Background and Aims

With medical linear accelerators, the dose is delivered in approximately a thousand of low-dose radiation pulses and is regulated by monitoring ionization chambers, which turn off the beam once the preset number of Monitor Units (MU) is reached. In FLASH electron beams, on the contrary, the dose-per-pulse is much higher (> 1 Gy/pulse), which, a) prevent the use of conventional monitoring systems, and b) implies that the complete treatment is delivered with a very limited number of pulses, sometimes only one. To guarantee that the planned dose is delivered as intended, new methodologies for monitoring must be elaborated for FLASH beam delivery.

Methods

In preclinical studies with ElectronFLASH4000 (SIT), we have defined FLASH-MU as a fraction of the pulse’s temporal profile integral, which is recorded with a non-destructive monitoring toroid. For the control experiments performed at conventional dose-rate, MU measured by classical monitor chambers have been cross-referenced with FLASH-MU, through calibration by film dosimetry.

Results

FLASH electron beams can be effectively monitored by toroidal current transformers, provided they have adequate performances. Prescribed doses have been translated in MU with different pulse length, pulse amplitude and/or number of pulses. Heterogeneous pulse sequences including decreasing doses-per-pulse allowed a smaller cut-off step.

Conclusions

This opens the discussion on techniques for FLASH monitoring and on beam cut-off strategies for radiotherapy treatments delivered with very few ultra-high-dose pulses. At least some of them can already be tested for dose accuracy and biological effectiveness.

Acknowledgement: This work is part of 18HLT04-UHDpulse project, which received funding from the EMPIR program.

Background and Aims

Currently, many research groups are more interested in the FLASH radiotherapy characterized by irradiation with ultra-high dose rate. A first usual step is to validate the beam line for FLASH studies by reproducing published FLASH effect in animals. However, it classically requires time consuming animal studies with dedicated skills, authorizations and infrastructures. Thus, to provide alternative methods and facilitate the implementation and validation of new FLASH beams, we aimed at developing in vitro and ex vivo models that will allow rapid and pertinent evaluation of the FLASH effect.

Methods

For our studies, we are using the ElectronFLASH LINAC manufactured by SIT company. To achieve this goal, we first used an in vitro model of human lung basal stem cells obtained from patients. Cultured in specific air-liquid conditions, this model allows the monitoring of stem cells survival and their capacity to differentiate after irradiation. In parallel, we adapted organotypic lung slices model, recapitulating lung complexity, architecture and microenvironment interactions, for radiation toxicity studies.

Results

Our results indicate that organotypic lung slices enables a rapid evaluation of the FLASH effect.

Conclusions

These models developed in the lab allow to rapidly determine the impact of the various beam parameters on FLASH effect with a robust and reproducible assay. With the inclusion of tumoral cells within the organotypic lung slices, we hypothesize that this ex vivo model can assess concomitantly the FLASH sparing effect on healthy tissue as well as the antitumoral efficacy. Moreover, the model can apply for human patient samples as well as rodent tissues.