Young-onset Pancreas Cancer (PC) in Patients Less Than or Equal to 50 Years Old at Memorial Sloan Kettering (MSK): Descriptors, Genomics, and Outcomes.

774 Background: For individuals ≤ 50 years old, cancer incidence is increasing, particularly gastrointestinal and obesity related cancers (Sung, Lancet Public Health 2019). Limited details are known about young onset PC. Herein, we report the epidemiologic, pathologic, and molecular characteristics of PC in patients (pts) ≤ 50 years. Methods: MSK institutional database was queried for medical and treatment history, genomics, and outcomes in pts ≤ 50 years old diagnosed with PC between January 2008 and July 2018. Neuroendocrine cancers were excluded. Overall survival (OS) from date of PC diagnosis was estimated using Kaplan-Meier methods. Results: N = 450 pts ≤ 50 years old with a diagnosis of PC were identified. Ninety-six percent had adenocarcinoma, and 4% had acinar cell carcinoma/other histologies. Table summarizes demographics. Median OS was 16 months in the entire cohort and 11.3 months in stage IV disease. For N = 236 pts diagnosed after 2014, 119 (50%) underwent successful somatic testing with at least one alteration identified, and 21/119 tumors were RAS wild-type with identification of several actionable alterations (NRG1 fusions (n=2), NTRK fusions (n=2), IDH1 R132C (n=1), and microsatellite unstable tumors (n=1) ). N = 114 pts had germline testing (routine after 2015), and 33/114 (29%) had pathologic germline alterations, including BRCA1/2 (n=18), CHEK2 (n=3), PALB2 (n=3), ATM (n=2), MLH1 (n=1), and MSH3 (n=1). Conclusions: Pathogenic germline alterations are present in a substantial percentage of pts with young onset PC, and actionable somatic alterations were seen frequently in the subgroup of young onset PC RAS-wild type tumors. These observations underpin the need for germline and somatic profiling in PC. [Table: see text]