ESTRO 2024 - Abstract Book

S5274 ESTRO 2024 III lung cancer or distal oesophageal patient, using α/β of 3.0, and the arc delivery solution provides a mild dose bath in the lungs, replicating contemporary treatment planning (Figure 1). Entresto was administered in drinking water, from one week prior until the end of the study, at a dose of 100mg/kg/day. Radiobiology - Normal tissue radiobiology

Figure 1. Experimental radiation exposure

Cardiac health was longitudinally monitored by two-dimensional speckle tracking transthoracic echocardiography (2D-STE) for 30 weeks after irradiation, at 10-weekly intervals. This was performed using the Vevo module (Visual Sonics), allowing assessment of systolic and diastolic structural (ventricular mass and volume) and functional (strain, ejection fraction, E/A ratio) parameters, as well as a 3-lead electrocardiogram. Plasma will be analysed for NT-proANP levels by ELISA at 30 weeks. Tissue levels of ANP will be ascertained by immunohistochemistry, along with conventional markers for microvascular, immune and connective tissue damage. Hearts will be snap-frozen for spatial transcriptomics using the Visium platform (10X) with validation using RNAscope (ACDBio). Values presented are means, p values were generated using unpaired t tests in this preliminary analysis.

Results:

Perturbations in heart structure and systolic cardiac function were detected at 10 weeks, and were accentuated at 20 weeks. At 20 weeks, the XRT+Entresto arm exhibited a marked increment in global longitudinal strain, compared with the XRT-only arm (means –17% versus –10%, p<0.0001) (Figure 2A). The cardioprotective effect of Entresto was not complete in that mean strain for the XRT-Entresto arm was lower that controls (p=0.01). Improvements in ejection fraction (58% versus 54%, p=0.0045) (Figure 2B) and fractional shortening (29% versus 26%, p=0.383) were also observed with the addition of Entresto to irradiation at 20 weeks, although the magnitude of these changes was less pronounced.