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因，2015年造成880万人死亡。据估计，放疗用于治疗大约一半的癌症患者。在英国，一个新的NHS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，一些新的私人质子束治疗设施正在开发中。这些新中心的使用，以及为提高它们提供的治疗效果而进行的研究，将大大增加需求。世界范围内对粒子束治疗（PBT）的兴趣正在增长，预计该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节省2690万生命年。这种扩大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放射治疗是一种广泛用于治疗癌症的既定治疗形式。现代x射线治疗机可以将剂量集中在肿瘤体积上。x射线剂量随深度呈指数级下降，因此在很大比例的病例中，与心脏、肺、食道和脊柱相关的原发肿瘤的位置限制了剂量强度。健康器官靠近重要的原发癌症部位，这意味着可能传递的光子剂量强度存在基本限制。质子和离子束在静止时失去了大部分能量。因此，能量损失分布在最大范围内具有明显的“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，很少（离子）或没有（质子）剂量沉积在肿瘤远端边缘以外。这节省了患者综合剂量的2-3倍。此外，由于布拉格峰出现在光束的最大范围内，治疗可以与肿瘤体积一致。能量在10MeV和250MeV之间的质子可以使用回旋加速器输送，回旋加速器可以从许多供应商那里“现成”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输送多种离子。同步加速器是用于质子束和离子束治疗的第二种最常见的加速器类型，在可以传递的光束能量范围内，同步加速器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比回旋加速器大，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，为开发一种自动化的、自适应的系统奠定技术基础，该系统需要提供个性化的质子和离子束治疗。在该计划的两年中，我们将：*提供“用于放射生物学应用的激光混合加速器”（LhARA）的概要CDR；*在克拉特桥癌症中心设立先进的放射生物学和临床放射治疗技术试验台；*建立一个广泛的、多学科的英国联盟，在国际生物物理学合作组织中工作，使英国处于有利地位，为这一令人兴奋的新的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.