{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:07:52Z","timestamp":1789067272404,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009729","name":"Ludwig Institute for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A randomized phase II screening trial of gemcitabine, nab\u2010paclitaxel, and cisplatin with a medically supervised ketogenic diet (MSKD) versus usual diet (non\u2010MSKD) was conducted in patients with treatment\u2010naive metastatic pancreatic ductal adenocarcinoma (PDAC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with untreated metastatic PDAC were randomized 1:1 to MSKD or non\u2010MSKD while receiving gemcitabine, nab\u2010paclitaxel, and cisplatin on days 1 and 8 of a 21\u2010day cycle. The MSKD was guided by a remote health care team and daily ketone (beta\u2010hydroxybutyrate) levels, with goal beta\u2010hydroxybutyrate of 0.5 to 3.0 mM. The primary endpoint was progression\u2010free survival (PFS) using a one\u2010sided alpha level of 0.20. Secondary endpoints included overall survival (OS), safety, and quality of life (QOL). Changes in microbiome were an exploratory endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Overall, there were 32 evaluable patients. In the MSKD arm, 15 of 16 patients achieved nutritional ketosis; the median proportion of days in ketosis was 39.4%. The median PFS was 8.5 months in MSKD patients and 6.2 months in non\u2010MSKD patients: hazard ratio, 0.53 (95% CI, 0.21\u20131.37); one\u2010sided\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.096. The median OS was 13.7 months with MSKD and 10.2 months in the non\u2010MSKD arm: hazard ratio, 0.58 (95% CI, 0.25\u20131.37); one\u2010sided\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.107). All MSKD\u2010related adverse events were grade 1\u20102. There were no significant differences in grade \u22653 chemotherapy\u2010related adverse events between the arms. MSKD patients had no decline in QOL and had significant enrichment of beneficial taxa in the microbiome (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05, log\u2010fold change \u22652).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The MSKD is feasible in patients with PDAC and, although not powered for definitive outcomes, shows trends in improved PFS and OS when combined with gemcitabine, nab\u2010paclitaxel, and cisplatin, without added toxicity or detriment to QOL. Larger studies are required to confirm these findings and establish the value of the MSKD in pancreatic cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70343","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T12:00:16Z","timestamp":1773316816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A randomized phase II trial of gemcitabine, nab\u2010paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-5965","authenticated-orcid":false,"given":"Gayle S.","family":"Jameson","sequence":"first","affiliation":[{"name":"Oncology Division HonorHealth Research Institute  Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise J.","family":"Roe","sequence":"additional","affiliation":[{"name":"The University of Arizona Cancer Center  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkut","family":"Borazanci","sequence":"additional","affiliation":[{"name":"Oncology Division HonorHealth Research Institute  Scottsdale Arizona USA"},{"name":"School of Medicine and Advanced Medical Engineering Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-5032","authenticated-orcid":false,"given":"Diana L.","family":"Hanna","sequence":"additional","affiliation":[{"name":"USC Norris Comprehensive Cancer Center Medical Oncology  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline G. 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University of Arizona Cancer Center  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-3043","authenticated-orcid":false,"given":"Keehoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen) TGen Integrated Microbiomics Center  Flagstaff Arizona USA"},{"name":"Translational Genomics Research Institute (TGen) Clinical Genomics and Therapeutics  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5630-0350","authenticated-orcid":false,"given":"Derek","family":"Cridebring","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen) Clinical Genomics and Therapeutics  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Rabinowitz","sequence":"additional","affiliation":[{"name":"Department of Chemistry 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