Multicenter Retrospective Study of Stereotactic Body Radiotherapy for Patients with Previously Untreated Initial Small Hepatocellular Carcinoma.

Abstract

The effectiveness of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been shown in many studies and its therapeutic effect is similar to radiofrequency ablation (RFA). However, many of these studies were done in combination with transcatheter chemoembolization (TACE), for recurrent HCC, or on a small scale. To better understand the specific outcomes of SBRT for HCC, we conducted a multicenter retrospective analysis of SBRT for previously untreated initial HCC at Japanese Society of Clinical Oncology (JCOG) member hospitals. Patientswho underwent SBRT for HCC at JCOG member hospitals between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤ 3 nodules, ≤ 5 cm in diameter; (3) a Child-Pugh (CP) score of A or B; and (4) unsuitability for or refusal of standard treatment, such as surgery, transplantation, RFA and TACE. We evaluated the overall survival (OS), recurrence-free survival (RFS) which was defined as the first instance of intra-hepatic recurrence after SBRT, disease-specific survival (DSS) using Kaplan-Meier analysis. Using Grey's test, patients who died of other diseases were analyzed as competing risks to estimate the cumulative incidence of local recurrence (CLR). Adverse events directly related to SBRT also analyzed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range; 50-89 years), and the median tumor size was 23 mm (range; 6-50 mm). The median radiation dose was 40 Gy (range; 35-60 Gy) in five fractions (range; 4-8). The median follow-up period was 45 months (range; 0-103 months). There were three cases where follow-up was not possible due to unexpected events unrelated to SBRT, while the remaining 70 patients were successfully followed for at least six months. The 2 and 3year OS, RFS, DSS, and CLR rates were 84.3% (95% CI: 75.8-92.8%) and 69.9% (95% CI: 58.7-81%), 67.5% (95% CI: 56.0-79.0%) and 57.9% (95% CI: 45.2-70.5%), 95.1% (95% CI:89.7-100%)/87.6% (95% CI:78.8-96.3%), and 11.4% (95% CI: 5.3-20.0%) and 20.0% (95% CI: 11.2-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: one case of grade 3 laboratory toxicities, one case of grade 3 liver failure, one case of grade 3 portal tumor thrombosis, and one case of grade 4 duodenal ulcer. No grade 5 toxicities were observed. The results of our study demonstrate that SBRT for HCC is highly effective in achieving local control and is safe to administer. In addition, survival outcomes are favorable. SBRT is a promising treatment modality, especially for small HCCs for that is not suitable for standard treatment.