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Changes in Myocardial Blood Flow in a Canine Model of Left Sided Breast Cancer Radiotherapy

Oi-Wai Chau, Omar El-Sherif, Matthew Mouawad, Jane M. Sykes, John Butler, Heather Biernaski, Robert deKemp, Jennifer Renaud, Gerald Wisenberg, Frank S. Prato, Stewart Gaede

Abstract

Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured.

Introduction

It is projected that in 2021, breast cancer will account for 25% of the total yearly female cancer incidence in Canada [1]. Advances in adjuvant radiation therapy of the breast improves both local control and overall survival [2, 3]. However, patients with left-sided breast cancer are at a greater risk for the later development of radiation-mediated effects on the heart, including effects on the major coronary arteries, as well as vasculature due to the proximity of the heart to the radiation beam [4]. A worldwide systematic review done by Drost et al. on whole breast radiotherapy studies after 2014, reported a 3.6 Gray (Gy) total mean whole heart dose based on 84 left-sided breast cancer studies without breathing control and a lower mean heart dose of 1.7 Gy from 65 regimens with breathing control [5].

Materials and method

In five adult female, bred-for-research hounds (21–26 kg), cardiac perfusion and inflammation imaging was performed on a hybrid PET/MRI system (Biograph mMR; Siemens AG). The study was approved by the Animal Care Committee of Western University (Protocol 2014–005). All animals at the start of the study were at 1 year old and were anesthetized during imaging and irradiation using propofol (4–6 mg/kg) and maintained with 2% isoflurane. Cardiac perfusion imaging was performed at baseline, 1-week, 1-month, 3-months, 6-months and 12-months following focused cardiac external beam irradiation.

Results

Shows the results for both MBF methods rendered onto the 16-segments canine cardiac model (Fig 3). Figs 7, 8 show the results over time for MBF measured with 13NH3 and DB DCE-MRI respectively for the entire myocardium which can be broken down to regions supplied by the LAD, LCX and that supplied potentially by both arteries as shown in Fig 3.

Discussion

In this study, an increase of myocardial blood flow developed as early as one-week post irradiation, with a dip at 3-months follow-up during rest perfusion. The 3-months follow-up was not different compared to baseline. The biphasic response of blood flow increase was unexpected although a similar response was observed in the FDG study, i.e. there was a pause at 3 months in the increase of FDG. Although it is purely speculative, we suggest that the endothelial population in the myocardium could experience an inflammatory response before it occurs in the myocytes with small increase in resting blood flow occurring in two waves with the first due to endothelial inflammation and the second due to cardiomyocyte inflammation and fibroblast activation.

Conclusions

In the canine, rest myocardial blood flow within the first year following heart irradiation generally progressively increases over time. This has been confirmed by two non-invasive independent methods. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation. Based on this data, future patient studies early after radiotherapy, should consider measurements of both myocardial blood flow and myocardial inflammation.

Citation: Chau O-W, El-Sherif O, Mouawad M, Sykes JM, Butler J, Biernaski H, et al. (2023) Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy. PLoS ONE 18(9): e0291854. https://doi.org/10.1371/journal.pone.0291854

Editor: Ismaheel Lawal, Emory University, UNITED STATES

Received: May 18, 2022; Accepted: August 25, 2023; Published: September 28, 2023

Copyright: © 2023 Chau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This work was partly supported through the Translational Breast Cancer Studentship Award to O.W.Chau from the Breast Cancer Society of Canada, a grant to F. S. Prato from the Ontario Research Fund, RE07-021, a London Regional Cancer Program Catalyst Grant, a Canadian Institutes of Health Research Grant 149080 through in-kind donations from the Thames Valley Veterinary Services to S Gaede. There was no additional external funding received for this study.

Competing interests: No conflicts of interest, financial or otherwise, are declared by the authors

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291854#sec014

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