Radiotherapy enhances triple therapy for conversion and survival in patients with unresectable hepatocellular carcinoma with portal vein tumor thrombus

Triple therapy (TT), consisting of transarterial chemoembolization, immune checkpoint inhibitors, and tyrosine kinase inhibitors, is recommended as a conversion therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, patients with uHCC with portal vein tumor thrombosis (PVTT) have a limited response to TT alone. This study evaluated whether combining TT with radiotherapy (TTR) could increase conversion resection rates and improve the prognosis of uHCC with PVTT. A total of 123 patients treated at our institution from 2020-2024 were retrospectively analyzed, comprising 103 patients receiving TT and 20 receiving TTR. The overlap weighting (OW) method was used to minimize bias. Compared with the TT group, patients in the TTR group had a significantly greater early tumor shrinkage rate (85.0% vs. 59.2%, p = 0.029). Moreover, conversion resection rates were significantly higher in the TTR group (65.0% vs. 35.0%, p = 0.012), and the median overall survival (OS) was notably prolonged (median OS not reached vs. 31.9 months, p = 0.031). Following OW adjustment of the data, we obtained similar results. Multivariate analysis confirmed TTR as an independent protective factor for both OS (HR = 0.354, 95% CI = 0.127-0.984, p = 0.046) and the conversion resection rate (OR = 0.261, 95% CI = 0.081-0.838, p = 0.024). Treatment-related adverse events were manageable. Thus, TTR offers an improved conversion resection rate and survival outcomes compared with TT alone in patients with uHCC with PVTT and represents a promising therapeutic strategy.