TY - JOUR
T1 - Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy
AU - Hsieh, Cheng En
AU - Venkatesulu, Bhanu Prasad
AU - Lee, Ching Hsin
AU - Hung, Sheng Ping
AU - Wong, Pei Fong
AU - Aithala, Sathvik Panambur
AU - Kim, Byung Kyu
AU - Rao, Arvind
AU - Tung-Chieh Chang, Joseph
AU - Tsang, Ngan Ming
AU - Wang, Chun Chieh
AU - Lee, Chung Chi
AU - Lin, Chen Chun
AU - Tseng, Jeng Hwei
AU - Chou, Wen Chi
AU - Wang, Yu Chao
AU - Krishnan, S.
AU - Hong, Ji Hong
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Purpose: To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT). Methods: This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined. Results: The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A “volume-response” relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively. Conclusions: The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.
AB - Purpose: To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT). Methods: This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined. Results: The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A “volume-response” relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively. Conclusions: The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.
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U2 - 10.1016/j.ijrobp.2019.02.032
DO - 10.1016/j.ijrobp.2019.02.032
M3 - Article
C2 - 30797890
AN - SCOPUS:85063326224
SN - 0360-3016
VL - 105
SP - 73
EP - 86
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -