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


CONCLUSIONS
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.
Cheng
Jason Chia-Hsien
JC
Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan. cheng38@ms15.hinet.net
Wu
Jian-Kuen
JK
Lee
Patricia Chiao-Tzu
PC
Liu
Hua-Shan
HS
Jian
James Jer-Min
JJ
Lin
Yu-Mong
YM
Sung
Juei-Low
JL
Jan
Gwo-Jen
GJ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D002353:Carrier State; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D019694:Hepatitis B, Chronic / Q000209:etiology; D006801:Humans; D008099:Liver / Q000528:radiation effects*; D008113:Liver Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*