Background: Pancreatic adenocarcinoma is a formidable malignancy with historically limited treatment options. This study aimed to assess the effectiveness of modified FOLFIRINOX as a first-line chemotherapy regimen in unresectable and metastatic cases, comparing it to established treatments. Methods: From November 2019 to June 2021, 34 patients with unresectable or metastatic pancreatic adenocarcinoma were treated with modified FOLFIRINOX at a North Indian tertiary cancer care institute. Patient demographics, treatment cycles, adverse events, and treatment response were analyzed. The study also explored the potential impact of patient characteristics on treatment outcomes. Results: Modified FOLFIRINOX demonstrated promising results, with a disease control rate of 88.2%. Partial and complete responses were observed in 52.9% and 11.7% of patients, respectively. Median progression-free survival was 8 months, and median overall survival was 11 months. Adverse events, although present, were manageable, highlighting the importance of patient selection and careful monitoring. Conclusions: Modified FOLFIRINOX emerged as an effective first-line treatment option for unresectable and metastatic pancreatic adenocarcinoma, offering improved response rates and survival compared to historical treatments. Patient selection based on performance status and comorbidities played a pivotal role in optimizing outcomes. While further multicenter trials are needed to validate these findings, this study suggests that modified FOLFIRINOX should be considered for eligible patients, potentially revolutionizing the management of this challenging malignancy. Personalized treatment approaches based on tumor molecular characteristics should also be explored to expand treatment options for specific patient subsets. This study contributes valuable insights into the evolving landscape of pancreatic adenocarcinoma therapy, offering hope and improved prospects for patients facing this devastating disease.

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.

Immune checkpoint inhibitor (ICI) restores an efficient antitumor T cell response against tumor cells fostering durable responses that can persist even after the treatment. However, these treatment effects can manifest as an unusual pattern of disease progression, pseudo-progression, or hyper-progression. Differentiating hyper progressive disease (HPD) from pseudo-progression has significant clinical implications and further decision-making for the patient on ICI. HPD is a dramatic acceleration of the rate of tumor progression with the advent of immunotherapeutic agents causing detrimental effects on the disease outcome. The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work. Publication Date: 18 April 2022 (online) © 2022. Indian Society of Medical and Paediatric Oncology. 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

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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.