Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters

Background: To investigate the clinical and dose-volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). Methods: Between March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10-20 Gy (median, 15 Gy) per fraction was given over 3-4 consecutive days for a total dose of 30-60 Gy (median, 45 Gy). The following clinical and dose-volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy). Results: Seventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in >= grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose-volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD. Conclusions: The Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.