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Purpose: Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion–mediated osimertinib resistance has not previously been published. Patients and Methods: Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected. Results: Fourteen patients with EGFR-mutant and RET fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%–75%, n = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4–ALK/STRN–ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms. Conclusions: For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination.

Combination therapy dosing

Purpose:Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion–mediated osimertinib resistance has not previously been published.Patients and Methods:Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected.Results:Fourteen patients with EGFR-mutant and RET fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%–75%, n = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4–ALK/STRN–ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms.Conclusions:For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination.

Patient Cohort Identification

Surgical resection is a generally accepted treatment for residual masses after chemotherapy for metastatic testicular germ cell tumour (GCT). About half the patients have necrosis in post-chemotherapy residual masses, whereas rest have viable tumour and teratoma. The likelihood of leaving behind teratoma with its subsequent complications such as growing teratoma syndrome necessitates resection outweighing its surgical complications. Ours is a retrospective observational study and aims at assessing post-chemotherapy residual masses in testicular GCTs and to predict importance of teratomatous and non-seminomatous components. A total of 62 cases of testicular GCTs resected after chemotherapy between January 2012 and June 2019 were included. Demographic, clinical, biochemical and imageological findings were noted and categorised according to WHO classification (2016). They were divided into two groups - those who underwent retroperitoneal lymph node dissection (RPLND) post-high inguinal orchidectomy (HIO) and chemotherapy (CT) as group 1 (

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

Introduction Acute adverse drug reactions (ADRs) in day-care chemotherapy are not uncommon and are easily manageable on most occasions. However, sometimes they may lead to untoward events. It is paramount to document and analyze such events in contemporary medical oncology practice for the best utilization and planning of available personnel and resources. Objective Our objective was to analyze the acute ADRs occurring in day-care cancer chemotherapy settings. Materials and Methods ADRs reported in a day-care cancer chemotherapy setting, during the administration of chemotherapy, were prospectively observed and analyzed from 01 June 2020 to 31 December 2020. ADRs were classified into anaphylactic, allergic, and gastrointestinal (GI) (nausea/vomiting/heart burns/chest tightness). All ADRs were graded according to the Common Terminology Criteria for Adverse Events Version 5.0. Suspected drugs, time to reaction, and corrective measures were analyzed. Results During the study period, a total of 10,120 sessions of day-care chemotherapy were administered. ADRs were noticed in 118 cases (1.18%). Among the reported ADRs, the mean and median age of the patients in this study was 52 years (21–88). Women outnumbered men (n = 81, 68.64% vs n = 37, 31.36%). Anaphylactic reactions (50.92%) were the most common followed by allergic (25.15%) and GI reactions (23.93%). No grade IV reaction was observed. Oxaliplatin-induced allergic reactions (n = 28, 23.73%) were noted most frequently. In majority of sessions (n = 93, 78.81%), the same chemotherapy regimen was readministered and completed uneventfully after the administration of antihypersensitivity medications. Conclusion Serious ADRs are rare in current day-care chemotherapy administration. Most acute ADRs were of mild grade and successfully managed with antihypersensitivity medication.

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients.

Background: CompLEEment-1 (NCT02941926) is an ongoing Phase IIIb trial of ribociclib (RIB) in combination with letrozole (LET) in the first-line setting for patients (pts) with HR+, HER2- ABC, reflecting a real-world clinical setting by including a more diverse pt population than those included in the pivotal MONALEESA trials. Here we report further analyses of the primary endpoint of safety from the completed Core Phase of the trial. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Premenopausal women and men received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). The primary endpoints were safety and tolerability. Updated analyses included dose reduction/interruption or treatment discontinuation due to adverse events (AEs), clinical impact of AEs of special interest (AESI), and exposure-adjusted incidence/occurrence rates (IRs) for AESI. Results: At data cutoff (November 8, 2019) 3,246 pts had been evaluated (median follow-up of 25.4 months), and median duration of exposure to RIB was 17.5 months; 1,301 (40.1%) pts completed Core Phase treatment, 415 of whom moved to the Extension Phase. Overall, 1,945 (59.9%) pts permanently discontinued treatment, mostly due to progressive disease (34.2%) and AEs (15.5%). Treatment-related AEs were reported in 3,091 (95.2%) pts, leading to dose modification in 2,235 (68.9%) pts. Dose modification occurred most often in pts with grade ≥3 neutropenia (dose interruption, 1,671 [51.5%] pts; dose reduction, 480 [14.8%] pts); treatment discontinuation occurred most frequently in pts with grade ≥3 increased alanine aminotransferase (ALT; 116 [3.6%] pts) or aspartate aminotransferase (AST; 68 [2.1%] pts). Grade ≥3 neutropenia occurred in 1,856 (57.2%) pts, with the median time to first occurrence of 4.1 weeks and median duration of first occurrence of 1.1 weeks. As measured by laboratory values, grade ≥2 increased ALT and AST occurred in 453 (14.0%) and 380 (11.7%) pts, respectively. Grade ≥2 QTcF prolongation was infrequent, occurring in 101 (3.1%) pts, leading 8 (0.2%) pts to discontinue from treatment. AESI rarely led to hospitalization (0 to 0.3%) and none were fatal. Exposure-adjusted IRs for AESI per 100 patient-years of exposure show that with increasing RIB exposure, the IR and the event rates for AESI decreased by a factor of ×2 to ×8 from 0-1 years compared with 1-2 years (Table 1). Conclusions: AEs associated with RIB + LET combination therapy were manageable, consistent with previous Phase III trials of RIB + LET - and adjusted IRs for AESI notably decreased from Year 1 to Year 2 of treatment. These data further support the use of RIB + LET for first-line treatment of HR+, HER2- ABC in both men and women of any menopausal status and in a broader and more diverse patient population. Table 1. Exposure-adjusted IRs for selected AESI per 100 patient-years of exposure0-1 years1-2 yearsAESIIR per 100 PTYaEvents per 100 PTYbIR per 100 PTYaEvents per 100 PTYbNeutropenia276.76410.2292.43200.83ALT increased20.3741.663.796.32AST increased17.5133.272.944.61QTcF prolongation8.4410.221.081.26aIR per 100 PTY: n/100 PTY, number of patients with an event divided by the corresponding sum of the exposure duration for patients, where duration of exposure in patient treatment-years (PTY) is counted up to the first qualifying event (or duration of exposure in time interval for patients without an event).bEvents per 100 PTY: n/100 PTY, number of events divided by the corresponding sum of the exposure duration, where duration of exposure in patient treatment-years (PTY) is duration of exposure in time interval. Citation Format: Janice Lu, Paul Cottu, Miguel Martín, Claudio Zamagni, Aleix Prat, Stephen Chia, Guy Jerusalem, Senthil Rajappa, Constanta Timcheva, Lyudmila Zhukova, Katie Zhou, Jiwen Wu, Lakshmi Menon-Singh, Michelino De Laurentiis. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Expanded safety analysis of the phase IIIb CompLEEment-1 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-05.

Coronavirus pandemic has increased human disease burden, as well as economic distress globally. Being in an immunocompromised state, patients with cancer comprise an important at-risk population for novel coronavirus disease 2019 (COVID-19) infection. It is necessary to modify individualized clinical management for every cancer patient in the context of the ongoing COVID-19 pandemic. Simultaneously, additional safety precautions for the cancer care providers are mandatory. This review will provide general recommendations in the Indian context optimizing the same.

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).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.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.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.NCT03853551.

Background Plasmablastic lymphoma (PBL) is a rare aggressive B cell lymphoma that is commonly encountered in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). In this case series, we describe the clinicopathological features of cases of PBL seen at a tertiary care center in South India. Materials and Methods Medical records of patients diagnosed with PBL between January 2009 and November 2017 were reviewed. PBL was defined as per the World Health Organization 2016 classification for hematopoietic and lymphoid neoplasms. The slides were reviewed with hematoxylin and eosin along with immunohistochemistry (IHC) including CD45, CD20, PAX5, CD79a, CD3, CD5, CD138, MUMI, EMA, ALK, and Ki67. Epstein-Barr virus (EBV) association was documented by rapid in situ hybridization (RISH) studies wherever possible. The demographic data, clinical presentation, treatment details, and outcomes are elaborated using descriptive statistics. Results During the study period, nine patients with PBL were identified. The median age at presentation was 47 years (range: 36–54 years). All patients had associated HIV/AIDS, eight (89%) had extranodal disease, and six (66%) had advanced clinical stage (stage III). All biopsies were positive for CD45, CD138, and MUM1, and negative for CD79a and T cell markers with a high Ki67 proliferation index (85–90%); CD20 was faint positive in one patient, and CD56 was positive in one (11%) patient. EBV-RISH was tested in two patients and was positive in one. Bone marrow was uninvolved in all the cases. At the time of last follow-up, three patients were alive. Treatment details were available in six patients. With frontline therapy, four patients achieved a complete remission (CR) and one patient developed progressive disease. Three of four patients in CR are alive till the last follow-up. Conclusion PBL is a rare form of lymphoma with predominant association with HIV, extranodal location, and characteristic IHC pattern.

Merkel-cell carcinoma (MCC) is a rare skin malignancy seen in elderly males. It is a highly aggressive tumor with a poor prognosis. Surgery is the mainstay of treatment for localized disease with adjuvant radiation depending on the locoregional extent, while chemotherapy has a role in metastatic disease. Emerging data from treatment with immune checkpoint inhibitors look promising. We report a case of MCC in an elderly male diagnosed and treated with chemotherapy and radiation, with a review of the literature of this rare malignancy.

Background Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies. Objective To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, “near real-world” study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC. Patients and Methods NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS). Results 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9–15.9), and median PFS was 12.1 months (95% CI 11.0–13.6). Median TTSP (13.8 months, 95% CI 12.7–16.1) and PFS (11.4 months, 95% CI 10.9–13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075). Conclusions Safety data for afatinib when used in a “near real-world” setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit. Trial Registration Number and Date of Registration NCT01953913 (1 October 2013). Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00859-6.

Diffuse large B-cell lymphoma (DLBCL) is the commonest subtype of lymphoma, standard CHOP was the treatment of choice, 42% of patients received rituximab, and 29% of patients were lost to follow-up during therapy, were reported in a study that collected retrospective data at 13 public and private hospitals for patients diagnosed with lymphoma between January 2005 and December 2009. The OncoCollect Registry was set up in 2017 to address the challenges in the collection of retrospective data through chart review, recording access to anthracycline and rituximab-based treatment, and to study outcomes and any improvement in the patient follow-up.The OncoCollect Lymphoma group registry was set up at a national level with 9 participating centers. Lymphoma patients registered at these centers between 2011 and 2017 were included. The clinical features, prognostic stratification, associated comorbidities, response to first-line treatment, and 3-year outcomes of adult patients with DLBCL were analyzed.Of the 5,886 lymphoma patients registered in the OncoCollect registry, 2,581 (44%) had DLBCL. A total of 1,961 were evaluable for frontline therapy. The median age at presentation was 57 years. Gender ratio was 1.6:1. At presentation, 43% were early stage, 70% had low and low intermediate IPI, 53% had extranodal disease, and 30.9% had one or more comorbidities (data available for 1,136 patients). The commonest extra nodal site was gastro-intestinal (23.98%) followed by head and neck (19.24%). The overall response rate was 79.29%. Complete remission was seen in 61.75%, partial response in 17.5%, stable disease in 4.3%, and progression in 7.9%. Patients who received anthracycline-based therapy (86.7%) and rituximab-based therapy (83.7%) had a 3-year event-free survival (EFS) of 69.67% and 68.48%, respectively. With a median follow-up of 33 months, the 3-year overall Survival (OS) and EFS were 75.37% and 66.58%, respectively.DLBCL remains the commonest (44%) lymphoma subtype and is curable with standard anthracycline- and rituximab-based therapies. The availability of rituximab has increased the proportion of patients receiving standard chemoimmunotherapy.

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.

Highlights • Systemic treatments in breast cancer can produce an excellent response. • Surgery in such patients may only serve the purpose of an excision biopsy. • Core biopsy of the tumor bed could be a novel technique of identifying responders. • This protocol studies the accuracy of core biopsies in predicting response., Introduction With the advent of taxanes and targeted agents in neoadjuvant chemotherapy (NACT) for breast cancer, the rates of pathologic complete response (pCR) have been steadily increasing. One of the roles of surgery in these women is to serve as a biopsy to confirm or negate a pCR. Design This is a prospective validation study. All newly diagnosed non-metastatic breast cancers, of any luminal subtype, planned for neoadjuvant chemotherapy (NACT) with a titanium clip placed in the tumor, will be screened. Eligible patients who have a complete/near complete response to NACT as seen on a mammogram and ultrasound of the breast, will undergo multiple core biopsies of the tumor bed under ultrasound guidance as an outpatient procedure. A minimum of four core biopsy specimens will be mandatory. An MRI will also be done for these patients for documentation and analysis. The core biopsy will be compared to the final histopathology report after definitive surgery. Objectives The objective is to study the false negative rate and accuracy of ultrasound guided core biopsies of the tumor bed in predicting pCR. Additionally, the correlation of pCR in the breast with axillary response and the incremental benefit of an MRI in predicting pCR will be evaluated. Discussion The concept of using image guided core biopsies to predict pCR could be useful in designing future studies aimed at avoiding redundant surgery in women with a complete response to NACT. This study is registered with Clinical Trials Registry of India (CTRI/2018/01/011122).

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors TKIs) are highly effective in EGFR-mutant advanced lung cancer. The most common resistance mechanism to EGFR-TKI is the development of T790M mutation in Exon 20. Osimertinib, a highly selective EGFR-TKI, has been approved for use in patients who progress on the first-line TKI and harbor the T790M mutation. Objective: The primary objective is to prospectively study the incidence of T790M mutation in patients who progress on the first-line EGFR-TKI. Secondary objectives include clinical characteristics that predict for T790M mutation and outcomes with osimertinib. Materials and Methods: This single-center, prospective observational study included 90 patients who progressed on first-line EGFR TKI. All patients had DNA extracted from tissue re-biopsy or plasma circulating tumor DNA (re-biopsy was not feasible or inadequate). T790M mutation was detected using amplification refractory mutation system-polymerase chain reaction, and patients harboring T790M mutation were started on osimertinib (80 mg once daily) until progression or unacceptable side effects. Results: At progression, T790M mutation was detected in 47/90 patients (52.2%). On binary logistic regression model analysis, variables that were independently predictive of the development of T790M were younger age (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.14–16.6, P = 0.031); nonerlotinib TKI use (OR 8.3, 95% CI 1.24–55.8, P = 0.029); and pure adenocarcinoma histology (OR 6.2, 95% CI 1.60–24.7, P = 0.008). Forty-six patients were started on osimertinib. The overall response rate and median progression-free survival were 65.21% and 12.45 months (standard deviation [SD] 1.03, 95% CI 10.41–14.48), respectively. Osimertinib was well tolerated with most toxicities being Grade 1 and 2 diarrhea and skin rash. Conclusions: In our prospective cohort, half of all patients had a T790M mutation at progression on the first-line EGFR TKI. Tissue biopsy is feasible in the majority of patients. Clinical outcomes with osimertinib were consistent with those reported.

Introduction:The diagnosis of Ewing sarcoma family of tumours (ESFT) is challenging, especially in adults and in extra-skeletal or visceral location. Several morphologic mimics with varied treatment options and prognosis confer diagnostic dilemmas. Application of ancillary diagnostic modalities in surgical pathology in clinical routine has enabled accurate diagnosis of ESFT in bone, soft tissues, and viscera.Aim:The study aims to assess the clinicopathological features including molecular test results of ESFT with emphasis on sex, age, and location, especially extra-skeletal soft tissue and visceral location.Material and Methods:Data of clinicopathological, molecular tests (wherever performed), diagnosis rendered in 302 ESFT over a decade from our centre were reviewed. Statistical comparison of skeletal and extra-skeletal tumours with reference to age and sex was done using SPSS package. The P value of Results:The cohort included 302 ESFTs with 49% skeletal and 51% extra-skeletal tumours. Thigh was most common site among skeletal tumours; chest wall, paraspinal location, and retroperitoneum among soft tissues (39.4%); and kidney, ovary, and cervix among visceral tumours (11.3%). Fluorescence in situ hybridisation for EWSR1 gene rearrangement was positive in 54 patients and reverse-transcriptase polymerase chain reaction in 19 patients. Predominance of male sex, younger age and location in extremities among skeletal tumours and lack of gender predilection, higher age and axial location in extra-skeletal tumours were noted, which were statistically significant. Molecular tests were performed more frequently in extra-skeletal tumours, especially in visceral tumours to establish the diagnosis.Conclusions:The study showed statistically significant differences in the age, sex, and location between skeletal and extra-skeletal ESFT. The increased percentage of extra-skeletal tumours especially in viscera was attributed to the increased awareness and availability of ancillary techniques.

Luteinizing hormone-releasing hormone agonist (LHRH-A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate-specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long-term follow-up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single-step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH-A in patients with preexisting CVD. There is considerable long-term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long-term follow-up.

Background: Esophageal cancer is the fourth most common cause of cancer-related deaths in India. In 2012, the CROSS trial evaluated the benefit of induction therapy using weekly carboplatin-paclitaxel with 41.4 Gy radiation versus surgery alone. Pathological complete response (pCR) rates were 28%. Overall survival was improved in the combined therapy arm. However, there is limited data regarding the outcomes of preoperative chemoradiation in Indian scenario. This study was conducted to determine the response to preoperative chemoradiation at a tertiary cancer center in India. Aims: Primary objective was to evaluate the rates of pCR. Secondary objective was to determine recurrence rate and patterns of recurrence. Materials and Methods: We retrospectively reviewed patients with locally advanced esophageal cancer and gastroesophageal junction treated from September 2013 to July 2015. Patients who received preoperative radiotherapy 41.4 Gy with chemotherapy (weekly paclitaxel-carboplatin or cisplatin-5 FU or cisplatin-capecitabine) were included in this study. Chi-square test and Fischer's exact test were used for analysis. Results:: Fifty patients were included in the analysis (76% – squamous cell carcinoma [SCC] and 24% – adenocarcinomas [ACC]). About 60% patients received weekly paclitaxel-carboplatin (CROSS protocol), 32% cisplatin-5 FU, and 8% cisplatin-capecitabine. pCR rate was 39.6%. pCR rate was higher in SCC versus ACC (44.7% vs. 20%) and in paclitaxel-carboplatin than cisplatin-5FU or cisplatin-capecitabine (48.3% vs. 25% vs. 33.3%). At a median follow-up of 12 months, 38 patients were alive, 8 died, and 4 lost to follow-up. Of the 10 patients that recurred, 8 were distant recurrences. Conclusion: Our study results show favorable pCR rate after preoperative CRT with significant higher rate in SCC and patients receiving CROSS regimen. Majority of the recurrences were distant recurrences.

Metastatic breast cancer (MBC) is cancer that has spread from the breast to another part of the body or has come back in another distant location. Treatment options for MBC depend on several factors. One of these factors is the levels of hormone receptors (HRs) in the tumor. Cancers with high levels of HRs, called HR-positive, use the hormones estrogen and progesterone to grow and spread. Hormonal therapy is a type of treatment specifically for HR-positive breast cancer. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of hormonal therapy and the management of HR-positive MBC for the benefit of community oncologists.

Background: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. Methods: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups – Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions. Answers of the two groups were analyzed to see the prevailing patterns of EGFR testing and differences between the two groups if any. Results: Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR mutations in patients with adenocarcinoma histology and 40% (44/111) recommended EGFR testing in squamous cell histology. The average time duration to get EGFR test results was 10 days in Group 1 centers versus 18 days in Group 2 centers. Ninety-six percent (106/111) of the medical oncologists from Group 1 centers requested for factoring additional sample for biomarker testing compared to 69% (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of medical oncologists in Group 1 centers would prefer to wait for the test results before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine-kinase inhibitors were used in only approximately 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy was initiated while waiting for test results, 50% (56/111) of medical oncologists would prefer to complete 4–6 cycles before switching to targeted therapy. At the time of progression, rebiopsy was possible in approximately 25% of the patients. Conclusions: Turnaround time for molecular testing should improve so that eligible patients can benefit from targeted therapies in the first line. There is a need to increase the awareness among pulmonologists, oncologists, and interventional radiologists regarding the importance of adequate samples required for molecular tests.

Background: Bacterial bloodstream infections are important causes of morbidity and mortality globally. The aim of the present study was to determine the bacterial profile of bloodstream infections and their antibiotic susceptibility pattern among the clinically diagnosed cases of sepsis in cancer patients. Methods: In the present study, etiological and antimicrobial susceptibility profile of blood cultures over a period of 1 year at a tertiary cancer care hospital was done. Blood culture positive isolates were identified using standard microbiological methods and by Fully automated BD Phoenix 100. The antibiotic susceptibility pattern of the organisms was performed by Kirby-Bauer disc diffusion method and MIC (Minimum inhibitory concentration) was done by Fully automated BD Phoenix 100. Results: There were 1178 blood culture samples, of which 327 (27.7%) were identified to be culture positive. Out of 327 positive cultures, 299 (91.4%) showed bacterial growth, Gram negative were 161 (53.8%) and Gram positive were 138 (46.1%). Candida species were isolated from 13 (3.97%) of positive samples and 15 samples showed contamination. The most common Gram-negative isolate was. Escherichia coli (37.80%) and Gram-positive isolate was coagulasenegative staphylococci (52.80%). Escherichia coli showed highest sensitivity to amikacin (83.60%) and sensitivity to piperacillin+ tazobactum and cefaperazone+sulbactam was 54.09% and 52.45% respectively. High degree of resistance was found to cephalosporins and levofloxacin. Conclusion: The results indicate high level of antimicrobial resistance among Gram negative bacilli in septicemic patients. The results warrant continuous monitoring of antimicrobial pattern so as to build geographical epidemiological data.

Bacground: First-line maintenance with erlotinib in nonsmall cell lung cancer (NSCLC) patients without progression after four cycles of chemotherapy was well tolerated and significantly prolonged progression-free survival (PFS) compared with placebo. Aim and Design: This open-label, single arm, Phase IV, interventional study was designed to evaluate erlotinib as first-line maintenance after chemotherapy in Indian NSCLC patients. Primary efficacy objective was to evaluate PFS rate (PFSR) at week 52 and secondary objectives were determination of PFS, overall survival (OS), overall response rate (ORR), disease control rate, and safety. Subjects and Methods: Patients were treated with erlotinib until disease progression/death/unacceptable toxicity or end of study. Patients with disease progression underwent scheduled clinical assessments every 12 weeks thereafter. Kaplan–Meier estimates were used to evaluate PFSR, PFS, and OS. The ORR was summarized using number and percentage along with two-sided 95% Clopper–Pearson confidence interval. The incidence of adverse events (AEs) and serious AEs (SAEs) was tabulated according to severity, outcome, and relationship to erlotinib. Results: Of the 51 enrolled patients, 47 patients completed the study (2: Continuing treatment, 41: Disease progression, and 4: Death) and four patients discontinued treatment (3: Lost to follow-up; 1: Withdrew consent). PFSR was 22.5% at 12 months, median PFS 99 days (14.14 weeks), and median OS was 671 days (22 months). The probability of OS was 74.5% at 14 months. The ORR was 25.5%, and disease control rate was 55.3%. AEs were reported in 62.7% and SAE in 7.8% of patients. Common AEs were diarrhea and rash. Conclusions: Erlotinib was well tolerated by Indian patients in first-line maintenance setting and resulted in median PFS of 14 weeks and median OS of 22 months better than previously reported and with no new safety concerns in this population.

Background Neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NACRT) have been demonstrated to improve survival compared to surgery alone in esophageal carcinoma, but the evidence is scarce on which of these therapies is more beneficial, particularly with regard to resectability rates, postoperative morbidity and mortality, and histological responses. Objective This study compares the resectability, pathological response rates, and short-term surgical outcomes in patients with carcinoma of the esophagus or gastroesophageal junction receiving NACT or NACRT prior to surgery. Methods Patients with resectable carcinoma of the esophagus or gastroesophageal junction adenocarcinoma, squamous cell carcinoma, and adenosquamous histologies were enrolled in this well-matched prospective non-randomized study. Thirty-five patients were given NACT, and 35 NACRT. In the NACT group, 25 patients received three cycles of three-weekly carboplatin and paclitaxel, and 10 received three cycles of cisplatin/5-fluorouracil, while all the patients in the NACRT group received 41.4 Gy of radiotherapy concomitant with five cycles of weekly paclitaxel and carboplatin-based chemotherapy. Results Twenty-two patients in the NACT group and 33 patients in NACRT group had resection (P value = 0.0027). The percentage of microscopically margin-negative resection (R0 resection) was similar in both the groups (86% versus 88%). The incidences of surgical and non-surgical complications were similar in both the groups (P=0.34). There was no 30-day mortality. There was a trend toward more pathological complete regression in the NACRT group (P=0.067). The percentage of patients achieving complete tumor regression at the primary site (pT0) was significantly higher in the NACRT group. The down-staging effect on nodal status was similar in both the groups (P=0.55). There was a statistically significant reduction in tumor size in the NACRT group. The median numbers of nodes harvested and positive nodes were similar in both the groups. Conclusion Patients receiving NACRT had better resectability rates and pathological response rates, but similar postoperative morbidity compared to the NACT group.

We report a rare case of Mycobacterium monacense isolated from the blood of a patient with carcinoma breast with an infected chemoport. Initial blood cultures from peripheral line and port were sterile. Repeated blood cultures signaled positive which showed weakly stained gram positive bacilli on smear from both the vials. Nontuberculous Mycobacterial infection and speciation were confirmed by real time polymerase chain reaction and sequencing. Chemoport was removed and patient responded to 3 drug regimen with Rifampicin, Ethambutol and Clarithromycin therapy with no recurrence at 15 month follow-up. Keywords: Mycobacterium monacense, rapidly growing mycobacteria, chemoport, real time, PCR

The management of breast cancer with advanced disease or metastasis is a common problem in India and other countries. A panel of 13 oncology experts deliberated on the sidelines of the 35th Indian Cooperative Oncology Network Conference held in Mumbai to formulate an expert opinion recommendation on the novel drug delivery system (NDDS) formulations in the treatment of metastatic breast cancer (MBC). The survey comprised of 39 questions related to limitations of conventional formulations and therapeutic positioning of NDDS formulations of docetaxel, paclitaxel and doxorubicin in the management of MBC. The experts used data from published literature and their practical experience to provide expert opinion and recommendations for use by the community oncologists. The experts opined that the newer NDDS formulations should provide a significant efficacy advantage in terms of overall survival and progression-free survival, or demonstrate better tolerability when compared with conventional formulations. The newer NDDS formulations of taxanes should be considered in special circumstances such as diabetes, in patients who have had hypersensitivity reactions and in cases where steroids need to be avoided. The novel formulations of doxorubicin should be used in the elderly and in patients with borderline cardiac function.

Background and objectives: Vitamin D involved in various conditions including signaling pathways that affects the numerous cellular processes. However, according to the recent observations, low level of serum vitamin D is associated with tumorogenesis. Materials and Methods: The study includes 426 individuals of solid malignancies along with age and sex matched healthy controls (n= 426). The serum vitamin D level was estimated by electrochemiluminescence method and the data analyzed statistically. Results: The mean of serum vitamin D in solid malignancies and control groups were 15.53ng/mL and 18.15ng/mL respectively. Vitamin D deficiency was found in the individuals of 380 cases of solid tumors (89.2%) and 355 of the control group (83.3%) and representing the risk association towards the disease (OR=1.65). The Sub group analysis also revealed that low vitamin D levels, i.e., less than 10 ng/mL was observed in all other categories of solid malignancies like breast, lung, gynecological, prostate, gastrointestinal, head & neck, sarcomas (bone & soft tissue) and various other solid malignancies. Conclusion: The serum vitamin D deficiency is significantly associated with all the categories of solid tumors in comparison to control and maintaining the adequate levels may reduce the risk and their associated overall outcomes.

BACKGROUND: There is limited Indian data on clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung. AIM: We aimed to prospectively study the clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung at a tertiary cancer center. MATERIALS AND METHODS: One hundred and ninetyfour patients with Stage IV adenocarcinoma of lung were prospectively analyzed for demographic and molecular profile (epidermal growth factor receptor [EGFR] and echinodermal microtubuleassociated proteinlike 4anaplastic lymphoma kinase [EML4ALK] mutations). Patients with EGFR and EML4ALK mutations were treated with tyrosine kinase inhibitors. Patients without these mutations were treated with standard chemotherapy regimens. Maintenance chemotherapy was offered to patients as per standard guidelines. Clinical outcomes measured were response rate (RR), progressionfree survival (PFS), and overall survival (OS). RESULTS: Median age of patients was 56 years (range, 26–82) with a male:female ratio of 2.3:1. EGFR and ALK mutation testing was feasible in 169 (87.1%) and 164 (84.5%), respectively, and detected in 37.9% and 5.5% patients, respectively. Overall RR, PFS and OS of whole cohort were 44.3%, 6.9, and 15.5 months, respectively. PFS and OS of mutated group (EGFR, EML4ALK) were longer than nonmutated group (10.5 vs. 5.4 months, P < 0.0001 and 21.5 vs. 11 months, P = 0.0001, respectively). PFS and OS of patients who received pemetrexed maintenance were longer than those who did not receive maintenance (8.5 vs. 6.5 months, P = 0.1613 and 18.5 vs. 12.5 months, P = 0.0219, respectively). CONCLUSIONS: Mutation testing at diagnosis is feasible in the vast majority of patients with Stage IV adenocarcinoma of the lung. Patients with EGFR or EML4ALK mutation and those who received pemetrexed maintenance had better clinical outcomes.

Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.