# Transformative Technology for FLASH Radiation Therapy
## FLASH Studies with Laser-Driven Particle Sources Developed at Lawrence Berkeley National Laboratory
### Potential of Laser-Driven Particle Sources for FLASH Radiation Therapy  
Preliminary in vitro experiments with LD ion sources have shown promise for FLASH radiotherapy [88]. However, stringent requirements concerning combined key beam parameters such as proton energy (up to 250 MeV), numbers of protons per bunch (\(10^{9}\)), stability and control of energy and proton numbers from shot to shot (\(<\)few percent variation), and repetition rate (\(>\)10 Hz) are yet to be experimentally demonstrated [104]. Currently, the primary challenge for the field of laser-ion acceleration is reaching clinically relevant particle energies. So far, peak LD proton energies achieved in experiments are approaching 100 MeV [72], which is well below energies necessary for clinically relevant penetration depths of \(>\)30 cm in humans [74]. In terms of ongoing efforts to develop a high repetition rate, several PW-class lasers can theoretically overcome this challenge when combined with improved gantry designs and treatment-planning strategies specific to LD particle sources [105; 106]. Currently, no unified reference dosimetry protocol exists for LD particle beams, which are unique in their ultra-high IDR and, in the case of ions, broad energy spectra. However, innovative dosimetry methods for radiobiological studies with LD proton sources have been developed that use online, minimally invasive, relative dose detectors, e.g., thin transmission ionization chambers, corrected for recombination effects [107], or integrating current transformers [108] that can be cross-referenced with independent absolute dosimetry methods such as radiochromic film [109] or Faraday cups [110]. These have enabled in situ dose-controlled LD proton irradiations of biological cell samples at a relative dose uncertainty below 10% [111]. Advances in laser technology are expected to deliver higher LD proton and ion energies because experiments and simulations have shown a consistent increase of maximum particle energies with laser pulse energy, power, or intensity [70; 71]. At the same time, theory and simulations predict higher proton and ion energies when harnessing advanced acceleration regimes including, for example, radiation pressure acceleration [112], magnetic vortex acceleration [113], and shock acceleration [114]. Given that the aforementioned ion-source requirements are met, designing a hypothetical compact LD FLASH radiotherapy machine requires careful consideration of not only the laser particle source but also the treatment beam delivery system that needs to reliably shape a six-dimensional dose profile matching the tumor profile, of which first designs exist [105]. As such, even after optimizing the LD particle sources for the footprint, which, on the laser side, may come naturally with advances in laser technology, it remains to be seen whether they can compete in compactness and cost with emerging conventional proton therapy machines, e.g., compact solutions by Mevion, IBA, Hitachi, and others, which have seen significant developments in recent years to reduce their footprint and cost [104]. However, these machines are typically not able to deliver comparable IDR as LD proton sources, and, so far, no such compact machines exist for heavier ions, which are automatically accelerated alongside protons in LD ion accelerators. With the current interest in using VHEE for radiotherapy, LWFA may well offer the most promising method for compact and affordable VHEE medical machines that \begin{table}
\begin{tabular}{l c} \hline \hline \multicolumn{1}{c}{**Beam Parameter**} & **Value** \\ \hline Dose per pulse & 1 Gy \\ Pulse length & 30 ns \\ Pulse repetition rate & 0.2 Hz \\ Instantaneous dose rate & \(3\times 10^{7}\) Gy/s \\ Mean dose rate & 0.2 Gy/s \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Proton beam parameters for cell sample irradiations at the BELLA PW. can operate in the ultra-high IDR regime [54].