ESTRO 2025 - Abstract Book

S3925

Radiobiology - Normal tissue radiobiology

ESTRO 2025

1 Radio-Oncology Service, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland. 2 Department of Oncology, Ludwig Center for Cancer Research Lausanne and University of Lausanne, Lausanne, Switzerland. 3 Radio-Oncology Service, Lausanne University Hospital, Lausanne, Switzerland. 4 Institute of Radiation Physics, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland. 5 Department of Pathology and Immunology, University of Geneva, Lausanne, Switzerland. 6 EPFL Bioengineering & Technology platform, AGORA Cancer Research Center, Lausanne, Switzerland. 7 Histology Core Facility, EPFL, Lausanne, Switzerland. 8 Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital, Lausanne, Switzerland. 9 Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. 10 Service de pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland Purpose/Objective: Delivering high-dose radiotherapy (RT) to tumors is constrained by dose-related normal tissue toxicities. FLASH-RT, which is delivered at ultra-high dose rates in a very short time, shows promise for sparing normal tissues without compromising the antitumoral effect. However, the biological mechanisms underlying the FLASH effect remain unclear. Material/Methods: Non-tumor bearing C57BL/6 mice were treated with either FLASH RT or conventional RT (CONV-RT) to the whole abdominal cavity at a sublethal dose of 15 Gy. Mice were sacrificed upon becoming symptomatic based on a composite score including weight loss, behavior activity and diarrhea. Middle portions of the small intestines (jejunum) were collected and analyzed using digital pathology and bulk RNA sequencing. Single cell suspensions of the crypt fraction were used for flow cytometry or lysed for western blot analysis. Epithelial barrier integrity was assessed through FITC dextran. Results: A better proliferative response after acute injury, together with enhanced reconstitution of the Lgr5 intestinal stem cell pool was observed upon FLASH RT. These results correlate with significantly longer survival times in the irradiated mice and conservation of the epithelial barrier integrity. Bulk RNA sequencing analysis revealed an enrichment of secretory-committed progenitors, tuft and enteroendocrine markers following FLASH-RT, along with enhanced Yap1 signature-driven expression of fetal-like genes, highlighting a de-differentiation program.

Conclusion: FLASH RT is less toxic to the healthy small intestine than CONV RT due to more efficient tissue repair

Keywords: Tissue repair, radiation injury, epithelial cells

2372

Proffered Paper Intravitreal injection of melatonin for the prevention of radiation retinopathy: an experimental study Alper Kahvecioglu 1 , Ecem Yigit 1 , Nargiz Rustamova 2 , Aysima Sezer 3 , Samiye Yabanoglu Ciftci 3 , Demet Yildiz 1 , Huseyin Selcuk Surucu 4 , Irem Koc 2 , Hayyam Kiratli 2 , Abdullah Faruk Zorlu 1 , Gozde Yazici 1 1 Radiation Oncology, Hacettepe University, Ankara, Turkey. 2 Ophtalmology, Hacettepe University, Ankara, Turkey. 3 Biochemistry, Hacettepe University, Ankara, Turkey. 4 Anatomy, Koc University, Istanbul, Turkey Purpose/Objective: Intravitreal bevacizumab has been utilized to mitigate radiation retinopathy, yet the potential role of intravitreal melatonin for its prevention remains unexplored. This study aims to evaluate and compare the efficacy of intravitreal melatonin and bevacizumab in preventing radiation retinopathy in an experimental animal model.