Background and Aims

One barrier to clinical implimentation of FLASH is the challenge of treating large clinical volumes at FLASH dose rates. The aim of this work is demonstrating the biological feasibility of delivering multiple volumes, each at FLASH dose rates, forming larger combined volumes, maintaining the FLASH effect globally even if the total treatment time exceeds a FLASH time scale.

Methods

Similar to previous work[1], proton radiation was delivered to the abdomens of 15 healthy mice using a 2 cm spread-out Bragg peak (SOBP). Treatment areas were irradiated to 15 Gy, with 9 mice receiving their dose at FLASH dose rates (100 Gy/s) and 6 mice at conventional dose rates (0.1 Gy/s). The mice received two adjacent fields, each an 11 mm-diameter circle, with the mouse repositioned between each delivery. Normal tissue damage was assessed by the EdU staining method[2], evaluating uptake in irradiated intestinal crypt cells.

[1] Int J Part Ther 2021; doi: https://doi.org/10.14338/IJPT-20-00095

[2] Int J Radiat Oncol Biol Phys . 2020 Feb 1;106(2):440-448. doi: 10.1016/j.ijrobp.2019.10.049.

Results

Separation was observed between FLASH and conventional mice in the number of regenerated cells per crypt (Figure 1) demonstrating that FLASH radiotherapy spares normal intestinal tissue at 3.5 days post 15 Gy SOBP radiation in comparison to standard proton radiotherapy.

Conclusions

These results demonstrate the feasilibity of “merged-field” FLASH. This efficient technique will allow for large, clinical volumes to be treated by combining smaller Bragg peak IMPT FLASH treatments and simultaneously maintaining the normal-tissue sparing benefits of the FLASH effect across the whole volume.