FLASH VHEE Radiotherapy for Cancer Treatment: Nanodosimetry and Dose Studies

放射治疗依赖于将一定量的剂量（足以杀死肿瘤）准确地输送到正确的位置。为此，现代放射治疗设备具有广泛的质量保证，并结合了先进的剂量测量能力。VHEE放射治疗（在~70至250 MeV的能量范围内）目前正在开发中，并有望通过电磁引导电子束快速输送剂量。由于能量高，发射距离不敏感，因此它通常适用于身体的非均匀部位。它也有可能比目前使用的放射治疗设备便宜得多。此外，VHEE具有极快和大剂量递送到癌组织的潜力。它还能够利用最近的体内“FLASH”研究——将高剂量极快地输送到组织中——允许完全根除肿瘤，同时有望减少影响正常组织的早期和晚期并发症的发生和严重程度。FLASH放射治疗是一个快速发展的领域，是一个“热门话题”，其机制鲜为人知，因此它是一个及时的博士研究生领域。这个学生将探索将高能光束输送到幽灵、质粒、细胞培养物中，并将在DNA键断裂的水平上研究细胞损伤。值得注意的是，快速给药（通常是亚秒给药）的优势已在动物和有限数量的人类患者中得到证明，但对其潜在机制的了解有限。这项研究将涉及剂量传递背后的工程和对癌细胞造成的损害的交叉融合，以了解健康组织在暴露于高剂量时几乎不会受到损害的潜在机制。在这个项目中，我们将研究：快速给药-利用达斯伯里实验室和欧洲核子研究中心的设施。质粒损伤dna水平的细胞损伤该项目需要与放射治疗师、临床医生和临床科学家密切合作。这项研究将建立在早期研究的基础上，尽管这些研究是有限的，一名曼彻斯特博士生对高能电子束（使用质粒）对DNA造成的损害进行了实验研究。实验将于2021年在欧洲核子研究中心的250 MeV电子束设施上进行，并于2022年在达斯伯里实验室的CLARA设施（将升级到250 MeV）上进行。这将是一个独特的机会，使用最近开发的高能加速器来开发放射治疗的潜在新范例。

Radiotherapy depends on accurate delivery of a certain amount of dose (enough to kill the tumour) to the right place. For this purpose modern radiotherapy equipment has extensive QA and is combined with advanced dose measurement capabilities.VHEE radiotherapy (in the energy range of ~70 to 250 MeV) is currently under development and promises rapid delivery of dose by means of electromagnetically steered e-beams. Because of the high energy, the delivery is range-insensitive and hence it is generally applicable even in inhomogeneous parts of the body. It also has the potential to be significantly cheaper than radiotherapy equipment in use at present.Furthermore VHEE has the potential for extremely rapid and large dose delivery to cancerous tissue. It is also able to take advantage of recent in vivo "FLASH" studies -in which a high dose is delivered to tissue extremely rapidly -allowing complete eradication tumours while promising reduction in the occurrence and severity of early and late complications affecting normal tissue. FLASH radiotherapy is a rapidly evolving field and is a "hot topic" with the mechanism little understood -and hence it is a timely area for a PhD studentship.This studentship will explore delivering high energy beams to phantoms, plasmids, cell cultures and will entail investigating cell damage at the level of the bond breakage of DNA. It notable that the advantage of rapid dose delivery (typically sub-second delivery) has been demonstrated in animals and also on a limited number of human patients -but with limited understanding of the underlying mechanism. This studentship will entail a cross-fertilisation of the engineering behind the delivery of dose and the damage incurred to cancerous cells, with a view to understanding the underlying mechanism that allows healthy tissue to show little damage to exposure to very high doses.In this project we will study:Rapid dose delivery -utilising the facilities at Daresbury laboratory and CERN.Damage to plasmids Damage to cells at the level of DNAThe project will entail close collaboration with radiotherapists, clinicians and clinical scientists. The research will build upon earlier studies, albeit limited, of a Manchester PhD student who performed experimental studies on the damage incurred to DNA (using plasmids) by very high energy electron beams.Experiments will be conducted on the 250 MeV electron beam facility at CERN in 2021 and at Daresbury laboratory's CLARA facility (due to be upgraded to 250 MeV) in 2022. This will be a unique opportunity to use a recently developed high-energy accelerators to develop a potential new paradigm in radiotherapy.