Varun Goel

Purpose: Gallbladder cancer is an aggressive malignancy with poor outcomes in advanced disease. Evidence specific to gallbladder cancer from routine clinical practice remains limited. We compared outcomes among patients treated with gemcitabine–cisplatin (GemCis) with or without durvalumab. Methods: This single-centre ambispective observational cohort included 98 patients with unresectable, recurrent, or metastatic gallbladder cancer treated from January 2023 through June 2025. Forty-eight received GemCis alone and 50 received GemCis plus durvalumab; treatment selection was based on drug availability and patient preference after counselling. Follow-up continued through December 2025. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: Median PFS was 6.1 months with GemCis plus durvalumab and 4.1 months with GemCis alone (unadjusted HR 0.55, 95% CI 0.36–0.85; p = 0.007). Median OS was 14.2 and 9.7 months, respectively (unadjusted HR 0.58, 95% CI 0.35–0.99; p = 0.041). In 6-month landmark analyses, the PFS difference persisted (HR 0.39, 95% CI 0.19–0.81) but the OS difference did not (HR 1.15, 95% CI 0.61–2.17). In multivariable Cox models, the adjusted HR was 0.55 (95% CI 0.35–0.85) for PFS and 0.58 (95% CI 0.34–0.98) for OS. Objective response rates were 30.0% (15/50) and 18.8% (9/48), and disease control rates were 56.0% (28/50) and 39.6% (19/48), respectively. The response-rate differences were not statistically significant (Fisher’s exact p = 0.243 and p = 0.112, respectively). Immune-related adverse events were reported in 20% of patients receiving durvalumab, including grade ≥3 events in 2%. Conclusion: In this nonrandomized cohort, durvalumab-containing treatment was associated with numerically longer PFS and OS, but the OS difference was not maintained in landmark analysis. Residual confounding, adjustment limited to measured baseline factors, possible bias related to maintenance exposure, and unavailable systematic biomarker and subsequent-treatment data limit causal interpretation. The findings are hypothesis-generating.

Purpose: Gallbladder cancer is highly prevalent in North India and associated with poor survival in advanced disease. Although chemoimmunotherapy improves outcomes in biliary tract cancers, prospective data specific to gallbladder cancer remain limited. We compared gemcitabine-cisplatin (GemCis) with or without durvalumab in patients with advanced gallbladder cancer. Methods: In this ambispective observational cohort study at a North Indian tertiary cancer center (Jan 2023–June 2025), 98 patients with unresectable/metastatic gallbladder cancer received GemCis alone (n=48) or GemCis+durvalumab (n=50) based on drug availability and patient preference after counseling. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: Baseline characteristics were balanced. ORR was 30.0% with durvalumab vs 18.8% with GemCis alone; DCR was 56.0% vs 39.6%. Median PFS was 6.1 vs 4.1 months (HR 0.62, 95% CI 0.45–0.88; P=0.007). Median OS was 14.2 vs 9.7 months (HR 0.69, 95% CI 0.52–0.91; P=0.012). Grade ≥3 adverse events were similar between arms. Immune-related adverse events occurred in 20% receiving durvalumab (grade ≥3: 2%), all manageable. Conclusions: In this gallbladder cancer-specific cohort, durvalumab added to GemCis was associated with improved PFS and OS without increased toxicity. These findings support further evaluation of chemoimmunotherapy for advanced gallbladder cancer in high-incidence regions.

Non-gestational choriocarcinomas (NGCCs) are extremely rare and aggressive tumours that can develop without pregnancy. We present three cases in postmenopausal women in their early 60s and 70s who presented with abdominal symptoms. Evaluation included imaging, histopathology, immunohistochemistry and elevated serum β-hCG. One patient showed a partial response to chemotherapy, while two had disease progression and died. The case series illustrates the need for consideration of NGCC in older women with elevated β-hCG and no recent pregnancy, and the crucial role of early immunohistochemical diagnosis.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) deficiency, an autosomal recessive metabolic disorder, causes a considerable deficit in the patient's metabolism of fluoropyrimidine drugs, most notably 5-fluorouracil (5-FU) and capecitabine. There is a higher frequency of severe toxicities after a fluoropyrimidine regimen among patients with GI and hepatopancreaticobiliary (HPB) malignancies on chemotherapy because of this metabolic deficiency. This prospective study aims to assess the rate of DPD deficiency and clinical significance of DPD deficiency in patients receiving fluoropyrimidine chemotherapy at a tertiary oncology center in India. MATERIALS AND METHODS: From March 2024 to February 2025, we prospectively recruited 146 patients with histologic confirmation of GI and HPB cancers who were commencing a 5-FU– or capecitabine-based regimen. We performed pretreatment DPD tests on all patients using TRUPCR DPYD reverse transcriptase polymerase chain reaction for four known variants. Severe toxicities (Common Terminology Criteria for Adverse Events v5.0) were assessed after the first cycle of chemotherapy. Dose reductions, advances in therapy, and admissions were also noted. RESULTS: Of the 146 study participants, 11 (7.5%) had a DPYD mutation. HapB3 (rs56038477) was the most commonly encountered variant (72.7% of patients), along with registries of DPYD*2A (18.2%) mutation and mutation c.2846A>T (9.1%). Severe toxicities (grade ≥3) were above other grade toxicities (61.6%) in mutation carriers (72.7%) as compared with mutation noncarriers (37.0%, P = .03). Neutropenia, diarrhea, and thrombocytopenia were the common toxicities at a frequency of 18.5%, 12.3%, and 15.1%, respectively. After dose reduction, 90.9% of mutation carriers required a dose reduction versus 14.8% of mutation noncarriers ( P < .001). Both groups had no problems in completing treatment. CONCLUSION: Individuals with DPYD mutations experience increased toxicity and dose adjustments; however, treatment efficacy was not affected. This indicates that a coordinated effort that incorporates routine DPYD testing can mitigate treatment toxicities and individualized fluoropyrimidine dosing for patients with GI and HPB cancers.

Background Muscle-invasive bladder cancer (MIBC) involves a high risk of progression and death. Neoadjuvant chemotherapy (NAC), prior to radical cystectomy (RC), has been shown to improve survival. Gemcitabine-cisplatin (GC) has emerged as a preferred NAC regimen based on its favorable toxicity profile, while dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) may yield better pathologic complete response (pCR) rates, as reported in some studies. Purpose The objective of this study is to compare the efficacy and toxicity profiles of GC and ddMVAC as neoadjuvant regimens in patients with MIBC. Methods This was a retrospective study of 120 patients with clinical stage cT≥2-4a, N+M0 MIBC, treated at a single tertiary cancer center from January 2023 to December 2024. GC was administered to 63 patients, and ddMVAC to 57 patients. Outcomes included pCR, pathologic downstaging, disease-free survival (DFS), overall survival (OS), and toxicity. Results The pCR rate was higher for ddMVAC (22/57 patients, 38.59%) than for GC (14/63 patients, 22.22%) (p = 0.04). Patients with downstaging (≤pT1N0) were more frequent in the ddMVAC group (34/57 patients, 59.64%) compared to the GC group (28/63 patients, 44.44%). The median OS was longer for the ddMVAC group (41.6 months; 95% CI: 35.2-48.9) compared to the GC group (36.8 months; 95% CI: 30.5-42.1) (p = 0.12; HR: 0.82; 95% CI: 0.63-1.06). The incidence of grade ≥3 toxicity was higher for ddMVAC, with 20/57 patients (35%) vs. 10/63 patients (15.87%) for GC. Febrile neutropenia occurred in 8/57 patients (14%) in the ddMVAC group, compared to 3/63 patients (4.76%) in the GC group. Conclusion ddMVAC exhibited higher pCR and downstaging rates than GC, with a tolerable - though higher - rate of toxicity. Both regimens are acceptable options for NAC in MIBC, with treatment choice dependent on each patient’s fitness and preferences.

Background The widespread use of oxaliplatin plus infusional 5-fluorouracil (5-FU) and folinic acid (FOLFOX) in advanced gastric cancers is mainly based on clinical trials conducted at Western/European countries. The prospective data on efficacy and safety of FOLFOX in advanced gastric cancer is lacking from the developing countries. In this prospective observational study, we evaluated the efficacy and toxicity of mFOLFOX-6 in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinomas, as first-line palliative chemotherapy. Methods Patients with previously untreated metastatic adenocarcinoma of stomach/GEJ, received mFOLFOX-6 (2 hours infusion of oxaliplatin [85 mg/m²] and folinic acid [400 mg/m²], followed by fluorouracil 400 mg/m² intravenous push, then a 46-hour continuous infusion of 5-FU [2,400 mg/m²]). Cycles were repeated every 2 weeks. The patients were prospectively followed up for response rates and toxicity. Results Sixty-six patients were included in the study with a median age of 57 years. Sixty-two patients were evaluable for response. The overall response rate was 53%, with a disease control rate (overall response and stable disease) of 81.8%. The median progression-free survival was 6 months (95% confidence interval [CI] 5.2–6.7 months) and the median overall survival was 11.5 months (95% CI 9.0–13.9 months). Ascites at presentation and more than one site of metastasis are associated with significantly lower survival on the log-rank test. Gastrointestinal and hematological toxicities were predominant, with rates of grade 3 to 4 nausea/vomiting (13.6%), anemia (15.1%), and neutropenia (13.6%). Among other toxicities, neurosensory toxicities were common. Four (6%) patients had grade 3 peripheral neuropathy. Conclusion mFOLFOX-6 is an active and well-tolerated chemotherapy regimen in advanced adenocarcinoma of stomach/GEJ. This regimen has similar response rates and treatment outcomes with lesser grade 3 or 4 toxicities than that of triplet regimens compared to historical studies. Received: 14 June 2023 Accepted: 26 June 2024 Article published online: 22 July 2024 © 2024. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

The molecular pathogenesis of breast cancer (BC), the second most common cancer, varies significantly between sexes, with minimal data in the transgender population. The overall prevalence of BC in transgenders is estimated to be 0.02%. Besides experiencing social disparities, transgenders have to face a lot of discrimination in the healthcare system. Adversities faced, along with the urge to identify with physical attributes to the gender felt by them, forces transgenders to use non-prescribed hormones. Gender affirming hormone therapy (GAHT) is a key feature of transition-related care, rehabbing mental health, and the quality of life of transgenders, but at the expense of their health. Studies have reported that GAHT is associated with severe health conditions such as cancer in transgenders. Estrogens and testosterone are associated with a moderate risk of developing BC. The types of BC diagnosed in transgenders after cross-sex hormone therapy include invasive ductal and neuroendocrine carcinoma, in addition to tubular adenocarcinoma. Although diagnosed at an age earlier compared with ciswomen, BC screening recommendations for transgenders are the same as for ciswomen. This review studies in detail the types of transgenders, their characteristics, different types of breast cancers associated, issues faced while treatment, and their best possible solutions. We also hope to have well-designed research in the future, which will fill the existing gaps in knowledge and provide scientific insight into the transgender population and issues related to their health. There are no international guidelines on screening and management of transgender patients but it appears that breast screening before cosmetic mastectomy, exposure to hormonal therapy for more than 5 years, and as per natal women screening guidelines should be offered to the patient with detailed discussion on the harms and benefits of the same.

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher’s exact test was used to compare categorical variables, and a Kruskal–Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue.