Determining the parameter space for effective oxygen depletion for FLASH radiation therapy

Bethany Rothwell, Norman Kirkby, Mike Merchant, Amy Chadwick, Matthew Lowe, Ranald Mackay, Jolyon Hendry, Karen Kirkby

Research output: Contribution to journalArticlepeer-review


There has been a recent revival of interest in the FLASH effect, after experiments have shown normal tissue sparing capabilities of ultra-high-dose-rate radiation with no compromise on tumour growth restraint. A model has been developed to investigate the relative importance of a number of fundamental parameters considered to be involved in the oxygen depletion paradigm of induced radioresistance. An example eight-dimensional parameter space demonstrates the conditions under which radiation may induce sufficient depletion of oxygen for a diffusion-limited hypoxic cellular response. Initial results support experimental evidence that FLASH sparing is only achieved for dose rates on the order of tens of Gy s-1 or higher, for a sufficiently high dose, and only for tissue that is slightly hypoxic at the time of radiation. We show that the FLASH effect is the result of a number of biological, radiochemical and delivery parameters. Also, the threshold dose for a FLASH effect occurring would be more prominent when the parameterisation was optimised to produce the maximum effect. The model provides a framework for further FLASH-related investigation and experimental design. An understanding of the mechanistic interactions producing an optimised FLASH effect is essential for its translation into clinical practice.

Original languageEnglish
Article number055020
JournalPhysics in Medicine & Biology
Issue number5
Publication statusPublished - 25 Feb 2021

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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