Pre-therapeutic molecular biomarkers of pathological response to neoadjuvant chemotherapy in gastric and esophago-gastric junction adenocarcinoma: A systematic review and meta-analysis.

PURPOSE: Multimodal treatment is the standard of care in patients with locally advanced gastric cancer. Unfortunately, the response rate after neoadjuvant treatment remains limited. The ability to predict the response has a potential to improve patient outcomes by promoting a more individualized approach. We sought to describe the current state of research in pre-treatment molecular biomarkers of response to neoadjuvant therapy in gastric adenocarcinoma available for testing before the initiation of treatment and to perform a systematic review and meta-analysis in order to summarize and evaluate the potential methods.

METHODS: A systematic MEDLINE, EMBASE and CENTRAL literature search was conducted to extract articles on potentially predictive molecular biomarkers of pathological response to neoadjuvant therapy in patients with gastric- and esophago-gastric junction adenocarcinoma. Fixed and random effects models were used to undertake the meta-analysis when appropriate.

RESULTS: Data on predictive biomarkers was reported in 38 studies. These articles described 47 biomarkers showing statistical significance. After evaluation of all reported biomarkers, 3 of them met the inclusion criteria for meta-analysis. The meta-analysis results indicate that >5 ​ng/mL pre-therapeutic serum concentration of carcinoembryonic antigen (CEA; norm <5 ​ng/mL) is significantly associated with tumor response (RR ​= ​5.13, 95% CI 2.53-10.43, P ​= ​0.026).

CONCLUSION: Previous studies describe a large number of candidate biomarkers. Our meta-analysis indicated pre-therapeutic serum concentration of CEA >5 ​ng/mL as a potential and easy-accessible biomarker available for use before initiation of treatment. However, it could be only an additional tool for complex qualification for neoadjuvant therapy.