It has been observed that a biological effect called FLASH effect, which spares normal tissues while maintaining the same tumor control, appears when the dose is delivered at an ultra-high dose rate (UHDR). The FLASH effect has been observed with typical irradiations of about 10-20 Gy in less than 100ms in different animal species (fish eggs, mice, cats and pigs). A first patient was treated in 2019 and two clinical protocols have since been established. Most experiments were performed with UHDR electron beams, but also with photons and protons. The redundant observations of FLASH effect on animals, make it relevant to consider a clinical transfer under specific conditions.
Nevertheless, important questions remain. There is still no metrological traceability of UHDR beams and redundant dosimetry must be used to characterize the reference dose. The dosimetric instruments needed for (absolute and) relative dosimetry are not yet optimized for UHDR even if some promising detectors are emerging. The detectors used today for UHDR measurements are those that were used for conventional beams. This leads to many practical problems during commissioning and quality assurance measurements, such as the difficulty of getting a direct reading from the detector or the difficulty related to radiation protection because the beam simply cannot be left on for a few seconds or minutes, as is the case during conventional commissioning.
Another concern is the monitoring and safety of the beam. In the case of UHDR irradiations, monitoring is not only related to the beam fluence, but also to the beam structure and in particular to the number of pulses that will be delivered. As the durations are related to µs for the pulse length and hundreds of ms for the total delivery, the corresponding flux makes the traditional transmission chambers obsolete due to saturation effect. Therefore, another device is needed that can control the beam (in terms of pulse structure and pulse counting), but also, and more problematically, adapt the pulse configuration to delivery variations and ensure patient safety. When talking about a dose delivered in 10 pulses, an error of one pulse results in a 10% difference! In addition, the current description of safety features needed for treatment machines in the usual guidelines may also be outdated or may not allow for a specific detector that could be used for these tasks.
Clinical transfer requires additional features for the beams, namely that they must be large and energetic enough to treat the usual deep-seated tumors. The question of which type of beam, between very high energy electrons (VHEE), protons or photons, should be used remains open.
Finally, the biological cause of the FLASH effect is not yet understood and the physical parameters of the beams that trigger the FLASH effect are not fully defined.
In summary, FLASH RT is very promising for cancer treatment in radiotherapy, but important questions remain to be answered before a wide diffusion of this treatment technique becomes possible in clinical practice.