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Context: Regional epidemiological data regarding the epidermal growth factor receptor (EGFR) mutation status in non-small-cell lung cancers (NSCLC) is an unmet need from the eastern part of India., Aims: To report the incidence of EGFR mutation and its correlation with the phenotypical characteristics, in NSCLC patients from Kolkata., Subjects and Methods: NSCLC patients, with adenocarcinoma histology, whose tissues had been tested for EGFR mutational status between March 2014 and February 2017, were considered for this study. The testing methods used were Real-time-based amplification refractory mutation system, polymerase chain reaction (ARMS PCR), PCR and gene sequencing, and cell-free DNA (CTDNA). Clinical characteristics and treatment details were collected from the patient's medical records in a de-identified manner., Statistical Analysis Used: Data were analyzed using simple descriptive statistical methods., Results: Between March 2014 and February 2017, 108 samples were tested and two were deemed inadequate for reporting. Of the remaining 106 patients, 65 (61.3%) were males, and 41 (38.6%) were females. Median age was 56 years (42-72), 59 years for males and 52 years for females. 73.6% were nonsmokers. 87.7% tests were done using the real-time ARMS-PCR; 9.4% underwent PCR and gene sequencing and 2.8% using CT-DNA. Of 106 patients, 35 (33%) patients were found to be EGFR mutation positive. Ratio of male:female was 16 (45.7%):19 (54.3%). Ratio of nonsmoker: smoker was 30 (85.7%):5 (14.3%). 18 patients had exon 19 deletion (51.4%), 15 had L858R exon 21 mutation (42.9%), 1 patient (2.9%) had mutation in S7681 exon 20 along with L858R 21 and one patient (2.9%) had a T790m mutation without any other detectable EGFR mutation., Conclusions: The incidence of EGFR mutation in NSCLC is 33% from Kolkata and is typically more common in females and nonsmokers.

Background: The aim of this study was to establish characteristics of lung cancer patients diagnosed at a tertiary care hospital in Bangalore., Methods: The retrospective study was undertaken comprising of 202 patients diagnosed of advanced lung cancer in a tertiary care setting. Data was analyzed to identify patients' characteristics, smoking history, tumor histology, stage of the disease, treatment received, and survival rates., Results: Among the 202 patients diagnosed, 134 were males, and 68 were females. Tumor histology testing revealed that 168 patients had adenocarcinoma, 24 patients had squamous carcinoma, 5 patients had small cell carcinoma, and 5 patients were poorly differentiated carcinoma. Among the patients of adenocarcinoma, complete response, partial response (PR), stable disease, and progressive disease (PD) were seen in 0.6%, 52%, 17%, and 23.2% of the patients respectively. The median progression-free survival (PFS) for first-line treatment was 6.5 months; the highest PFS was seen with nab-paclitaxel/platinum combination. The mean overall survival was 11.7 months and the highest OS of 12.3 months with gefitinib therapy. In the squamous subset of patients, PR was observed in fourteen patients, of which five patients were treated with nab-paclitaxel/platinum. The mean overall survival of 10.5 months and mean PFS was 6.2 months with the highest PFS of 6.8 months were seen with weekly nab-paclitaxel. Among the small cell lung cancer patients, nine were treated with etoposide/platinum regimen with a compliance of 6 cycles. Three patients had a PR, and one had a PD on etoposide/platinum regimen. The mean overall survival in these patients was 4.6 months.

Context: There are very limited data regarding clinical, radiological and etiological aspects of malignant pleural effusion (MPE) from Eastern India., Aims: To review natural history, clinical features, radiological features and etiology of MPEs., Setting and Design: Hospital based cross-sectional descriptive study., Materials and Methods: We had reviewed166 diagnosed cases of MPEsregarding demography; clinical, radiological and biochemical characteristics, diagnostic modalities and etiologies., Results: Out of 166 patients, 72.89% were males and 27.11% were females. Mean age of presentation among males was 64.3 ± 12.7 and among females was 52.5 ± 14.8. Most common presenting symptom was dry cough (87.9%) and most common presenting sign was clubbing (54.5%). Massive effusion was found in 45.78% of cases. Pleural fluid macroscopic appearance was haemorrhagic in 54.82% of cases. Mean adenosine deaminase activity in MPE was 24.05 U/L. Mean pleural fluid/serum protein ratio was 0.65, mean pleural fluid/serum lactate dehydrogenase ratio was 1.01. Most of the cases (84.94%) were diagnosed by pleural fluid cytology for malignant cells. Primary cancer was diagnosed in 136 (81.93%) cases; among which 121 (88.97%) cases were lung cancers, among which adenocarcinoma (52.89%) was the most common histology., Conclusions: Pleural fluid cytologies for malignant cells are usually sufficient to diagnose MPE in nearly 85% of cases and in remaining cases if thoracoscopyis not available, blind pleural biopsy can be helpful. The most common primary in cases of MPE is lung cancer with adenocarcinoma being the commonest culprit.

Background: Lung cancer continues to remain as one of the leading causes of morbidity and mortality worldwide, despite the decreasing trends in smoking prevalence worldwide. An earlier study from the authors' institute reported the increasing trends of "Nonsmoking associated lung cancers.", Materials and Methods: All consecutive histologically confirmed patients with lung cancer who presented to the outpatient department over a year (November 2014-October 2015) were included in this current prospective study., Results: Seven hundred and thirteen patients presented with clinicoradiologically suspicious findings of lung cancer in the said period. A pathological confirmation of lung cancer could be ascertained in 495 patients, and this cohort was further analyzed. The mean age of presentation was 57.76 years; the male to female ratio was approximately 2.5:1. Interestingly, 55.35% of the patients were nonsmokers. Adenocarcinoma (63%) was the predominant histology. Never smokers, both among men (P = 0.02) and women (P = 0.001), presented more frequently with adenocarcinoma histology. Further, 84.9% (45/53) of rural and 76.1% (19/25) of urban women who were never smokers reported exposure to indoor air pollution (secondhand smoke/fuel used for cooking purposes) which was significantly associated with adenocarcinoma histology., Conclusion: Our study confirmed our initial observation of the changing epidemiology of lung cancer in the Indian subcontinent, paralleling the global trends of rise in adenocarcinoma. Lung cancer in never smokers outnumbering that among smokers was another interesting observation. The take-home message for both the clinicians as well as the policymakers is to study factors beyond tobacco exposure to understand the direction of the current lung cancer epidemic.

Background: Adenocarcinoma is the most prevalent histological type of lung cancer (LC) in developed countries while squamous cell carcinoma (SqCC) has so far been the most common type at our center. Herein, we report our continued assessment of the epidemiological trend of LC aimed at determining any change in the histological distribution., Methods: Retrospective analysis involving all consecutive newly diagnosed LC patients over a 4-year period (March 2011-February 2015). Demographic characteristics, histology, and staging data for current data set were compared with our previously published data (2008-2011). As before, smoking index (SI) was used to group patients as never (SI = 0), light (SI = 1-100), moderate (SI = 101-300), and heavy (SI ≥301) smokers., Results: Majority of 1301 patients had advanced disease (Stages IIIB = 30.1%; IV = 53.3%), were males (82.3%) and current/ex-smokers (76.9%). Adenocarcinoma and SqCC (36.4% each) were equally prevalent. As compared to our previous study, adenocarcinoma increased (36.4% vs. 27.5%) and nonsmall cell lung cancer-not otherwise specified (NSCLC-NOS) decreased (5.1% vs. 10.9%) significantly (P < 0.001). The current study had more heavy smokers (68.3% vs. 61.1%; P = 0.013) and median SI was also higher (500 vs. 400; P = 0.001). Among SI-based groups, significant differences were observed for age, gender, body mass index, histology, TNM stage, and metastatic disease distribution., Conclusion: Reduction in NSCLC-NOS has led to adenocarcinoma and SqCC being equally prevalent at our center in North India despite an increase in heavy smokers. Accurate histological NSCLC subtyping is necessary for optimal epidemiological assessment.

XRCC1 is a scaffold protein that provides for interaction of DNA polymerase, DNA ligase and damaged DNA. Genotyping was done for the five non-synonymous and synonymous variants of XRCC1 i.e. XRCC1, Arg 194 Trp, Pro 206 Pro, Arg 280 His, Arg 399 Gln, Gln 632 Gln. Logistic regression analysis was used to analyze the association of XRCC1 with lung cancer, followed by data mining analysis which included both Multi-dimensionality reduction (MDR) and Classification and Regression tree (CART) analysis so as to find possible interaction between SNPs on XRCC1 gene. Statistical analysis revealed XRCC1 Gln 632 Gln (OR=2.67, p=<0.001) depicted an overall high risk towards lung cancer. Histological subdivision revealed carriers of mutant genotype in case of XRCC1 Arg 399 Gln imposed a protective effect towards SQCC subtype. Likewise, mutant genotype in XRCC1 Pro 206 Pro implied a protective effect for SCLC subtype (OR=0.29, p=0.0017) on the contrary XRCC1 Gln 632 Gln showed a high risk in SQCC diseased group (OR=4.16, p=<0.0001). Combination of XRCC1 Gln 632 Gln with other SNPs revealed XRCC1 Gln 632 Gln with Arg 194 Trp (OR=2.10, p=0.03) and Pro 206 Pro (OR=5.6, p<0.0004) increased an overall risk towards lung cancer. Haplotype analysis illustrated haplotype block 11 (CGAGG) carrying minor allele for XRCC1 206 was associated with the highest risk towards lung cancer on the contrary block 4 (CAGAG) carrying mutant allele for XRCC1 399 significantly decreased the risk. Multi-dimensionality reduction (MDR) results showed the three factor model comprising XRCC1 206, 632, 280 as the best model (CVC=10, prediction error=0.34). Further Classification and Regression tree (CART) analysis revealed terminal node 1 carrying mutant of XRCC1 632 and wild type of XRCC1 280 represented the highest risk group. Our results demonstrated high order interaction between SNPs of XRCC1 gene. This study depicted a positive association of XRCC1 Gln 632 Gln towards lung cancer, however XRCC1 Arg 399 Gln, Arg 194 Trp showed an overall no effect or protective effect., (Copyright © 2016 Elsevier B.V. All rights reserved.)

ALK gene rearrangement in the lung adenocarcinomas is the second most common (1.6-11.7% of NSCLC) targetable genomic change after EGFR mutations. However, the prevalence and clinicopathological features of ALK-rearranged lung adenocarcinomas from North India are lacking. A total of 240 cases of lung adenocarcinoma were screened for EGFR mutations and for ALK expression. Smoking status, TNM stage, and treatment response were recorded in all cases. Out of 240 cases screened, 37 cases were positive for EGFR mutations and 17 cases (7.08%) showed ALK positivity with immunohistochemistry and break-apart FISH. On excluding 37 EGFR mutation-positive cases, the incidence of ALK-positive adenocarcinoma appears to be higher (17/203 cases, 8.03%). Eight were men and nine were women with mean age of 51.7 years. Majority (62.5%) were non-smokers and had unresectable disease (70.6% stage IV, 17.6% IIIB). The morphological patterns noted were solid (12 cases), papillary (four cases), and micropapillary (one case). Signet ring (two cases) and clear cell change (one cases) were noted. Out of five patients who received crizotinib, three had partial response and two had stable disease. ALK-rearranged lung adenocarcinomas account for a minor proportion of NSCLC with prevalence similar to that reported in literature. However, as contrast to published data in our series, patients were in older age group and had solid and papillary pattern on morphology with an aggressive course., (© 2016 APMIS. Published by John Wiley & Sons Ltd.)

Background: Lung cancer is one of the most common malignant neoplasms worldwide and accounts for more deaths than any other cancer. The clinicopathological profile of lung cancer has shown marked regional and geographical variation., Aims: We aimed to compare the demographic and pathological profile of lung cancer patients from North India with other Indian and International series., Setting and Design: A retrospective study over a period of 5 years from January 2008 to May 2013 was conducted in the Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi., Patients and Methods: A total of 397 newly diagnosed patients with lung cancer from January 2008 to May 2013 were included in the study. The clinical, demographic, and pathological features were reviewed and compared with other major National and International reports. Data were entered and analyzed using SPSS software (SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc., Results: A total of 397 patients (86% men, mean age 57.8 years) were studied. The ratio of men to women was 7.4. Majority of patients (78.3%) were current/previous smokers. Small cell carcinoma was diagnosed in 14.6% (58) of patients while 85.4% (339) had nonsmall cell lung carcinoma (NSCLC). Within NSCLC, the most common histology types were squamous cell carcinoma (30%), followed closely by adenocarcinoma (ADC) (28.3%) and large cell carcinoma (1.7%). Majority (87%) of the patient were staged III and IV. About 30.1% patients received anti-tubercular treatment during the current episode before a diagnosis of lung cancer was made., Conclusion: The clinicopathological profile of lung cancer has undergone noticeable changes over the last four decades, especially in the increase in ADC incidence and their frequent presence in smokers. Lung cancer is often mistreated as tuberculosis in the Indian subcontinent and hence continues to be diagnosed late.

Background: The epidermal growth factor (EGF) plays important roles in non-small cell lung cancer (NSCLC) susceptibility and functional polymorphism in the EGF (+61A/G) gene has been linked to increased risk of NSCLC. This study aimed to evaluate the role of the EGF +61A/G polymorphism in risk of NSCLC adenocarcinoma (ADC) occurrence and survival in an Indian population., Materials and Methods: This case- control study included 100 histopathologically confirmed NSCLC (ADC) patients and 100 healthy controls. EGF (A61G) was genotyped by AS-PCR to elucidate putative associations with clinical outcomes. The association of the polymorphism with the survival of NSCLC patients was estimated by Kaplan-Meier curves., Results: It was found that EGF 61AG heterozygous and GG homozygous genotype is significantly associated with increased risk of NSCLC (ADC) occurrence compared to AA genotype, [OR 2.61 (1.31-5.18) and 3.25 (1.31-8.06), RR 1.51(1.15-2.0) and 1.72 (1.08-2.73) and RD 23.2 (6.90-39.5) and 28.53(7.0-50.1) for heterozygous AG (p=0.005) and homozygous GG (p=0.009)]. Patients homozygous for the G allele exhibited a significantly poor overall survival. The median survival time for patients with EGF 61 AA, AG, and GG genotypes was 10.5, 7.4, and 7.1 months (p=0.02), respectively. NSCLC (ADC) patients with GG + AG exhibited 7.3 months median survival compared to the AA genotype (p=0.009)., Conclusions: The present study revealed that the EGF A61G genotype may be a novel independent prognostic marker to identify patients at higher risk of occurrence and an unfavourable clinical outcome.