A systematic review of publications on charged particle therapy for hepatocellular carcinoma.

Charged particle therapy (proton beam therapy and carbon ion therapy) is a form of radiotherapy which has the unique characteristic of superior depth dose distribution, and has been used for the treatment of hepatocellular carcinoma (HCC) in a limited number of patients, especially in Japan. We undertook a systematic review to define the clinical utility of charged particle therapy for patients with HCC. We searched the MEDLINE database from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC. Primary outcomes of interest were local control, overall survival, and late radiation morbidities. A total of 13 cohorts from 11 papers were selected from an initial dataset of 78 papers. They included a randomized controlled trial comparing proton beam therapy with transarterial chemoembolization, 9 phase I or II trials and 2 retrospective studies. The reported actuarial local control rates ranged from 71.4-95% at 3 years, and the overall survival rates ranged from 25-42.3% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥3 late adverse events were reported among the 787 patients included in this analysis. Charged particle therapy for HCC was associated with good local control with limited probability of severe morbidities. The cost-effectiveness and the distinctive clinical advantages of charged particle therapies should be clarified in order to become a socially accepted treatment modality for HCC.