ESTRO 2024 - Abstract Book

S5242 ESTRO 2024 Kevin Liu 1 , Trey Waldrop 2 , Edgardo Aguilar 2 , Nefititi Mims 3 , Denae Neill 2 , Abagail Delahoussaye 3 , Cullen Taniguchi 3 , Devarati Mitra 3 , Emil Schueler 2 1 Houston, Houston, Houston, USA. 2 MD Anderson, Radiation Physics, Houston, USA. 3 MD Anderson, Radiation Oncology, Houston, USA Radiobiology - Normal tissue radiobiology

Purpose/Objective:

FLASH radiation therapy (RT) is an emerging treatment modality that has reported selective sparing in normal tissue toxicity while maintaining isoeffective tumor cure when compared to conventional irradiation. Although FLASH RT was originally defined as having a mean dose-rate greater than 40 Gy/s, new data is indicating a more complicated relationship between the FLASH effect and irradiation parameters. A more detailed evaluation is warranted in quantifying the dependence of specific beam parameters for the FLASH effect. In this study, we are evaluating how the dose-per-pulse (DPP) and mean dose-rate influence the magnitude of the normal tissue sparing through the evaluation of acute gastrointestinal (GI) toxicity.

Material/Methods:

Female C57BL/6 mice received a single fraction total abdominal dose of 12 Gy. In the DPP evaluation, ten mice were treated at each DPP investigated ranging from 1-6 Gy/pulse with a constant mean dose-rate (180 Gy/s) in all groups. In the mean dose-rate evaluation, ten mice were treated at the investigated mean dose-rates ranging from 0.3-1440 Gy/s with a constant DPP of 6 Gy/pulse. 84 hours post-irradiation, the mice were sacrificed, and the jejunum of the small intestines were extracted and processed to evaluate the regenerating crypt count. Nine transverse sections per mouse were evaluated and the number of regenerative crypts per circumference were scored.

Results:

Our findings show a significant (p < 0.05) DPP dependence in the magnitude of the FLASH effect, with greater tissue sparing associated with higher DPP settings. Furthermore, the dependence on mean dose-rate disappeared when evaluated at high DPP. The mean crypt count per circumference at a mean dose-rate of 180 Gy/s but with a DPP of 1.3 , 3 ,and 6 Gy/pulse were a factor of 1.4, 1.6, and 2 higher compared to mice irradiated with conventional dose rate beam, respectively. The mean crypt count per circumference in mice treated with a mean dose rate of 0.3, 60, 1440 Gy/s and constant DPP of 6 Gy/pulse were constant at a factor of 1.5 higher compared to mice treated a conventional dose-rate beam.

Conclusion:

The magnitude of normal tissue sparing induced from FLASH treatment was observed to be dependent on the DPP and not on mean dose rate based on toxicity models of the GI tract. The data presented here provides insight as to redefining the criteria of the FLASH effect and the beam parameters required to maximize the normal tissue sparing potential of FLASH.

Keywords: FLASH, Gastrointestinal, In vivo