Efficacy and safety of radiotherapy in patients with microsatellite stable or proficient mismatch repair colorectal cancer liver metastasis.

Abstract

Background: Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally, and the occurrence of liver metastasis significantly affects patient survival prognosis. In recent years, the application of immune checkpoint inhibitors (ICIs) in cancer treatment has made important progress, especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency. However, for the majority of patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) colorectal cancer, the efficacy of ICIs is limited, prompting researchers to explore combination therapy strategies to improve efficacy. Targeted drugs such as tyrosine kinase inhibitors (TKIs) and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.

Aim: To investigate the efficacy and safety of the combination therapy of radiotherapy, ICIs, and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis (CCLM), in order to provide new clinical treatment references.

Methods: A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024. Based on the treatment interventions received, the patients were divided into a control group (n = 21, receiving ICIs and TKIs combination therapy) and an observation group (n = 22, receiving radiotherapy, ICIs, and TKIs triple therapy). The therapeutic effects, serum tumor markers (carcinoembryonic antigen and carbohydrate antigen 199), survival status, and adverse reactions were compared between the two groups.

Results: The disease control rate in the observation group (63.64%) was significantly higher than that of the control group (23.81%) (P < 0.05). Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment, with the observation group demonstrating a more significant change (P < 0.05). The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months, respectively, while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months, respectively. The control group had longer survival times than the observation group, but the differences were not statistically significant (P > 0.05). The incidence of adverse reactions, including nausea and vomiting, gastrointestinal reactions, skin reactions, bone marrow suppression, liver and kidney function impairment, neurotoxicity, leukopenia, neutropenia, and thrombocytopenia, showed no significant differences between the two groups (P > 0.05).

Conclusion: Compared to the ICIs and TKIs combination therapy, the radiotherapy, ICIs, and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions, making it a treatment regimen worthy of further validation.