Description
After 10 years of collection of an impressive amount of positive experimental data in FLASH radiotherapy research, fundamental limitations still impact its full clinical exploitation. Indeed, the demonstration of a sparing effect, observed in vivo on normal tissues when a ultra high dose rate (UHDR) radiation delivery is adopted instead of a conventional one, with the parallel finding of no difference on tumoral control, has been accumulating evidence for broadly different particle types, energies and pulse structures from one side, as well as for several target tissues and biological endpoints on the other. Still, an intense worldwide research effort in unraveling the mechanistic features underpinning the observed effect has still not been paralleled by satisfactory comprehension of the latters, with several hypotheses explored and later abandoned for demonstrated inconsistencies. However, some consensus on several aspects is arising, together with a deeper understanding of radiobiology in general, beyond the pure FLASH effect itself, which is transferable to other applications.
In this context, multiscale radiation biophysical modeling of the UHDR response had an important role in complementing the experimental findings on in-vitro and in-vivo approaches. I will overview the status of the research in this field with a focus on the approaches deepening in the radiation chemical stages.
