Proton Bragg Peak FLASH Enables Organ Sparing and Ultra-High Dose-Rate Delivery: Proof of Principle in Recurrent Head and Neck Cancer

SIMPLE SUMMARY: Bragg peak proton FLASH is a novel way to deliver radiotherapy to cancer that combines ultra-high dose rates and conformal organ sparing provided by the physical characteristics of protons. Increasing the dose rate to ultra-high rates may decrease normal tissue toxicity through unique biological mechanisms that allow normal organs to be preserved. Most investigations of FLASH radiotherapy have used transmission beams that traverse the entire patient in order to generate high enough dose rates. We were able to create Bragg peak FLASH by making novel modifications to the planning software and the treatment delivery of the machine. This study demonstrates that conventional dose rate proton therapy and proton Bragg peak FLASH display similar organ sparing when plans were created and compared within the same patient. Bragg peak proton FLASH improves organ sparing over transmission proton FLASH, while both modalities have similar target and FLASH dose-rate coverage. Thus, Bragg peak proton FLASH may improve the therapeutic ratio in head and neck reirradiation. ABSTRACT: Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared dosimetry and dose rate coverage between PBS Bragg peak FLASH and PBS transmission FLASH in head and neck reirradiation. PBS Bragg peak FLASH plans were created via the highest beam single energy, range shifter, and range compensator, and were compared to PBS transmission FLASH plans for 6 GyE/fraction and 10 GyE/fraction in eight recurrent head and neck patients originally treated with quad shot reirradiation (14.8/3.7 CGE). The 6 GyE/fraction and 10 GyE/fraction plans were also created using conventional-rate intensity-modulated proton therapy techniques. PBS Bragg peak FLASH, PBS transmission FLASH, and conventional plans were compared for OAR sparing, FLASH dose rate coverage, and target coverage. All FLASH OAR V40 Gy/s dose rate coverage was 90–100% at 6 GyE and 10 GyE for both FLASH modalities. PBS Bragg peak FLASH generated dose volume histograms (DVHs) like those of conventional therapy and demonstrated improved OAR dose sparing over PBS transmission FLASH. All the modalities had similar CTV coverage. PBS Bragg peak FLASH can deliver conformal, ultra-high dose rate FLASH with a two-millisecond delivery of the minimum MU per spot. PBS Bragg peak FLASH demonstrated similar dose rate coverage to PBS transmission FLASH with improved OAR dose-sparing, which was more pronounced in the 10 GyE/fraction than in the 6 GyE/fraction. This feasibility study generates hypotheses for the benefits of FLASH in head and neck reirradiation and developing biological models.