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.