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World J Gastrointest Oncol. Aug 15, 2019; 11(8): 579-588
Published online Aug 15, 2019. doi: 10.4251/wjgo.v11.i8.579
Hypofractionated particle beam therapy for hepatocellular carcinoma–a brief review of clinical effectiveness
Che-Yu Hsu, Chun-Wei Wang, Ann-Lii Cheng, Sung-Hsin Kuo
Che-Yu Hsu, Chun-Wei Wang, Sung-Hsin Kuo, Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
Che-Yu Hsu, Chun-Wei Wang, Ann-Lii Cheng, Sung-Hsin Kuo, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
Che-Yu Hsu, Chun-Wei Wang, Sung-Hsin Kuo, Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
Ann-Lii Cheng, Department of Internal Medicine and Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan
Sung-Hsin Kuo, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
Author contributions: Hsu CT generated the tables and figures and wrote the manuscript; Wang CW and Cheng AL contributed to the writing of the manuscript; Kuo SH designed, wrote the manuscript and contributed to critical revision for important intellectual content and final approval of the version to be published.
Supported by the Ministry of Science and Technology, Taiwan, No. MOST 107-2314-B-002-217-MY3; and National Taiwan University Hospital, Taiwan, No. NTUH 108-S4143.
Conflict-of-interest statement: All authors declared no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sung-Hsin Kuo, MD, PhD, Professor, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. shkuo101@ntu.edu.tw
Telephone: +886-2-23123456-67144Fax: +886-2-23711174
Received: March 18, 2019
Peer-review started: March 20, 2019
First decision: June 5, 2019
Revised: June 22, 2019
Accepted: July 16, 2019
Article in press: July 17,2019
Published online: August 15, 2019
Processing time: 151 Days and 12.5 Hours
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer mortality worldwide. The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment. Although radiotherapy has not been considered a preferred treatment modality for HCC, charged particle therapy (CPT), including proton beam therapy (PBT) and carbon ion radiotherapy (CIRT), possesses advantages (for example, it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation) and has emerged as an alternative treatment option for HCC. With the technological advancements in CPT, various radiation dosages of CPT have been used for HCC treatment via CPT. However, the efficacy and safety of the evolving dosages remain uncertain. To assess the association between locoregional control of HCC and the dose and regimen of CPT, we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes. Overall, CPT provides a better local control rate compared with photon beam therapy, ranging from 80% to 96%, and a 3-year overall survival ranging from 50% to 75%, and it results in rare grade 3 toxicities of the late gastrointestinal tract (including radiation-induced liver disease). Regarding CPT for the treatment of locoregional HCC, conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract. In contrast, the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

Keywords: Hepatocellular carcinoma; Proton beam therapy; Carbon ion radiotherapy; Local control; Toxicity; Overall survival

Core tip: Charged particle therapy (CPT) for hepatocellular carcinoma (HCC), including proton beam therapy and carbon ion radiotherapy, offers physics-related advantages and results in better local control rates and lesser adverse effects. For peripherally large-sized HCC tumors, the hypo-fractionation regimen of CPT provides the benefit of increasing local control rates through overcoming radio-resistance, whereas conventional CPT is preferred for treating central tumors of HCC in terms of avoiding late toxicities of the biliary tract. Prospective data that will add to the accumulated evidence on the dosimetric constraints of hypofractionated CPT for the treatment of HCC are needed.