A multidisciplinary experimental and methodological investigation of electron and proton minibeams in the framework of the INFN MIRO project

The clinical translation of Minibeam RT (MBRT) has recentlystarted thanks to the first human treatments recently performed. However,despite experimental evidence, the impact of the dose distribution parametersinvolved on the magnitude of the effect itself and the underlying radiobiologicalmechanisms are still only partially understood. To address this issue, systematicinvestigations are needed through the implementation of advanced quantitativeexperiments with a multidisciplinary approach, which is the one proposed in theframework of the INFN funded MIRO (MInibeam RadiOtherapy) project.Purpose: The aim of this work is to report on the on-going main activitiesrecently carried out in the framework of the project, showing some of the mainresults achieved during the first 2 years of the project, in terms of: (i) facilitiesdevelopment and characterization; (ii) new dosimetric approaches; (iii) biolog-ical investigation of the effect; and (iv) development of the first tools for doseplanning. The multidisciplinary approach adopted by this national Collaborationto tackle the main challenges of minibeam radiotherapy for a reliable and solidclinical translation is discussed.Methods: The facilities involved in the project are: (i) two facilities dedicatedto low (up to 9 MeV) and medium (up to 18 MeV) energy electron minibeamstudies, one of them also equipped with an electron FLASH LINAC to studypossible synergistic effects with UHDR beams; (ii) one facility dedicated toproton minibeam studies, with energies from 70 to 140 MeV. Novel dosimet-ric approaches, are presented, mainly based on scintillators, silicon and siliconcarbide detectors. Novel techniques for the analysis of biological samples aredescribed, leveraging both integrated averaged data and spatially resolvedanalysis. Furthermore, a framework for biological modeling using a multiscaleapproach is presented. A dedicated dose-planning tool is currently underdevelopment to compare “virtual” minibeam plans with conventional ones and,consequently, to quantitatively investigate the potential for clinical translation.Results: All the facilities were dosimetrically characterized, demonstratingthe capability of producing controlled and reproducible electron and protonminibeams. These beams exhibited diverse physical parameters, includingpeak-to-valley ratios between 3 and 30 at the entrance and center-to-center dis-tances between 2 and 3 mm. The developed detectors, specifically scintillatorsand silicon detectors, successfully measured the minibeam patterns with sub-millimeter resolution, while large-area silicon carbide detectors were used foraverage dose measurements. First in-vitro biological investigations performedwith low energy minibeams clearly showed an enhanced survival fraction in the16HBE healthy lung cells, while maintaining iso-effective cell killing in A549 can-cer cells.Furthermore,a synergy was observed when combining UHDR electronbeams with minibeams.Conclusions: The multidisciplinary approach was consolidated during thesefirst 2 years of the MIRO project, as demonstrated by the results obtainedboth in terms of dosimetric characterization and biological investigations. Thededicated framework for modelling is being optimized to support the biolog-ical findings, allowing for a better interpretation of the results. The tool fordose planning, still under development, will allow the investigation of peculiarconfigurations to explore new frontiers in the perspective of future human trials.