Introduction: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. Methods: Here, we report efficacy and updated safety data from primary efficacy analysis of the ASCEND-8 study. Key secondary endpoints were overall response rate and duration of response, assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors 1.1. Results: In total, 306 patients were randomized to ceritinib 450-mg fed (n ¼ 108) or 600-mg fed (n ¼ 87) or 750-mg fasted (n ¼ 111), of which 304 patients were included in safety analysis and 198 treatment-naive patients (ALK receptor tyrosine kinase [ALK]-positive by immunohistochemistry) were included in the efficacy analysis (450-mg fed [n ¼ 73], 600-mg fed [n ¼ 51], and 750-mg fasted [n ¼ 74]). The BIRC-assessed overall response rate was 78.1% (95% confidence interval [CI]: 66.9-86.9), 72.5% (95% CI: 58.3-84.1), and 75.7% (95% CI: 64.3-84.9), respectively; and the median duration of response (months) by BIRC was not estimable (NE) (95% CI: 11.2-NE), 20.7 (95% CI: 15.8-NE), and 15.4 (95% CI: 8.3-NE), respectively. Based on the safety analysis (n ¼ 304), the 450-mg fed arm showed the highest median relative dose intensity (100% versus 78.5% versus 83.7%), lowest proportion of patients with dose reductions (24.1% versus 65.1% versus 60.9%), and lowest proportion of patients with gastrointestinal toxicities (75.9% versus 82.6% versus 91.8%). Conclusion: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.

Correct staging is the most crucial for the treatment outcome in cancer management. Molecular imaging with 18F-fluoroestradiol (FES) positron emission tomography-computed tomography (PET-CT) targets estrogen receptor (ER) and may have a higher incremental value in diagnosis by aiding specificity. We enrolled 12 female breast cancer patients prospectively and did 18F-FES PET-CT and 18F-fluorodeoxyglucose (FDG) PET-CT within 1 week interval time. Lesion detection sensitivity was compared for a total number of lesions and for nonhepatic lesions only by McNemar test. 18F-FES PET-CT was taken as reference in case of indeterminate lesions. The incremental value reported by identifying 18F-FES exclusive lesions and by characterization of 18F-FDG indeterminate lesions. Spearman rank test was used to correlate ER expression and maximum standardized uptake value (SUVmax). Two ER-negative patients with no 18F-FES uptake were excluded. Ten ER-positive patients with 154 disease lesions were finally analyzed. 18F-FDG picked-up 142 lesions (sensitivity 92.21%), whereas 18F-FES picked-up 116 lesions (sensitivity 75.32%) and this difference was statistically significant. For nonhepatic lesions (n = 136) detectability, 18F-FDG picked-up 124 (sensitivity 91.18%), whereas 18F-FES picked-up 116 (sensitivity 85.29%) lesions and this difference was not statistically significant. Beside 12 exclusive lesions, 18F-FES characterized 41 (27.5%) 18F-FDG indeterminate lesions. Overall 18F-FES impacted 20% patient management. The positive trend was also seen with 18F-FES SUVmax with ER expression and negative with 18F-FDG SUVmax. We conclude, 18F-FDG has overall better sensitivity than 18F-FES PET-CT, however for nonhepatic metastasis difference was not significant. 18F-FES PET-CT better-characterized lesions and impacted 20% patient management. Therefore, 18F-FES PET-CT should be used with 18F-FDG PET-CT in strongly ER expressing patients for better specificity.

Background:Adenocarcinoma, a subgroup of non-small cell lung cancer, is the most frequent form occurring in the non-smokers. Mutation in tyrosine kinase domain of epidermal growth factor receptor (EGFR) has been a common feature observed in lung adenocarcinoma. The study was carried out to detect the prevalence of EGFR mutation in lung adenocarcinoma.Materials and Methods:EGFR mutation status in 166 lung adenocarcinoma patients was obtained retrospectively. Mutation tests were performed on paraffin embedded tissue blocks as a routine diagnostic procedure by polymerase chain reaction followed by direct nucleotide sequencing. Patient’s demographics and other clinical details were obtained from the medical records.Results:EGFR mutation was detected in 43/166 (25.9%) patients. Gender wise mutation was observed as 18/55 (32.7%) in females and 25/111 (22.5%) in males. Overall, EGFR mutation was correlated with never smokers and distant metastasis (P < 0.05), but not associated with the gender, disease stage and pleural effusion. Exon 19 deletions were significantly correlated with females, never smokers, pleural effusion and distant metastasis (P < 0.05). However, point mutation on exon 21 did not show any statistical association with the above variables. Median overall survival was 22 months (95% confidence interval, 15.4-28.6). Female sex, EGFR mutation and absence of metastasis are associated with good prognosis.Conclusion:EGFR mutation in lung adenocarcinoma was higher in never smokers, females and patients with distant metastasis. However, it was not linked with tobacco smoking. The prevalence of EGFR mutation observed is in range with the previously published reports from the Asian countries.

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value <0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

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The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/ HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25-94.98), 96.17% (95.2-97.15) and 91.83% (90.36-93.31), respectively, and the corresponding DFS were 88.1% (86.96-89.31), 92.0% (90.64-93.39) and 83.93% (82.03-85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12-97.1), 92.74% (90.73-94.8) and 90.62% (88.17-93.15), respectively, and the corresponding DFS were 91.59% (90.19-93.02), 85.46% (82.79-88.22) and 81.29% (78.11-84.61), respectively. this is the largest dataset of early breast cancer patients from india with survival outcome analysis and can therefore serve as a benchmark for future studies. Breast cancer, an increasing public health dilemma, represents a heterogeneous group of diseases and still remains today the leading cancer in women and a major cause of morbidity and mortality worldwide 1. As per the GLOBOCAN 2018 statistics, there were a total of 1157294 new cancer cases in the year 2018 in both sexes across all ages in India. Among these, there were 162468 cases of breast cancer with a mortality of 87090 cases. The five-year prevalence across all age groups was 405456 cases 2. A high-incidence cancer of high-resource nations, breast cancer has swiftly become a global healthcare challenge. Improvements in screening, imaging, awareness and diagnostic strategies have led to improvement in the early detection of the disease. Owing to the advent of newer regimes and options, treatment stratification has greatly developed in the past decade 1. A multitude of therapeutic options have been developed and tested leading to major oncologic breakthroughs. Molecular based classifications and personalized treatment have also evolved in the past decade. This has also led to improvements in overall, progression-free and relapse-free survival 3,4. Nevertheless, a patient's survival is related to several prognostic factors, including number of positive lymph nodes, tumor size, hormone receptor status, histological type and grade, and patient's age 5. Although much has been reported by the Western world, it is imperative to have a large population-based data to study the disease

Background:Triple negative breast cancer (TNBC) is a recent concept and the burning topic of research today. Various studies have been reported in western literature on TNBCs or the similar group of basal like cancers, all highlighting the poor prognostic features of this molecular subtype in comparison to the other types of breast cancers. However extensive data from India is lacking. The aim of this study was to analyze the epidemiological and clinical profile of TNBcs at our institute.Materials and Methods:Data on 171 patients of TNBCs registered at this hospital between 2005 and 2008 and followed up until December 2010 was collected and reviewed for epidemiological and clinical features.Results:The median age at presentation was 49 years (22-75 years). Sixty eight patients (40%) had lump in the breast of less than 1 month duration. Fourteen (8%) were nulliparous and 10 (7%) patients had crossed the age of 30 years at first full-term pregnancy, 89 (52%) were pre or peri-menopausal at presentation. Only 8 (5%) patients had a family history of breast or ovarian cancer. One hundred and six (62%) patients were stage II, 26 (15%) stage III, 21 (12%) stage I and 18 (10%) stage IV at presentation. One hundred and twenty eight patients (75%) had early breast cancer eligible for surgery at presentation, 25 (15%) were locally advanced and received neoadjuvant chemotherapy (NACT) and 18 (10%) were found to be metastatic. Modified radical mastectomy was the preferred surgical option by most patients (76%) who underwent upfront surgery in our study. The pathological overall response rates (complete and partial response) after NACT was 75% with complete response rate of 25% and there were no relapses in the complete responders. The median follow-up was 30 months (9-70 months). One hundred and twenty two patients (71%) were alive at last follow-up, 34 (22%) had relapsed, 18 (11%) had died due to progressive disease. Thirty one patients (18%) were lost to follow-up. Most of the relapses were systemic and rarely preceded by local relapses.Conclusions:TNBCs are aggressive cancers with high rates of systemic relapses within the first 3 years of presentation. Longer follow-up of these patients is required for more mature data on these cancers.