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.

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 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.

Background and Aims

We present the current status and outcomes of the joint radiobiological experiment performed at eight European proton therapy centers or research institutes. The study aims to spot the potential differences in the in vitro proton RBE values measured by different groups sharing a similar setup and identify its causes.

Methods

A phantom and a protocol for sample preparation and post-processing are shared among the participants to ensure minimal differences in the biological part of the experimental procedure. In this phantom, V79 cells grow on the polyester slides that can be inserted at different depths, which enables their simultaneous irradiation at multiple positions within the radiation field. The setup is irradiated with proton beams with two SOBP configurations (6 cm, 6 Gy, and 4 cm, 8 Gy), followed by the reference photon irradiation (LINAC or x-ray), and the biological effect is evaluated using a colony-forming assay.

Results

The study is still ongoing, and the spread of data for measured cell survival is yet to be evaluated. However, some non-obvious differences in the experimental procedures and setups are already revealed, e.g. post-processing timing or varying dose distributions in the beam plateau/fall-off regions.

Conclusions

As an outcome of the experiment, we plan to summarize the details of the experimental procedure for biological experiments with proton beams, differing between the centers across Europe. Accounting for these details would help to harmonize future studies in the field.

This work was supported by EU Horizon2020 grant 730983 (INSPIRE).