Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis

Clinical question
What are the delayed effects of transarterial radioembolization on the liver?

Take-away point
13% of patients were noted to have delayed radiation-induced hepatotoxicity with tumor involving more than 50% of the liver and cirrhosis as notable predisposing factors.

Reference
Brian M. Currie, et al. Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis. Journal of Vascular and Interventional Radiology. Dec, 2019: 30; 12, 1915-1923.

Click here for abstract

Study design

Retrospective

Funding source

Self-funded or unfunded

Setting

Single-center





Table 6. Demographics and Treatment Details: Subset Analysis

Summary

Radioembolization-induced liver disease (REILD) is defined as jaundice and/or ascites occurring within the first one or two months and resolving by 6 months following radioembolization in the absence of tumoral progression or biliary obstruction. This study attempted to define criteria that develop outside of this window. The study included all patients status post radioembolization between 2005 and 2014 and survived a year. All malignancies were included with 54% neuroendocrine tumor, 16% hepatocellular carcinoma, and 14% colorectal cancer. Radioembolization procedures were performed with both Sirspheres and Theraspheres.

The authors defined a classification system called radioembolization-induced chronic hepatotoxicity (RECHT) to be clinically distinct from radioembolization induced liver disease (REILD) and radiation induced liver disease (RILD). In RECHT, toxicity occurs 6 months or greater from treatment and must be permanent. Lab criteria included INR, bilirubin, ALT, AST, alkaline phosphatase, albumin, and platelets and were classified from grade 1-4 based on CTCAE classification. Clinical toxicity criteria included hepatic necrosis, hepatic failure (encephalopathy), portal hypertension (varices), ascites, and portal vein thrombosis and were classified grade 3 or 4. The authors defined RECHT as any new and permanent Grade 3 or 4 clinical and laboratory hepatotoxicity that could not be attributed to disease progression or other factors.

While 50% of patients had chronic hepatotoxicity, only 13% were classified as RECHT. The remaining were excluded due to disease progression, additional therapies complicating the clinical picture, or REILD. 92% of patients with RECHT had clinical complications. 5% of all patients and 36% of patients with RECHT died.

Using univariate and subgroup analysis, tumoral burden (greater than 50%) and cirrhosis were found to be predisposing factors for developing RECHT. Notably, patients who developed RECHT received on average a lower radiation dose. 

Commentary

A major difficulty with many radioembolization papers is heterogeneity and incomplete dosing information. This paper is no exception with their 98 patients including both glass and resin microspheres, 13 different primary malignancies represented, and a spectrum of laboratory and clinical toxicities were noted to quality for RECHT. That being said, the goal was to create an all encompassing definition for a toxicity that many IRs have experienced but did not fit into the standard definition of REILD, and the authors succeeded. Unsurprisingly, high tumoral burden and background baseline liver disease were noted to be risk factors for RECHT. This also speaks to the view that radioembolization may be better served earlier in a disease process than as salvage therapy.

Post Author:
David M Mauro, MD
Assistant Professor
Department of Radiology, Vascular and Interventional Radiology
University of North Carolina
@DavidMauroMD