Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes. (23rd March 2021)

• Record Type: Journal Article
• Authors: Varghese, Anna M; Singh, Isha; Singh, Rituraj; Kunte, Siddharth; Chou, Joanne F; Capanu, Marinela; Wong, Winston; Lowery, Maeve A; Stadler, Zsofia K; Salo-Mullen, Erin; Saadat, Lily V; Wei, Alice C; Reyngold, Marsha; Basturk, Olca; Benayed, Ryma; Mandelker, Diana; Iacobuzio-Donahue, Christine A; Kelsen, David P; Park, Wungki; Yu, Kenneth H; O'Reilly, Eileen M
• Is Part Of: Journal of the National Cancer Institute. Volume 113:Number 9(2021)
• Page Start: 1194
• Page End: 1202
• Publication Date: 2021-03-23
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djab038
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: 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.