Single-field-uniform-dose-per-fraction simultaneous dose and dose rate optimization (SFUDPF-SDDRO) method for proton...

The FLASH effect can significantly reduce radiation-induced normal tissue damage while maintaining tumour control, but requires ultra-high dose rates and high doses.

This work proposes a single-field-uniform-dose-per-fraction simultaneous dose and dose rate optimization (SFUDPF-SDDRO) method for proton FLASH radiotherapy to ensure both dose rate and dose meet FLASH effect thresholds.

The SFUDPF method focuses on delivering the prescription dose for each fraction from only a single field instead of multiple fields, which inherently supports the ultra-high dose rate and high dose necessary for the FLASH effect. We performed retrospective FLASH treatment planning utilizing SFUDPF-SDDRO on four clinical head-and-neck (HN) cases for this study. SFUDPF planning involves delivering each prescription fraction (8 Gy x 5 fx) in 1 beam angle as opposed to multiple beam angles per fraction for IMPT. For each beam delivery, we maximized the FLASH effect in a 1 cm expansion of the HN CTV (CTV+1 cm) by enforcing FLASH dose-rate and dose thresholds of 40 Gy/s and 5 Gy, respectively, in this region. The pencil-beam-scanning dose rate (PBSDR) was calculated voxel-wise by modeling the raster-scanning spot trajectory, while neglecting energy switching times under the assumption of a range modulator capable of expanding a single-energy beam into a spread-out Bragg peak (SOBP). Robust optimization at 3 mm/3.5% was performed to address setup and range uncertainties. We employed iterative convex relaxation and alternating direction method of multipliers algorithms to solve the non-convex optimization problem posed by the SFUDPF-SDDRO model. The FLASH effect was modelled within this work by multiplying the proton dose with a constant 0.7 dose modification factor for voxels fulfilling the dose-rate and dose thresholds to obtain the FLASH effective dose (FED). Effects of FLASH sparing maximization via SFUDPF-SDDRO are verified by comparing with IMPT and VMAT on plan qualities such as (i) high-dose area sparing, (ii) conformity index (CI), and (iii) OAR doses.

FLASH RT via SFUDPF-SDDRO compared with IMPT and VMAT was evaluated for four clinical HN cases with different tumor geometries. When compared with their VMAT counterparts, SFUD-SDDRO achieved a considerable reduction of FED for OAR directly adjacent to the CTV. Specifically in case 1, the brainstem D_1% decreased from 87.57% to 62.26%, and the spinal cord D_10% decreased from 87.36% to 60.74%; in case 2, the D_10% of the carotid decreased from 102.46% to 63.30%; in case 3, the D_10%of the oral cavity decreased from 94.72% to 62.66%, and the D_10% of the oropharynx decreased from 102.5% to 69.09%; in case 4, the D_10% of the oral cavity decreased from 88.56% to 59.81%. The SFUDPF-SDDRO achieved a satisfactory CI in terms of FED, indicating that conformity was not sacrificed to achieve the FLASH effect.

The proposed SFUDPF-SDDRO method is feasible and shows potential clinical benefits for FLASH treatment planning. Maximizing the FLASH effect within a 1 cm ring around the target substantially limits high-dose spillage and enhances OAR sparing compared with conventional approaches.