ESTRO 2023 - Abstract Book

S481

Sunday 14 May 2023

ESTRO 2023

No significant differences were detected in E/a ratio between groups, suggesting diastolic function was preserved. Analysis of ECGs revealed increased PR interval following base irradiation at 10 weeks and 30 weeks, in keeping with potential atrioventricular node pathology. The P wave duration was also increased at 30 weeks, which is suggestive of abnormal conduction throughout the atria. The QRS widths were fairly consistent throughout the study indicating ventricular conduction was largely preserved following base irradiation. Plasma ANP levels were shown to be similar across groups, with a drop following irradiation at 10 weeks followed by a rebound increase, which was larger in the animals receiving atorvastatin. ANP levels were subsequently lower at 50 weeks, and less so in the animals receiving atorvastatin.

Conclusion Provisional analyses indicate that atorvastatin protects against LV dysfunction following cardiac base irradiation, and this observation was matched with less pronounced reductions in ANP. Together with signals from retrospective clinical data, these data may provide the rationale for a clinical trial of statin therapy for the mitigation of RC. OC-0599 Characterization of irradiated colonic stroma for therapeutic treatment of Pelvic Radiation Disease M. Jestin 1 , N. Mathieu 1 , C. Squiban 1 , C. Demarquay 2 , F. Milliat 3 , M. Benadjaoud 4 1 Institute for Radiological Protection and Nuclear Safety, Radiobiology of Medical Exposure Laboratory, Fontenay-aux- Roses, France; 2 Institute for Radiological Protection and Nuclear Safety, Radiobiology of Medical Exposure Laboratory , Fontenay-aux-Roses, France; 3 Institute for Radiological and Nuclear Safety , Radiobiology of Medical Exposure Laboratory, Fontenay-aux-Roses, France; 4 Institute for Radiological and Nuclear Safety, Radiobiology and Regenerative Medicine Research Service, Fontenay-aux-Roses, France Purpose or Objective Pelvic cancers have a high prevalence and are mainly treated by radiotherapy. While it provides tumor control, it also causes damage to surrounding healthy tissues, leading to disabling complications defined as the Pelvic Radiation Disease (PRD). Today, no curative treatment exists for this fibrosing pathology. This project aims to study the colonic microenvironment ( µ E) after irradiation and identify new target to improve the management of PRD in the colon. Materials and Methods We use a mouse model developing fibrotic colonic damage like those observed in patients with PRD. This model consists of a single colorectal irradiation of 26Gy. Two study times were defined after irradiation: at two weeks (W2) to study acute effects of irradiation; at twelve weeks (W12) to explore fibrosis. Histological immunostaining was performed to assess proliferation (Ki67) and differentiation (MUC2; ChgA) capacities of the colonic epithelium as well as expression of epithelial junction proteins (ZO-1; P120/cat). We then studied in vitro the impact of the colonic µ E on epithelial proliferation. To this aim, colonic organoids were cultured in presence of sorted CD45- & EpCAM- stromal cells from irradiated or unirradiated mice at W2 & W12. Colonoids development was assessed according to , number and type of colonoids. Finally, colonic µ E remodeling was studied at the molecular level on sorted stromal cells by single-cell transcriptomic analysis at W2 & W12. Results Based on immunohistochemistry, we observed epithelial junctions impaired after irradiation at W2 & W12. However, epithelial proliferation and differentiation are increased at W2 after irradiation at the lesion’s edge. Interestingly, this rise persists and even increased at W12 leading to anarchic crypt structures. Coculture experiments show a higher growth of colonoids when cocultured with stromal cells. Among coculture conditions, stromal cells from W12-irradiated mice allow the greatest growth of colonoids in term of and number. Single-cell transcriptomic analysis allowed the identification of different populations constituting the colonic µ E based on the literature. We also highlighted an undefined fibroblastic population. Moreover, analyzes carried out at the level of specific populations have defined molecular modifications after irradiation. Conclusion After irradiation, colonic epithelium shows impaired barrier, however a regenerative process with enhanced proliferation and differentiation is set up at W2 and still rise at W12. Coculture results demonstrate that stroma promotes colonoids development with a significant impact of stromal cells from irradiated mice W12. These results suggest the direct role of W12-irradiated stromal cells on epithelial disorders. Analyzes carried out at the transcriptomic level have defined cellular and molecular pathways modifications that could be involved in epithelial dysfunctions and explained coculture results. These pathways could be modulated to reduce colonic damage after irradiation.

OC-0600 The early and late effects of high-dose irradiation on cardiac injury in a rat model H.I. Lee 1 , J. Koh 2 , M. Cha 3 , J.H. Chang 1 , H.J. Kim 1

1 Seoul National University Hospital, Department of Radiation Oncology, Seoul, Korea Republic of; 2 Seoul National University Hospital, Department of Pathology, Seoul, Korea Republic of; 3 Asan Medical Center, Division of Cardiology, Seoul, Korea Republic of