Development of Ultra-High Dose-Rate (FLASH) Particle Therapy

Abstract

Research efforts in FLASH radiotherapy have increased at an accelerated pace recently. FLASH radiotherapy involves ultra-high dose rates and has shown to reduce toxicity to normal tissue while maintaining tumor response in pre-clinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies performed to-date with proton, electron, and heavy ion FLASH radiotherapy, with particular emphasis on the physical aspects of each study and the advantages and disadvantages of each modality. Beam delivery parameters, experimental set-up, and the dosimetry tools used are described for each FLASH modality. In addition, modeling efforts and treatment planning for FLASH radiotherapy is discussed along with potential drawbacks when translated into the clinical setting. The final section concludes with further questions that have yet to be answered before safe clinical implementation of FLASH radiotherapy.

Keywords: FLASH effect modeling; FLASH radiotherapy; electron radiation; heavy-ion radiation; proton radiation.

Fig. 1.

(a) Representative percent depth dose curves for photon (blue, ~6 MV), electron (yellow, ~18 MeV), proton (green, ~145 MeV), and carbon ion (red, ~300 MeV/u) beams in water. (b) Representative depth dose curve for a proton spread out Bragg peak (black) with the weighted monoenergetic Bragg peaks (multicolored) used to generate the spread out Bragg peak.

Fig. 2.

Setup geometry of radiobiological studies with electron FLASH. The mouse was placed inside the linac head to achieve the desired dose rate (adapted from [19])

Fig. 3.

Dose distribution visualized in a water/tissue equivalent material (plastic scintillator BC-400, Saint-Gobain Crystals, with optical emission at 423 nm) from a 6 MeV electron beam at ultra-high dose rates at the linear accelerator at the University of Oxford (courtesy of Prof Borivoj Vojnovic).

Fig. 4.

Schematic of typical macropulse and micropulse structure of (a) an isochronous cyclotron with quasi-continuous beam, (b) a synchrocyclotron with pulsed output, and (c) a medical linear accelerator with pulsed output (drawn not to scale). In (b) and (c), each macro pulse consists a number of micro pulses (adapted from [7]).

Fig. 5.

Proton FLASH study setup geometry for (a) synchrocyclotron and (b) isochronous cyclotron implementations (adapted from [7,23]).

Fig. 6.

A 3D model of Heidelberg Ion Therapy Center (HIT) showing the magnitude of a carbon ion facility (with permission from University Hospital Heidelberg).