Infrastructure in FLASH radiotherapy

Background: Ultra-high dose rate radiotherapy (FLASH) (typically > 40 Gy/s) is attracting worldwide interest as it offers the potential of increased normal tissue sparing, compared to conventional radiotherapy, while still supressing tumour growth. However, large gaps exist in the mechanistic understanding of the “FLASH” effect in both normal tissue and tumours.

This is why we need an experimental infrastructure that allows researchers access to state of the art technology to deliver FLASH beams and the in vitro and in vivo biological systems to investigate it.

Aims: to provide a FLASH infrastructure with world-leading capabilities that will draw on the strengths of the CRUK RadNet partners to provide solutions to the questions that confront FLASH research now and, in the future, and to allow a seamless transition from mechanistic discovery science to early phase clinical evaluation.

Methods This RadNet FLASH infrastructure will have access to FLASH proton and electron beams at Manchester and Oxford respectively, it will also have access to a range of in vitro and in vivo biological models (Cambridge) combined with access to the RadNet multidisciplinary expertise across all 7 RadNet centres.

The infrastructure will intersect with the RadNet working groups e.g. drug radiation combinations, immune therapy and quality assurance and standardisation.

Three FLASH Fellows (PDRA) will be recruited who will be based in Manchester, Oxford and Cambridge and will work together and with the other RadNet centres.

The strength of the infrastructure will be demonstrated using exemplar projects which challenge existing ideas and create novel biological datasets to inform the exploitation of the FLASH effect and take molecular biology through to tumour and normal tissue.

How this research will be used: The FLASH Fellows will work with RadNet and the wider scientific community on pump-priming and student projects.

These projects will provide results for RadNet networking and larger project or programme grants and high impact publications.

Funding for infrastructure access from these grants and industry provides a route to the long-term sustainability of this infrastructure, both in terms of funding the FLASH Fellows and running equipment.

The infrastructure will report through the RadNet Emerging Radiotherapy Technologies Working Group (ERT) to the RadNet Directors meeting.

Applications to access the infrastructure will be presented at ERT where they will be prioritised, each will be supported by a FLASH Fellow.

All applications will be dealt with in a fair and transparent manner with evaluators selected to eliminate conflicts of interest.