Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates.

This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Spot-reduced plans contained 17-52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates.