Stereotactic body radiotherapy plus lenvatinib and sintilimab with and without transarterial embolization for advanced hepatocellular carcinoma with portal vein tumor thrombus: a dual-center, propensity score-matched retrospective analysis

Introduction: Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is associated with poor prognosis and limited efficacy of current first-line therapies. Combining locoregional and systemic therapies may enhance antitumor immunity. However, the safety and efficacy of dual locoregional therapy (LRT) with stereotactic body radiotherapy (SBRT) and transarterial embolization (TAE) along with targeted immunotherapy is unclear. Methods: In this retrospective real-world study, we analyzed 204 patients with Barcelona Clinic Liver Cancer stage C HCC and PVTT treated with SBRT plus lenvatinib and sintilimab, with or without TAE, between June 2018 and December 2022. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints included local control (LC) and safety. Results: After PSM (64 patients per group), the TAE group showed significantly longer median PFS (11.0 vs. 6.0 months; HR = 0.71, p=0.044) and a trend toward improved LC than the non-TAE group (51.0 vs. 36.0 months; HR = 0.54, p=0.066), but comparable OS (19.0 vs. 18.0 months; p=0.606). Multivariate analysis confirmed TAE as an independent predictor of reduced risk of progression (HR = 0.52, 95% CI: 0.36-0.76). Objective response rates (40.6% vs. 39.1%, p=0.861) and grade ≥3 treatment-related adverse events (50.0% vs. 50.0%, p=0.854) were similar between groups. TAE did not increase hematologic or hepatic toxicity, supporting its tolerability. Discussion: Adding TAE to SBRT, lenvatinib, and sintilimab prolonged the median PFS in patients with advanced HCC and PVTT, showing comparable safety. This real-world study supports dual LRT combined with targeted immunotherapy as a feasible treatment option and merits prospective validation.