ESTRO 2024 - Abstract Book

S5293 ESTRO 2024 CONV-RT, but also potentially with less macrophage-to-myofibroblast transition. These results support a further exploration of the implication of senescence and macrophage function in the FLASH effect. Radiobiology - Normal tissue radiobiology

Keywords: FLASH radiotherapy, lung, senescence

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Proffered Paper

Captopril mitigates radiation-induced cardiopulmonary side effects only if the lung is spared

Julia Wiedemann 1 , Uilke Brouwer 2 , Jeffery Sewdihal 1 , Herman H.W. Silljé 3 , Michael G. Dickinson 3 , Rudolf A. de Boer 3 , Robert P. Coppes 1,2 , Peter van Luijk 1 1 University Medical Center Groningen, Department of Radiation Oncology, Groningen, Netherlands. 2 University Medical Center Groningen, Department of Biomedical Sciences of Cells and System, Groningen, Netherlands. 3 University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands

Purpose/Objective:

Even with modern radiation technologies, radiotherapy for thoracic tumours is associated with considerable radiation doses to heart and lungs. The resulting damage potentially leads to severe cardiac and pulmonary side effects. In line with this, growing evidence suggests that patient survival is negatively associated with dose to heart and lungs. As such, interventions are needed to prevent these radiation-induced side effects, leading to reduced quality of life or even reduced survival of patients. We previously showed in a rat model that heart and lung irradiation can cause fibrotic remodelling of the left ventricle (LV) and vascular remodelling in the lung (1), causing a long-term reduction of cardiac function, pulmonary inflammation and fibrosis. Inhibiting the renin-angiotensin-aldosterone system (RAAS) using an angiotensin-converting-enzyme (ACE) inhibitor reduces LV remodelling, fibrosis and vasoconstriction. ACE inhibition is therefore a cornerstone of the treatment of cardiac failure in non-oncology patients. In line with this, in pre-clinical models, RAAS inhibition reduced early radiation-induced heart and lung damage (2). However, clinical studies investigating the protective effect of RAAS inhibition on normal tissue after radiotherapy in lung cancer patients remained inconclusive (3,4). Interestingly, in our rat model, combined irradiation of the heart and lungs led to aggravated, persisting effects. We hypothesize that heart dose is potentially the critical factor for the effectiveness of Captopril treatment in radiotherapy patients. Therefore, we aim to investigate the protective effect of Captopril after heart and lung irradiation alone or in combination in our pre-clinical rat model.

Material/Methods:

The heart, 50% of the lateral lung, or both were irradiated using protons. Animals were randomly assigned to receive Captopril (45mg/kg of BW per day) or normal drinking water (n=11-14 animals per group). LV dimensions and cardiac output were measured using echocardiography. Cardiac tissue was collected 38 weeks after irradiation, and a Masson-trichrome staining was performed to assess collagen deposition.