Varghese, Anna M.Singh, IshaSingh, RiturajKunte, SiddharthChou, Joanne F.Capanu, MarinelaWong, WinstonLowery, Maeve A.Stadler, Zsofia K.Salo-Mullen, ErinSaadat, Lily V.Wei, Alice C.Reyngold, MarshaBasturk, OlcaBenayed, RymaMandelker, DianaIacobuzio-Donahue, Christine A.Kelsen, David P.Park, WungkiYu, Kenneth H.O’Reilly, Eileen M.2023-05-252023-05-252021Varghese AM, Singh I, Singh R, et al. Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes. J Natl Cancer Inst. 2021;113(9):1194-1202. doi:10.1093/jnci/djab038https://hdl.handle.net/1805/33309Background: Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC). Methods: Institutional databases were queried for demographics, treatment history, genomic results, and outcomes. Overall survival from date of diagnosis was estimated using Kaplan-Meier method. Results: Between 2008 and 2018, 450 patients with EOPC were identified at Memorial Sloan Kettering. Median overall survival was 16.3 (95% confidence interval [CI] = 14.6 to 17.7) months in the entire cohort and 11.3 (95% CI = 10.2 to 12.2) months for patients with stage IV disease at diagnosis. Of the patients, 132 (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1, and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. A total of 138 patients (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV), and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a PGV. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared with patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95% CI = 0.26 to 0.69). Conclusions: PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.en-USPublisher PolicyPancreatic ductal carcinomaPancreatic neoplasmsGenomicsArticle