Comparison of liver-directed combined radiotherapy versus sorafenib in patients with locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: An Asian Liver Radiotherapy Group Study.

Abstract

565 Background: While 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-CRT) compared to sorafenib, a recommended treatment until recently in locally advanced HCC presenting portal vein tumor thrombosis (PVTT) using a multinational patient cohort. Methods: We identified HCC patients presenting PVTT treated with either sorafenib or LD-CRT in 10 tertiary hospitals over Asia during 2005-2014. Propensity score matching (PSM) was performed to minimize the imbalance in patient and tumor characteristics of the two groups. The primary endpoint was overall survival (OS), and secondary endpoints were distant metastasis free survival (DMFS), local failure free survival (LFFS), and treatment related toxicity. Results: Total 1,035 patients including 360 patients in the sorafenib group and 675 patients in the LD-CRT group were enrolled. The majority of patients in the sorafenib group received 400 mg of sorafenib twice a day initially, and the dose was reduced to 50% or 25% if adverse reactions were noted. LD-CRT was given in liver-directed concurrent chemoradiotherapy in 502 (74.4%) patients, followed by transarterial chemoembolization plus radiotherapy in 149 (22.1%) patients. After PSM, 336 patients from each group were matched, and all features were well balanced between the two groups. At a median follow up of 28.8 months (interquartile range, 16.5-63.6), the median OS was 11.0 and 17.1 months for the sorafenib and LD-CRT groups, respectively ( p=0.001). In addition, LD-CRT group showed significantly improved DMFS and LFFS compared to the sorafenib group (median DMFS 14.9 vs 9.6 months, p=0.004, and median LFFS 15.7 vs 9.6 months, p=0.002). Conversion rate to curative surgery was significantly higher in the LD-CRT group (8.6% vs 0.9%, p=0.002). Those who underwent surgery had younger median age (54 vs 59, p=0.024), smaller median tumor size (6.5 cm vs 8.9 cm, p=0.012), and more unilateral disease (75.0% vs 43.8%, p<0.001). OS and LFFS were significantly prolonged in patients who underwent surgical treatment. Grade 3 or higher toxicity was more frequently noted in the sorafenib group compared to the LD-CRT group (7.7% vs 0.7%, p<0.001). Conclusions: Analysis of a propensity score matched multinational patient cohort revealed that liver-directed combined RT improved survival outcomes of locally advanced HCC patients presenting PVTT. While further prospective studies are warranted, we carefully suggest active multimodal local treatment for locally advanced HCC presenting PVTT.