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. 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. A particular focus will be given to minibeam radiation therapy (MBRT) and its advantages. MBRT, originated at synchrotrons, can now explored outside large facilities thanks to its successful transfer into cost-effective equipment . This allows a widespread implementation, the realisation of comprehensive and systematic biological studies and an esiy transfer to potential clinical trials. In the recent years, the exploration of the possible synergies between the advantages of MBRT and the benefits of charged particles for therapy has started with techniques like proton and heavy ions MBRT [2-7]. In particular, proton MBRT  has been implemented at a clinical center (Orsay proton therapy center) and it has already shown an effectiveness of tumor control equivalent or superior than that of standard PT without the important side effects observed in the latter, thus opening the possibility for more aggressive irradiation schemes [3-5]. Concerning heavy ions MBRT, the dosimetric data obtained supports the exploration of this radiotherapy approach [6,7]. Among the different ions species evaluated, Ne stands as the one leading to the best balance between high peak-to-valley dose ratio and peak-to-valley-LET ratio in normal tissues and high LET values in the target region . The biological mechanisms in MBRT, 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.
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