BACKGROUND: Perioperative chemotherapy is considered the standard of care for patients with resectable gastric cancer (GC). Still, there is large variability in response to the treatment among patients. Also, the majority of these patients encounter severe chemotherapy-induced side effects.
Microsatellite instability (MSI) is a distinct molecular subtype that is present in approximately 10-20% of GCs. The positive prognostic value of MSI has been well established. Data on the predictive value are still limited.
HYPOTHESIS: These limited data however suggest that MSI tumours show poor histopathological response to neoadjuvant chemotherapy and have worse overall survival compared to surgery alone.
AIM of this study is to gain evidence that patients with MSI-GC have worse overall survival when treated with perioperative chemotherapy compared to MSS-GC
PATIETNS & METHODS: Tumor tissues from patients treated in the phase III clinical trial (CRITICS) that compared perioperative chemotherapy with preoperative chemotherapy, surgery and postoperative chemoradiotherapy, will be analysed for MSI status. MSI status will be correlated to survival and histopathological response.
SAMPLE SIZE CALCULATION: Assuming 10% prevalence of MSI tumours 155 events are required to detect a hazard ratio (MSI/MSS) of 2.0 with 80% power at the two-sided alpha level 0.05. A total of 250 patients from each treatment arm (N=500 in total) will be included in this study.
ANTICIPATED RESULTS: We expect that patients with MSI-GCs do not benefit from perioperative chemotherapy and have limited or no histopathological response. If we can confirm our hypothesis this would indicate that all resectable GCs should be tested for MSI and that patients with MSI-GCs no longer should be treated with perioperative chemotherapy. We estimate that this would save 50-100 lives annually in the Netherlands. Testing of all resectable GCs for MSI status in the Netherlands would be cost-effective.