Establishing a UK National Preclinical Photon-FLASH Radiotherapy Facility (FLASH-SARRP)

点击翻译按钮获取中文摘要

Radiotherapy treats cancers through the precise delivery of high doses of radiation to tumours, killing cancerous cells by damaging their DNA. While radiation can be precisely targeted to tumours, some normal tissue is also necessarily exposed to radiation, and avoiding excessive damage to normal tissue is a major limitation in the treatment of many cancers.Currently, most radiotherapy is delivered using X-rays (photons) with individual treatments delivered over a period of minutes. However, recent evidence has suggested that delivering radiotherapy much more rapidly - with treatment times of less than a second - significantly reduces the damage radiation causes to normal tissue while retaining its efficacy against tumours. This has been dubbed the "FLASH effect", and has the potential to significantly improve the flexibility and efficacy of radiotherapy.This effect has been unexpected, given established knowledge of how tumours respond to radiotherapy, and as a result is the subject of a significant amount of research. However, most of this research has been carried out using custom-designed radiation sources which expose cells to electrons, rather than photons as used in most clinical practice. Due to the novel nature of the FLASH effect, it is currently unknown if these different types of radiation interact with the FLASH effect in different ways, and how current information on the FLASH effect may be related to clinical practice.This proposal seeks to provide funding for a first preclinical photon FLASH-SARRP (Small Animal Radiotherapy Research Platform). This would offer a unique resource, able to reproduce FLASH dose rates using photons in small animal models of cancer. This would enable the detailed exploration of the mechanisms of FLASH in the same modality as is used clinically, providing a unique insight into its underlying mechanisms and a valuable complement to existing resources within the UK. We will use this source to validate the FLASH effect in photon exposures, and then explore its mechanistic basis, based on physical, chemical and biological effects within tumours and normal tissues. This work will be intergated into our established radiation biology research portfolio, and used to support the translation of FLASH into an effective clinical tool for the treatment of cancer.