Abstract Body

FLASH radiotherapy has an important potential to improve patient’s treatment by limiting the development of side-effects while maintaining a similar anti-tumoral efficacy. In comparison to conventional radiotherapy, the FLASH effect has been demonstrated in vivo in different healthy organs (e.g. brain, lung, gut, skin). Most of these in vivo studies spread classically over several weeks and months to observe the FLASH effect and require ethical authorization for animal experiments. These limiting factors slow down FLASH investigations and prevent any in vivo validation of new FLASH beams in radiation facilities that does not allow animal studies. To circumvent these issues, some groups have developed new models for FLASH studies that allow a rapid detection of the FLASH effect. In my presentation, I will briefly review some of these recently published models as well as present some in vitro and ex vivo models we developed in the team. These models open new possibilities for FLASH research and will allow to investigate specific questions of great interest for the community, such as the importance of beam parameters or the determination of early molecular events occurring after FLASH radiotherapy.

Acknowledgements: Part of the work that will be presented have received funding from Varian, a Siemens Healthineers company

Abstract Body

FLASH radiotherapy has an important potential to improve patient’s treatment by limiting the development of side-effects while maintaining a similar anti-tumoral efficacy. In comparison to conventional radiotherapy, the FLASH effect has been demonstrated in vivo in different healthy organs (e.g. brain, lung, gut, skin). Most of these in vivo studies spread classically over several weeks and months to observe the FLASH effect and require ethical authorization for animal experiments. These limiting factors slow down FLASH investigations and prevent any in vivo validation of new FLASH beams in radiation facilities that does not allow animal studies. To circumvent these issues, some groups have developed new models for FLASH studies that allow a rapid detection of the FLASH effect. In my presentation, I will briefly review some of these recently published models as well as present some in vitro and ex vivo models we developed in the team. These models open new possibilities for FLASH research and will allow to investigate specific questions of great interest for the community, such as the importance of beam parameters or the determination of early molecular events occurring after FLASH radiotherapy.

Acknowledgements: Part of the work that will be presented have received funding from Varian, a Siemens Healthineers company

Background and Aims

Dosimetry for FLASH radiotherapy, VHEE radiotherapy as well as for laser-driven beams cause significant metrological challenges due to the ultra-high dose rates and pulsed structure of these beams, in particular for real time measurements with active dosimeters. It is not possible to simply apply existing Codes of Practice available for dosimetry in conventional external radiotherapy here. However, reliable standardized dosimetry is necessary for accurate comparisons in radiobiological experiments, to compare the efficacy of these new radiotherapy techniques and to enable safe clinical application. UHDpulse aims to develop the metrological tools needed for reliable real-time absorbed dose measurements of electron and proton beams with ultra-high dose rate, ultra-high dose per pulse or ultra-short pulse duration.

Methods

Within UHDpulse, primary and secondary absorbed dose standards and reference dosimetry methods are developed, the responses of available state-of-the-art detector systems are characterised, novel and custom-built active dosimetric systems and beam monitoring systems are designed, and methods for relative dosimetry and for the characterization of stray radiation are investigated.

Results

Prototypes of different active dosimetry systems show promising results for real-time dosimetry for particle beams with ultra-high pulse dose rates. The results of the UHDpulse project will be the input data for future Codes of Practice.

Conclusions

A brief overview of the progress in the UHDpulse project and the involved institutions will be given.

Acknowledgement: This project 18HLT04 UHDpulse has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.

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.