Session Item

The FLASH-effect, a reduction in normal tissue toxicity with similar tumor control after ultra-high dose-rate radiotherapy (UHDR-RT), requires not only high dose-rates, but probably also a minimum dose delivered in a certain time period. The exact dose threshold is unknown but could be in the range of 4-8Gy, which, if this is the case, would limit the possible clinical applications. In addition, for scanning proton beams, it is unclear how to define the dose-rate for the dose-rate threshold. In this work we aimed to identify factors that might limit the ability to achieve the FLASH-effect in a scenario attractive for UHDR-RT (high fractional beam dose, small target, few OARs): single-fraction 34Gy lung SBRT.

Clinical VMAT-plans, 3-field IMPT-plans and 5-field UHDR transmission beam (TB) plans were compared for six small and one large lung lesion. For the TB-plans the dose-rate was calculated using four methods (Figure 1B): (1) UHDR-contribution (UHDRc) is the percentage of dose delivered at spot dose-rates higher than an UHDR-threshold, (2) dose-averaged dose-rate (DADR) is the average dose-rate weighted by the dose contribution, (3) pencil-beam scanning dose-rate (PBS-DR) considers a certain part of the dose and the time it takes to deliver that dose and (4) the average dose-rate (ADR) divides the total dose of a field by its total irradiation time. The FLASH-percentage (percentage of dose delivered at dose-rates ≥40/100Gy/s and ≥4/8Gy) was determined for various variables: a minimum spot time (minST) of 0.5/2ms, maximum nozzle current (maxN) of 200/400nA and two gantry current (GC) techniques (energy-layer based [EB]: GC is based on the lowest number of monitor units within the energy-layer; spot-based [SB]: GC varies per spot).

Doses to OARs were similar between TB and VMAT-plans, but TB-plans have higher rib, skin and ipsilateral lung dose than IMPT, due to TB exit dose. Figure 1A shows the different dose-rates in a single beam. Dose-rate calculation methods not considering scanning time (UHDRc, DADR) achieve FLASH-percentages between ~30-80%, while methods considering scanning (PBS-DR, ADR) often achieve <30% (Table 1). FLASH-percentages increase for lower minST/higher maxN and when using SB GC instead of EB GC, often approaching the percentage of dose exceeding the dose threshold. For the small lesions average TB beam irradiation times (including scanning) varied between 0.06-0.31s and total irradiation times between 0.28-1.57s, for the large lesion beam times were between 0.16-1.47s with total irradiation times of 1.09-5.89.

In a theoretically advantageous scenario for FLASH we found that UHDR proton TB-plan dosimetry was similar to VMAT, but inferior to IMPT, and that decreasing minST or using a 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 could be the primary limiting factor.