Case Control Study
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World J Gastrointest Oncol. Mar 15, 2025; 17(3): 102873
Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.102873
Efficacy and safety of radiotherapy in patients with microsatellite stable or proficient mismatch repair colorectal cancer liver metastasis
Jie Ni, Chu-Gen Wan, Zi-Qi Sui
Jie Ni, Chu-Gen Wan, Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou 311100, Zhejiang Province, China
Zi-Qi Sui, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
Author contributions: Ni J designed the research study; Wan CG performed the research; Sui ZQ performed the experiments and analyzed the data; and all authors contributed to editorial changes, and read and approved the final manuscript.
Institutional review board statement: This study was approved by the ethics committee of The Second Affiliated Hospital of Zhejiang Chinese Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zi-Qi Sui, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 88 Jiefang Road, Hangzhou 310005, Zhejiang Province, China. ziqisui@163.com
Received: November 1, 2024
Revised: December 5, 2024
Accepted: January 14, 2025
Published online: March 15, 2025
Processing time: 106 Days and 0.2 Hours
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.

Keywords: Microsatellite stability; Proficient mismatch repair; Colorectal cancer; Liver metastasis; Radiotherapy; Immune checkpoint inhibitors; Tyrosine kinase inhibitor; Efficacy; Safety

Core Tip: This study investigates the efficacy and safety of a combined therapy involving radiotherapy, immune checkpoint inhibitors, and tyrosine kinase inhibitors in patients with colorectal cancer liver metastasis characterized by microsatellite stability or proficient mismatch repair, who traditionally show limited response to immune checkpoint inhibitors alone. The combination approach aims to leverage the potential of radiotherapy and tyrosine kinase inhibitors to modify the tumor microenvironment, improve antigen presentation, and boost immune activation, offering a new therapeutic strategy to improve disease control rates without increasing the risk of adverse effects. This study provides valuable insights into optimizing treatment regimens for microsatellite stability/proficient mismatch repair colorectal cancer liver metastasis patients.