Patient specific outcomes of charged particle therapy for hepatocellular carcinoma – A systematic review and quantitative analysis

Hepatocellular carcinoma (HCC) is a raising condition world-wide. Most of patients are ineligible for surgery at diagnosis due to the advanced stage of the disease or poor medical condition of the patient. Charged particle therapy (CPT) is a radiotherapy modality showing promising results. The aim of this systematic review was to summarize current knowledge on patient-specific outcomes of CPT for HCC, including overall survival, local control, the effect of radiation dose and the toxicity burden. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After comprehensive database search 17 cohorts (16 studies, 1516 patients) were included into qualitative and quantitative analyses; 11 of 16 studies were retrospective. Eleven studies were on protons, 2 studies were on protons and carbon ions and 4 on carbon ions alone, were identified. Median BED10 (biologically equivalent dose) range was 68.75–122.5 GyE. Mean weighted overall survival across studies was 86%, 62%, 59% and 35% at 1, 2, 3 and 5 years, respectively. Mean weighted local control was 86%, 89%, 87% and 89% at 1, 2, 3 and 5 years, respectively. Adjusted morbidity rates were: 54% for acute G1-2 toxicities and 6% for acute ≥G3 toxicities; 9% for late G1-2 toxicities and less than 4% for late ≥G3 toxicities. There was no treatment-associated mortality. Conclusions: CPT offers high local control, acceptable overall survival and low post-treatment morbidity. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of available studies. Therefore, there is a strong need for better reporting and prospective studies.