Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study.

BACKGROUND: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. METHODS: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan-Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. RESULTS: In total, 76 patients with a median age of 71 years (range, 45-86 years) were evaluated. Among them, 68 had Child-Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5-180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7-79.4%), 32.7% (95% CI: 22.0-43.8%), and 8.9% (95% CI: 1.7-23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. CONCLUSIONS: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Clinical impact of carbon-ion radiotherapy on hepatocellular carcinoma with Child-Pugh B cirrhosis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) patients with Child-Pugh (CP)-B not eligible for surgery nor other focal therapy options due to impaired liver function, have very limited treatment options. This study aims to retrospectively investigate the toxicity and efficacy of Carbon-ion radiotherapy (C-ion RT) on HCC with CP-B patients. MATERIALS AND METHODS: Patients with CP-B, no extrahepatic metastasis, and treated with C-ion RT between May 2000 and March 2020 were retrospectively extracted and included in this study. RESULTS: Sixty-nine lesions of 58 patients were included. The median follow-up duration was 20.5 (2.7-108) months. During follow-up, recurrence was observed in 43 patients, including 2 local recurrences and 39 intrahepatic recurrences beyond the irradiation field. A grade 3 acute hepatotoxicity was observed in one patient during the observation period. No acute or late adverse event of grade ≥4 was observed. Overall survival was 80.4% and 46.0% at 1 and 2 years, respectively, and the median survival time was 22.6 months. Local control rate was 96.4% at both 1 and 2 years, and progression-free survival was 38.6% and 6.9% at 1 and 2 years, respectively, with a median of 9.7 months. CONCLUSION: The C-ion RT showed low toxicity and good local effect in patients with HCC and CP-B. Therefore, C-ion RT could be an appropriate treatment for patients with HCC with poor liver function.

Progressive hypofractionated carbon-ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) in patients with hepatocellular carcinoma (HCC) with stepwise dose escalation and hypofractionation in 2 combined prospective trials. METHODS: Sequential phase 1/2 (protocol 9603) and phase 2 (protocol 0004) trials were conducted for patients with histologically proven HCC. The phase 1 component of protocol 9603 was a dose-escalation study; CIRT was delivered in 12, 8, or 4 fractions. After determination of the recommended dose, 2 phase 2 trials were performed in an expanded cohort, and the data were pooled to analyze toxicity, local control, and overall survival. RESULTS: In the phase 1 component of protocol 9603, 69.6, 58.0, and 52.8 Gy (relative biological effectiveness [RBE]) in 12, 8, and 4 fractions, respectively, constituted the maximum tolerated doses, and 52.8 Gy (RBE) in 4 fractions was established as the recommended dose regimen for the 2 phase 2 studies. In 124 patients with a total of 133 lesions, few severe adverse effects occurred, and local-control and overall survival rates at 1, 3, and 5 years were 94.7% and 90.3%, 91.4% and 50.0%, and 90.0% and 25.0%, respectively; this included 1-, 3-, and 5-year local-control rates of 97.8%, 95.5%, and 91.6%, respectively, in the phase 2 study. In a multivariate analysis, Child-Pugh class B and the presence of a tumor thrombus were significant factors for mortality. CONCLUSIONS: The safety and efficacy of CIRT in 12, 8, and 4 fractions were confirmed, with 52.8 Gy (RBE) in 4 fractions established as the recommended treatment course for eligible HCC patients. Cancer 2017;123:3955-65. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.