Radiotherapy (RT) is one of the most frequently used methods for cancer treatment (above 50% of patients will receive RT). Despite remarkable advancements, the dose tolerances of normal tissues continue to be the main limitation in RT. Finding novel approaches that allow increasing normal tissue resistance is of utmost importance. This would make it possible to escalate tumour dose, resulting in an improvement in cure rate. With this aim, we propose a new approach, called proton minibeam radiation therapy (PROTONMBRT), which combines the prominent advantages of protons for RT and the remarkable tissue preservation provided by the use of submillimetric field sizes and a spatial fractionation of the dose, as in minibeam radiation therapy (MBRT). The main objectives of this project are to explore the gain of therapeutic index for radioresistant tumours, to disentangle the biological mechanisms involved and to evaluate the clinical potential of this novel approach. For this purpose, a method for minibeam generation adequate for patient treatments and a complete set of dosimetric tools will be developed. Then, tumour control effectiveness will be evaluated, and the possible biological mechanisms involved both in tumour and normal tissue responses will be disentangled. The gain in normal tissue recovery can foster one of the main applications of proton therapy, paediatric oncology, as well as open the door to an effective treatment of very radioresistant tumours, such as high-grade gliomas, which are currently mostly treated palliatively.
