Simple Summary
Liver cancer is a leading cause of cancer-related mortality, and many patients are not eligible for potentially curative resection or transplant. Treatment options have expanded considerably in recent years, including systemic therapies that stimulate the immune system or inhibit pathways that regulate tumor biology. Combining radiation therapy with systemic therapy may improve treatment response by targeting the tumor through complementary mechanisms involving cancer cells, blood vessels, and the immune system. This review examines the scientific and clinical evidence for combining radiation therapy with systemic therapy in liver cancer.
Abstract
The therapeutic landscape of hepatocellular carcinoma (HCC) has evolved with advances in systemic therapy and radiotherapy. Immune-checkpoint inhibitors, anti-angiogenic agents, stereotactic body radiotherapy (SBRT), and yttrium-90 transarterial radioembolization (TARE) have expanded treatment options across multiple stages of disease. Radiotherapy may complement systemic therapy through biological interactions involving tumor vasculature, hypoxia, and the immune microenvironment. These observations have generated growing interest in combined-modality therapy, although optimal approaches continue to be defined. In this review, we summarize the biological rationale and clinical evidence for integrating SBRT or TARE with targeted and immunotherapy-based regimens. We also highlight ongoing trials and emerging strategies for biologically informed therapy sensitization targeting tumor and immune-cell biology.