Multicenter Phase Ii Study Of Stereotactic Ablative Radiotherapy For Hepatocellular Carcinoma <= 5 Cm (Krog 12-02)

To evaluate the efficacy of stereotactic ablative radiotherapy (SABR) for hepatocellular carcinoma (HCC) ≤ 5 cm. A total of 54 patients with unresectable HCC showing an incomplete response after 1-5 sessions of transarterial chemoembolization were enrolled in a phase II clinical trial of SABR from 6 institutions between July 2012 and June 2015. SABR was delivered with a total dose of 60 Gy in 3 fractions within 14 days, with ≥ 48 hour-intervals between each fraction. The treatment response was evaluated using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Radiation-induced liver disease (RILD) was analyzed at 2 months. Survival outcomes were analyzed with the Kaplan-Meier method. This trial is registered with Clinical Trials.gov, number NCT01825824. Forty-eight patients were evaluable with a median follow-up of 41 months (range, 2-61 months). The median tumor size was 2.0 cm (range, 1.0?4.5 cm) and most patients (89.6%) had a single lesion. Thirty-six patients (75%) received TACE ≤ 2 times. Local control rate at 2 and 5 years were 97.4% and 94.7%, respectively. Overall survival rate at 2 and 3 years were 90.9% and 78.3%, respectively. Progression-free survival rate at 2 and 3 years were 50.3% and 27.0%, respectively. One patient experienced non-classic RILD with acute toxicity at 2 month after SABR. The high-dose SABR for HCC ≤ 5 cm is and effective as evidenced by the high rates of tumor control, overall survival, and acceptable treatment-related toxicity.