Survival of patients with resected microsatellite instability-high, mismatch repair deficient, and Lynch syndrome-associated pancreatic ductal adenocarcinomas Journal Article
| Authors: | Eikenboom, E. L.; Nasar, N.; Seier, K.; Gönen, M.; Spaander, M. C. W.; O’Reilly, E. M.; Jarnagin, W. R.; Drebin, J.; D’Angelica, M. I.; Kingham, T. P.; Balachandran, V. P.; Soares, K. C.; Wagner, A.; Wei, A. C. |
| Article Title: | Survival of patients with resected microsatellite instability-high, mismatch repair deficient, and Lynch syndrome-associated pancreatic ductal adenocarcinomas |
| Abstract: | Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressiveness, late-stage diagnosis, and limited treatment options. Microsatellite instability-high (MSI-H) cancers are susceptible to immune checkpoint inhibitors. Survival outcomes for patients with MSI-H PDAC are unknown as the disease is rare. Methods: This study included patients with PDACs surgically resected from 1990 to 2023, and those with germline or sporadic pathogenic variants in DNA mismatch repair genes were identified. The study matched MSI-H, mismatch repair-deficient (MMRd), and Lynch syndrome (LS)-associated PDAC cases (on age, gender, and year of surgery) with microsatellite-stable (MSS), mismatch repair-proficient, or non-LS-associated PDAC cases in a 1:2 ratio. A generalized estimating equation Cox model with a robust sandwich estimator was used to compare overall survival (OS) in the matched cohorts. Results: Of 936 cases, 18 were included. Eight cases were MSI-H/MMRd, two were MSI/IHC-indeterminate, seven were MSS, and one was not tested for MSI. Nine patients had LS (MLH1 [n = 1], MSH2 [n = 4], MSH6 [n = 1], PMS2 [n = 3]), and nine patients had sporadic pathogenic variants in DNA MMR genes (MLH1 [n = 4], MSH6 [n = 5]). After matching to 36 control patients, the MSI-H/MMRd/LS PDACs had a significantly better OS (hazard ratio [HR], 0.36 [95% confidence interval [CI], 0.18–0.73; p = 0.005]; 5-year OS: MSI-H 77% [95% CI 58–100%] vs. MSS 27% [95% CI 15–51%]). Conclusion: Before routine use of immune checkpoint inhibitors, the patients with MSI-H, MMRd, and LS-associated PDACs displayed significantly better survival than the patients with MSS, MMR-proficient, non-LS-associated PDACs. It is expected that survival for this cohort will further improve with increased availability of immunotherapy. © Society of Surgical Oncology 2024. |
| Keywords: | overall survival; microsatellite instability; lynch syndrome; pancreatic ductal adenocarcinoma; mismatch repair deficient |
| Journal Title: | Annals of Surgical Oncology |
| Volume: | 32 |
| Issue: | 5 |
| ISSN: | 1068-9265 |
| Publisher: | Springer |
| Date Published: | 2025-05-01 |
| Start Page: | 3568 |
| End Page: | 3577 |
| Language: | English |
| DOI: | 10.1245/s10434-024-16621-x |
| PUBMED: | 39656390 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Alice C. Wei -- Source: Scopus |
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