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.

In the UK one in two people are diagnosed with cancer during their lifetimes and of those who survive 41% can attribute their cure to a treatment including radiotherapy. Proton beam therapy (PBT) is a radical new type of radiotherapy, capable of delivering a targeted tumour dose with minimal damage to the surrounding healthy tissue. The NHS is investing £250m in two new "state of the art" PBT centres in London and Manchester. In addition, Oxford has attracted £110m (from HEFCE and business partners) for its new Centre for Precision Cancer Medicine, incorporating PBT. This EPSRC Network+ proposal seeks to bring the EPS community together with clinical, consumer and industrial partners and develop a national research infrastructure and roadmap in proton therapy. It capitalises on ~£300m of government investment and affords an opportunity for those not directly involved in the new proton centres to be actively involved in the national research effort in this area. This project has the backing of NCRI Clinical and Translational Radiotherapy Working Group and NHS England and will work with the national Proton Physics Research and Implementation Group of the National Physical Laboratory. It also involves industrial stakeholders, consumer groups and international partners (including PBT centres in Europe and USA and CERN). While PBT offers patients many advantages it also presents a wealth of technical challenges and opportunities where there is an unmet research and training need. This is where there the involvement of the EPS community is vital since this challenge in Healthcare Technologies requires expertise from across the EPS spectrum and maps on to themes in ICT, Digital Economy, Engineering, Mathematics, Manufacturing the Future, and the Physical Sciences and also finds synergies within quantum technologies. It directly maps onto the cross cutting capabilities identified in the Healthcare Technologies Grand Challenges. This is a highly multi-disciplinary area at the frontiers of physical intervention, which achieves high precision treatment with minimal invasiveness. This Network+ is particularly timely; it will afford the UK the opportunity to develop a world-leading research capability to inform the national agenda, capitalising on existing research excellence and the synergies that can be developed by bringing the clinical and EPS areas together. It will also collaborate with existing doctoral training provision to train the next generation of leaders where a national need has been identified. This proposed Network+ will create a national infrastructure to meet a national research and training need and will allow the UK community to work together in the multi-disciplinary field of proton research. This proposed Network+ will create a sustainable national proton beam infrastructure by drawing together sites where proton beams are already available (albeit at lower energies) and providing a route for the research community to access these facilities. As the new proton centres come on line they will add to this national resource and the centres will work together to provide a virtual national infrastructure for the UK, which by the end of the Network+ will be fully sustainable. The Network+ will also provide a route for those interested in the field but not requiring proton experiments to become involved. In addition, the Network+ will offer secondments ("Discipline Hops") into the clinical environment in both the UK and in PBT centres overseas. Working with NHS England the Network+ will develop a PBT training scheme. This will link the existing NHS provision with EPSRC Centres for Doctoral Training and allow equivalencies to be established and so provide a "fast track" to a skilled workforce and the next generation of leaders. The Network+ will also seek to engage with industry through joint research and secondments and with consumer groups, policy makers and the general public.

This proposal describes a programme of research on single-particle and collective radiation-beam-plasma interactions at high field intensities, production of high-brightness particle beams with femtosecond to attosecond duration, new sources of coherent and incoherent radiation that are both compact and inexpensive, new methods of accelerating particles which could make them widely available and, by extending their parameter range, stimulate new application areas. An important adjunct to the proposal will be a programme to apply the sources to demonstrate their usefulness and also provide a way to involve industry and other end-users. The project builds on previous experiments and theoretical investigations of the Advanced Laser Plasma High-energy Accelerators towards X-rays (ALPHA-X) project, which has demonstrated controlled acceleration in a laser-plasma wakefield accelerator (LWFA), initial applications of beams from the LWFA and demonstrations of gamma ray production due to resonant betatron motion in the LWFA. The programme will have broad relevance, through developing an understanding of the highly nonlinear and collective physics of radiation-matter interactions, to fields ranging from astrophysics, fusion and nuclear physics, to the interaction of radiation with biological matter. It will also touch on several basic problems in physics, such as radiation reaction in plasma media and the development of coherence in nonlinear coupled systems.

The lab in a bubble project is a timely investigation of the interaction of charged particles with radiation inside and in the vicinity of relativistic plasma bubbles created by intense ultra-short laser pulses propagating in plasma. It builds on recent studies carried out by the ALPHA-X team of coherent X-ray radiation from the laser-plasma wakefield accelerator and high field effects where radiation reaction becomes important. The experimental programme will be carried out using high power lasers and investigate new areas of physics where single-particle and collective radiation reaction and quantum effects become important, and where non-linear coupling and instabilities between beams, laser, plasma and induced fields develop, which result in radiation and particle beams with unique properties. Laser-plasma interactions are central to all problems studied and understanding their complex and often highly non-linear interactions gives a way of controlling the bubble and beams therein. To investigate the rich range of physical processes, advanced theoretical and experimental methods will be applied and advantage will be taken of know-how and techniques developed by the teams. New analytical and numerical methods will be developed to enable planning and interpreting results from experiments. Advanced experimental methods and diagnostics will be developed to probe the bubble and characterise the beams and radiation. An important objective will be to apply the radiation and beams in selected proof-of-concept applications to the benefit of society. The project is involves a large group of Collaborators and Partners, who will contribute to both theoretical and experimental work. The diverse programme is managed through a synergistic approach where there is strong linkage between work-packages, and both theoretical and experiential methodologies are applied bilaterally: experiments are informed by theory at planning and data interpretation stages, and theory is steered by the outcome of experimental studies, which results in a virtuous circle that advances understanding of the physics inside and outside the lab in a bubble. We also expect to make major advances in high field physics and the development of a new generation of compact coherent X-ray sources.