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Abstract
Purpose: 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.

Affiliations

Jina Kim 1, Jason Chia-Hsien Cheng 2, Taek-Keun Nam 3, Jin Hee Kim 4, Byoung Kuk Jang 5, Wen-Yen Huang 6, Hiroshi Aikata 7, Myungsoo Kim 8, Jung Hyun Kwon 9, Jinbo Yue 10, Victor Ho Fun Lee 11, Zhaochong Zeng 12, Jinsil Seong 1
1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
2Department of Radiation Oncology, National Taiwan University Hospital, Taipei 100229, Taiwan.
3Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea.
4Department of Radiation Oncology, Keimyung University, Dongsan Hospital, Daegu 42601, Republic of Korea.
5Department of Internal Medicine, Keimyung University, Dongsan Hospital, Daegu 42601, Republic of Korea.
6Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan.
7Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima 734-0004, Japan.
8Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Republic of Korea.
9Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Republic of Korea.
10Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.
11Department of Clinical Oncology, The University of Hong Kong, Hong Kong SAR, China.
12Department of Radiation Oncology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200031, China.