Combination of Lenvatinib and Proton Beam Therapy in the Management of Patients With Advanced Hepatocellular Carcinoma

Background/Aim: This retrospective study was designed to investigate the efficacy and safety of concurrent lenvatinib and proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients. Patients and Methods: Twenty HCC patients were identified, including Child–Pugh classification A in 16 patients and B (7) in four patients. Sixteen patients had macrovascular invasion, including four with main portal vein thrombosis (Vp4). The dose of lenvatinib depends on body weight; the median PBT dose was 72.6 Gy. Results: The median progression-fee survival (PFS) and overall survival (OS) of the entire population were 8.3 months and 18.4 months, respectively. For PBT targeting intrahepatic lesions and great vessels, the objective response rate (ORR) showed a complete response and partial response (PR) of 20% and 65%, respectively. In the analysis of concurrent lenvatinib and PBT, the ORR included PR of 55% and stable disease of 25%, with disease control rate of 80%. For patients without distant metastasis upon treatment initiation, the time to local control failure (including proton infield and out-field) was 14.3 months and distant metastasis-free survival was 17.7 months. There was no statistical difference in the analysis of PFS and OS in patients with or without portal vein thrombosis. The severity of most adverse events was grades 1-2, wherein most patients tolerated the toxicities. Conclusion: Our study confirmed the efficacy and safety of concurrent lenvatinib and PBT. Thus, this combination therapy may be a reasonable treatment option for selected patients with advanced HCC in clinical practice.