meier method. RESULTS: The male-to-female ratio was 2.6:1 with a mean age of 13.29 ± 4.53 years (range 2-18 years). Headache with or without vomiting (n = 51, 78 %), followed by seizures (n = 42, 65 %), and focal deficits (n = 31, 47 %) were the leading symptoms. Forty-nine (75 %) patients had tumors located superficially, whereas there were 16 patients with deeply located glioblastomas (25 %). Gross total tumor excision was achieved in 43 (66 %) patients, while the remaining patients had incomplete excision (n = 22, 34 %). Mean follow-up was 17.7 months (range 1.5-119 months). The median progression-free and overall survivals were 10 and 20 months, respectively. Extent of resection was found to be the independent predictor of survival (p value = 0.002). CONCLUSION: Pediatric glioblastomas are associated with longer progression-free as well as overall survivals. Extent of tumor resection is the strongest predictor of survival in pediatric glioblastoma. Hence, an aggressive surgical resection may fetch a better outcome in children with glioblastoma.

Investigating the effect of dose rate and maximum allowable MLC leaf velocity in dynamic IMRT.

The purpose of this study is to analyze the effect of various dose rates (DR) and maximum allowable MLC leaf velocities (MLV) in dynamic Intensity Modulated Radiotherapy (IMRT) planning and delivery of head and neck patients. Five head and neck patients were retrospectively included in this study. The initial dynamic IMRT 'reference plans' were created for all these patients, using a DR of 400 MU/min and MLV of 2.5 cm/s. Additional plans were generated by varying the DR and MLV values. The DR value was varied from 100 to 600 MU/min, in increments of 100 MU/min, for a MLV of 2.5 cm/s. Also the MLV was varied from 0.5 to 3 cm/s, in increments of 0.5 cm, for a DR of 400 MU/min. In order to maintain the prescribed dose to the PTV, the DR was allowed to vary ('beam hold or DR modulation' during delivery) when the MLV was changed and the MLV was allowed to vary when the DR was changed. The mean doses to the PTV as well as parotids, maximum dose of spinal cord and total MU were recorded for analysis. The effect of DR and MLV on treatment delivery was analyzed using the portal dosimetry for all the above plans. The predicted portal dose fluences of the TPS were compared with the measured EPID fluences using gamma evaluation criteria of 2% dose difference and 2 mm distance to agreement. A small proportional increase in OAR doses with DR was observed. Increases to MLV value resulted in decreases of the OAR doses and this effect was considerable for values below 1.5 cm/s. DR and MLV both resulted in no appreciable dose variation to the target. The total MU to deliver the plan increases with increasing DR and decreasing MLV. When comparing portal images derived from the treatment plans with portal images obtained by delivering the treatments, it was observed that the treatments was most reliably delivered when the DRs were set to lower values and when the MLVs were set to higher values.

A comparative study of gemcitabine and cisplatin versus oral capecitabine alone in metastatic gallbladder cancer.

Aims: There is no consensus for palliative chemotherapy regimen in metastatic gallbladder cancer. We did a retrospective study to compare the treatment outcome in patients of metastatic gallbladder cancer treated with either gemcitabine + cisplatin (regimen A) or oral capecitabine (regimen B) alone. Subjects and Methods: A total of 67 patients between January 2015 and September 15 treated with either regimen A or regimen B were retrospectively evaluated. Statistical analysis was done in June 2019. Kaplan-Meir and Log rank test were used to compare survival between two arms. Results: Out of 67 patients, 31/67 (46%) received regimen A, and 36/67 (54%) received regimen B. Male to female ratio was 1:3. About 42% patients in regimen A and 20% in regimen B required palliative stenting. Median number of chemotherapy cycles was 4 in both regimen A (range 1->6) and regimen B (range 1->6). Patients receiving 3 cycles and 6 cycles of chemotherapy in regimen A and regimen B was 68% and 31% versus 70% and 63%, respectively (P = 0.86). Response assessment as any response (complete response + partial response + disease was stable) after 3 cycles and 6 cycles was 71% and 57% (P = 0.20), 44% and 39% (P = 0.29), in regimen A and B, respectively. Median survival was 23 weeks (range 2-106 weeks) in regimen A and 15 weeks (range 4-83 weeks) in regimen B (P = 0.40). Conclusions: The present study shows gemcitabine and cisplatin has nonsignificant better survival compared to oral capecitabine. However, oral capecitabine is more convenient and easy to administer. Studies with larger sample size are needed to further establish the standard chemotherapy guidelines.

Role of survivin gene promoter polymorphism (-31G>C) in susceptibility and survival of esophageal cancer in northern India.

BACKGROUND AND AIM: Survivin is an upregulated inhibitor of apoptosis protein in esophageal cancer (EC), and a promoter region polymorphism (-31G>C) in the survivin gene has been reported as a modulator of gene expression. We aim to explore the role of survivin -31G>C polymorphism in susceptibility and survival of EC patients in northern Indian population. MATERIALS AND METHODS: A case-control study was performed in 500 subjects (250 EC patients and 250 controls), and genotyping was done by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: Survivin CC genotype was found to be significantly associated with EC susceptibility [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.27-4.14; P = 0.006], particularly in males (OR = 4.91; 95% CI = 2.19-11.02; P = 0.0001) having squamous cell carcinoma (SCC) histopathology (OR = 2.4; 95% CI = 1.36-4.21; P = 0.002) at middle third esophagus location (OR = 2.60; 95% CI = 1.40-4.82; P = 0.002). Patients carrying CC genotype were found to have higher susceptibility to lymph node metastasis (OR = 2.82; 95% CI = 1.46-5.48; P = 0.002). However, on survival analysis, no prognostic role of survivin -31G>C polymorphism was detected. In case-only analysis, no gene-environment interaction was observed. CONCLUSION: Survivin promoter region polymorphism (-31G>C) is associated with susceptibility and clinical characteristics but not prognosis of esophageal cancer in northern Indian population.

CASP8 -652 6N del and CASP8 IVS12-19G>A gene polymorphisms and susceptibility/prognosis of ESCC: a case control study in northern Indian population.

BACKGROUND: Caspase8 influences carcinogenesis through regulation of apoptosis, hyperproliferation, and metastasis. Role of genetic variations in caspase8 has been explored in various cancers; however, their predictive and prognostic role in esophageal cancer is poorly understood. METHODS: We investigated the association of two potential caspase8 polymorphisms: CASP8 -652 6N del and CASP8 IVS12-19 G>A polymorphisms with susceptibility and survival of 259 esophageal squamous cell carcinoma (ESCC) cases and 259 cancer-free controls from northern Indian population using PCR/PCR RFLP method. RESULTS: CASP8 IVS12-19 AA genotype was found to be associated with significant increased risk of ESCC (odds ratio (OR) 3.28, 95% confidence interval (CI) 1.04-10.29) specifically in male subjects (OR 3.71, 95% CI 1.01-13.35) with lower third tumor anatomical location (OR 6.00, 95% CI 1.60-22.55). Kaplan-Meier and Cox Regression analysis showed lower median survival (7.13 months vs. 25.21 months) and greater hazard of death (HR 3.40, 95% CI 1.38-7.90) with CASP8 IVS12-19 AA genotype in ESCC cases compared to IVS12-19 GG genotype. However, no association of CASP8 -652 6N del polymorphism with susceptibility and prognosis of ESCC was observed. CONCLUSION: CASP8 IVS12-19 G>A but not CASP8 -652 6N del polymorphism may modulate risk of ESCC and its survival outcome in northern Indian population.

Assessing failure patterns of radical intent radiation strategies in patients with locally advanced carcinoma of the esophagus.

BACKGROUND: Patterns of failure following definitive CRT (dCRT) are different as compared to neoadjuvant chemoradiotherapy (NACRT) with increased locoregional failures documented with dCRT. AIM: To document failure patterns in patients with esophageal carcinoma treated with neoadjuvant and definitive intent radiation strategies. METHODS: Subjects were 123 patients treated with two chemoradiotherapy strategies. Group 1 (n = 99) underwent dose escalated definitive chemoradiotherapy (dCRT), Group 2 (n = 24) received neoadjuvant chemoradiotherapy (NACRT) followed by surgery. Cumulative incidence of locoregional failure (LRF), local failure (LF), regional lymph node failure (RLNF), and distant metastasis (DM) were computed; differences between the groups was evaluated using log rank test. Univariable and multivariable predictors of failure were identified using Cox regression analysis. RESULTS: Cumulative LRF: 64% in Group 1 vs 35% in Group 2 (P = .050). Cumulative LF: 59% in Group 1 vs 12% in Group 2 (P = .000). Cumulative RLNF: 30% in Group 1 vs 24% in Group 2 (P = .592). Most common RLNF: mediastinum for both groups (6% vs 12.5%, respectively). Distant metastasis: 40.4% Group 1 vs 17% Group 2 (P = .129), predominantly lung (Group 1, 5%), and nonregional nodes (Group 2, 8.3%). Univariate analysis identified age ≤50, absence of concurrent chemotherapy, dose ≤50 Gy, and incomplete radiotherapy to predict higher odds of LRF and DM for Group 1; absence of comorbidities predicted for lower odds of LRF for Group 2. Age ≤50 predicted for higher odds of RNLR for Group 1, while absence of comorbidities predicted for lower odds of RNLR in Group 2. Multivariate analysis identified age ≤50, incomplete radiotherapy, and absence of concurrent chemotherapy to predict higher odds of LRF for Group 1. Age ≤50, absence of concurrent chemotherapy predicted higher odds of DM for Group 1. Absence of comorbidity predicted lower odds of LRF in Group 2. CONCLUSION: LRF is common in both groups, with LF being predominant in dCRT as opposed to RNLF in NACRT. Age ≤50, absence of concurrent chemotherapy is a predictor of LRF and DM in dCRT.

A Pilot Study of Perioperative Cisplatin-Capecitabine Chemotherapy With Preoperative Chemoradiation for Resectable Gastric Cancers.

OBJECTIVES: The standard of care for resectable gastric cancers (GCs) includes perioperative chemotherapy (CT) or postoperative chemo/chemoradiotherapy (CRT) strategies. Poor treatment compliance postsurgery suggests that intensified surgical adjuvant treatment is more likely deliverable preceding surgery and, therefore, the safety and efficacy of perioperative cisplatin-capecitabine (CX) with preoperative chemoradiation (preopCRT) were ascertained. MATERIALS AND METHODS: Between January 2017 and December 2018, 28 potentially resectable locally advanced GC patients were offered neoadjuvant CT-2 cycles of CX at 3-weekly intervals, followed by preopCRT 45 Gy/25 fractions/5 weeks and concurrent capecitabine, followed by surgical resection and 3 adjuvant cycles of CX. RESULTS: Neoadjuvant CT was commenced in 28 patients (100%), preopCRT in 18 patients (64%), and surgery performed in 13 patients (46%). At each treatment step, decreasing patient numbers were due mainly to disease progression (12 [43%]) or other reasons, including (3 [11%]) from treatment-related toxicity. The R0 resection rate was 92% (12/13); a median of 18 nodes was obtained after D2 nodal clearance in 92% (12/13). There were 20%/4%/4% grade 3/4/5 toxicities. The median radiotherapy dose/duration was 45 Gy/5.4 weeks. Adjuvant CT was started in 11 patients (39%) and the third cycle was received by 7 patients (25%). No tumor (ypT0N0) was noted in 23% of the operated patients (3/13), or 11% of the intention-to-treat population (3/28). The median, 1-year, and 2-year survivals were 12 months, 53%, and 32%, respectively. CONCLUSIONS: Intensified preoperative treatment is doable in relatively unselected advanced GC patients in real-world settings of a public-sector hospital from a low-middle-income country. Disease progression during preoperative therapy allows patients destined for early clinical evidence of disease dissemination to avoid futile surgery, as opposed to a surgery-first strategy, without an overt increase in surgical morbidity or mortality, with encouraging R0 resection rates.