Currently, radiotherapy patients are treated lying on their backs. Complex machinery weighing at least six tonnes is rotated around them. As it rotates, this machinery delivers radiation beams from different angles. Leo Cancer Care are a small British company who adopted a "design thinking" approach to re-imagine and simplify radiotherapy. Together with ergonomics experts, they developed a flexible and comfortable robotic positioning system that rotates an upright patient. The radiotherapy beam remains fixed. This project draws upon the fellow's international clinical experience and strong scientific track-record to optimise Leo Cancer Care's simplified radiotherapy solution for clinical use. This will enable the fellow and Leo Cancer Care to deliver cancer treatments that are better, cheaper, more efficient and more accessible. Better treatments: radiotherapy side-effects can be devastating. For certain types of cancer, treating patients upright will enable us to better target radiotherapy treatment beams, reducing normal-tissue damage. For breast cancer, sitting upright with a forward tilt moves the breast away from the heart and lungs, improving beam access. For prostate cancer, day-to-day variations in bladder filling and rectal gas will have less impact for upright patients. For lung cancer, lung volumes are greater and lung motion is reduced when patients are upright, enabling better sparing of the heart. Additionally, upright positioning will make many patients feel physically more comfortable (e.g. by enabling patients with lung cancer to breathe more easily) helping them to tolerate their treatment. Cheaper treatments: the cost of a LCC upright X-ray treatment room is half that of a conventional, supine treatment: £2m compared to £4m. More efficient treatments: LCC's simpler technology will lead to (1) reduced equipment maintenance costs (2) easier upgrades of beam delivery technology (3) simpler machine QA & therefore lower expertise barriers (4) substantial reductions in shielded treatment room volume (5) improved patient throughput due to upright positioning. More accessible treatments: worldwide access to radiotherapy is unacceptably low. There is potential to save one million lives per year by 2035 through optimal access to radiotherapy. 80% of cancer patients live in low- and middle-income countries which host only around 5% of the world's RT resources. By halving the cost of an X-ray treatment room and also delivering more efficient RT, LCC solutions stand to make RT more affordable and accessible, improving cancer survival worldwide. To conduct this research the fellow will build new partnerships between Leo Cancer Care, the NHS and universities/hospitals worldwide. Partners include: University College London NHS Foundation Trust, Clatterbridge Cancer Centre, the Royal Surrey NHS Foundation Trust, Massachusetts General Hospital, Centre Léon-Bérard, University College London, the University of Surrey, Sheffield Hallam University, Loughborough University and the University of Sydney. The shared goal is to rapidly deliver the benefits of upright radiotherapy to patients. To do this, a number of key scientific challenges will be addressed: Challenge 1: patient immobilisation systems must be developed. These must enable the patient to sit/stand comfortably for ~20 mins for each radiotherapy treatment. Radiotherapy is delivered daily, in up to 30 treatment 'fractions', each lasting ~20 mins. Challenge 2: upright radiotherapy workflows (for patient treatments and machine testing) must be streamlined. Streamlined workflows will reduce the expertise barrier associated with treatments, improving access. Challenge 3: algorithms must be developed to transfer biological data from MRI/PET to upright radiotherapy. Challenge 4: to incorporate tomorrow's imaging technologies into upright RT, bringing live MRI-guidance to our treatment rooms. This will further improve tumour targeting.

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.