Moderator of 1 Session
Presenter of 2 Presentations
Pre-clinical Proton Flash Experiments in a Mouse Model and Possible Implications for Clinical Application
Abstract
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.IN VIVO MEASUREMENT OF SPOT DOSE PROFILES AND DOSE RATES DURING PRE-CLINICAL PENCIL BEAM SCANNING PROTON FLASH TREATMENTS
Abstract
Background and Aims
In pencil beam scanning (PBS) proton FLASH, the scan pattern and spot dose profile determine the instantaneous dose rate variations in a point and consequently metrics such as the PBS dose rate. During mice experiments, a scintillator-based detector directly measured the instantaneous dose rate, spot dose profile, PBS dose rate, and dose contamination caused by irradiations of neighboring mice.
Methods
Three 2cm x 3cm proton PBS FLASH fields were delivered to the hind legs of three mice placed in a water bath at 13.5cm depth (Figure 1). An in-house developed detector based on a small (0.5x0.5x0.5mm3) fiber-coupled scintillating crystal was placed behind the leg and measured the instantaneous dose rate with 50kHz sampling rate. Combining the measured instantaneous dose rate for each individual spot with the spot-to-detector distance directly yielded the spot dose profile. The in vivo measurements furthermore provided the PBS dose rate DRPBS98% defined as 98% of the measured field dose divided by the time interval between reaching 1% and 99% of the field dose. The out-of-field dose from irradiations of neighboring mice was also measured. The measurements were compared with simulations assuming a Gaussian spot profile.
Results
The in vivo measured spot dose profile had a non-Gaussian tail extending more than 50mm (>10 standard deviations) from the spot position (Figure 2). The measured DRPBS98% was 122Gy/s, while simulations with a Gaussian spot profile gave an over-estimated value of 173Gy/s (Figure 3). The measured out-of-field dose from irradiation of neighboring mice was 1.2-1.5% of the field dose.
Conclusions
A scintillator-based dosimeter allowed direct in vivo measurement of three important quantities for PBS proton FLASH: (1) The spot dose profile, (2) the PBS dose rate and (3) dose contamination from irradiation of neighboring mice. A large non-Gaussian tail of the spot dose profile substantially impacted these three quantities.