Abstract: FLASH radiotherapy is an innovative cancer treatment method that delivers radiation at ultra-high dose rates to effectively spare healthy tissue while maintaining tumor control. Proton therapy has emerged as a promising modality for FLASH due to its dosimetric advantages, ability to reach deep-seated tumors, and clinical availability. However, the mechanisms underlying the FLASH effect are still unknown. This work employs an in silico approach to explore the parameter space for FLASH radiotherapy, focusing on oxygen depletion as a potential explanation. A computational model has been developed to identify key parameters involved, assess their plausibility in facilitating the sparing effect, and guide experimental investigations. Additionally, the model can be applied to investigate how oxygen levels are influenced by the spatio-temporal nature of radiation delivery in pencil-beam scanning. Case studies will be presented to demonstrate the mechanistic exploration of FLASH sparing in proton treatment plans. Empirical approaches for exploring FLASH treatment planning in the absence of an established mechanism will also be discussed, with the need for flexibility and convergence in research emphasised. Ultimately, understanding the mechanism behind FLASH sparing is crucial for optimizing its benefits for patients.

About the speaker: Bethany Rothwell is a postdoctoral fellow at Massachusetts General Hospital and Harvard Medical School. She recently completed her PhD at the University of Manchester in the UK, where her work used mathematical modelling to understand the mechanisms involved in FLASH radiotherapy and the role of cellular oxygen depletion. Her current work continues to focus on understanding the FLASH sparing effect, and its translation into clinical settings.