Background and Aims

A common methodology to report dose rates for pulsed and scanned FLASH beams is missing. We propose the dose-rate dose-fraction (DR-DF) histogram as a common method across all FLASH modalities.

Methods

The DR-DF histogram specifies the fraction of the dose in a point that is delivered with a given minimum mean dose rate (Figure 1). Two parameters can directly be extracted from the DR-DF histogram: (1) the mean dose rate that X% of the dose is at minimum delivered with (DR_X%) and (2) the fraction of the dose that is delivered with a minimum mean dose rate of Y Gy/s (DF_YGy/s,). As an example, DF_40Gy/s is the fraction of the dose that is delivered under FLASH conditions if the FLASH effect is triggered at 40Gy/s mean dose rate. The DR-DF histogram concept was applied to characterize the proton PBS field used in pre-clinical FLASH experiments at our institution.

Results

Figure 2 shows the distribution of dose and dose rate DR_95% for the pre-clinical FLASH beam and the FLASH fraction and FLASH weighted dose in illustrative simulations with the dose rate reduced to 10% of the actual value. In the FLASH weighted dose, the dose delivered with FLASH (DF_40Gy/s) was given a weight of 80% while the remaining dose (100% - DF_40Gy/s) was given a weight of 100%.

Conclusions

The concept of DR-DF histograms was proposed as a common framework to characterize the time structure of scanned and pulsed FLASH beams through mapping of minimum mean dose rate, FLASH fraction and FLASH weighted dose.

Background and Aims

A common methodology to report dose rates for pulsed and scanned FLASH beams is missing. We propose the dose-rate dose-fraction (DR-DF) histogram as a common method across all FLASH modalities.

Methods

The DR-DF histogram specifies the fraction of the dose in a point that is delivered with a given minimum mean dose rate (Figure 1). Two parameters can directly be extracted from the DR-DF histogram: (1) the mean dose rate that X% of the dose is at minimum delivered with (DR_X%) and (2) the fraction of the dose that is delivered with a minimum mean dose rate of Y Gy/s (DF_YGy/s,). As an example, DF_40Gy/s is the fraction of the dose that is delivered under FLASH conditions if the FLASH effect is triggered at 40Gy/s mean dose rate. The DR-DF histogram concept was applied to characterize the proton PBS field used in pre-clinical FLASH experiments at our institution.

Results

Figure 2 shows the distribution of dose and dose rate DR_95% for the pre-clinical FLASH beam and the FLASH fraction and FLASH weighted dose in illustrative simulations with the dose rate reduced to 10% of the actual value. In the FLASH weighted dose, the dose delivered with FLASH (DF_40Gy/s) was given a weight of 80% while the remaining dose (100% - DF_40Gy/s) was given a weight of 100%.

Conclusions

The concept of DR-DF histograms was proposed as a common framework to characterize the time structure of scanned and pulsed FLASH beams through mapping of minimum mean dose rate, FLASH fraction and FLASH weighted dose.

Background and Aims

The sharp energy deposition of a pulsed ion beam (ideally using short pulses of a few microseconds) results in thermoacoustic waves (ionoacoustics). Signals acquired at multiple positions could allow to infer the in-vivo dose, to localize the Bragg peak or be used for dosimetry. This study assesses dose reconstruction for a small-animal proton irradiator under FLASH conditions (94Gy/s instantaneous dose rate, at the Bragg peak, delivery duration below 200ms). Particular attention is paid to the reconstruction from transient waves emerging from millisecond-long proton pulses at clinical cyclotron facilities.

Methods

The ionoacoustic signals recorded by a realistic 32-element linear array were simulated in water, accounting for the sensor response and acquisition noise (Fig.1). 10ms square proton pulses (30ns rising/falling time and 50% duty cycle) were considered, giving rise to transient ionoacoustic emissions from the pulse edges. The array geometry and piezoelectric material thickness were optimized to improve the accuracy of 2D-dose reconstruction obtained from time-reversal method.

Results

Using the detection of transient ionoacoustic waves from millisecond proton pulses, the dose can be reconstructed (Fig.2.) under FLASH conditions. Optimizing the sensor response and number of pulses to average the signal, the error in the range can be reduced to as low as 0.5% (30µm).

Conclusions

This feasibility study shows that transient ionoacoustics-based dose reconstruction allows for accurate range verification at cyclotron accelerators, assuming dedicated pulsing structure. Thanks to the direct relation between dose and pressure, this method could be applied for in-vivo dosimetry.

Acknowledgements: ERC-725539, H2020-EU INSPIRE-730983, CALA

Background and Aims

A graphite calorimeter with a small core (5 mm diameter, 7 mm height) has been designed with the objective to characterize solid-state detectors in new radiotherapy modalities with respect to response changes resulting from changes in LET, dose rate and other parameters. Using a replica of the calorimeter, one can, for example, substitute the graphite core with the detector under investigation to obtain paired measurements with the graphite core and the detector under investigation under near-identical scatter conditions. In this study, we used the calorimeter to test alanine dosimetry for dose-rate effects in proton FLASH beams.

Methods

Measurements were performed at the Varian ProBeam system at the Danish Center of Particle beam using 250 MeV PBS beams with nozzle currents ranging from 4 nA to 215 nA (FLASH). For the main tests, we compared alanine pellets placed in the beam entrance with the temperature increase in the graphite core placed about 8 cm downstream.

Results

14 proton irradiations delivered doses of 10-11 Gy at different nozzle currents using a fixed 7 x 7 spot pattern (30 mm x 30.6 mm field size with a 50 Gy/s field dose rate for 215 nA nozzle current). The alanine doses correlated strongly with the temperature increases in the graphite core. Within experimental uncertainty, the ratio between alanine dose and temperature increase was found to be independent of the nozzle current in the tested dose rate range.

Conclusions

This study supports that alanine can be used for proton FLASH dosimetry without correction for dose-rate effects.

Background and Aims

The aim of this study was to test the effect of proton FLASH delivered with a pencil beam scanning (PBS).

Methods

The right hind limb of CDF1 mice were irradiated in a single fraction in the entrance plateau of a scanning proton pencil beam using either conventional dose rate (0.4 Gy/s field dose rate, 244 MeV) or FLASH (69.7-88.7 Gy/s field dose rate, 250 MeV). The study included 292 non-tumor bearing mice and 80 mice with a C3H mouse mammary carcinoma implanted in the foot. The mice were irradiated with doses of 26-40Gy (non-tumor, conventional), 40-60Gy (non-tumor, FLASH) or 45-67Gy (tumor). The endpoints were the level of acute moist desquamation to the skin of the foot within 25 days post irradiation, and tumor control.

Results

Full dose response curves for acute damage to skin for both conventional and FLASH dose rate demonstrated a distinct normal tissue sparing effect in the FLASH arm of the study, with a mean value for the tissue sparing factor of 1.46. For tumor control, the pre-liminary dose response curves shows no difference between conventional and FLASH dose rates (follow up on tumor control is ongoing).

Conclusions

This study demonstrates a normal tissue sparing effect of proton FLASH delivered with pencil beam scanning, while no differences was found in tumor control rates. Compared to conventional dose rate, 41-55% higher dose were required to give the same biological toxicity in the normal tissue when using FLASH dose rates.