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

BACKGROUND

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

PURPOSE: 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.

METHODS

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.

RESULTS

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 D1% decreased from 87.57% to 62.26%, and the spinal cord D10% decreased from 87.36% to 60.74%; in case 2, the D10% of the carotid decreased from 102.46% to 63.30%; in case 3, the D10%of the oral cavity decreased from 94.72% to 62.66%, and the D10% of the oropharynx decreased from 102.5% to 69.09%; in case 4, the D10% 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.

CONCLUSION

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.