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

Neutrophil/Lymphocyte Ratio Predicts Increased Risk of Immediate Progressive Disease following Chemoembolization of Hepatocellular Carcinoma

Clinical question
Do patients with hepatocellular carcinoma (HCC) and elevated neutrophil/lymphocyte ratio (NLR) have a greater risk of progressive disease following initial transarterial chemoembolization (TACE)?

Take-away point
Elevated baseline NLR is associated with higher rates of HCC tumor progression at 2-month follow-up imaging after TACE.

Reference

Cruz, J et al. Neutrophil/Lymphocyte Ratio Predicts Increased Risk of Immediate Progressive Disease following Chemoembolization of Hepatocellular Carcinoma. Journal of Vascular and Interventional Radiology, Volume 30, Issue 12, 1887 – 1892.

Click here for abstract

Study design

Retrospective review

Funding source

Self-funded or unfunded

Setting

Single institution

Summary

As an indicator of inflammation, serum neutrophil to lymphocyte ratio (NLR) is being increasingly utilized as a prognostic marker for a variety of disease states. As the survival for locoregional therapies for HCC varies widely, the authors of this study looked at NLR to determine a potential association with disease progression after TACE.

The authors reviewed 190 patients who underwent 254 TACE procedures. TACE was performed with both lipiodol-based conventional technique and drug-eluting embolics (DEB) and followed with CT or MRI 2 months following treatment to assess response using mRECIST. Treatment outcomes did not differ between conventional TACE and DEB-TACE. Thirty-nine patients developed progressive disease at the 2 month follow up imaging study. Mean NLR for this group was 4.1, compared to 2.76 or less for patients with complete response, partial response, or stable disease. Regression analysis showed that NLR and the presence of more than 1 tumor were predictive of mRECIST progression whereas age, liver function, tumor size, and cause of cirrhosis did not predict response (or progression). If one were to use NLR of 3.5 as a cutoff, objective response was achieved in 74% of treatments with NLR <3.5, compared with 52% with a higher NLR. Disease control was also significantly higher in patients with an NLR <3.5 (87% vs 76%; P = .002 by chi-squared analysis).

Commentary

In the era of personalized medicine, this study provides prognostic information for our oncology patients and allows us to better determine which patients might respond best to our therapies. NLR is being actively investigated for its prognostic impact and role in a variety of conditions, including colorectal and prostate cancer, patients undergoing transcatheter aortic valve replacement, atrial fibrillation, and even psychosis (1-5). As such, it is no surprise that an inflammatory environment has implications for our treatments. This study showed that elevated baseline NLR is associated with higher rates of HCC progression at 2 month follow-up after TACE. The authors acknowledge that the relationship between NLR and tumor multiplicity, tumor markers, and Child-Pugh score still needs to be further elucidated. However, this work is a good early step in understanding the role NLR plays in HCC patients.

Post-Author:

Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@ZagumBhatti