Abstract Body

Since 2020 we have performed a series of pre-clinical proton FLASH experiments at the experimental beamline at the Danish Centre for Particle Therapy. This lecture will give an overview of the experiments and briefly discuss some potential implication for clinical application of FLASH. In all experiments, the right hind leg of CDF1 mice was irradiated with a 2cm x 3cm PBS transmission proton beam in a treatment depth of 13.5 cm in a water bath. The beam energy was 244 MeV for conventional dose rate (0.4Gy/s field dose rate) and 250 MeV for higher dose rates. In the first experiment, the acute skin damage as function of dose was investigated for both CONV and the highest attainable field dose rate of 80Gy/s (FLASH). The skin damage was scored using five toxicity levels that ranged from moderate damage (moist desquamation in one small area) to severe damage (moist desquamation of entire skin area). Depending on the toxicity level, 44-58% higher dose was needed with FLASH compared to CONV to obtain toxicity in 50% of the animals. In the second experiment, tumor control as function of dose was investigated for CONV and FLASH through full dose response curves. While FLASH had the same tumor control as CONV it reduced normal tissue damage. The third experiment investigated skin toxicity as function of field dose rate for a constant dose of 39.3 Gy. For this dose, the toxicity occurrence in general decreased from high to low as the field dose rate was increased from 0.4Gy/s to 80Gy/s. The field dose rate to induce skin damages in 50% of the animals (MDR50) depended on the toxicity level with higher MDR50 found for lower toxicity levels. There was therefore no common lower dose rate threshold for inducing the FLASH effect across the skin toxicity levels.