Advances in radiation therapy for HCC: Integration with liver-directed treatments

HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.