# Exploratory case series of conversion to carbon ion radiotherapy after systemic therapy in advanced hepatocellular carcinoma

## TL;DR

This study explores using carbon ion radiotherapy after systemic treatment for advanced liver cancer, showing it may be safe and effective in some patients.

## Contribution

The study presents a novel approach of using carbon ion radiotherapy following systemic therapy for advanced hepatocellular carcinoma.

## Key findings

- Carbon ion radiotherapy achieved radiological cancer-free status in five out of eight patients.
- No significant liver function deterioration occurred during treatment.
- Short-term disease control was maintained in patients achieving cancer-free status.

## Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with advanced cases often presenting macrovascular invasion (MVI) or extrahepatic spread (EHS), limiting curative options. Latest systemic therapies, such as atezolizumab plus bevacizumab, have demonstrated potential in converting advanced HCC into treatable states. Carbon ion radiotherapy (C-ion RT), with its superior dose localization and biological effectiveness, has emerged as a promising treatment for advanced HCC. This retrospective exploratory case series reviewed eight patients with advanced HCC who received C-ion RT following systemic therapy at a single Japanese institution between 2021 and 2023. Data collection and follow-up were completed in October 2024. During the study period, 188 patients with advanced HCC received systemic therapy at our institution. Among these, 176 patients (93.6%) continued systemic therapy alone or received additional transarterial chemoembolization (TACE) for local disease control, while 12 patients (6.4%) were evaluated for curative-intent local therapy through multidisciplinary discussion. Patients were considered for conversion therapy after showing tumor shrinkage or loss of contrast enhancement during systemic therapy, but surgical resection was judged infeasible due to poor liver function or surgical tolerance. Therefore, C-ion RT was selected to treat all residual intrahepatic lesions. Clinical characteristics, treatment details, radiological responses, and safety outcomes were evaluated. The median age was 71 years, with 62.5% presenting MVI and 62.5% having tumors ≥ 90 mm in diameter. Systemic therapy included atezolizumab plus bevacizumab in seven cases and lenvatinib in one case. Following systemic therapy, C-ion RT achieved radiological cancer-free (rCF) status in five patients, including four with MVI and three with major portal vein invasion (Vp4). No clinically meaningful deterioration in liver function was observed during treatment, and adverse events were minimal. Patients achieving rCF maintained short-term disease control. Median follow-up was 11 months (range, 5–16). This exploratory case series suggests that C-ion RT following systemic therapy may be a feasible and safe local consolidation approach for highly selected patients with advanced HCC. C-ion RT achieved short-term local control without deterioration of liver function in this small cohort. Given the limited sample size and follow-up duration, these findings are preliminary and warrant validation in prospective studies with larger cohorts to establish its role in multidisciplinary management.

The online version contains supplementary material available at 10.1007/s13691-025-00839-x.