A novel dose rate optimization method to maximize ultra-high dose rate coverage of critical organs-at-risk without compromising dosimetry metrics in proton pencil beam scanning FLASH radiotherapy

Purpose To investigate a dose rate optimization framework based on the spot scanning patterns to improve ultra-high dose rate coverage of critical organs-at-risk (OARs) for proton PBS FLASH radiotherapy, and to present implementation of a genetic algorithm (GA) method for spot sequence optimization to achieve PBS FLASH dose rate optimization under relatively low nozzle beam currents. Materials and Methods Firstly, a multi-field FLASH plan was developed to meet all the dosimetric goals and optimal FLASH dose rate coverage by considering the deliverable minimum MU (MMU) constraint. Then, a GA method was implemented into the in-house treatment platform to maximize the dose rate by exploring the best spot delivery sequence. A phantom study was performed to evaluate the effectiveness of the dose rate optimization. Then, 10 consecutive plans for lung cancer patients previously treated using PBS intensity-modulated proton therapy (IMPT) were optimized using 45 GyRBE in 3 fractions both transmission and Bragg peak FLASH-RT for further validation. The spot delivery sequence of each treatment field was optimized using this GA. The ultra-high dose rate volume histogram (DRVH) and dose rate coverage V40GyRBE/s were investigated to assess the efficacy of dose rate optimization quantitatively. Results Using a relatively low MU/spot of 150, corresponding to nozzle beam current of 65 nA, the FLASH dose rate ratio V40GyRBE/s of the OAR contour of the core was increased from 0 to ∼60% in the phantom study. In the lung cancer patients, the ultra-high dose rate coverage V40GyRBE/s were improved from 15.2%, 15.5%, 17.6%, and 16.0% before the delivery sequence optimization, to 31.8%, 43.5%, 47.6%, and 30.5% after delivery sequence optimization, in the lungs-GTV, spinal cord, esophagus, and heart (p-values all<0.001). When beam current increased to 130 nA, V40GyRBE/s was improved from 45.1%, 47.1%, 51.2%, and 51.4%, to 65.3%, 83.5%, 88.1%, and 69.4% (p-values<0.05). The averaged V40GyRBE/s for the target and OARs was increased from 12.9% to 41.6%, and 46.3% to 77.5% for 65 and 130 nA, respectively, showing significant improvements based on a clinical proton system. After optimizing the dose rate for the Bragg peak FLASH technique with a beam current of 340 nA, the V40GyRBE/s for the lung-GTV, spinal cord, esophagus, and heart were increased by 8.9%, 15.8%, 22%, and 20.8%, respectively. Conclusion An optimal plan quality can be maintained as the spot delivery sequence optimization is a separate independent process after the plan optimization. Both the phantom and patient results demonstrated that novel spot delivery sequence optimization can effectively improve the ultra-high dose rate coverage for critical OARs, which can potentially be applied in clinical practice for better OARs sparing efficacy.