Stereotactic body radiation therapy for hepatocellular carcinoma: a comprehensive review

Hepatocellular carcinoma (HCC) presents significant challenges in modern surgical and radiation oncology, primarily due to biological heterogeneity and the complexities of underlying liver cirrhosis. This review evaluates stereotactic body radiation therapy (SBRT) as a mature, curative-intent modality within the multidisciplinary management of primary hepatic malignancies. Drawing parallels with high-dose-per-fraction successes in early-stage non-small cell lung cancer, pancreatic adenocarcinoma, and spinal metastases, we analyze the physical evolution, radiobiological principles, and functional dosimetric constraints specific to the hepatic microenvironment. Specifically, we examine advanced motion management, distinguishing pre-treatment setup from real-time intrafractional monitoring via kilovoltage projection streaming images (kV-PSI) and MR-guidance. We evaluate the prognostic value of metabolic imaging parameters, specifically SUL_peak and radiomic signatures, alongside the therapeutic synergy between SBRT and systemic agents, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Additionally, the review explores the emerging role of artificial intelligence (AI) in automating planning and executing real-time online adaptive radiotherapy (ART). Finally, by synthesizing pathological evidence of complete necrosis in explanted specimens following conversion therapy, this work provides a roadmap for optimizing SBRT across the clinical spectrum of HCC.