Advanced concepts and novel technologies for the study of the impact of ionising radiation on tissue

癌症是全球第二大常见死亡原因，2015年死亡人数为880万人。据估计，大约一半的癌症患者使用放射治疗。在英国，英国国民健康保险制度的一个新的质子束治疗设施最近在曼彻斯特上线，第二个将很快在伦敦投入使用。此外，几个新的私人质子束治疗设施正在开发中。这些新中心的使用，以及为提高其提供的治疗效果而进行的研究，将大大增加需求。全世界对粒子束治疗(PBT)的兴趣正在增长，预计这项技术的需求将显著增长。到2035年，如果能够扩大放射治疗能力，低收入和中等收入国家可以节省2690万个生命年。这种扩展所需的投资将产生可观的经济收益。使用X射线束或放射源进行的放射治疗是一种广泛用于治疗癌症的既定治疗形式。现代的X射线治疗机允许剂量集中在肿瘤体积上。X射线剂量随深度呈指数下降，因此原发肿瘤与心脏、肺、食道和脊柱的位置限制了相当大一部分病例的剂量强度。健康的器官靠近重要的原发癌症部位意味着可能传递的光子剂量强度有一个基本的限制。质子和离子束在静止时会损失大部分能量。因此，能量损失分布在最大范围内有一个明显的‘布拉格峰’。质子和离子束克服了X射线治疗的基本限制，因为与光子相比，在远端肿瘤边缘沉积的(离子)或没有(质子)剂量很少。这样可以节省2-3倍的综合患者剂量。此外，由于布拉格峰值出现在束流的最大范围内，治疗可以与肿瘤的体积相一致。能量在10 MeV到250 MeV之间的质子可以使用回旋加速器输送，这些回旋加速器可以从许多供应商那里获得。今天，回旋加速器最常用于质子束治疗。这种机器不能在治疗所需的能量范围内提供多种离子物种。同步加速器是用于质子和离子束治疗的第二种最常见的加速器类型，在可以提供的束流能量范围内比回旋加速器更灵活。然而，同步加速器的占地面积、复杂性和维护要求都大于回旋加速器，这增加了必要的投资和运行成本。我们建议通过实施一种致力于放射生物学研究的新型激光驱动混合加速器系统，为开发提供个性化质子和离子束治疗所需的自动化、自适应系统奠定技术基础。在这项计划的两年中，我们将：*为拉拉的‘激光-混合放射生物应用加速器’提供一个概要CDR；*在克莱特布里奇癌症中心为先进的放射生物学和临床放射治疗技术建立一个试验台；以及*创建一个广泛的、多学科的英国联盟，在国际生物物理学合作中使英国处于有利地位，为这一令人振奋的新生物医学科学和创新计划做出贡献并从中受益。

Cancer is the second most common cause of death globally, accounting for 8.8 million deaths in 2015. It is estimated that radiotherapy is used in the treatment of approximately half of all cancer patients. In the UK, one new NHS proton-beam therapy facility has recently come online in Manchester and a second will soon be brought into operation in London. In addition, several new private proton-beam therapy facilities are being developed. The use of these new centres, and the research that will be carried out to enhance the efficacy of the treatments they deliver, will substantially increase demand. Worldwide interest in particle-beam therapy (PBT) is growing and a significant growth in demand in this technology is anticipated. By 2035, 26.9 million life-years in low- and middle-income countries could be saved if radiotherapy capacity could be scaled up. The investment required for this expansion will generate substantial economic gains.Radiotherapy delivered using X-ray beams or radioactive sources is an established form of treatment widely exploited to treat cancer. Modern X-ray therapy machines allow the dose to be concentrated over the tumour volume. X-ray dose falls exponentially with depth so that the location of primary tumours in relation to heart, lungs, oesophagus and spine limits dose intensity in a significant proportion of cases. The proximity of healthy organs to important primary cancer sites implies a fundamental limit on the photon-dose intensities that may be delivered.Proton and ion beams lose the bulk of their energy as they come to rest. The energy-loss distribution therefore has a pronounced 'Bragg peak' at the maximum range. Proton and ion beams overcome the fundamental limitation of X-ray therapy because, in comparison to photons, there is little (ions) or no (protons) dose deposited beyond the distal tumour edge. This saves a factor of 2-3 in integrated patient dose. In addition, as the Bragg peak occurs at the maximum range of the beam, treatment can be conformed to the tumour volume.Protons with energies between 10MeV and 250MeV can be delivered using cyclotrons which can be obtained `off the shelf' from a number of suppliers. Today, cyclotrons are most commonly used for proton-beam therapy. Such machines are not able to deliver multiple ion species over the range of energies required for treatment. Synchrotrons are the second most common type of accelerator used for proton- and ion-beam therapy and are more flexible than cyclotrons in the range of beam energy that can be delivered. However, the footprint, complexity and maintenance requirements are all larger for synchrotrons than for cyclotrons, which increases the necessary investment and the running costs. We propose to lay the technological foundations for the development of an automated, adaptive system required to deliver personalised proton- and ion-beam therapy by implementing a novel laser-driven hybrid accelerator system dedicated to the study of radiobiology. Over the two years of this programme we will: * Deliver an outline CDR for the 'Laser-hybrid Accelerator for Radiobiological Applications', LhARA; * Establish a test-bed for advanced technologies for radiobiology and clinical radiotherapy at the Clatterbridge Cancer Centre; and * Create a broad, multi-disciplinary UK coalition, working within the international Biophysics Collaboration to place the UK in pole position to contribute to, and to benefit from, this exciting new biomedical science-and-innovation initiative.