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Aim: To evaluate whether the retention rate of indocyanine green 15 min after administration (ICG-R15) could predict radiation hepatotoxicity in patients treated with radiotherapy (RT) for hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed data of 146 HCC patients treated with RT between February 1994 and December 2008. The ICG-R15 was measured within 1 month prior to the start of RT. Radiation hepatotoxicity was evaluated by incidence of radiation-induced liver disease (RILD) between 2 weeks and 3 months after completion of RT. We analysed the correlation between the incidence rate of RILD and the ICG-R15 before RT (pre-RT ICG-R15)., Results: The classic and non-classic RILD occurred in 15 patients (10.3%): classic type in five patients (3.4%) and non-classic RILD in 10 patients (6.9%). A positive correlation was shown between the probability of RILD and increase in pre-RT ICG-R15 (P < 0.0001). Univariate analysis indicated that cut-off value of pre-RT ICG-R15 could predict RILD significantly. The incidence of RILD for the patients with 22% or higher pre-RT ICG-R15 levels was 40.7% as compared to 3.4% for those with levels lower than 22% (P < 0.0001). There was no clinical factor that significantly affected RILD in univariate analysis. Multivariate analysis indicated that the pre-RT ICG-R15 value was the only significant factor affecting RILD (P < 0.0001)., Conclusion: These results suggest that pre-RT ICG-R15 could be a useful factor in predicting radiation hepatotoxicity in HCC patients treated with RT., (© 2012 John Wiley & Sons A/S.)