Comparative Performance of Stereotactic Body Radiotherapy and Lenvatinib in Unresectable Hepatocellular Carcinoma Complicated by Portal Vein Tumor Thrombosis: A Propensity Score-Matched Cohort Analysis.

Abstract

Purpose: To investigate whether adding stereotactic body radiotherapy (SBRT) to lenvatinib improves outcomes for patients with unresectable hepatocellular carcinoma (uHCC) and portal vein tumor thrombosis (PVTT).

Methods: This retrospective cohort study enrolled 133 cases of uHCC with PVTT treated with either lenvatinib plus SBRT (n = 65) or lenvatinib alone (n = 68) between 2021 and 2023. To minimize baseline imbalances, 1:1 propensity score matching (PSM, caliper width, 0.02) was performed. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results: Across the full study population, patients receiving lenvatinib in combination with SBRT experienced significantly longer median OS relative to those who received lenvatinib alone (24.7 vs 16.4 months; HR=0.521, 95% CI: 0.338-0.802, p = 0.003). A similar advantage was observed for PFS (13.0 vs 8.6 months; HR=0.494, 95% CI: 0.335-0.728, p < 0.0001). These findings remained consistent after PSM, with hazard ratios of 0.589 for OS and 0.540 for PFS. The objective response rate was also substantially higher in the combination arm than in the monotherapy arm (55.4% vs 30.9%, p = 0.004). Subgroup analyses revealed that the survival advantage was confined to patients with Cheng's type I-II PVTT, whereas no significant benefit was observed in those with type III-IV disease. Furthermore, salvage hepatectomy was an independent protective factor for survival in 33 cases (24.8%), with a significantly higher conversion rate in the combined treatment group (30.8%). Both treatment groups had comparable and manageable safety profiles.

Conclusion: Lenvatinib in combination with SBRT confers meaningful advantages in both survival and tumor response over lenvatinib monotherapy in individuals with uHCC and PVTT, particularly among those with Cheng's type I-II involvement. Moreover, this multimodal approach appears to be an effective strategy for achieving tumor downstaging and enabling subsequent salvage hepatectomy.