Translate 
Abstract
In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs’ efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.
Highlights
Cancers of the gastrointestinal (GI) tract are the major leading causes of cancer-related death
As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture to address the questions of how effective are immune checkpoint inhibitors (ICIs) in various GI cancers? Which GI cancer is most likely to benefit from ICI therapy? Which type of ICI has the best performance? Can predictive biomarkers like programmed-death ligand 1 (PD-L1) expression and microsatellite status help to select patients who benefit the most from ICI therapy? In terms of adverse events (AEs), how does ICIs work compare with conventional therapy? And on which types of GI cancer or drug should future studies be focused?
The results of the pooled analysis showed that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are most likely to benefit from ICI therapy, while it is less useful in gastric cancer (GC) and colorectal cancers (CRC) patients
Summary
Cancers of the gastrointestinal (GI) tract are the major leading causes of cancer-related death. Neoadjuvant therapy is used to shrink the cancer before an operation This approach has proven to be highly effective, making surgery an option for patients with otherwise inoperable tumors. It can make the operation safer and more effective, increasing the patient’s chances of a successful outcome [3, 4]. Most patients are diagnosed in the advanced stages, so the opportunity for an extreme cure is lost [5] Due to their prevalence as well as the limited number of treatment options, there is an urgent need to identify innovative evidence-based treatments for these insidious cancers
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
