Stereotactic Body Radiotherapy with Carbon Ions As Local Ablative Treatment in Patients with Primary Liver Cancer

Abstract Background and aims Liver cancer is the third leading cause of cancer related death due to treatment resistance and late onset of symptoms (Rumgay in J Hepatol 77: 1598–1606, 2022). The role of external beam radiotherapy (EBRT) in treatment of unresectable liver cancer needs to be defined. The use of particle therapy such as carbon ion radiation therapy (CIRT) with high linear energy transfer (LET) could increase efficacy of EBRT while limiting the toxic effects of radiation on non-cancerous liver tissue. Promising effects of CIRT have been described in several studies during the past decades, mostly in Japan. To date, no standardized treatment protocol has been established and European data on CIRT for liver cancer is lacking. This retrospective analysis aims to investigate efficacy and safety of hypofractionated CIRT compared to photon-based stereotactic body radiation (SBRT) in primary liver cancer. Method Thirty-six (n = 36) and twenty (n = 20) patients with primary malignant liver tumors were treated with hypofractionated CIRT (4 fractions) and photon-based SBRT, respectively, between 2011 and 2022 and were retrospectively evaluated for survival, local control, and toxicity. Results Two-year local control rate after CIRT was 92.3%. Compared to photon- based SBRT, CIRT scores with a significantly longer median distant progression free survival (3.1 versus 0.9 years). In a matched pair comparison of the two treatment regimens, the CIRT cohort demonstrated both longer 2-year overall survival (100% versus 59.6%) and longer 2-year distant PFS (75.7% versus 22.9%). No significant impairment of liver function was observed in either cohort. Conclusion In this retrospective analysis, patients who received CIRT presented excellent local tumor control and had better oncologic outcomes than patients who received photon-based SBRT. SBRT with carbon ions is a promising local ablative treatment option that needs further investigation in large prospective trials.