[I147] New approaches in radiotherapy: Spatial fractionation of the dose

Cancer is responsible for one out of four deaths in Europe. Radiotherapy (RT) has a key role in cancer treatment. In fact, about half of the patients will receive RT at some point during their illness. The therapeutic use of ionizing radiation has been largely guided by the goal of directly eliminating all cancer cells while minimizing the toxicity to adjacent tissues. Nowadays, technological advances in radiation delivery, including image guidance and particle therapy (i.e. proton therapy), have notably improved tumor dose conformation, thus reducing the dose to the organs-at-risk. Despite remarkable advancements, the dose tolerances of normal tissues continue to be the main limitation in RT and still compromise the treatment of some radioresistant tumors, tumors close to a sensitive structure (e.g. central nervous system (CNS)) and pediatric cancer. Therefore, why not to change the strategy? Why not make use of the evolving wealth of biological knowledge to seek for new approaches that might substantially increase the normal tissue resistance? One possible way to overcome this limitation is to employ new modes of radiation dose deposition that activate biological processes different from those in standard radiotherapy. An example is the spatial fractionation of the dose. This lecture will give a general overview about this strategy. Different studies on the challenging dosimetry of the very small (submillimetric) field sizes used will be presented. Some of the promising results obtained in the pre-clinical studies will be shown: a very significant increase in tolerance doses (doses of up to 100 Gy in a single fraction) and the remission of extremely aggressive tumors, such as gliomas, even with a very heterogeneous dose coverage, are observed. The biological mechanisms, which are not completely known, seem to contradict the classic RT paradigms. Its exploration offers a whole new horizon of both scientific research and potential future clinical practice. The spatial fractionation of the dose could especially benefit paediatric oncology (central nervous system), whose treatments are limited to the high risk of complications in the development of the infants.