Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease

Purpose: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the difference in normal tissue complication probability (NTCP) between subgroups of hepatocellular carcinoma patients undergoing three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 89 hepatocellular carcinoma patients who completed 3D-CRT for local hepatic tumors were included. The average isocenter dose was 49.9 ± 6.2 Gy. Logistic regression analysis was used for the association between statistically significant factors and RILD (defined as Grade 3 or 4 hepatic toxicity of elevated transaminases or alkaline phosphatase within 4 months of completing 3D-CRT) in multivariate analysis. Maximal likelihood analysis was conducted to obtain the best estimates of the NTCP model parameters. Results: Of the 89 patients, 17 developed RILD. In univariate analysis, hepatitis B virus (HBV)-positive status and the mean radiation dose to the liver were the two factors significantly associated with the development of RILD. Of the 65 patients who were HBV carriers, 16 had RILD compared with 1 of 24 non-carrier patients (p = 0.03). The mean radiation dose to liver was significantly greater in patients with RILD (22.9 vs. 19.0 Gy, p = 0.05). On multivariate analysis, HBV carrier status (odds ratio, 9.26; p = 0.04) and Child-Pugh B cirrhosis of the liver (odds ratio, 3.65; p = 0.04) remained statistically significant. The best estimates of the NTCP parameters were n = 0.35, m = 0.39, and TD ₅₀(1) = 49.4 Gy. The n, m, TD ₅₀(1) specifically estimated from the HBV carriers was 0.26, 0.40, and 50.0 Gy, respectively, compared with 0.86, 0.31, and 46.1 Gy, respectively, for non-carrier patients. Conclusion: Hepatocellular carcinoma patients who were HBV carriers or had Child-Pugh B cirrhosis presented with a statistically significantly greater susceptibility to RILD after 3D-CRT.