Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma

SIMPLE SUMMARY: Ablation, arterially directed therapies and external beam radiation therapy are among the locoregional therapies considered for patients with hepatocellular carcinoma (HCC) who are ineligible for transplant or resection or as bridging therapy prior to transplant. Combinations of locoregional therapies along with systemic therapies constitute a growing area of interest with the objective of attaining superior therapeutic outcomes. We present herein an up-to-date review of the current and developing treatment modalities in this regard for HCC. ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.