Synapse - Early-onset pancreas cancer: Clinical descriptors, genomics, and outcomes

Early-onset pancreas cancer: Clinical descriptors, genomics, and outcomes Journal Article

Authors:	Varghese, A. M.; Singh, I.; Singh, R.; Kunte, S.; Chou, J. F.; Capanu, M.; Wong, W.; Lowery, M. A.; Stadler, Z. K.; Salo-Mullen, E.; Saadat, L. V.; Wei, A. C.; Reyngold, M.; Basturk, O.; Benayed, R.; Mandelker, D.; Iacobuzio-Donahue, C. A.; Kelsen, D. P.; Park, W.; Yu, K. H.; O'Reilly, E. M.
Article Title:	Early-onset pancreas cancer: Clinical descriptors, genomics, and outcomes
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.
Keywords:	survival; gemcitabine; adenocarcinoma; folfirinox
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	113
Issue:	9
ISSN:	0027-8874
Publisher:	Oxford University Press
Date Published:	2021-09-01
Start Page:	1194
End Page:	1202
Language:	English
ACCESSION:	WOS:000733845200016
DOI:	10.1093/jnci/djab038
PROVIDER:	wos
PMCID:	PMC8418394
PUBMED:	33755158
Notes:	Article -- djab038 -- Source: Wos