Technical challenges for FLASH proton therapy.

There is growing interest in the radiotherapy community in the application of FLASH radiotherapy, wherein the dose is delivered to the entire treatment volume in less than a second. Early pre-clinical evidence suggests that these extremely high dose rates provide significant sparing of healthy tissue compared to conventional radiotherapy without reducing the damage to cancerous cells. This interest has been reflected in the proton therapy community, with early tests indicating that the FLASH effect is also present with high dose rate proton irradiation. In order to deliver clinically relevant doses at FLASH dose rates significant technical hurdles must be overcome in the accelerator technology before FLASH proton therapy can be realised. Of these challenges, increasing the average current from the present clinical range of 1-10 nA to in excess of 100 nA is at least feasible with existing technology, while the necessity for rapid energy adjustment on the order of a few milliseconds is much more challenging, particularly for synchrotron-based systems. However, the greatest challenge is to implement full pencil beam scanning, where scanning speeds 2 orders of magnitude faster than the existing state-of-the-art will be necessary, along with similar improvements in the speed and accuracy of associated dosimetry. Hybrid systems utilising 3D-printed patient specific range modulators present the most likely route to clinical delivery. However, to correctly adapt and develop existing technology to meet the challenges of FLASH, more pre-clinical studies are needed to properly establish the beam parameters that are necessary to produce the FLASH effect