Supplementary Material for: Proton beam therapy for untreated hepatocellular carcinoma unsuitable for transcatheter arterial chemoembolization

Introduction: Intermediate-stage hepatocellular carcinoma (HCC) derives limited benefit from transarterial chemoembolization (TACE), which has led to introduction of the concept of “TACE-unsuitable HCC”. Drug therapy may be more beneficial, but intrahepatic lesion control tends to be a problem. Particle therapy including proton beam therapy (PBT) provides high local control with minimal toxicity, even in advanced cases. On this study, we retrospectively assessed the efficacy and safety of PBT in patients with TACE-unsuitable previously untreated HCC.
Methods: Between 2010 and 2018, 202 patients underwent definitive PBT for previously untreated HCC. TACE-unsuitable HCC was defined as one or more of the following; cases exceeding up-to-seven criteria, of ALBI grade 2-3, non-simple nodular type or presence of macroscopic vascular invasion (MVI). Overall survival (OS), local control (LC), progression free rate (PFR), and time to progression (TTP) were analyzed by the Kaplan-Meier method. Risk factor analysis was performed using a Cox regression model. Adverse events were evaluated based on CTCAE v. 5.0.
Results: TACE-unsuitable criteria were present in 165 cases. The median follow-up time was 3.35 years. The 3-year OS was 62.9%, 3-year PFR was 42.4%, and 3-year LC was 89.3%. In multivariate analysis, there were significant associations of ECOG PS, ALBI and tumor size with OS; and of sex and tumor size with TTP; but no factors related to LC. Two cases had acute adverse events of dermatitis grade 3; and 7 cases had chronic adverse events, including 4 cases of gastrointestinal bleeding grade 3, and one each of hemobilia, pleural effusion and erosive dermatitis.
Conclusion: PBT for TACE-unsuitable previously untreated HCC, which can be a non-inferior treatment option if the number of tumors is limited, but suppression of out-of-field recurrence is needed for further prolongation of survival.