Abstract
Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC). Clinical studies comparing adjuvant chemotherapy and surgery alone in dMMR/MSI-H GCs through June 2021 were retrieved to assess the survival of patients managed with both treatments. Two approaches were used to pool the hazard ratio (HR) of survival: (1) if Kaplan-Meier curves and number of patients at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with its 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models. Seven clinical studies were assessed. For dMMR/MSI-H versus mismatch repair-proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L) status, the estimated 5-year disease-free survival (DFS) rate was 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001) and the estimated 5-year OS rate was 60.5% versus 49.1% (HR, 0.71; 95% CI, 0.60-0.85; P < 0.001). The study-level data showed pooled HRs of 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.65 for OS (95% CI, 0.38-1.11; P = 0.114). For adjuvant chemotherapy versus observation of dMMR/MSI-H, the estimated 5-year DFS rate was 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171) and the estimated 5-year OS rate was 73.5% versus 59.7% (HR, 0.62; 95% CI, 0.46-0.83; P = 0.001). Significant survival differences also were observed at study level. The study findings confirm the benefit of adjuvant chemotherapy for dMMR/MSI-H GC patients.
Highlights
Over 1 billion new gastric cancer (GC) cases and 783 000 deaths are estimated to occur globally in 2018, ranking GC as the fifth most frequently diagnosed cancer and the third leading cancer-related death worldwide [1, 2]
To the best of our knowledge, this study is the first systematic review and meta-analysis to investigate the efficacy of adjuvant chemotherapy in GC with DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H)
Using the published data from 6 studies, our pooled analysis suggested that patients with dMMR/MSI-H had superior disease-free survival (DFS) and overall survival (OS), compared to those with pMMR/microsatellite stable (MSS)/microsatellite instability-low (MSI-L)
Summary
Over 1 billion new gastric cancer (GC) cases and 783 000 deaths are estimated to occur globally in 2018, ranking GC as the fifth most frequently diagnosed cancer and the third leading cancer-related death worldwide [1, 2]. Cheong et al reported that four classifier genes (GZMB, WARS, SFRP4, and CDX1) could serve as a prognostic and predictive tool to predict the survival and adjuvant chemotherapy response after surgery in stage II-III GCs [9]. Mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) serves as a predictor poor response to adjuvant chemotherapy in stage II colon cancer patients. Methods: We searched literatures through December, 2020 to identify clinical studies that reported survival comparing adjuvant chemotherapy with surgery alone in dMMR/MSI-H GCs. Two approaches were used to pool the hazard ratio (HR) of survival: (1) If Kaplan-Meier curves and number at risk were provided, individual patient data were extracted. For adjuvant chemotherapy versus observation in dMMR/MSI-H, the estimated 5-years DFS were 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.451.15; P = 0.171); the estimated 5-years OS were 74.9% versus 60.2% (HR, 0.60; 95% CI, 0.44-0.83; P = 0.001). Conclusions: This study further suggested adjuvant chemotherapy could be beneficial even in dMMR/MSIH GC patients
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.