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.