The safety and efficacy of stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) is well established. However, the effect of repeated SBRT for intra-hepatic recurrent HCC is unclear. This study aimed to retrospectively evaluate the safety and efficacy of repeated SBRT for intra-hepatic recurrent HCC. We enrolled 24 patients with 53 tumors who had undergone ≥ 2 two courses (median 2 times; range 2- 4 times). Sixteen patients (66.7%) had previously undergone surgery or ablation therapy, and 45 lesions (84.9%) underwent trans-arterial chemo-embolization using lipiodol before SBRT. Median tumor size was 17 mm (range 5- 47 mm). Child-Pugh (CP) scoring system was used to classify 20 and 4 patients (first course), and 18 and 6 patients (second course or beyond) into classes A and B, respectively. SBRT was performed using a 3-dimensional conformal method which delivered a single high dose radiation to the tumor. Prescribed dose was evaluated at the isocenter in 27 lesions (median dose: 48 Gy in 4 fractions) and at D95% prescription in 26 lesions (median dose: 40 G y in 4 fractions) for the first and rest of the courses. Local progression was defined as growth of the irradiated tumor and early arterial enhancement remaining for more than 6 months on follow-up with dynamic CT. Treatment-related toxicities were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version. The median follow-up duration was 42 months (range, 9- 79 months). The median interval between the first and the repeated SBRT was 21 months (range 4 - 61 months). Three- year overall survival rates, and local control rates for patients were 75.0 % (95 % CI: 56.0 - 94.0 %) and 97.4 % (95 % CI: 92.5 – 100 %), respectively. Grade 3 toxicities such as AST/ALT elevation, decreased platelet count, and ascites were observed in 4 patients (16.7 %) in the first course and 5 patients (20.8 %) in the second course or beyond. Seven patients developed grade 3 during all the courses, which was significantly higher in CP class B than in CP class A (p=0.0196). All sessions were fused using deformable registration software (Velosity, Varian) to evaluate the median mean liver dose (MLD), 13.1 Gy (range, 5.5- 24.6 Gy) and the percentage of the uninvolved liver (liver volume other than GTV) volume exceeding 20 Gy (V20Gy), 20.7 % (range, 6.2- 48.3 %). There was no significant difference in MLD and V20Gy between patients with or without grade 3 toxicities. Repeated SBRT can be used safely and effectively for patients with intra-hepatic recurrent HCC. However, caution should be exercised in repeated SBRT usage for CP class B patients due to high rates of severe liver toxicities.
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