Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review

Radiother Oncol. 2014 Apr;111(1):1-10. doi: 10.1016/j.radonc.2014.02.001. Epub 2014 Feb 20.


This paper aimed to review the literature concerning the use of proton therapy systematically in the treatment of hepatocellular carcinoma, focusing on clinical results and technical issues. The literature search was conducted according to a specific protocol in the Medline and Scopus databases by two independent researchers covering the period of 1990-2012. Both clinical and technical studies referring to a population of patients actually treated with protons were included. The PRISMA guidelines for reporting systematic reviews were followed. A final set of 16 studies from seven proton therapy institutions worldwide were selected from an initial dataset of 324 reports. Seven clinical studies, five reports on technical issues, three studies on treatment related toxicity and one paper reporting both clinical results and toxicity analysis were retrieved. Four studies were not published as full papers. Passive scattering was the most adopted delivery technique. More than 900 patients with heterogeneous stages of disease were treated with various fractionation schedules. Only one prospective full paper was found. Local control was approximately 80% at 3-5years, average overall survival at 5years was 32%, with data comparable to surgery in the most favorable groups. Toxicity was low (mainly gastrointestinal). Normal liver V0Gy<30%volume and V30Gy<18-25%volume were suggested as cut-off values for hepatic toxicity. The good clinical results of the selected papers are counterbalanced by a low level of evidence. However, the rationale to enroll patients in prospective studies appears to be strong.

Keywords: Hepatocellular carcinoma; Proton therapy; Systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Hepatocellular / radiotherapy*
  • Dose Fractionation, Radiation
  • Humans
  • Liver Neoplasms / radiotherapy*
  • Prospective Studies
  • Proton Therapy* / methods*


  • Protons