PurposeIn early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen. Material and methodsBetween 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3Gy/fraction were retrospectively included. ResultsSixty of the 61 included presented Child-Pugh A cirrhosis (A5, n=41, 67.2%; A6: n=19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n=12). All patient received a TACE followed by 3Gy per fraction hRT. Mean radiation dose was 54Gy (range: 48–60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54Gy (HR: 2, P=0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P=0.03) and overall hRT time (HR: 1.06, P=0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n=7). ConclusionIn BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.