Promising Radiotherapy techniques at the beginning of clinical implementation: microbeam- and FLASH therapy

Recent technical developments have enabled to implement ideas raised a few decades earlier. Extensive radiobiology experiments have demonstrated the potential clinical benefit from novel irradiation techniques with ultra high spatial and temporal resolution. A large number of preclinical studies have proven that instead of using homogeneous irradiation fields, arrays of tenths of millimeter beams spaced some hundred micrometer (microbeam radiotherapy – MRT) result in a significant increase in the therapeutical index. The similar radiobiological advantage could be achieved with high dose (>10 Gy) delivery, with extreme high dose rate (≥106 Gy/s), within maximal 500 ms (flash radiotherapy), promising better normal tissue protection but similar tumour treatment efficacy compared to conventional, continuous dose delivery over minutes. A century back the first type of spatial fractionation (SFRT) at cm level the GRID therapy was proposed, which was developed to a 3-dimensional format to the LATTICE irradiation providing significant clinical experiences. The highly promising renascent of SFRT at µm level (MRT) is just prior to clinical investigation. Meanwhile one year after a case of human flash irradiation, the first clinical trial launched in the USA in October 2020. In this review, we summarize the basics of the two emerging radiation modalities, MRT and flash irradiation, technical conditions, possible mechanisms of action, preclinical results to date, and potential clinical applications.