Targeting HCC With SBRT: Practical Strategies and Immunologic Synergies

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, characterized by high recurrence rates despite curative-intent therapies. While surgical resection, ablation, transarterial therapies, and systemic agents form the backbone of current management, advances in radiation technology have positioned stereotactic body radiotherapy (SBRT) as an increasingly important modality across the HCC disease spectrum. Historically limited by concerns for hepatic toxicity and presumed radioresistance, modern SBRT enables precise delivery of ablative doses while sparing functional liver parenchyma, resulting in excellent local control with acceptable toxicity. This review summarizes contemporary evidence supporting SBRT in early-stage, intermediate, and advanced HCC, including its roles as definitive therapy, salvage after transarterial chemoembolization, cytoreduction in macrovascular invasion, palliation, and as a bridge to liver transplantation. Practical considerations are emphasized, including dose selection, biologically effective dose thresholds, volumetric liver sparing, functional imaging, and the delayed radiographic response characteristics of post-SBRT HCC, which challenges conventional response assessment criteria. In addition, emerging insights into the radiobiology of HCC suggest that high-dose hypofractionation overcomes prior assumptions of radio resistance through direct cytotoxicity and microenvironmental modulation. Finally, this review explores the immunologic synergy between SBRT and immune checkpoint inhibitors, highlighting early clinical data and ongoing trials combining SBRT with immunotherapy. As multimodal strategies evolve, SBRT is poised to become a cornerstone of personalized, liver-directed therapy in HCC.