Predictors of Radiation-Induced Liver Disease in Patients with Hepatocellular Carcinoma Undergoing Proton Beam Therapy

Abstract

To identify the dose-volumetric predictors for radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) who were treated with proton beam therapy (PBT). We retrospectively reviewed 102 HCC patients who underwent PBT between November 2015 and May 2017 in the absence of intrahepatic tumor progression within 4 months of treatment completion. The median cumulative dose was 72.6 GyE (range, 72.6-46.2 GyE), and pretreatment Child-Pugh class A and B were recorded in 90 and 12 patients, respectively. The RILD was defined as elevation of alkaline-phosphatase for more than twice the upper normal limit and non-malignant ascites, Grade ≥3 hepatic toxicity according to Common Terminology Criteria for Adverse Events, version 3.0, or Child-Pugh score worsening by ≥2 within 4 months of PBT completion. The radiation doses were converted to equivalent doses in 2 Gy per fraction (EQD2; α/β = 2 Gy). Possible correlations of clinical and dose-volumetric parameters with RILD were examined. Fifteen (15%) patients developed RILD (unrecoverable, N = 8; fatal, N = 3). Multivariate analysis identified gross tumor volume (GTV, P = 0.001), unirradiated-liver-volume (normal liver volume receiving <1 Gy; P = 0.003) and Child-Pugh classification (P = 0.007) as significantly independent predictors for RILD, and the mean liver dose (MLD) was not associated with RILD development. For the Child-Pugh class A patients with unirradiated-liver-volume ≥500, 499-400, 399-300 and <300 cm3, the incidence of RILD were 0%, 10%, 21% and 46% (P < 0.001), respectively. In the Child-Pugh class B group, RILD was recorded in 0%, 25% and 100% patients with unirradiated-liver-volume ≥700, 699-450 and <450 cm3 (P = 0.010), respectively. The unirradiated-liver-volume, not MLD, predicts RILD development in patients with HCC undergoing PBT. Our results suggested the relative and absolute limits of unirradiated-liver-volume being ≥500 and ≥300 cm3 for Child-Pugh class A patients and ≥700 and ≥450 cm3 for Child-Pugh class B patients, respectively.Abstract 275; TableChild-Pugh class AChild-Pugh class BUnirradiated-liver-volume (cm3)≥500 (N = 43)499-400 (N = 20)399-300 (N = 14)<300 (N = 13)P≥700 (N = 5)699-450 (N = 4)<450 (N = 3)POverall RILD, N (%)0 (0)2 (10)3 (21)6 (46)<0.0010 (0)1 (25)3 (100)0.010Non-recoverable RILD, N (%)0 (0)1 (5)1 (7)3 (23)0.0120 (0)0 (0)3 (100)0.005Fatal RILD, N (%)0 (0)0 (0)0 (0)1 (8)0.1140 (0)0 (0)2 (67)0.045 Open table in a new tab