Transarterial radioembolisation combined with targeted therapy and immune checkpoint inhibitors in advanced hepatocellular carcinoma with portal vein tumour thrombus: efficacy, safety, and dosimetric analysis.

Abstract

Advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) carries a dismal prognosis. This study evaluated the efficacy and safety of transarterial radioembolisation (TARE) combined with targeted therapy and immune checkpoint inhibitors (ICIs) in patients with HCC and Vp2-Vp4 PVTT, and explored the tumour absorbed dose (TAD) threshold associated with survival benefit. We retrospectively analysed 31 patients with HCC and Vp2-Vp4 PVTT treated with this triplet regimen. Tumour responses were assessed per mRECIST and RECIST 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The optimal TAD cutoff was identified through dose-threshold exploration and internally validated by bootstrap resampling. The objective response rate was 77.4% per mRECIST and 54.8% per RECIST 1.1 (P = 0.023), with a disease control rate of 93.5%. Median PFS and OS were 10.0 months (95% CI, 7.9-NR) and 16.4 months (95% CI, 9.1-NR), respectively. Grade ≥ 3 treatment-related adverse events occurred in 22.6% of patients; no treatment-related death occurred. Exploratory analysis identified TAD ≥ 140 Gy as independently associated with improved PFS after multivariable adjustment (HR = 0.33, 95% CI, 0.11-0.95; P = 0.039), with a concordant trend for OS. Bootstrap validation confirmed robustness. TARE combined with targeted therapy and ICIs demonstrates encouraging efficacy with an acceptable safety profile in advanced HCC with Vp2-Vp4 PVTT. TAD ≥ 140 Gy was associated with improved survival, providing a hypothesis-generating basis for personalised dosimetric optimisation in future prospective trials.