ORIGINAL RESEARCH article
Front. Oncol.
Sec. Radiation Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1623753
This article is part of the Research TopicRecent Advances in Radiation Oncology for the Management of Thoracic MalignanciesView all 8 articles
Preclinical characterisation of changes in cardiac function and circulating biomarkers following differential irradiation of thoracic volumes
Provisionally accepted
Refik Kuburas1
Mihaela Ghita-Pettigrew1
Gerard M Walls1Brianna N Kerr1
Kathryn H Brown1Cecilia Facchi2
Alan McWilliam3
Marcel van Herk3
Kaye Williams4
Karl T Butterworth1*- 1Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom
- 2Division of Cancer Sciences, University of Manchester, Manchester, UK, Manchester, United Kingdom
- 3Department of Radiation Related Research, University of Manchester, Manchester, Manchester, United Kingdom
- 4Division of Pharmacy and Optometry, University of Manchester, Manchester,, Manchester, United Kingdom
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The heart and lungs are critical organs at risk in patients receiving radiotherapy for thoracic tumours.Preclinical studies in rat models have provided evidence indicating consequential effects of lung radiation on the heart through vascular remodelling which leads to pulmonary arterial hypertension. In this study, we aimed to assess the impact of lung irradiation on a long-term model of cardiac base irradiation that recapitulates clinical observations of the heart base as a radiosensitive region and to understand relationships between cardiopulmonary irradiation and circulating cytokines profiles. Female C57BL6J mice were irradiated under CT image-guidance targeting the heart base, right lung or co-irradiation of the heart base and the right lung. Mice were monitored by transthoracic echocardiography for 50-weeks after irradiation with lung histology and cytokine profiling at 10 and 50 weeks. Lung and heart co-irradiation leads to small changes in the cardiac function and histological changes in the right lung with distinct changes in serum cytokines for different irradiated volumes compared to heart irradiation. In contrast to previous studies in rat models, these data demonstrate a minimal contribution of lung irradiation to cardiac response in this model. Understanding the potential interplay between the heart and lungs is important in the context of optimising cardiac dose distributions that may increase lung doses and minimising the impact of lung dose on cardiac function.
Keywords: Radiotherapy, preclinical model, cardiotoxicity, heart irradiation, Lung irradiation, Cardio-pulmonary, radiation-induced cardiac fibrosis, Cytokines
Received: 06 May 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Kuburas, Ghita-Pettigrew, Walls, Kerr, Brown, Facchi, McWilliam, van Herk, Williams and Butterworth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Karl T Butterworth, Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, BT9 7BL, United Kingdom
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