Convergence of Local and Systemic Therapies: A Comprehensive Society of Interventional Oncology Framework for ⁹⁰Y...

Combination approaches using systemic immunotherapy agents are now standard of care for patients with advanced-stage hepatocellular carcinoma (HCC), resulting in improved overall survival. However, even with optimal systemic regimens, fewer than 40% of cases respond to treatment, presumably due to resistance mechanisms, including antidrug antibodies and acquired resistance related to alterations in the tumor immune microenvironment (TIME). As a result, new strategies are needed to improve immunotherapeutic efficacy in this setting. Early investigations into the local and systemic effects of yttrium 90 (⁹⁰Y) radioembolization using resin and glass microspheres demonstrated activation of both innate and adaptive immune systems, leading to sustained therapeutic efficacy in a subgroup of patients with HCC undergoing curative surgical resection after downstaging procedures. Preliminary prospective and retrospective studies have confirmed the safety of combining liver-directed interventions with immunotherapy. Based on these findings, clinical trials are being designed to evaluate the efficacy of different therapeutic strategies combining ⁹⁰Y radioembolization and immune checkpoint inhibitor therapy. The Society of Interventional Oncology is committed to advancing research on how local-regional therapies influence the TIME and systemic inflammatory response. This review aims to inform the interventional and medical oncology community about essential considerations and strategies for implementing these combination therapies involving ⁹⁰Y radioembolization and immunotherapy.