Demographic Characteristics and Treatment Outcomes of Advanced Renal Cell Carcinoma With Clear Cell Histology: A Single-Center Experience From India.

Background Treatment of metastatic renal cell cancer (mRCC) has revolutionized with the introduction of anti-VEGF tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). There is limited data in the literature on the outcomes of Indian patients treated with TKI. Here, we report the outcome of mRCC treated with first-line TKI in a resource-poor setting. Material and methods This is a single-center retrospective study of clear cell mRCC treated with first-line TKI from June 2012 to December 2022. Demographic characteristics and treatment details, including outcome data, were captured from electronic medical records. Patients who received at least one week of therapy were eligible for survival analysis. Results A total of 345 patients with metastatic clear cell histology were analyzed, with a median age of 61 years (range: 20-84 years). One hundred and eighty patients (52%) underwent nephrectomy before systemic therapy. The majority received pazopanib (257 patients, 75%), followed by sunitinib (36 patients, 10%) and cabozantinib (21 patients, 6%); 145 (45%) patients required dose interruption, and 143 (43%) required dose modification of TKI for adverse events. After a median follow-up of 44 months, the median progression-free survival (PFS) was 20.3 months (95% CI: 17.8-24.8), and the median overall survival (OS) was 22.7 months (95% CI: 18.8-28.3). In the poor-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS in multivariate analysis. Conclusion This is the largest single-center cohort of clear cell mRCC from Asia. Median PFS was 20.3 months with predominantly TKI monotherapy. In the poor-risk IMDC group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS.

Multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteraemia rates among cancer patients in an oncology hospital in eastern India: an 11-year retrospective observational study.

Background: Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India. Aims: To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India. Methods: A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously. Findings: 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli (E. coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients. Conclusion: This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians.

Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Results from a Phase IV study in India.

Background: A Phase IV, single-arm study was conducted to assess the safety of osimertinib in Indian patients with epidermal growth factor receptor (EGFR) T790M mutation-positive stage IV non-small cell lung cancer (NSCLC). Methods: Enrolled patients received 80 mg osimertinib for six cycles or until disease progression or unacceptable toxicity or withdrawal. Primary safety variables included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation/interruption/change (D/I/C) of drug dose, and AEs of special interest (AESIs). AEs were summarized by the percentage of patients experiencing at least one occurrence of each event. Results: Of the 60 enrolled patients (median age 58 [range: 34-81] years; 51.7% women) at eight sites, nine patients were discontinued prematurely due to disease progression (n = 7) and death (n = 2); median (range) duration of treatment was 126 (1-134) days. Median age of patients was 58 (34-81) years; 51.7% (n = 31) were women; 86.7% (n = 52) were nonsmokers; and most of them (98.3%) had adenocarcinoma. About 75% (n = 45) of patients experienced any of the TEAEs, with the most frequent being fatigue and creatine phosphokinase (CPK) increase (n = 6, 10% each). TEAEs in 11 (18.3%) patients were judged as study treatment related, with CPK increase being the most common (n = 4, 6.7%). TEAEs led to D/I/C of drug dose in eight (13.3%) patients, with one being study treatment related. Nine (15%) patients had AESIs of dyspnea (n = 6), chest pain (n = 2), and cardiorespiratory arrest (n = 1); two of them had a fatal outcome. One AESI (mild dyspnea) was considered study drug related. TEAEs of grade ≥3 were reported in seven (11.7%) patients, including dyspnea in two (3.3%), followed by diarrhea, mucosal inflammation, cardiorespiratory arrest, and others (n = 1, 1.7% each). None of the SAEs and fatal events were considered as study treatment related. Seven (11.7%) patients had abnormal electrocardiogram (ECG; not clinically significant) at the end of the study. Conclusion: Our study confirms the favorable safety profile of osimertinib without any new safety concerns in Indian patients with EGFR T790M mutation-positive stage IV NSCLC. ClinicalTrials.gov Identifier: NCT03853551.

Expert survey on management of prostate cancer in India: Real-world insights into practice patterns.

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web-based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence.

Sequencing of Systemic Therapies in the Management of Advanced Prostate Cancer in India: a Delphi-Based Consensus.

INTRODUCTION: With the availability of an increasing number of therapeutic options for advanced prostate cancer (APC), optimal sequencing and combination of therapies have emerged to be the areas of challenges. In the Indian context, there is a dearth of consensus recommendations to guide clinicians regarding optimal sequencing of therapy in APC management. A Delphi-based consensus regarding optimal therapy sequencing in APC management was developed by an expert panel of medical oncologists from across India. METHODS: An expert scientific committee of 11 medical oncologists and an expert panel of 53 medical oncologists from India constituted the panel for the Delphi consensus. In the first phase, a questionnaire with 41 clinical statements was developed in several critical controversial areas in APC treatment. In the second phase, 29 clinical statements were reworked and sent to eight experts to obtain their opinions on best practices. The consensus ratings were based on a 9-point Likert scale. Based on the overall response, statements with a mean score of ≥ 7 with 1 outlier were considered as "consensus." RESULTS: Degarelix was the preferred androgen deprivation therapy (ADT). While ADT plus docetaxel was the preferred option for metastatic castrate-sensitive/naïve prostate cancer patients with high-volume disease, ADT with abiraterone was the preferred choice for low-volume disease. Docetaxel was the preferred first-line treatment option in men who received ADT alone in the castrate-sensitive/naïve setting. For patients progressing on or after docetaxel for metastatic castrate-resistant prostate cancer (without prior abiraterone or enzalutamide), the experts reached a consensus on the use of enzalutamide as the preferred second-line treatment option. No consensus was reached for the third-line treatment options. CONCLUSION: This article is intended to serve as a guide to help clinicians discuss with their patients as part of the shared and multidisciplinary decision-making for improved APC management in India.

Early Experience with Dabrafenib-Trametinib Combination in Patients with BRAF-Mutated Malignant Melanoma-A Single-Center Experience.

Background Combination of dabrafenib-trametinib is one of the standard treatments in patients with BRAF-mutated advanced malignant melanoma (MM). Real-world data on the usage of this combination is scarce, especially from India. Here, we are reporting our early experience with the usage of this combination therapy. Materials and Methods This is a single institutional data assessment of patients with BRAF-mutated MM registered and treated with BRAF-MEK inhibitors in our hospital. Clinico-pathological features and treatment details were reviewed for all patients. Results A total of seven patients with BRAF-mutated MM treated with this combination therapy with a median age of 66.5 years (range: 49-72 years) and a male:female ratio of 3:4. Six (85.7%) patients had metastatic disease at presentation. In total, 80% of our patient population had two or less than two sites of metastasis at presentation. The initial response rate of the study population was 71%. The drug was well tolerated with fever being the most common side effect which was seen in two (28.5%) of the patients. Conclusion Combination of dabrafenib-trametinib is effective in patients with BRAF-mutated MM with good tolerability. Further studies are required to look for improvement in outcome in this group of patients.

Multidisciplinary management of ovarian germ cell tumours-a single institutional study from India.

BACKGROUND: Ovarian germ cell tumours constitute a heterogeneous group of neoplasm with malignant potential being seen in 5% of cases. There is limited data on treatment outcomes of patients with malignant ovarian germ cell tumours (MOGCT). Here, we present our hospital audit of patients with MOGCT. MATERIAL AND METHODS: This is a retrospective data review of patients with MOGCT treated between May 2011 and December 2019. Patients were treated with staging laparotomy and adjuvant chemotherapy, wherever applicable. Surveillance was allowed for those at low risk for recurrence. Clinicopathologic features and treatment details were recorded, and survival analysis was performed. RESULTS: Sixty-five patients with a median age of 25 years (range: 11-52 years) were treated during the study period. The most common histology was immature teratoma in 35.3% of cases. International Federation of Gynecology and Obstetrics stage IC was the most common stage of presentation (47%). Surveillance was advised for 12.3% of cases. Systemic therapy was given in 51 (78%) patients. At a median follow-up of 46 months (range: 1-109 months), the median progression-free survival (PFS) was not reached. Five-year PFS was 79.3% (95% CI: 65.8-88). The most common toxicity was febrile neutropenia (22%) among those who received systemic therapy. CONCLUSION: Immature teratoma was the most common histology in our series. The majority presented in the early stage. MOGCT is a highly curable disease with surgery and systemic therapy.

Clinicopathological characteristics, prognostic factors and treatment outcomes of seminomatous germ cell tumours from a tertiary cancer centre in eastern India.

Background: . Seminomatous germ cell tumour (SGCT) is a rare but curable malignancy of young adults. The literature on management and outcome of SGCT is scarce from India. We report the demography and treatment outcome of SGCT at our centre. Methods: . We did a retrospective analysis of patients with SGCT treated from March 2011 to December 2018. Patients were staged appropriately with imaging, and pre- and postoperative tumour markers. High inguinal orchiectomy was performed in all with a testicular primary and received subsequent stage-adjusted adjuvant treatment. Patients were monitored for metabolic syndrome during follow-up after completion of treatment. Results: . We treated 85 patients with a median age of 37 (range 20-68) years. The primary site of the tumour was the testis in 80 (94%) and mediastinum in 5 (6%) patients. Cryptorchidism was present in 20 (25%) patients and testicular violation was present in 11 (14%) patients. Stage of the disease was I in 61, II in 13 and III in 6 patients. Adjuvant treatment in stage I disease was single-agent carbo-platin (area under the curve ×7) in 38 (62%), surveillance in 20 (33%) and radiotherapy in 3 (5%) patients. Five patients in the surveillance group relapsed. The 7-year mean (SD) relapse-free survival and overall survival were 83.1% (8%) and 98.7% (1.3%), respectively. Thirty-one patients (n = 52, 60%) had features of metabolic syndrome. Conclusions: . SGCTs have a high cure rate. Long-term follow-up is essential for monitoring toxic effects. Early diagnosis, avoidance of testicular violation and multidisciplinary management are the key features for better long-term outcome in SGCT.

Outcome of COVID-19 in Solid Organ Malignancies: Experience From a Tertiary Cancer Center in Eastern India.

PURPOSE: The COVID-19 pandemic has imposed a unique challenge to oncology patients. Outcome data on COVID-19 in patients with cancer from the Indian subcontinent are scarce in the literature. We aimed to evaluate the outcome of patients with COVID-19 on active systemic anticancer therapy. MATERIALS AND METHODS: This is a retrospective study of patients with solid organ malignancies undergoing systemic therapy with a diagnosis of COVID-19 between March 2020 and February 2021. COVID-19 was diagnosed if a reverse transcriptase polymerase chain reaction assay from oropharyngeal or nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2. The objectives were to evaluate the outcome of COVID-19 and factors predicting the outcome. RESULTS: A total of 145 patients were included with a median age of 58 years (range, 20-81 years). Treatment was curative in 60 (42%) patients. Of all symptomatic cases (n = 88, 61%), 50 had mild, 27 had moderate and 19 had severe COVID-19-related symptoms as per WHO criteria. Fifty (34%) patients required hospitalization with a median duration of hospital stay of 12 days (range, 4-25 days); five patients required intensive care unit admission. The rest were treated with home isolation and did not require further hospitalization. Twenty-two (15%) patients died, and the risk of death was significantly associated with severity of symptoms (odds ratio, 91.3; 95% CI, 9.1 to 919.5, P = .0001) but not with any other clinical factors. Drug holiday was given to 63 (44%) patients with a median duration of 25 days (range, 7-88 days). The median duration to reverse transcriptase polymerase chain reaction-negative was 16 days (range, 7-62 days). CONCLUSION: COVD-19-related death rate was 15% among patients with solid organ malignancies. The severity of the symptoms was related to mortality. The majority of patients with mild symptoms were treated at home isolation.

PDL1 expression and its correlation with outcomes in non-metastatic triple-negative breast cancer (TNBC).

PURPOSE: Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes, even in those with early disease. Immune checkpoint inhibitors (ICIs) have been approved in metastatic diseases and are being tested as a neoadjuvant strategy also. The response to ICIs is largely determined by the programmed death ligand 1 (PDL1) score, which also acts as a prognostic marker for outcomes. Here, we report the proportion of PDL1 expression in non-metastatic TNBC and its correlation with response to chemotherapy and outcomes. METHODS: We included all patients who had non-metastatic TNBC treated with neoadjuvant chemotherapy, followed by surgery with/without adjuvant radiotherapy between September 2011 and November 2017. PDL1 testing was carried out on pre-treatment tumour cells with immunohistochemistry (Ventana SP142) and was correlated with pathological response, relapse-free survival (RFS) and overall survival (OS). PDL1 staining was interpreted as negative or positive (more than 1% staining). RESULTS: A total of 107 patients were included for analysis with a median age of 47 years (28-65 yrs). The PDL1 expression of more than 1% was seen in 31 (28.97%) patients. After a median follow-up of 55 months (range: 4-93 months), median RFS and OS were not reached. PDL1 expression did not affect the achievement of pathological complete response (pCR). However, PDL1 expression improved OS (p = 0.016) and trend towards RFS (p = 0.05). Patients who achieved pCR had better RFS and OC compared to those who did not. CONCLUSION: Our study shows PDL1 expression in 29% of the cases. PDL1 expression leads to better RFS and OS. Also, pCR improves survival.

Metastatic colo-rectal cancer: real life experience from an Indian tertiary care center.

BACKGROUND: No data exist for the long-term outcome of metastatic colorectal cancer (mCRC) from the Southern part of Asia. The primary objective of the study is to evaluate the survival outcome of mCRC from an Indian tertiary care center. The study also aims to highlight the treatment pattern practiced and the unique clinico-pathologic characteristics. METHODS: This is a single-center retrospective observational study done at a large referral tertiary care center in North India. All patients with synchronous or metachronous mCRC who received at least one dose of chemotherapy for metastatic disease, registered between 2003 to 2017 were included. Primary outcome measures were overall survival and progression-free survival and prognostic factors of overall survival. Descriptive analysis was done for the clinicopathological characteristics and treatment patterns. Kaplan Meier method for overall survival and progression-free survival. Cox regression analysis was performed for the determination of the prognostic factors for overall survival. RESULT: Out of 377 eligible patients, 256 patients (68%) had de novo metastatic disease and the remaining 121 (32%) progressed to metastatic disease after initial treatment. The cohort was young (median age, 46 years) with the most common primary site being the rectum. A higher proportion of signet (9%) and mucinous histology (24%). The three common sites of metastasis were the liver, peritoneum, and lung. In the first line, most patients received oxaliplatin-based chemotherapy (70%). Only 12.5% of patients received biologicals in the first-line setting. The median follow-up and median overall survival of study cohort were 17 months and 18.5 months. The factors associated with poor outcome for overall survival on multivariate analysis were ECOG performance status of > 1, high CEA, low albumin, and the number of lines of chemotherapy received (< 2). CONCLUSION: The outcome of mCRC is inferior to the published literature. We found a relatively higher proportion of patients with the following characteristics; younger, rectum as primary tumor location, the signet, and mucinous histology, higher incidence of peritoneum involvement. The routine use of targeted therapies is limited. Government schemes (inclusion of targeted therapies in the Ayushman scheme), NGO assistance, and availability of generic low-cost targeted drugs may increase the availability.

Outcome of testicular non-seminomatous germ cell tumours: report from a tertiary cancer centre in eastern India.

Non-seminomatous germ cell tumour (NSGCT) is a rare but highly curable malignancy. The literature on the management and outcomes of NSGCT is scarce from India. Here, we report the demography and treatment outcomes of NSGCT treated at our centre. This is a retrospective analysis of testicular and retroperitoneal NSGCT patients treated from March 2011 to December 2019. Patients were staged appropriately with imaging, pre- and post-operative tumour marker. Patients received stage adjusted adjuvant treatment after high inguinal orchiectomy. Patients with advanced disease were risk stratified as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A total of 100 patients were treated with a median age of 28 years (Range: 18-51). Primary site was testis in 92 and retroperitoneum in 8 patients. Testicular violation was present in 17 (18%) patients. The stage of the disease was I in 32, II in 19 and III in 49 patients, respectively. IGCCCG risk groups were good in 29 (46%), intermediate in 13 (21%) and poor in 21 (33%) patients. Eleven patients (24%) underwent retroperitoneal lymph node dissection amongst 45 with post-chemotherapy residual disease. After a median follow-up of 26.6 months (range: 2.2-100.7), 3-year event-free survival and overall survival (OS) were 70.7% ± 5.6% and 78.2% ± 5.4%, respectively. S3 tumour marker (p = 0.01) and non-pulmonary visceral metastasis (p < 0.001) emerged as independent poor prognostic factors for OS in multivariate analysis. To conclude, testicular NSGCT has very high cure rate. Two-third patients present with advanced disease and one-third of them had poor risk disease. S3 tumour marker and non-pulmonary visceral metastasis are poor risk factors for OS.

Outcomes of metastatic neuroendocrine carcinoma of the gallbladder.

BACKGROUND: Neuroendocrine carcinoma of the gallbladder (NECGB) is a rare pathological entity. They are found to be aggressive cancers. Treatment strategies are based largely on extrapolation from other small cell cancers. Survival is poor compared to adenocarcinoma. Data from low- and middle-income countries are sparse. METHODS: All patients with metastatic NECGB treated in our centre were identified. Their treatment details were captured from electronic medical records. Baseline characteristics were noted and survival was estimated using Kaplan-Meir method. RESULTS: A total of 15 patients were included. The median age was 55 years. Large cell comprises 2/15 and small cell was found in 13/15 patients. Chemotherapy was platinum-based in 12 patients. The response to first-line chemotherapy was partial in 3 (20%), stable disease in 2 (13.3%) and progressive disease in 10 (66.6%). After a median duration of follow-up of 12 months, the median progression free survival was 3 months and the median overall survival was 5 months. CONCLUSION: The outcomes of small cell gallbladder cancer are dismal, despite good response rate. More prospective data are required.

Multimodality treatment outcome in patients with primary malignant mediastinal germ cell tumor in adults.

BACKGROUND: Malignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource-poor countries are scarce in the literature. AIMS: To evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center. METHODS AND RESULTS: Single institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non-seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18-36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre-treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non-seminoma histology with poor-risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non-seminoma histology underwent complete resection of residual disease post-chemotherapy and five revealed residual viable tumors. After a median follow-up of 10.8 months (range:2.9-75), 3-year progression-free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3-year PFS and OS estimate was 100% in patients with seminoma histology. CONCLUSIONS: This is the largest data set of MGCT patients' outcomes reported from India with multi-modality treatment. All patients were male and one-fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non-seminoma histology had a poor outcome even with chemotherapy and surgery.

Not so 'rare'-an example of malignant melanoma in India: report from a tertiary cancer centre.

PURPOSE: Malignant melanoma (MM) is rare in India. Indian data on demography and treatment outcome on advanced MM is very limited in the literature. MATERIALS & METHODS: This is a retrospective study of advanced MM treated between January 2013 and December 2020. We evaluated the clinicopathologic features, mutational profiles, survival outcome and prognostic factors in advanced MM patients. RESULTS: Out of a total 460 patients, 185 (42%) had metastatic disease at presentation and were enrolled in this study with a median age of 63 years (range: 28-93) and male:female ratio of 94:91. The mucosal primary was predominant (n = 110, 59%) than cutaneous primary (38%) and anorectum was the most common site (n = 84, 45%). Tumour mutational analysis was performed in 65 (35%) patients. BRAF mutations were detected in 12 patients and KIT mutations in 7 patients. Thirteen patients didn't have any mutations and 22 patients had mutations other than KIT & BRAF. Only 59 (32%) patients took any systemic treatment - immune checkpoint inhibitors (ICIs) in 17, temozolomide in 18 and paclitaxel/carboplatin in 18, tyrosine kinase inhibitors in 6 patients. After a median follow-up of 26 months (95% confidence interval (CI): 11.6-not reached), median progression-free survival (PFS) was 7.1 months (95% CI: 4.4-9.1) and median overall survival was 14.8 months (95% CI: 7.7-18.2 months). The use of ICI emerged as an only significant good prognostic factor (p ≤ 0.001) for PFS, on multivariate analysis. CONCLUSION: Mucosal origin was more common than cutaneous primary with anorectum being the most common site. BRAF mutation was less as compared to published literature. Very few patients received systemic therapy and the use of ICI showed superior PFS.

Perspective of Oncology Patients During COVID-19 Pandemic: A Prospective Observational Study From India.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has imposed a unique challenge to oncology patients and their treatment. There is no study related to the patients' preference for systemic therapy during this pandemic. We have conducted a prospective study to analyze that aspect. METHODS: All consecutive patients who visited during the lockdown period from April 1-10, 2020, for systemic chemotherapy were included in the study for a questionnaire-based survey to evaluate the willingness to continue chemotherapy during this pandemic and factors influencing the decisions. RESULTS: A total of 302 patients were included (median age, 56 years; range, 21-77 years). Most common sites of cancer were breast (n = 114), lung (n = 44), ovary (n = 34), and colon (n = 20). Home address was within the city for 125 patients (42%), outside the city for 138 (46%), and outside the state for 37 (12%). Treatment was curative in 150 patients and palliative in 152. Educational status was primary and above for 231 patients and no formal schooling for 71. A total of 203 patients wanted to continue chemotherapy, 40 wanted to defer, and 56 wanted the physician to decide. Knowledge about COVID-19 strongly correlated with intent of treatment (P = .01), disease status (P = .02), knowledge about immunosuppression (P < .001), home location (P = .02), and education status (P = .003). The worry about catching SARS-CoV-2 was high in those with controlled disease (P = .06) and knowledge about immunosuppression (P = .02). Worry about disease progression was more with palliative intent (P < .001). CONCLUSION: This study shows that oncology patients in our country are more worried about disease progression than the SARS-CoV-2 and wish to continue chemotherapy during this pandemic. The treatment guidelines in the COVID-19 scenario should incorporate patients' perspectives.

Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: A multicenter study from India.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearranged metastatic non-small cell lung cancer (NSCLC) comprises 5%-7% of all lung cancer and carries a good prognosis with available ALK-inhibitors. Majority of registration trials in ALK-inhibitors did not include Indian patients. Hence, this study was planned to analyze the outcome of Indian patients treated with ALK-inhibitors and associated challenges. METHODS: This is a multi-center study in 5 major tertiary care cancer centers across India treating ALK-rearranged NSCLC patients from April 2013 to April 2019. ALK rearrangement was determined by Ventana immunohistochemistry with D5F3 clone and/or by break-apart FISH. Patients treated with ALK-inhibitors in any lines of treatment were included in this study. Patients were evaluated for clinicopathologic features, patterns of ALK-inhibitors use and outcome. Progression free-survival (PFS) and overall survival (OS) were calculated and data were censored on April 30, 2019. RESULTS: A total of 274 patients were studied, out of which 250 patients received ALK inhibitor and were analyzed further for outcome. The median age was 50 years (range: 24-82) and male to female ratio of 1.17:1. ALK was evaluated by immunohistochemistry in majority of patients (97%), 3 patients by FISH and 3 more patients were evaluated by both methods. Sixty-five percent (n = 162) of the patients received ALK-inhibitor as first line therapy, 51 patients received ALK-inhibitor as switch maintenance therapy after initial chemotherapy. Crizotinib and Ceritinib were used in 88% and 12%, respectively. One patient received Alectinib. Forty-one percent of patients had CNS progression. After median follow up of 27 months (1-72 months), the median OS was 24.7 months with OS rate of 72%, 51%, and 18% at 1, 2, and 4-years respectively. Median OS was 21.2, 26, and 38 months in the first line ALK-inhibitors use (n = 162), switch maintenance group (n = 51) and second line ALK-inhibitors use (postchemotherapy progression) (n = 33), respectively. No baseline variable predicted PFS. Presence of brain metastasis (P = 0.039) and first line ALK-inhibitors use (P = 0.032) emerged as poor prognostic factor for OS on multivariate analysis. PFS rate was 70%, 47%, and 31% at 6, 12, and 18 months respectively. CONCLUSION: This is one of the largest real-world data on outcome of ALK inhibitors in ALK-rearranged NSCLC from Asia. In absence of second line ALK inhibitor, initial chemotherapy followed by ALK-inhibitors (switch maintenance) had better outcome. This fact may be studied in individual patient data meta-analysis. Poor performance status and brain metastases at presentation are poor prognostic factors for overall survival. Second-line ALK inhibitor use crucial for better outcome and access to clinical trials are much needed in Indian patients.

Next generation sequencing in lung cancer: An initial experience from India.

INTRODUCTION: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients. MATERIAL AND METHOD: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform. RESULTS: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%). CONCLUSION: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.

Utility and safety of maintenance chemotherapy in advanced non-small cell lung cancer across various performance status categories: real-world experience.

Maintenance chemotherapy (MC) with pemetrexed is a commonly used strategy in nonsquamous non-small cell lung cancer. However, most of the available evidence is from subjects with good performance status (PS), while data on the real-world utility and safety of this strategy in subjects with various categories of PS is limited. We performed a retrospective analysis of multicentric data of 3 centers from India. All patients with advanced nonsquamous non-small cell lung cancer who received MC with pemetrexed after induction chemotherapy were included. Subjects were divided into 2 groups based on baseline Eastern Cooperative Oncology Group score before initiation of induction chemotherapy as good PS (<2) and poor PS (≥2). Progression-free survival, overall survival, and toxicity were assessed in the study population. A total of 290 subjects were included in the study, of whom a significant proportion (n = 104, 35.9%) had poor PS. Survival was better in subjects with good PS as compared to those with poor PS (1-year progression-free survival: 43.5% vs 29.8%, P = 0.021; 1-year overall survival: 61.8% vs 48.1%, P = 0.023). Grade 3/4 toxicity was observed in 14.5% of subjects during MC and was not different between both groups (P = 0.287). Renal dysfunction was more common in subjects who received ≥10 cycles of MC (10.7% vs 4.2%, P = 0.040). MC with pemetrexed appeared to be beneficial and safe in the real-world setting regardless of the baseline PS. However, survival benefit was more pronounced in subjects with good PS at baseline. Renal dysfunction was more frequently encountered in subjects who received prolonged MC.

Immune checkpoint inhibitors in advanced non-small cell lung cancer: A metacentric experience from India.

BACKGROUND: Immune check point inhibitors (ICIs) have changed the treatment paradigm of driver mutation negative non-small cell lung cancer (NSCLC) and they are increasingly incorporated in first-line treatment. Real-world experience of use of these drugs is limited. We aim to evaluate the real-world experience of use of ICIs in patients with advanced NSCLC. PATIENTS AND METHODS: Medical records of patients with NSCLC treated with ICIs at 4 major academic cancer centers in India between January 2016 and December 2018 were analyzed. The type of ICI taken, response rates, survival, and toxicity profiles were analyzed. RESULTS: The median age at presentation was 60 years (range: 27-79 years). Nivolumab was the most commonly used ICI drug [80%, n = 70] followed by pembrolizumab [10%, n = 9], and atezolizumab [10%, n = 9]. The median number of ICIs cycles received were 4 (range 2-65). Among the evaluable responses in 74 patients, the objective response rates was 25.6% and clinical benefit rate was 46%. Immune related toxicity occurred in 39.9% of patients but, severe toxicity of Grade III and Grade IV occurred in 5 (5.6%) patients. After a median follow-up time of 8.86 months (95%CI 5.2-11.1) the progression-free survival was 4.73 months (95%CI 3.7-8.9), and overall survival was 11.6 months (95%CI 7.33-NR). ECOG PS at the time of start of ICIs was found to be significant determinant of Progression-free survival and overall survival. CONCLUSION: Our study demonstrates the feasibility of usage of ICIs in advanced NSCLC in Indian setting with acceptable safety profile and comparable responses with the published studies.