Portal vein tumor thrombosis (PVTT) occurs in 10% to 40% of patients with hepatocellular carcinoma (HCC) and has historically presented a major therapeutic challenge. Patients with PVTT more commonly present with distant metastasis, decreased hepatic function reserve, and compromised performance status compared with patients with HCC without PVTT. Additionally, tumor access to the bloodstream may lead to occult metastases and high rates of recurrence after locoregional therapy. In the natural history of this disease, the median overall survival is 2 to 4 months for patients with HCC with PVTT compared with 10 to 24 months for those without PVTT.1 Based on the Barcelona Clinic Liver Cancer staging system, HCC with PVTT is classified as advanced stage (stage C), and the standard of care for this population is targeted therapy with either sorafenib or lenvatinib.2-4 These agents, however, only marginally improve survival in patients with HCC with PVTT, highlighting the critical unmet need for management options in this population.