Patients with operable gastroesophageal cancer with mismatch repair deficiency (MMRD) and high microsatellite instability (MSI) did not derive benefit from perioperative chemotherapy, according to a study published in JAMA Oncology.1

MMRD and MSI are prognostic for numerous cancer types and for resistant to fluoropyrimidines in early colon cancer, though no studies have assessed the impact of MMRD and MSI in patients with curatively resected gastric cancer treated with perioperative chemotherapy.

To evaluate associations between MMRD, MSI status, and overall survival among patients with resectable gastroesophageal cancer, investigators conducted a secondary post hoc analysis of 503 patients with operable gastroesophageal cancer who were randomly assigned to undergo surgery alone or perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as part of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial.

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Among the 303 patients with MSI results available, 283 had microsatellite stability or low MSI and 20 had high MSI. Among patients treated with surgery alone, results showed no significant difference in overall survival between patients with high MSI or MMRD and those without high MSI or MMRD (hazard ratio, 0.42; 95% CI, 0.15-1.15; P = .09).

Patients with high MSI or MMRD who underwent surgery alone had a median overall survival that was not reached (95% CI, 11.5-not reached) compared with 20.5 months (95% CI, 16.7-27.8) in those with neither high MSI nor MMRD.

Among patients treated with perioperative chemotherapy, those who had high MSI or MMRD had a 2-fold higher risk of death compared with those with neither high MSI nor MMRD (hazard ratio, 2.18; 95% CI, 1.08-4.42; P = .03); median overall survival was 9.6 months (95% CI, 0.1-22.5) and 19.5 months (95% CI, 15.4-35.2), respectively.

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The findings suggest that patients with operable gastroesophageal cancer and high MSI or MMRD should not receive perioperative chemotherapy. Independent validation of these results is needed to confirm whether MSI or MMRD could inform treatment decision-making.


  1. Smyth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival: An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017 Feb 23. doi: 10.1001/jamaoncol.2016.6762 [Epub ahead of print.