{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:19:10Z","timestamp":1790983150005,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: Metastatic pancreatic adenocarcinoma carries a dismal prognosis, and treatment options after progression on standard chemotherapy remain limited. We report a metabolic response in a patient with drug-resistant disease treated with a combined multimodal regimen that paired dose-reduced (\u201cactivated\u201d) multi-agent chemotherapy with targeted agents and metabolic\/microenvironmental support, set against an unusually long overall survival. Case Presentation: A 46-year-old man was diagnosed with inoperable, locally advanced\/stage IV pancreatic adenocarcinoma in June 2023 and maintained disease control for approximately 2.5 years on a combined multimodal regimen, termed here metabolically controlled oncologic therapy (MCOT): dose-reduced chemotherapy given with regional hyperthermia, hyperbaric oxygen, and a carbohydrate-restricted diet. In February 2026 he developed local recurrence and diffuse liver metastases, and by May 2026 had deteriorated rapidly, with 18F-FDG PET\/CT showing a peak SUVmax of 18.2 and CA 19-9 of 2788 U\/mL. His regimen was intensified to a low-dose, multi-agent \u201cactivated\u201d chemotherapy protocol combined with lenvatinib, everolimus, hyperthermia, and hyperbaric oxygen. Clinical Findings and Outcomes: One month later, his performance status had recovered from ECOG PS 2 to PS 0, CA 19-9 was 31 U\/mL, and follow-up PET\/CT showed a 63.7% decrease in SUVmax (from 18.2 to 6.6). Treatment-related adverse events included Grade 1 nausea, Grade 1 vomiting, and thrombocytopenia; no Grade 2 or higher non-hematological toxicity was observed. Conclusions: In selected patients who are considered to have exhausted standard options, a combined multimodal regimen pairing dose-reduced chemotherapy with metabolic and microenvironmental support may produce a well-tolerated metabolic response. As a single, uncontrolled observation, these findings cannot establish causality and require confirmation in prospective, controlled studies.<\/jats:p>","DOI":"10.3390\/curroncol33080489","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:12:58Z","timestamp":1787155978000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Response to an Individualized Multimodal Treatment Strategy in Advanced Pancreatic Adenocarcinoma: A Case Report"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4677-2236","authenticated-orcid":false,"given":"Mehmet Salih","family":"\u0130yikesici","sequence":"first","affiliation":[{"name":"Neolife Oncology Centre, 34340 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oral","family":"Oncul","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Division of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metin","family":"Halla\u00e7","sequence":"additional","affiliation":[{"name":"Neolife Oncology Centre, 34340 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3967-8903","authenticated-orcid":false,"given":"Sena","family":"\u015een","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Oncology Institute, Istanbul University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eirin","family":"Taflan","sequence":"additional","affiliation":[{"name":"Neolife Oncology Centre, 34340 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4912-236X","authenticated-orcid":false,"given":"Selin","family":"Oncul","sequence":"additional","affiliation":[{"name":"Medical School, Kings College of London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7778-0194","authenticated-orcid":false,"given":"Tomas","family":"Duraj","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Boston, MA 02467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-3989","authenticated-orcid":false,"given":"Thomas N.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Boston, MA 02467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4298","DOI":"10.3748\/wjg.v27.i27.4298","article-title":"Pancreatic cancer: A review of epidemiology, trend, and risk factors","volume":"27","author":"Hu","year":"2021","journal-title":"World J. 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