ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1643304
Efficacy and Safety of Radiotherapy Combined with Immunotherapy and Targeted Therapy Versus Immunotherapy Plus Targeted Therapy Alone in Unresectable Hepatocellular Carcinoma: A Retrospective Study
Provisionally accepted
- 1Department of Oncology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China
- 2The Sixth Affiliated Hospital of South China University of Technology, Foshan, China
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Purpose: To evaluate the efficacy and safety of radiotherapy combined with immunotherapy and targeted therapy (RT+IO+T) versus immunotherapy plus targeted therapy alone (IO+T) in patients with unresectable hepatocellular carcinoma (HCC). Given the limited prospective evidence supporting the integration of radiotherapy into systemic regimens, particularly in realworld populations with advanced disease, this study aims to clarify the clinical value of this multimodal approach. Methods: This retrospective study analyzed 71 patients with unresectable HCC treated between 2020 and 2025. Patients received either IO+T (n=42) or RT+IO+T (n=29), including immune checkpoint inhibitors (ICIs) (e.g., camrelizumab), targeted agents (e.g., lenvatinib), and RT.Outcomes were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Survival analysis was performed using Kaplan-Meier and Cox regression models.Results: Compared with the IO+T group, the RT+IO+T group demonstrated superior short-term efficacy, as indicated by the objective response (69.0% vs. 35.7%, p=0.006) and disease control (89.7% vs. 57.1%, p=0.003) rates. Additionally, the median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in the RT+IO+T group compared with the IO+T group (PFS: 12.6 vs. 4.6 months, p<0.001; OS: 17.8 vs. 10.9 months, p=0.009). Subgroup analyses confirmed consistent survival benefits across patient characteristics. However, the RT+IO+T group showed increased hematologic toxicity (grade ≥3 lymphopenia: 62.1% vs.19.0%, p<0.001) and hepatic enzyme elevation (aspartate aminotransferase: 75.9% vs.35.7%, p<0.001).Adding RT to IO+T significantly improved tumor response and survival in unresectable HCC, despite higher manageable hematologic and hepatic toxicities.The results of this study support RT+IO+T as a promising strategy for advanced HCC, particularly in patients with high tumor burden or portal vein invasion. The synergistic effect of RT, immunotherapy, and target therapy highlights its potential to redefine treatment paradigms, although toxicity monitoring remains critical.
Keywords: Hepatocellular Carcinoma, Immunotherapy, Radiotherapy, targeted therapy, combination therapy, Survival outcomes, Toxicity profile
Received: 08 Jun 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Yuan, Chen, Huang, Liu, Tong, Tang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wubing Tang, Department of Oncology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China
Wen Yang, Department of Oncology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China
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