Tongji Hospital Affiliated to Tongji Medical College of Huazhong University Wuhan, Hubei
Y. Zong, A. Huang, Z. Liang, T. Zhang, K. Yang, and H. Ma; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Purpose/Objective(s): The efficacy of immunotherapy in patients with primary or metastatic liver tumors is limited, especially in cases where tumors are large, hypoxic, poorly vascularized, and sparsely infiltrated by lymphocytes, presenting as "cold tumors" and leading to resistance to immunotherapy. This study explores a novel mixed-dose liver radiotherapy strategy aimed at reversing immunotherapy failure by improving the tumor microenvironment and sensitizing the treatment through the activation of tumor-associated antigens. Materials/
Methods: This study enrolled 11 patients with primary or metastatic liver tumors who had failed immunotherapy, including 2 cases of hepatocellular carcinoma, 4 cases of bile duct cancer with liver metastases, 4 case of colorectal cancer with liver metastases, and 1 cases of gastric cancer with liver metastases. The treatment strategy employed low-dose radiotherapy (DT 5Gy/5F) to the necrotic areas of the liver tumors and high-dose radiotherapy (25Gy/5F) to the solid tumor regions. The endpoints were overall survival (OS), progression-free survival (PFS), local control rate, and treatment-associated toxicities such as gastrointestinal symptoms, appetite loss, and hematological effects. Results: The study successfully administered Mixed-Dose Liver Radiotherapy to all participants without treatment interruptions, with a median follow-up of 24 months. Early results indicated a median PFS of 12 months, and an 82% local control rate at the 3-month mark, with OS endpoints pending. No participant experienced treatment-related toxicities above grade 3, highlighting the procedures safety profile. Only one patient experienced Grade I elevation of liver enzymes, which quickly resolved with symptomatic treatment. These preliminary results suggest that the mixed-dose liver radiotherapy strategy effectively reverses resistance to immunotherapy in solid tumors, improving response rates. Conclusion: This exploratory study confirms the potential of a novel mixed-dose liver radiotherapy strategy in reversing failure of liver solid tumors to respond to immunotherapy. By improving the tumor microenvironment and activating tumor-associated antigens, this strategy significantly enhances the efficacy of immunotherapy. Although these preliminary findings are encouraging, further research is required to validate the effectiveness and safety of this treatment strategy in a broader population of tumor patients.
