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

Authors
  • Rothwell, B C1
  • Kirkby, N F1, 2
  • Merchant, M J1, 2
  • Chadwick, A L1, 2
  • Lowe, M1, 3
  • Mackay, R I1, 3
  • Hendry, J H1, 3
  • Kirkby, K J1, 2
  • 1 Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. , (United Kingdom)
  • 2 The Christie NHS Foundation Trust, Manchester, United Kingdom. , (United Kingdom)
  • 3 Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Physics in Medicine and Biology
Publisher
IOP Publishing
Publication Date
Feb 25, 2021
Volume
66
Issue
5
Identifiers
DOI: 10.1088/1361-6560/abe2ea
PMID: 33535191
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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-1or 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. Creative Commons Attribution license.

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