Combining External Beam Radiotherapy and Immunotherapy for the Treatment of Hepatocellular Carcinoma

The advent of immune checkpoint inhibitors has driven progress in hepatocellular carcinoma (HCC) treatment outcomes and enabled opportunities for combining therapeutic modalities. Growing evidence substantiates the utility of radiotherapy, particularly at ablative doses, in the management of HCC. Given the potential for radiotherapy to induce an immunostimulatory environment and potentiate immune checkpoint inhibitor activity, the expanding HCC treatment landscape compels exploration of the combination of radiotherapy and immunotherapy. This review highlights recent advances in the treatment of HCC using radiotherapy and immunotherapy in combination. Radiation can potentiate an anti-tumor response and tumor microenvironment permissive to immunotherapy. Results from randomized clinical trials and retrospective studies consistently show that combinations of radiotherapy and immunotherapy improved the treatment outcomes of unresectable or advanced HCC-especially HCC with macrovascular invasion. Active research to further improve treatment efficacy and reduce side effects is exemplified by more than 20 ongoing clinical trials combining external beam radiotherapy and immunotherapy to treat HCC. Ongoing research aims at prolonging survival and downstaging advanced or unresectable HCC.