{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:16:35Z","timestamp":1789769795762,"version":"4.0.1"},"reference-count":33,"publisher":"Harborside Press, LLC","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The benefit of adjuvant chemotherapy (AC) for ampullary adenocarcinoma is unclear. The Hidden Genome model classifies prognostic subtypes with greater accuracy than standard histologic classification (intestinal [INT] vs pancreatobiliary [PB]), but its predictive capacity to guide the use of AC remains unstudied. <jats:bold>Methods:<\/jats:bold> We applied the Hidden Genome model to an international cohort of 183 patients with resected ampullary adenocarcinoma who underwent genomic sequencing. The model quantified the predicted cell of origin (colorectal vs pancreas\/distal bile duct) in all specimens. Overall survival (OS) was compared using Kaplan-Meier estimates, stratified by AC use versus surgery alone (SA). <jats:bold>Results:<\/jats:bold> Most patients (n=128; 69.9%) received AC, which was not associated with a significant improvement in OS (median, 50.9 months [95% CI, 36.5\u201376.9] vs 53.8 months [95% CI, 32.4\u2013119.0]; <jats:italic>P<\/jats:italic>=.816). Histologic subtype was neither associated with prognosis (<jats:italic>P<\/jats:italic>=.241) nor predictive of chemotherapy efficacy for INT-subtype (<jats:italic>P<\/jats:italic>=.379) or PB-subtype (<jats:italic>P<\/jats:italic>=.544) tumors. When stratified by genomic subtype, the colorectal group had a favorable prognosis regardless of AC use (median OS, 74.4 months [95% CI, 33.8\u201397.8] for AC vs 98.7 months [95% CI, 32.4\u2013140.9] for SA; <jats:italic>P<\/jats:italic>=.889). Among patients with pancreas\/distal bile duct tumors, those who received AC had longer survival compared with those who underwent SA (78.2 months [9.8\u2013not reached] vs 22.7 months [2.3\u2013not reached], respectively; hazard ratio, 0.17 [95% CI, 0.04\u20130.80]; <jats:italic>P<\/jats:italic>=.024). <jats:bold>Conclusions:<\/jats:bold> AC regimens were not associated with improved survival in histologically defined INT- or PB-subtype ampullary adenocarcinoma. However, genomic classification better stratified risk groups and identified patients more likely to benefit from AC.<\/jats:p>","DOI":"10.6004\/jnccn.2025.7008","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T12:39:20Z","timestamp":1749645560000},"page":"234-240","source":"Crossref","is-referenced-by-count":2,"title":["Histologic- and Genomic-Directed Adjuvant Therapy for Ampullary Adenocarcinoma: A Hidden Genome\u2013Derived Analysis"],"prefix":"10.6004","volume":"23","author":[{"given":"Brett L.","family":"Ecker","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Rutgers Cancer Institute, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Seier","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankur","family":"Choubey","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin M.","family":"Eckhoff","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella N.","family":"Tortorello","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod P.","family":"Balachandran","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Blackburn","sequence":"additional","affiliation":[{"name":"The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I.","family":"D\u2019Angelica","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.","family":"DeMatteo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Blazer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Drebin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Surgery, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Gill","sequence":"additional","affiliation":[{"name":"The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia"},{"name":"Royal North Shore Hospital, St Leonards, New South Wales, Australia"},{"name":"University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Claude","family":"Gingras","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Peter","family":"Kingham","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Major K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Lidsky","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Overman","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaswinder S.","family":"Samra","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronglai","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlie S.","family":"Sigel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Vollmer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabino","family":"Zani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"_","family":"_","sequence":"additional","affiliation":[{"name":"The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Roses","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithat","family":"Gonen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Jarnagin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"JAMA Surg","first-page":"706","article-title":"Role of adjuvant multimodality therapy after curative-intent resection of ampullary carcinoma","volume":"154","author":"Ecker BL","year":"2019","unstructured":"Ecker BL, Vollmer CM, Behrman SW,  Role of adjuvant multimodality therapy after curative-intent resection of ampullary carcinoma. 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Ann Surg 2020;272:1086\u20131093."},{"key":"B32","series-title":"Ann Surg","first-page":"1025","article-title":"Surrogacy of recurrence-free survival for overall survival as an endpoint of clinical trials of perioperative adjuvant therapy in hepatobiliary-pancreatic cancers: a retrospective study and meta-analysis","volume":"279","author":"Imamura T","year":"2023","unstructured":"Imamura T, Ohgi K, Mori K,  Surrogacy of recurrence-free survival for overall survival as an endpoint of clinical trials of perioperative adjuvant therapy in hepatobiliary-pancreatic cancers: a retrospective study and meta-analysis. Ann Surg 2023;279:1025\u20131035."},{"key":"B33","series-title":"Cancer Cell","first-page":"229","article-title":"Genomic sequencing identifies ELF3 as a driver of ampullary carcinoma","volume":"29","author":"Yachida S","year":"2016","unstructured":"Yachida S, Wood LD, Suzuki M,  Genomic sequencing identifies ELF3 as a driver of ampullary carcinoma. 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