Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy

• DOI: 10.1016/j.ijrobp.2019.02.032
• Publication Date: 2019-02-21T21:52:24Z
• Authors: Cheng-En Hsieh; Bhanu Prasad Venk...; Ching-Hsin Lee; Sheng-Ping Hung; Pei-Fong Wong; Sathvik Panambur ...; Byung Kyu Kim; Arvind Rao; Joseph Tung-Chieh...; Ngan-Ming Tsang; Chun-Chieh Wang; Chung-Chi Lee; Chen-Chun Lin; Jeng-Hwei Tseng; Wen-Chi Chou; Yu-Chao Wang; Sunil Krishnan; Ji-Hong Hong
• Keywords: Aged, 80 and over; Male; Analysis of Variance; Carcinoma, Hepatocellular; Liver Diseases; Liver Neoplasms; Ascites; Radiotherapy Dosage; Organ Size; Alkaline Phosphatase; Hepatitis B; Radiation Tolerance; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Liver; Proton Therapy; Hepatectomy; Humans; Regression Analysis; Female; Aged; Retrospective Studies

To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT).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.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.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.