Do Biliary Complications after Hypofractionated Radiation Therapy in Hepatocellular Carcinoma Matter?

The purpose of this study is to evaluate the efficacy of hypofractionated radiation therapy (RT) in the treatment of unresectable hepatocellular carcinoma (HCC) after failure of transarterial chemoembolization (TACE) or in cases of refractory HCC, and to investigate biliary complications after hypofractionated RT.

We retrospectively enrolled patients with unresectable, TACE-unresponsive, or refractory HCC treated with hypofractionated RT between July 2006 and December 2012. The perihilar region was defined as the 1-cm area surrounding the right, left, and the common hepatic duct, including the gallbladder and the cystic duct. Significant elevation of total bilirubin was defined as an increase of more than 3.0 mg/dL, and more than two times that of the previous level after completion of RT.

Fifty patients received hypofractionated RT and 27 (54%) had a tumor located within the perihilar region. The median follow-up period was 24.7 months (range, 4.3 to 95.5 months). None of the patients developed classic radiation disease symptoms, but four patients (8%) showed significant elevation of total bilirubin within 1 year after RT. During follow-up, 12 patients (24%) developed radiologic biliary abnormalities, but only two patients had toxicities requiring intervention. Estimated local progression-free survival, progression-free survival, and overall survival of the patients at 3-year post-hypofractionated RT were 89.7%, 11.2%, and 57.4%, respectively.

Biliary complications associated with a higher dose exposure of hypofractionated RT were minimal, even in the perihilar region. Hypofractionated RT provided excellent local control and may be a valuable option for treatment of unresectable cases of TACE-unresponsive or refractory HCC.