BACKGROUND: The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC).METHODS: The main eligibility criteria were a greatest tumor dimension (LD sum) <10 cm, inoperable HCC, and incomplete response after TACE. Prescribed SBRT doses were up to 60 gray (Gy) in 3 fractions, but doses were reduced until normal tissue constraints were allowed.RESULTS: Between May 2008 and February 2011, 50 patients were enrolled in this phase 2 trial, of which 47 patients were evaluable. Forty‐one patients had Child‐Pugh class A disease (A5/A6 were 32/9), 6 patients had class B7 disease, and 5 patients had portal vein tumor thrombosis. All patients underwent TACE 1 to 5 times before SBRT. SBRT doses ranged from 42 to 60 Gy in 3 fractions (median dose, 57 Gy), and the median LD sum was 29 mm (range, 13‐78 mm). Eighteen patients (38.3%) achieved complete remission within 6 months of completing of SBRT, and 18 patients (38.3%) had a partial response. The 2‐year local control rate was 94.6%, the overall survival rate was 68.7%, and the progression‐free survival rate was 33.8%. Three patients (6.4%) experienced grade 3 gastrointestinal toxicity, and 2 patients (4.3%) experienced grade 4 gastric ulcer perforation.CONCLUSIONS: This trial demonstrated that SBRT after incomplete TACE for inoperable HCC achieves promising rates of response and local control. On the basis of these study results, a modified, multi‐institutional, phase 2 trial to reduce gastrointestinal toxicity is recommended. Cancer 2012. © 2012 American Cancer Society.

Background: Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. Methods: Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy). Results: LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. Conclusions: This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).