Safety and Efficacy of Radiotherapy Plus Immunotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

[BACKGROUND] The role of combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) in advanced hepatocellular carcinoma (HCC) remains unclear. We aimed to evaluate the efficacy and safety of RT plus ICI compared to ICI alone.

[METHODS] We systematically searched PubMed, Web of Science, and Cochrane CENTRAL from inception to April 2025. Eligible studies were clinical trials or retrospective cohorts comparing RT + ICI with ICI alone in patients with advanced HCC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Risk of bias was assessed using ROBINS-I. Data were synthesized using a random-effects meta-analysis.

[RESULTS] Eight studies comprising 392 patients were included. RT + ICI was associated with improved outcomes: OS (62.8% vs. 45%), PFS (25.4% vs. 3.6%), ORR (51.1% vs. 27.6%), and DCR (83.1% vs. 60.6%) compared with ICI alone. AEs were more frequent with combination therapy (76.2% vs. 61%). Heterogeneity was moderate to high across several outcomes, and all included studies were retrospective.

[CONCLUSIONS] RT combined with ICIs shows promising improvements in survival and tumor response compared to ICI alone in advanced HCC, albeit with increased toxicity. Large randomized trials are needed to confirm efficacy, optimize RT regimens, and identify patients most likely to benefit.