Toward consensus reporting of radiation-induced liver toxicity in the treatment of primary liver malignancies: Defining clinically relevant endpoints

Background: Our purpose was to define the most clinically relevant "nonclassic" radiation-induced liver disease (RILD) endpoints in cirrhotic patients receiving stereotactic body radiation therapy or proton beam therapy for primary liver cancer. Methods and materials: We retrospectively collected pretreatment, detailed toxicity (<= 6 months posttreatment), and outcomes data from 48 patients. Deaths were examined for association with RILD. Univariate and multivariate Cox models defined significant predictors of overall survival (OS)/RILD-specific survival (RILD-SS). Results: With median follow-up of 13 months, 23 patients (48%) had an increase in Child-Pugh (CP) score(>= 2, 25%) and 3 (6%) had >= G3 transaminase elevation. Of 18 deaths, 6 were potentially ascribed to RILD. Univariate analysis showed that CP score increases of >= 1 and >= 2 and CP class change predicted OS, as did >= G3 aspartate transaminase (AST) elevation and Common Terminology Criteria for Adverse Events (CTCAE) AST toxicity grade change. On multivariate analysis, CP score increase of >= 2 and >= 1 CTCAE AST toxicity grade change were the strongest independent nonclassic RILD predictors of OS. For RILD-SS, CP score increases >= 2, >= grade 3 CTCAE alanine transaminase, and >= grade 2 bilirubin elevations were predictive. Conclusions: Increased CP score >= 2 strongly predicts for both OS and RILD-SS and should be reported in future studies along with transaminase elevations, which are also predictive of outcomes. (C) 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.