High-throughput Pre-clinical Platform for Proton Therapy Research

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Research in FLASH (ultra high dose rate radiotherapy) was ignited in 2014 by a paper by Vincent Fauvadon at Institute Curie, which showed reduced side-effects without compromise to efficacy of tumour treatment. This discovery has impelled an international research interest in FLASH. However the radiobiological mechanisms of FLASH are still not understood, and discovery is challenged by conflicting results limiting clinical implementation. The reduced side-effects promise of FLASH is critically important for proton therapy. In the UK, a high proportion of patients treated with proton therapy are children, where side effects can have a significant impact on their development, cognition and quality of life. This proposal will create a proton-FLASH in vivo research capability for the first time in the UK. There is an urgent need for highly repeatable research on proton-FLASH to bridge the gap between discovery science and clinical trials. This proposal will address this need, enabling research in FLASH and across a range of important themes in proton therapy. We are working with XStrahl, a UK company and world leader in the field, to develop an automation solution to enable high-throughput experiments which will transform the statistical significance which can be achieved in these experiments. The platform will also enable a capability to address emerging themes to keep UK proton therapy research at the cutting edge.Spatially Fractionated Radiotherapy is an emerging theme where new evidence also suggests a possibility of fewer side effects, and is highly likely to be an important theme of radiotherapy research in the future. Whilst there may be some overlap in the mechanisms of FLASH and SFRT, what these are and how to optimise them is unknown. This proposal will enable the UK to contribute and lead in this research.The NHS vision for proton therapy always included a research capability. The Proton Research Room in Manchester was funded by the Christie Charity largely from public donations. Since 2019, when the first proton beam was delivered in the Research Room, we have started developing collaborations and have an active programme of research. We now plan to expand this into a national resource for proton therapy. The equipment requested in this proposal adds an in vivo capability which provides the missing component in the continuum of research from discovery science to the clinic.