Single-fraction 34 Gy Lung Stereotactic Body Radiation Therapy Using Proton Transmission Beams: FLASH-dose Calculations and the Influence of Different Dose-rate Methods and Dose/Dose-rate Thresholds.

Purpose: Research suggests that in addition to the dose-rate, a dose threshold is also important for the reduction in normal tissue toxicity with similar tumor control after ultrahigh dose-rate radiation therapy (UHDR-RT). In this analysis we aimed to identify factors that might limit the ability to achieve this "FLASH"-effect in a scenario attractive for UHDR-RT (high fractional beam dose, small target, few organs-at-risk): single-fraction 34 Gy lung stereotactic body radiation therapy. Methods and Materials: Clinical volumetric-modulated arc therapy (VMAT) plans, intensity modulated proton therapy (IMPT) plans and transmission beam (TB) plans were compared for 6 small and 1 large lung lesion. The TB-plan dose-rate was calculated using 4 methods and the FLASH-percentage (percentage of dose delivered at dose-rates ≥40/100 Gy/s and ≥4/8 Gy) was determined for various variables: a minimum spot time (minST) of 0.5/2 ms, maximum nozzle current (maxN) of 200/40 0nA, and 2 gantry current (GC) techniques (energy-layer based, spot-based [SB]). Results: Based on absolute doses 5-beam TB and VMAT-plans are similar, but TB-plans have higher rib, skin, and ipsilateral lung dose than IMPT. Dose-rate calculation methods not considering scanning achieve FLASH-percentages between ∼30% to 80%, while methods considering scanning often achieve <30%. FLASH-percentages increase for lower minST/higher maxN and when using SB GC instead of energy-layer based GC, often approaching the percentage of dose exceeding the dose-threshold. For the small lesions average beam irradiation times (including scanning) varied between 0.06 to 0.31 seconds and total irradiation times between 0.28 to 1.57 seconds, for the large lesion beam times were between 0.16 to 1.47 seconds with total irradiation times of 1.09 to 5.89 seconds. Conclusions: In a theoretically advantageous scenario for FLASH we found that TB-plan dosimetry was similar to that of VMAT, but inferior to that of IMPT, and that decreasing minST or using SB GC increase the estimated amount of FLASH. For the appropriate machine/delivery parameters high enough dose-rates can be achieved regardless of calculation method, meaning that a possible FLASH dose-threshold will likely be the primary limiting factor.