{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:48:07Z","timestamp":1790624887079,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente funding from the Italian Ministry of Health"},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["30711"],"award-info":[{"award-number":["30711"]}]},{"name":"Italian Ministry of University and Research","award":["-M4C2- I1.3"],"award-info":[{"award-number":["-M4C2- I1.3"]}]},{"name":"Italian Ministry of University and Research","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>International guidelines recommend 5FU\/LV, Nal-IRI + 5FU\/LV, FOLFIRI, FOLFOX, or (m)FOLFIRINOX as second-line (2L) chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after failure of gemcitabine+Nab-paclitaxel (GnP). However, a head-to-head comparison has not been performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We conducted an observational cohort study of consecutive mPDAC patients treated with 2L chemotherapy after GnP failure at 41 Italian centers. Progression-free survival (PFS) and overall survival (OS) were compared using inverse probability of treatment weighting. Interpretable artificial intelligence methods were applied to optimize treatment allocation. A counterfactual Cox model was trained on baseline characteristics to estimate 12-month PFS under each regimen, and an Optimal Policy Tree (OPT) was derived to generate treatment recommendations, validated in a test set. Net-benefit curves evaluated clinical utility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 704 eligible patients, 56 (8.0%) received 5FU\/LV, 153 (21.7%) FOLFIRI, 209 (29.7%) FOLFOX, 209 (29.7%) Nal-IRI\u2009+\u20095FU\/LV, and 77 (10.9%) FOLFIRINOX. FOLFIRINOX was associated with the longest PFS and OS. Median PFS was comparable among doublets (3.5\u2009months FOLFOX, 3.6 FOLFIRI, 3.3 Nal-IRI\u2009+\u20095FU\/LV), though Nal-IRI\u2009+\u20095FU\/LV showed a long-term benefit. The OPT recommended Nal-IRI\u2009+\u20095FU\/LV for patients with head\/body tumors, Eastern Cooperative Oncology Group performance status (PS) 0, or CA19.9\u2009&amp;lt;\u2009109 U\/mL in those with PS &amp;gt; 0. Net-benefit analysis showed that the OPT consistently outperformed uniform treatment strategies, achieving a 2.5 percentage-point net benefit at a threshold probability of \u223c9%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FOLFIRINOX appears the most effective option for carefully selected, fit patients eligible for 2L chemotherapy after GnP failure. Interpretable artificial intelligence-derived treatment policies may provide superior net clinical benefit compared to uniform approaches and guide individualized therapy, warranting integration with upcoming targeted strategies such as RAS inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag085","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:59:29Z","timestamp":1773932369000},"source":"Crossref","is-referenced-by-count":1,"title":["Second-line chemotherapy after gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: comparative outcomes and AI-guided treatment selection"],"prefix":"10.1093","volume":"31","author":[{"given":"Letizia","family":"Procaccio","sequence":"first","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS Medical Oncology 1, , Padova, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Policlinico Riuniti di Foggia, Unit of Medical Oncology and Biomolecular Therapy and University of Foggia , Foggia, 71122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-4207","authenticated-orcid":false,"given":"Federico","family":"Nichetti","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS Medical Oncology 1, , Padova, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Milella","sequence":"additional","affiliation":[{"name":"Division of Oncology, Verona University and Hospital Trust (AOUI Verona) , Verona, 37126,","place":["Italy"]},{"name":"Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona , Verona, 37134,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pretta","sequence":"additional","affiliation":[{"name":"Medical Oncology, University Hospital and University of Cagliari , Cagliari, 09124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Iacono","sequence":"additional","affiliation":[{"name":"Department of Oncology, Academic Hospital of Udine ASUFC , Udine, 33100,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9055-5338","authenticated-orcid":false,"given":"Monica","family":"Niger","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, 20133,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Casalino","sequence":"additional","affiliation":[{"name":"Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata Verona , Verona, 37126,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Vivaldi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa, 56126,","place":["Italy"]},{"name":"Unit of Medical Oncology 2, Pisa University Hospital , Pisa, 56124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"De Vita","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania \u201cL. Vanvitelli\u201d , Naples, 81100,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pusceddu","sequence":"additional","affiliation":[{"name":"Medical Oncology, University Hospital and University of Cagliari , Cagliari, 09124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Landriscina","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Policlinico Riuniti di Foggia, Unit of Medical Oncology and Biomolecular Therapy and University of Foggia , Foggia, 71122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS Medical Oncology 1, , Padova, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sperotto","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS Medical Oncology 1, , Padova, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Masucci","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Policlinico Riuniti di Foggia, Unit of Medical Oncology and Biomolecular Therapy and University of Foggia , Foggia, 71122,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS , Rome, 00136,","place":["Italy"]},{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore , Rome, 00168,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bianco","sequence":"additional","affiliation":[{"name":"Medical Oncology, University of Federico II , Naples, 80138,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Vasile","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology 2, Pisa University Hospital , Pisa, 56124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zaniboni","sequence":"additional","affiliation":[{"name":"Oncology, Fondazione Poliambulanza , Brescia, 25124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Carmen","family":"Miceli","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania \u201cL. Vanvitelli\u201d , Naples, 81100,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-7092","authenticated-orcid":false,"given":"Elena","family":"Ongaro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico (CRO) IRCCS Aviano , Aviano, 33081,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Giommoni","sequence":"additional","affiliation":[{"name":"Medical Oncology Division, Azienda Ospedaliero-Universitaria Careggi , Firenze, 50134,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Tin\u00e8","sequence":"additional","affiliation":[{"name":"Biostatistics for Clinical Research Unit, Epidemiology and Data Science Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , Milan, 20133,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Barsotti","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS Medical Oncology 1, , Padova, 35128,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, 20133,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariacristina","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna , Bologna, 40126,","place":["Italy"]},{"name":"Medical Oncology Unit, IRCSS, Azienda Ospedaliero Universitaria di Bologna , Bologna, 40138,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ortolani","sequence":"additional","affiliation":[{"name":"Ospedale P. 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