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

Background : 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 conformality, and these beams are separated by minutes to allow patient and equipment repositioning. Purpose : To evaluate the impact of multibeam vs single beam proton radiation on the FLASH sparing effect on skin toxicity. Materials and Methods : The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a “Anonymized” proton beam scanning gantry system at conventional (1Gy/s) or FLASH (100Gy/s) average field dose rate. We scored the skin toxicity after different doses for 7 weeks. The treatment was delivered as 1, 2 or 3 equal beams with an interruption of 2 min. 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 single beam interruption of 2 min (2×15 Gy or 2×17.5 Gy) reduced the FLASH sparing effect, which remained significant (p<0.001). However, two interruptions (3×10 Gy or 3×11.6 Gy) abrogated the normal tissue sparing effect. Conclusion : 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.