Survival of patients with microsatellite instability-high and Lynch syndrome-associated pancreatic ductal adenocarcinomas.

• DOI: 10.1200/jco.2024.42.3_suppl.640
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Naaz Nasar; Ellis Eikenboom; Kenneth Seier; Mithat Gonen; Anja Wagner; William R. Jarnagin; Jeffrey A. Drebin; Michael Ian D'Ang...; T. Peter Kingham; Vinod P. Balachan...; Kevin Soares; Manon C.W. Spaander; Alice Chia-Chi Wei
• Keywords: Microsatellite Instability; MSH2; MLH1; MSH6; Lynch Syndrome; PMS2

640 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressive nature, late-stage diagnosis, and limited treatment options. There is an increased interest in cancers which harbor microsatellite instability (MSI) their susceptibility immune checkpoint inhibitors. MSI PDAC rare, little known about survival this subtype of pancreas cancers. Our aim was assess overall surgically resected high (MSI-H), mismatch repair deficient (MMRd), Lynch Syndrome (LS) associated PDACs treated our center. Methods: Patients with from 1990 2023 were identified. A total 936 cases sequenced utilizing MSK-IMPACT, targeted next generation sequencing platform. germline or sporadic pathogenic variants likely one the DNA MMR genes MLH1, MSH2, MSH6, PMS2, 3’ end EpCAM MSI-H, MMRd, LS-associated matched patients stable proficient, non-LS-associated 1:2 ratio direct match on age (±5 years), gender, year surgery (±3 years). Kaplan-Meier curves used visualize data. generalized estimating equation (GEE) cox model robust sandwich estimator compare cohorts. Results: 17 MMRd Five classified as 3 MSI-indeterminate, 9 stable. Eight found have genes. The remaining nine had gene ( MLH1 n=3, MSH6 n=6). Median at 66 (interquartile range (IQR) 60-77), 41% female, median 2014. 34 control patients. time 12 years vs. 1.9 group. Five-year rate 81% (IQR 60-100%) 18% (7.4%-43%), respectively. LS-associated, MSI-H status resectable strong predictor good prognosis (hazard 0.17, 95% CI 0.07-0.38, p value <0.001). Conclusions: displayed significantly better compared MSI-stable, counterparts, era before routine use immunotherapy. It expected that will be further more frequent availability