07.06.2024

New data presented in two recent publications by Brita Singers Sørensen and Per Poulsen et. al. highlight new insights to the FLASH effect, telling a more complex story.

 

The recent years of research in FLASH radiotherapy have worked towards proving a FLASH effect when delivering ultra-high dose rates, i.e. a sparing of the healthy tissue with comparable tumour response (incl. BS Sørensen et. al. 2022: In vivo validation and tissue sparing factor for acute damage of pencil beam scanning proton FLASH, Radiotherapy and Oncology). Researchers at the Danish Centre for Particle Therapy, led by prof. Brita Singers Sørensen on the biology side and prof. Per Poulsen in physics, have demonstrated exciting new results in two recent publications in International Journal of Radiation Oncology, Biology, Physics.

In one publication, a mouse model to evaluate acute skin toxicity was used to study the biological effect of varying dose rates, time structure and of introducing pauses in the beam delivery. The data demonstrates that a FLASH effect can be seen at lower field dose rates down to below 1 Gray pr. second (Gy/s); far lower than what has been reported so far, where 40 Gy/s has been assumed as a threshold. Another interesting finding is that splitting the total dose into more deliveries, in other words pausing the beam, compromised the FLASH effect. This is slowly, but fundamentally shifting the way researchers look at FLASH.

‘What we have shown with these biological data is that the FLASH effect gradually occurs with different factors in play, including dose rate and time structures,’ says Brita Singers Sørensen.

‘We are shifting our focus in the sense that it is no longer a question of whether or not the FLASH effect is there, but which factors that enable and influence it. For instance, we saw that beam pauses reduced the FLASH effect. This highlights the need for more research in the factors influencing the FLASH effect and how they interact,’ Brita Singers Sørensen elaborates.

First worldwide to quantify the FLASH effect in different scenarios

The strong local collaboration between physics, dosimetry and radiobiology has moved the Aarhus research further. The other publication builds upon the biological data, adding an oxygen enhancement ratio-weighted dose to describe the acute skin toxicities.

A major step forward here involves the quantifiable element, Per Poulsen explains:
‘The data is important for guiding future research, as we are now able to precisely estimate the degree of FLASH sparing that can be expected with changing doses and beam time structures. Not least, this is enabling us to compare different scenarios such as FLASH with proton beams and electron beams,’ Per Poulsen says.

The important groundwork and data are vital to build upon in upcoming research on fractionation, i.e. how to divide the FLASH dose optimally in fractions. This means that there is still a lot of research to be done before moving forward with FLASH for patients in Denmark. Furthermore, the technical equipment for using proton FLASH in the clinic is not yet available at DCPT.

‘FLASH is not a question of yes or no, and these data are showing us a more complex image, and deepening our knowledge of the interplay between the different factors is an important step towards translating these results into clinical practice’, Brita Singers Sørensen concludes.

About

Brita Singers Sørensen is a biologist and professor at the Danish Centre for Particle Therapy and Dept. of Experimental Clinical Oncology, Aarhus University Hospital and Dept. of Clinical Medicine, Aarhus University. More information about the radiobiology group of Brita Singers Sørensen here.

Per Rugaard Poulsen is a physicist and professor at the Danish Centre for Particle Therapy and Dept. of Clinical Medicine, Aarhus University. More information about the motion management and FLASH group of Per Poulsen here.

Publications:

Proton FLASH: impact of dose rate and split dose on acute skin toxicity in a murine model. Published: May 13, 2024. DOI: https://doi.org/10.1016/j.ijrobp.2024.04.071
Brita Singers Sørensen, Eleni Kanouta, Christina Ankjærgaard, Line Kristensen, Jacob G. Johansen, Mateusz Krzysztof Sitarz, Claus E. Andersen, Cai Grau, Per Poulsen

Oxygen Enhancement Ratio–Weighted Dose Quantitatively Describes Acute Skin Toxicity Variations in Mice After Pencil Beam Scanning Proton FLASH Irradiation With Changing Doses and Time Structures. Published: March 08, 2024. DOI: https://doi.org/10.1016/j.ijrobp.2024.02.050
Per Rugaard Poulsen, Jacob G. Johansen, Mateusz Krzysztof Sitarz, Eleni Kanouta, Line Kristensen, Cai Grau, Brita Singers Sørensen