Year: 2021
Type: article
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 −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.
Source: Physics in Medicine and Biology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,850
Funders: Cancer Research UK, National Institute for Health and Care Research, Cancer Research UK Manchester Centre, Horizon 2020 Framework Programme, Manchester Biomedical Research Centre, Engineering and Physical Sciences Research Council, Science and Technology Facilities Council, H2020 Research Infrastructures
Awards: Global Challenge Network+ in Advanced Radiotherapy, G2554727787, Cockcroft Institute, G281382011, Advanced Radiotherapy Network + (ARN+) extension, Cockcroft Phase 4, G4166448620, Grand Challenge Network+ in Proton Therapy, G4217450915, G4472528609, G592232424, BioProton: Biologically relevant dose for Proton Therapy Planning, G6797592505, G737588927, INfraStructure in Proton International REsearch, G8761459490, G8820180728
OpenAlex ID: W3127620575
