Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2016; 22(10): 3006-3014
Published online Mar 14, 2016. doi: 10.3748/wjg.v22.i10.3006
Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies
John D Roberson II, Andrew M McDonald, Craig J Baden, Chee Paul Lin, Rojymon Jacob, Omer L Burnett III
John D Roberson II, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-3412, United States
Andrew M McDonald, Craig J Baden, Rojymon Jacob, Omer L Burnett III, Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, United States
Chee Paul Lin, Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL 35205, United States
Author contributions: Roberson JD collected and analyzed the data and drafted the manuscript; Lin CP provided analytical oversight; Jacob R and Burnett OL designed and supervised the study; McDonald AM, Baden CJ, Jacob R and Burnett OL revised the manuscript for important intellectual material support; all authors have read and approved the final version to be published.
Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR00165 through our institution’s Center for Clinical and Translational Science (in part). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Institutional review board statement: This study was reviewed and approved by the University of Alabama at Birmingham Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to inclusion in the study.
Conflict-of-interest statement: We have no conflicts-of-interest to report.
Data sharing statement: Dataset is available upon request from corresponding author at jdr25@uab.edu. Consent was not obtained for data sharing but presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: John D Roberson II, BS, Medical Student, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave. S. FOT 1203, Birmingham, AL 35294-3412, United States. jdr25@uab.edu
Telephone: +1-205-9345670 Fax: +1-205-9750784
Received: August 18, 2015
Peer-review started: August 18, 2015
First decision: September 29, 2015
Revised: November 5, 2015
Accepted: December 8, 2015
Article in press: December 8, 2015
Published online: March 14, 2016
Processing time: 199 Days and 14.8 Hours
Abstract

AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (90Y) microspheres.

METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following 90Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.

RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).

CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for 90Y microsphere therapy.

Keywords: Yttrium-90 microspheres; Liver metastases; Multivariate analysis; Toxicity incidence; Colorectal adenocarcinoma

Core tip: Factors associated with the development of severe (grade ≥ 3) toxicities were identified using multivariate logistic regression models using Common Terminology Criteria for Adverse Events version 4.03. We found that severe toxicities were present following 21.5% of treatments. Abnormal pre-treatment albumin and international normalized ratio (INR) were associated with development of severe hepatic toxicity. Abnormal pre-treatment aspartate aminotransferase (AST) and hemoglobin were associated with development of severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) was associated with severe total bilirubin toxicity, and colorectal adenocarcinoma with severe alkaline phosphatase toxicity. Pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology should be considered when selecting appropriate candidates for 90Y microsphere therapy.