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Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13–75 years with an Eastern Cooperative Oncology Group performance status of 0–2, who were receiving doxorubicin–cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0–120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference –1·0% [one-sided 95% CI –100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. Progressive Ladies Welfare Association.

There is sparse data on the outcomes of combined chemotherapy and hormonal therapy (CHT) in patients with metastatic breast cancer (MBC). This retrospective analysis of HR-positive, HER2-negative MBC patients treated between January 2015 and December 2020 with a combination of chemotherapy (capecitabine or oral cyclophosphamide) and hormonal therapy evaluated their progression-free survival (PFS) and overall survival (OS).The study included 224 patients with a median age of 53 (26–91) years, a median of 3 (0–12) prior treatment lines and a median follow-up of 21.2 (1.7–87.0) months. There were 195 (87.1%) PFS events and 154 (68.8%) deaths, with a median PFS of 8.8 (95% CI 7.0-10.6) months and a median OS of 16.7 (95% CI 13.5–19.9) months. In univariable analyses, ECOG PS (≤ 1 vs. ≥ 2, PFS 14.9 vs. 6.0 months, HR 0.32, 95% CI 0.23–0.44, p  < 0.001; OS 36.2 vs. 11.0 months, HR 0.29, 95% CI 0.20–0.42, p  < 0.001) and duration of most recent endocrine therapy (> 12 vs. ≤ 12 months, PFS 11.7 vs. 6.9 months, HR 0.32, 95% CI 0.23–0.44, p  = 0.023; OS 21.9 vs. 15.0 months, HR 0.70, 95% CI 0.49–0.99, p  = 0.047) were significantly associated with survival. In multivariable Cox analyses, better ECOG PS (HR 0.29, 95% CI 0.19-0.43, p<0.001) and capecitabine-based chemotherapy (HR 0.60, 95% CI 0.37-0.99, p=0.043) were significantly associated with higher OS. The chemo-hormonal therapy regimens were well tolerated, with 21 (9.4%) patients experiencing any grade ≥3 toxicity. Chemo-hormonal therapy is an effective treatment in heavily pre-treated MBC patients, including those with visceral metastases. Trial registration: CTRI/2022/01/039242

Isolated sinus node dysfunction with its pursuant long‐term risk for atrioventricular (AV) conduction disease poses a unique dilemma for proponents of CSP due to paucity of imprimatur guidelines. In such scenarios, the risk and prognosis of iatrogenic AV block is not well elucidated but is a valid concern. We report a case where CSP was complicated by iatrogenic AV block and peculiarly the rare phenomenon of intra‐Hisian Wenckebach.

Limited success has been achieved in the development of patient-derived xenografts (PDX) models of hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2-negative (HER2-negative) metastatic breast cancers that are resistant to hormone therapy (HT). We aimed to establish and characterize PDX models from HR+/HER2-negative breast cancer. A total of 28 tumors were orthotopically implanted in the fourth mammary fat pad of female NOD-SCID mice. Seven PDXs were developed, five from heavily pretreated HT-resistant patients and two from treatment-naïve patients. Three of the seven PDXs (two from HT-resistant and one from treatment-naive) converted into lymphoma by generation 2 (G1). The median time for developing palpable G0 PDX was 100 (45–150) days for five HT-resistant tumors, and the mean time was 178 (160–196) days for two treatment-naïve tumors. Successful PDXs were developed from three HT-resistant tumors (two up to G4, one up to G0), including one of solid papillary morphology, and one treatment-naïve tumor (up to G2). Histopathological analyses showed complete concordance for all 14 PDX generations (11 resistant, 3 treatment-naïve) with their corresponding patient’s tumor for estrogen receptor (ER), progesterone receptor (PR) and HER2. Short tandem repeat (STR) profiling using 18 markers was done in 8/11 HT-resistant generations and 3/3 treatment-naïve generations and showed good concordance of 51–100% and 91–100%, respectively, with patient tumors. We successfully established PDXs of HT-resistant and treatment-naïve HR+/HER2-negative breast cancer, which will be valuable tools for understanding molecular resistance mechanisms and for exploring novel treatment strategies.

Scar‐related ventricular tachycardia (VT) ablation involves localizing the critical isthmuses by overdrive pacing maneuvers and three‐dimensional activation mapping. Implantable prosthetic devices have been known to complicate this by covering sites of potential isthmuses. We herein present a sentinel report of scar‐VT ablation with a protected isthmus localized over an endothelialized post‐myocardial infarction ventricular septal defect occluder device.

Denovo metastatic young breast cancer (dnmYBC), defined as age <40 years, is a challenging entity, with a significant burden and sparse data from low and middle-income countries. We analysed the prospectively collected data of dnmYBC women from 2015 to 2016. There were 188 dnmYBC with a median age of 35.5 years. Of these, hormone receptor positive (HR+) were 72 (38.3) %, triple-negatives (TNBC) were 45 (23.9) %, Human Epidermal Growth Factor Positive (HER2+) were 42 (22.4) % and triple positives were 29 (15.4) %. TNBC women predominantly had visceral 40 (88.9%) metastasis, HR+ had nodal 51 (70.8%) and skeletal 10 (13.8%), while HER2+ women had higher brain metastasis (BM) 16 (38.1%).At a median follow-up of 39.8 [Interquartile range (IQR): 24-55.5] months, the median event-free survival (EFS) was 9.3 (95% CI; 8.1-10.4) months for the entire cohort and 1-year, 2-year and 3-year predicted EFS were 47.8%, 13.4% and 3%, respectively. The median EFS was superior in HR+ women.[15.7 months, hormone receptor (HR)-0.53;95% CI-9.8-21.7; p-0.013] versus (11.4 months, 95 %CI-5.9-16.8) in TNBC versus (7.7 months, 95% CI-6.0-9.5) in HER-2 + women and without BM at baseline [9.3 versus 3.0 months (with BM), HR-5.65; CI-1.72-17.9; -0.001]. Median EFS was superior in the treatment-naïve (155, 82.4%) versus prior-treated (33, 17.5%) women, 35.5 (95% CI:12.24-58.72) versus 12.4 (95% CI:11.45-13.51) months; -0.000]. The HER2+ women who received targeted therapy in the first line had a significantly superior median EFS of 13.0 versus 7.7 months (HR -0.465:CI 0.22-0.57: -0.038). Denovo mYBC is associated with an aggressive course, poor prognosticators include HR negative disease, brain metastasis, inadvertent prior treatment and inadequate access to targeted therapies. Early diagnosis, prompt treatment and expanding accessibility are warranted to improve care.

To evaluate the prognostic impact of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) on overall survival (OS) among Indian older patients with cancer. This observational study was conducted in the geriatric oncology clinic of Tata Memorial Hospital (India). We included all patients who underwent a geriatric assessment (GA) and had a complete blood count available for analysis. The NLR was dichotomized at 3.5, PLR and LMR at the median. Our primary study outcome was OS. Between June 2018 and November 2021, 786 patients were enrolled (median age: 69 years). The most common primary tumour was lung (308, 39.5%), followed by gastrointestinal (261, 33.5%). Metastatic disease was present in 54.3% of patients. Univariate analysis revealed that patients with NLR >3.5 had shorter OS (9.1 months) than NLR <3.5 (15.7 months) (HR: 1.56). Similarly, patients with PLR >183.5 had reduced OS (9.3 months) compared to PLR <183.5 (16.6 months) (HR: 1.56). Conversely, patients with LMR >3.1 showed better OS (14.2) compared to LMR <3.1 (9.8 months) (HR: 0.74). After adjusting for age, performance status, primary tumour, metastatic status and GA-derived factors (function, nutrition and cognition), NLR (HR: 1.25, 95%CI: 1.03-1.52), PLR (HR: 1.34, 95%CI: 1.11-1.63) and LMR (HR: 0.79, 95%CI: 0.65-0.95) were associated with OS. In our study of older cancer patients, we identified three key inflammatory markers (NLR >3.5, PLR >183.5, LMR <3.1) as strong predictors of poor OS. These markers remain predictive even after accounting for traditional prognostic factors and GA-derived scales.

Background In developed countries, there has been a definite change in the histopathological spectrum of esophageal cancer towards adenocarcinoma. There are limited data from India regarding the histopathological profile of patients with esophageal cancer. Materials and Methods We retrospectively evaluated patients with histologically proven esophageal cancer who were registered at the Tata Memorial Hospital (Mumbai, India) between 2003 and 2018. The primary aim of the study was to analyze the time-trend of the histological pattern of esophageal cancer. Our secondary objectives included evaluating whether there was any correlation between the histology of the esophageal cancer and the age, sex, socioeconomic status (the paying ability of the patient, which was reflected in the treatment category of the patient, i.e., private [full payment], general [subsidized payment], or no charge), comorbidities, and a history of substance abuse. Results Among 7874 patients with esophageal cancer, 5092 (64.7%) were men, with a male-to-female ratio of 1.8:1. The median age was 57 years (IQR, 50–65). Of the 4912 patients in whom a history of tobacco or alcohol use had been elicited, 1360 (27.7%) had no history of substance abuse. A majority of the tumors (2942, 37.4%) originated in the middle-third of the esophagus. Squamous cell carcinoma was the predominant histological type, noted in 6413 (81.4%) patients and remained the most common histologic type consistently through the study with no evidence of a time-trend in the histological pattern. On the multivariate analysis, female sex and a history of substance abuse were associated with higher odds of squamous cell carcinoma, while the presence of comorbidities and lower esophageal/gastroesophageal junction primaries were associated with higher odds of adenocarcinoma. Conclusions There is no evidence of an epidemiological shift in the histopathologic spectrum of esophageal cancer in India over the last two decades. Four out of five Indian patients with esophageal cancer have squamous cell histology, with the commonest site of origin being the middle third. This is important to recognize, given the varying molecular spectrum and efficacy of therapeutic modalities based on histopathology.

Background There is limited data from India with regard to presentation, practice patterns and survivals in resected pancreatic ductal adenocarcinomas (PDACs). Methods The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) included data from 8 major academic institutions across India and presents the outcomes in upfront resected PDACs from January 2015 to June 2019. Results Of 288 patients, R0 resection was achieved in 81% and adjuvant therapy was administered in 75% of patients. With a median follow-up of 42 months (95% CI: 39–45), median DFS for the entire cohort was 39 months (95% CI: 25.4–52.5), and median overall survival (OS) was 45 months (95% CI: 32.3–57.7). A separate analysis was done in which patients were divided into 3 groups: (a) those with stage I and absent PNI (SI&PNI-), (b) those with either stage II/III OR presence of PNI (SII/III/PNI+), and (c) those with stage II/III AND presence of PNI (SII/III&PNI+). The DFS was significantly lesser in patients with SII/III&PNI+ (median 25, 95% CI: 14.1–35.9 months), compared to SII/III/PNI + (median 40, 95% CI: 24–55 months) and SI&PNI- (median, not reached) ( p  = 0.036)). Conclusions The MIPPAP study shows that resectable PDACs in India have survivals at par with previously published data. Adjuvant therapy was administered in 75% patients. Adjuvant radiotherapy does not seem to add to survival after R0 resection.