Hypofractionated particle beam therapy for hepatocellular carcinoma–a brief review of clinical effectiveness

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.