4.7 Article

Survival of Locally Advanced MSI-high Gastric Cancer Patients Treated With Perioperative Chemotherapy A Retrospective Cohort Study

Journal

ANNALS OF SURGERY
Volume 277, Issue 5, Pages 798-805

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0000000000005501

Keywords

microsatellite instability; mismatch repair defect; neoadjuvant chemotherapy; gastric cancer; gastric adenocarcinoma; immunotherapy

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This study evaluated the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer. The results showed that patients with MSI-high tumors had better overall survival compared with those with microsatellite stable (MSS) tumors, despite a worse response to chemotherapy.
Objective: To evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer. Background: Although MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population. Methods: Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible. MSI status, determined by next-generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, overall survival (OS), disease-specific survival, and disease-free survival were assessed. Results: In 535 patients, 82 (15.3%) had an MSI-high tumor and similar to 20% better OS, disease-specific survival, and disease-free survival. Grade 1 (90%-100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone (P = 0.48). In the MSS group, this was 61% versus 59%, respectively (P = 0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (hazard ratio= 0.53, 95% confidence interval: 0.28-0.99) or treated with surgery alone (hazard ratio = 0.15, 95% confidence interval: 0.02-1.17). Conclusions: MSI-high locally advanced gastric cancer was associated with superior survival compared with MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was similar to 9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival.

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