Immune checkpoint inhibitors and radiotherapy in gastrointestinal cancer treatment

Abstract

Background. In recent decades, immunotherapy has become a topical area of research in the complex treatment of oncological diseases. A significant achievement in the immunotherapy of oncological diseases was the discovery of immune checkpoint proteins, which are effective inhibitors of the immune response. Immune checkpoint inhibitors (ICIs) have been approved for the treatment of certain gastrointestinal malignancies. However, the clinical efficacy of ICIs monotherapy remains low. To improve the outcome of treatment, numerous studies are conducted in which immunotherapy is combined with other standard methods of anticancer treatment. Radiation therapy (RT) may enhance the antitumor immune response when combined with ICIs and is worth considering when combined with immunotherapy. The effectiveness of the combined strategy is actively being investigated in clinical trials. Purpose – to highlight the latest achievements in the field of combined use of immunotherapy with ICIs and RT in malignant neoplasms of the gastrointestinal tract. Materials and methods. Data searches for the review were conducted using PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The data of works published in 2013-2023 were analyzed and systematized. Results and discussion. The rationality of the combination of RT and immunotherapy was substantiated. The results of the combined use of neoadjuvant chemoradiotherapy (CRT) and immunotherapy with ICIs in patients with resectable esophageal cancer and combined treatment in patients with advanced disease are analyzed. The clinical results of the use of ICIs in combination with RT or CRT in patients with gastric cancer and the combination of ICIs and RT in patients with hepatocellular carcinoma are presented. The clinical effects of adding ICIs to neoadjuvant RT or CRT in patients with locally advanced and borderline resectable pancreatic cancer and the results of trials of a combined strategy in patients with advanced disease are characterized. The clinical efficacy of the combined approach in locally advanced rectal cancer, which is a routine area of RT application, and in metastatic disease is reviewed. The results of small studies of combined treatment involving patients with metastatic colorectal cancer are presented. Conclusions. Over the past decade, research in the field of immunotherapy for gastrointestinal tumors has increased significantly. Based on the synergistic effects of radiation therapy and immune checkpoint inhibitors, the combination of these therapeutic approaches is increasingly being tested in gastrointestinal cancer to improve treatment outcomes. Published studies have shown encouraging results with satisfactory toxicity. However, most clinical trials are retrospective, non-comparative phase I/II trials and are limited to a small number of patients. The results of these studies can serve as a basis for conducting multicenter prospective studies with large sample sizes to confirm the effectiveness of combined therapy.