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Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third cause of cancer death in the world. In unresectable  HCC patients with intermediate-stage disease, transcatheter arterial embolization (TAE)  +/- co-administration of arterial chemotherapy (TACE) has shown partial responses in 15–55% of cases, and significantly delays tumor progression and vascular invasion. However while repeated courses of TAE/TACE  can be administered in case of incomplete response, alternative treatment options may be considered to maximize local control. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, is an emerging treatment option for radical treatment of inoperable HCC and may be proposed in case of local relapse following one or more TAE/TACE courses. 

This is a multicentre, prospective, randomised controlled, unblinded, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of intermediate stage of HCC after incomplete reponse following one TAE/TACE cycle (NCT02323360). Primary endpoint was Local Control (LC). Secondary endpoints were Progression Free-Survival (PFS), Overall Survival (OS) and incidence of acute and late complications. In order to detect an HR=0.18 (which translates in  45% difference at the analysis time) with a power of 80% at 5% 2 sided of the log-rank test , 18 events (approximately 50 patients, 25 per arm) are needed. A preliminary analysis was performed when the preplanned number of events (n=20) was reached.

RESULTS:At the time of our analysis 40 patients were enrolled, 19 (49%) in the TAE/TACE and 21 (51%) in the SBRT arm respectively. Median age was 75 (range 52-86) years. All patients received at least ≥ 1 TAE/TACE course prior to enrolment; no significant differences were found between the 2 arms with regard to prior resection (n=8, 20%), Radiofrequency Ablation (RFA, n=14, 35%) or Percutaneous Ethanol Injection (PEI, n=4, 10%). Median follow-up was 18 months (range, 2-56 months). Patients were classed stage A and B according Barcelona Clinic Liver Cancer (BCLC) staging system in 7 (18%) and 33 (82%) respectively. One and 2-year LC rates were 57% and 36%, with a median LC of 12 months  (CI95% 16-33 months). Use of SBRT resulted in superior LC as compared to TAE/TACE (median not reached versus 8 months, p=0.0002). PFS was 29% and 16% at 1 and at 2 years, respectively. At the event of progression, 8 patients in the SBRT arm received a further TAE/TACE administration while 10 patients in the TAE/TACE arm received SBRT. OS was 96% and 90% at 1 year and at 2 years, respectively. No grade ≥3 toxicity was recorded, and no differences in overall toxicities were found between the 2 arms.

In patients affected by unoperable HCC experiencing incomplete response following  ≥1 cycle of TAE/TACE, SBRT  was correlated to significantly higher LC rates as compared to rechallenge with TAE/TACE.