Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes.

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). Institutional databases were queried for demographics, treatment history, genomic results, and outcomes. Overall survival from date of diagnosis was estimated using Kaplan-Meier method. 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). 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. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Anna M Varghese, Isha Singh, Rituraj Singh, Siddharth Kunte, Joanne F Chou, Marinela Capanu, Winston Wong, Maeve A Lowery, Zsofia K Stadler, Erin Salo-Mullen, Lily V Saadat, Alice C Wei, Marsha Reyngold, Olca Basturk, Ryma Benayed, Diana Mandelker, Christine A Iacobuzio-Donahue, David P Kelsen, Wungki Park, Kenneth H Yu, Eileen M O'Reilly. Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes. Journal of the National Cancer Institute. 2021 Sep 04;113(9):1194-1202

Mesh Tags

PMID: 33755158

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