Simple SummaryIn this multinational, multi-institutional study, we investigated the efficacy of liver-directed combined radiotherapy compared with sorafenib in hepatocellular carcinoma patients presenting portal vein tumor thrombosis. Propensity score matching was performed to minimize the imbalance between the two groups. The median overall survival was significantly improved in the LD combined RT group, and the conversion rate to curative surgery was also significantly higher in the LD combined RT group. Despite the multimodality of the treatments, toxicity rates of LD combined RT were comparable to those of sorafenib.AbstractPurpose: Although systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD combined RT) compared with that of sorafenib, a recommended treatment until recently for locally advanced HCC presenting portal vein tumor thrombosis (PVTT), using a multinational patient cohort. Materials and Methods: We identified patients with HCC presenting PVTT treated with either sorafenib or LD combined RT in 10 tertiary hospitals in Asia from 2005 to 2014. Propensity score matching (PSM) was performed to minimize the imbalance between the two groups. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and treatment-related toxicity. Results: A total of 1035 patients (675 in the LD combined RT group and 360 in the sorafenib group) were included in this study. After PSM, 305 patients from each group were included in the analysis. At a median follow-up of 22.5 months, the median OS was 10.6 and 4.2 months for the LD combined RT and sorafenib groups, respectively (p< 0.001). The conversion rate to curative surgery was significantly higher (8.5% vs. 1.0%,p< 0.001), while grade ≥ 3 toxicity was fewer (9.2% vs. 16.1%,p< 0.001) in the LD combined RT group. Conclusions: LD combined RT improved survival outcomes with a higher conversion rate to curative surgery in patients with locally advanced HCC presenting PVTT. Although further prospective studies are warranted, active multimodal local treatment involving radiotherapy is suggested for locally advanced HCC presenting PVTT.