Impact of Multiple Beams on the FLASH Effect in Soft Tissue and Skin in Mice

Purpose: FLASH proton pencil beam scanning (p-PBS) showed a reduction in mouse skin toxicity and fibrosis when delivered as a single, uninterrupted, high-dose fraction. Clinical p-PBS treatment usually requires multiple beams to achieve good con -formality, and these beams are separated by minutes to allow patient and equipment repositioning. We evaluate the impact of multibeam versus single-beam proton radiation on the FLASH sparing effect on skin toxicity.Methods and Materials: The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a Varian ProBeam pro-ton beam scanning gantry system at conventional (1 Gy/s) or FLASH (100 Gy/s) average field dose rate. We scored the skin toxic-ity after different doses for 7 weeks. The treatment was delivered as 1, 2, or 3 equal beams with an interruption of 2 minutes. For each beam delivery, the equipment remained in the same position so that there was a full overlap of beams administered.Results: Single-beam delivery confirmed a benefit for p -PBS FLASH in this model at 30, 35, and 40 Gy. At 30 and 35 Gy, a sin-gle beam interruption of 2 minutes (2 x 15 Gy or 2 x 17.5 Gy) reduced the FLASH sparing effect, which remained significant (P < .001). However, 2 interruptions (3 x 10 Gy or 3 x 11.6 Gy) abrogated the normal tissue sparing effect.Conclusions: Our results indicate that the FLASH sparing effect in areas of beam overlap can be compromised by interruptions in delivery time. Time gap between overlapping beams and spatial arrangement of the delivered beams are important parameters for FLASH studies. The effect of multibeam needs to be studied on different organs of interest. (c) 2023 Elsevier Inc. All rights reserved.