Kuburas Refik, Ghita-Pettigrew Mihaela, Walls Gerard M, Kerr Brianna N, Brown Kathryn H, Facchi Cecilia, McWilliam Alan, van Herk Marcel, Williams Kaye J, Butterworth Karl T
Patrick G. Johnston Centre for Cancer Research, Queens University Belfast, Belfast, United Kingdom.
Division of Cancer, University of Manchester, Manchester, United Kingdom.
Front Oncol. 2025 Jun 27;15:1623753. doi: 10.3389/fonc.2025.1623753. eCollection 2025.
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.
心脏和肺部是接受胸部肿瘤放疗患者的关键风险器官。大鼠模型的临床前研究提供了证据，表明肺部放疗通过血管重塑对心脏产生后续影响，进而导致肺动脉高压。在本研究中，我们旨在评估肺部照射对心脏底部照射长期模型的影响，该模型概括了心脏底部作为放射敏感区域的临床观察结果，并了解心肺照射与循环细胞因子谱之间的关系。
雌性C57BL6J小鼠在CT图像引导下接受针对心脏底部、右肺或心脏底部与右肺联合照射。照射后通过经胸超声心动图对小鼠进行50周监测，并在第10周和第50周进行肺组织学和细胞因子分析。
与心脏照射相比，心肺联合照射导致心脏功能出现微小变化，右肺出现组织学变化，不同照射体积的血清细胞因子有明显变化。
与之前大鼠模型的研究不同，这些数据表明在该模型中肺部照射对心脏反应的贡献极小。在优化可能增加肺部剂量的心脏剂量分布以及最小化肺部剂量对心脏功能的影响方面，了解心脏和肺部之间的潜在相互作用非常重要。
