High-throughput Pre-clinical Platform for Proton Therapy Research

2014年，居里研究所文森特·福瓦东（Vincent Fauvadon）的一篇论文引发了对FLASH（超高剂量率放疗）的研究，该研究表明，在不影响肿瘤治疗效果的情况下，副作用减少了。这一发现引起了国际上对FLASH的研究兴趣。然而，FLASH的放射生物学机制仍然不清楚，并且发现受到相互矛盾的结果的挑战，限制了临床应用。FLASH减少副作用的前景对质子治疗至关重要。在英国，接受质子治疗的患者中有很大比例是儿童，副作用会对他们的发育、认知和生活质量产生重大影响。该提案将在英国首次创建质子- flash体内研究能力。迫切需要对质子- flash进行高度可重复的研究，以弥合发现科学与临床试验之间的差距。该提案将解决这一需求，使FLASH研究和质子治疗的一系列重要主题成为可能。我们正在与英国XStrahl公司合作，该公司是该领域的世界领导者，开发一种自动化解决方案，以实现高通量实验，这将改变这些实验中可以实现的统计显著性。该平台还将使解决新兴主题的能力，以保持英国质子治疗研究的前沿。空间分割放疗是一个新兴的主题，新的证据也表明副作用可能更小，很有可能成为未来放疗研究的一个重要主题。虽然在FLASH和SFRT的机制中可能有一些重叠，但这些是什么以及如何优化它们是未知的。这项提案将使英国能够在这项研究中作出贡献并发挥领导作用。NHS对质子治疗的愿景一直包括研究能力。曼彻斯特的质子研究室是由克里斯蒂慈善机构资助的，大部分来自公众捐款。自2019年第一束质子束在研究室交付以来，我们已经开始发展合作，并有一个积极的研究计划。我们现在计划将其扩展为质子治疗的国家资源。本提案中要求的设备增加了体内功能，提供了从发现科学到临床研究连续体中缺失的部分。

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.