Evaluation of Electron FLASH effect in skin tissue models of radiation damage - Project Summary & Abstract In the past decade, FLASH radiotherapy has emerged as a novel methodology to improve therapeutic outcomes in preclinical models, The FLASH effect occurs when using Ultra-High Dose Rates (UH DR) (>40 Gy/s) causing normal tissue to be spared relative to conventional dose rates (CDR), while maintaining tumor control, The FLASH effect has been robustly studied in mouse models and has been loosely explored in other large animal models, Despite this effort, little is known about what induces a FLASH effect other than U HOR are required and high single dose per fraction (>8 Gy), As the field moves towards translating this modality as seen by the completion of phase one clinical trials and beginning of phase 2 clinical trials, understanding the mechanism of the FLASH effect is crucial for the optimization of key radiotherapy parameters to ensure safe and effective clinical translation of this modality, Dose is the most important parameter in radiotherapy causing damage to both normal tissue and tumor tissue, Maximizing the difference in damage is key to ensuring curative outcome while minimizing normal tissue effects, Two of the most impactful parameters that modify the dose required for damage to tissue are fractionation, and oxygenation, Despite their importance the field has not fully characterized these parameters in the context of the FLASH effect The primary objective of this proposed research is to investigate how these parameters can cause a FLASH effect through analysis of radiation chemistry and how they relate to biological effects, with the ultimate goal of optimizing the FLASH effect through these parameters, This will be achieved through collaboration that the research applicant has formed between the University of Wisconsin Medical Radiation Research Center (UWMR RC) and the University of Wisconsin School of Veterinary Medicine (SVM), The UWMRRC will ensure accurate dose delivery and use of the UHDR capable Linac, and the SVM will collaborate with the MOXI Lab in first-of-its-kind large animal veterinary trial, The applicant's training objectives include multi-lab collaboration, enhancing knowledge of medical physics, and developing both clinical and technical skills for a future career in medical physics, Through formal presentations, participation in seminars and journal clubs, teaching and mentoring students, and creation of peer-reviewed papers will contribute to the research applicant's development as a future researcher, With the support from the sponsor and various collaborators to ensure the success of this proposal, this fellowship will serve to advance the applicant towards a productive career in medical physics and contribute meaningful research towards his own career and the field at large,
