ESTRO 2024 - Abstract Book

S5278

Radiobiology - Normal tissue radiobiology

ESTRO 2024

Keywords: CBCT, chromosome aberrations, biodosimetry

2306

Poster Discussion

Effects of heart base irradiation on myocardial strain and remodelling in C57BL/6j mice

Mihaela Ghita 1 , Kevin S Edgar 2 , Refik Kuburas 1 , Kathryn H Brown 1 , Gerard M Walls 1,3 , Cecilia Facchi 4 , David J Grieve 2 , Chris J Watson 2 , Alan McWilliam 5 , Marcel van Herk 5 , Kaye J Williams 4 , Karl T Butterworth 1 1 Queen's University Belfast, Patrick G Johnston Centre for Cancer Research, Belfast, United Kingdom. 2 Queen's University Belfast, Welcome-Wolfson Institute for Experimental Medicine, Belfast, United Kingdom. 3 Belfast Health and Social Care Trust, Cancer Centre Belfast City Hospital, Belfast, United Kingdom. 4 University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom. 5 University of Manchester, Department of Radiotherapy Related Research, Manchester, United Kingdom

Purpose/Objective:

Cardiovascular effects manifest clinically years or even decades after radiation therapy (RT) for thoracic malignancies. The risk of developing radiation induced cardiac toxicity (RICT) increases linearly by >7% per Gy of mean dose to the heart, with no apparent threshold. Clinical studies including patients treated for lung cancer identified a highly significant region across the base of the heart (superior region), where higher RT dose was associated with worse survival. Differential regional radiosensitivity was reverse translated in a mouse model using a small animal radiation research platform (SARRP) coupled with serial preclinical transthoracic echocardiography (TTE). In this study, we aimed to assess the functional consequences of cardiac base irradiation to establish the dose response relationship to specific biologically effective doses (BEDs). Furthermore, we aimed to demonstrate the predictive potential of global and segmental longitudinal strain as early biomarkers for late occurring RICT. Female C57BL/6J mice were irradiated under cone-beam computed tomography (CBCT) image-guidance with a single-fraction of 16 Gy or 20 Gy or with 3 consecutive fractions of 8.66 Gy targeting the heart base, or sham irradiation, using an anterior-posterior field arrangement. The respective BEDs were 101.3 Gy, 153.3 Gy and 101.3 Gy using an α/β value for the heart 3 Gy. Longitudinal TTE was performed at baseline and at 10-week intervals up to 50 weeks after irradiation. This was coupled with two-dimensional speckle tracking (2D-STE) to analyse early changes in global and segmental strain in response to RT. At the endpoint, mice were culled, hearts were removed, and midline dissected in the transverse plane. After fixation, hearts were paraffin embedded and processed for histological evaluation. Staining was performed using Mayer’s haematoxylin and eosin stain or picrosirius red stain. Fibrosis was analysed as the myocardial collagen, as the average percentage of the picrosirius red staining, relative to the total tissue. Material/Methods:

Results: