FLASH radiotherapy: ultra-high dose rates to spare healthy tissue

A recent addition to the treatment options in external beam therapy, so-called FLASH radiotherapy, shows remarkable healthy-tissue-sparing properties in a number of pre-clinical studies without impacting the overall treatment efficacy. Its potential in clinical applications is attracting a great deal of interest in the medical community. The use of ultra-high dose rates at extremely short irradiation times has been shown to significantly enhance the differential effects between normal and tumor tissue. This makes it possible to increase treatment doses without further harming the surrounding healthy tissue. While most studies to date have focused on the use of electron beams, X-ray and proton FLASH radiotherapy have also shown beneficial effects, although for these latter two the results still need to be independently confirmed. Furthermore, the mechanisms underlying the biological effects remain to be elucidated. Very recently, the FLASH effect has been demonstrated in the first human patient, with promising results, supporting further clinical studies. This review will present an overview of the investigations into FLASH radiotherapy to date.