Fractionation dose optimization facilities the implementation of transmission proton FLASH-RT.

Objective: The beam switching time and fractional dose influence the FLASH effect. A single-beam-per-fraction (SBPF) scheme using uniform fractional dose (UFD) has been proposed for FLASH-RT to eliminate the beam switching time. Based on SBPF schemes, a fractionation dose optimization algorithm is proposed to optimize nonuniform fractional doses (non-UFD) plans to maximize the fractionation effect and dose-dependent FLASH effect. Approach: The UFD plan, containing five 236-MeV transmission proton beams, was optimized for 11 patients with peripheral lung cancer, with each beam delivering a uniform dose of 11 Gy to the target. Meanwhile, the non-UFD plan was optimized using fractionation dose optimization. To compare the two plans, the equivalent dose to 2 Gy (EQD2) for the target and normal tissues was calculated with an α/ß ratio of 10 and 3, respectively. Both UFD and non-UFD plans ensured that the target received an EQD2 of 96.3 Gy. To investigate the overall improvement in normal tissue sparing with the non-UFD plan, the FLASH-enhanced EQD2 was calculated. Main results: The fractional doses in non-UFD plans ranged between 5.0 Gy and 24.2 Gy. No significant differences were found in EQD22%and EQD298%of targets between UFD and non-UFD plans. However, the D95%of the target in non-UFD plans was significantly reduced by 15.1%. The sparing effect in non-UFD plans was significantly improved. The FLASH-enhanced EQD2meanin normal tissue and ipsilateral lung was significantly reduced by 3.5% and 10.4%, respectively, in non-UFD plans. The overall improvement is attributed to both the FLASH and fractionation effects. Significance: The fractionation dose optimization can address the limitation of multiple-beam FLASH-RT and utilize the relationship between fractional dose and FLASH effect. Consequently, the non-UFD scheme results in further improvements in normal tissue sparing compared to the UFD scheme, attributed to enhanced fractionation and FLASH effects.

Biological-equivalent-dose-based integrated optimization framework for fast-energy-switching Bragg peak FLASH-RT using single-beam-per-fraction.

BACKGROUNDS: When comparing the delivery of all beams per fraction (ABPF) to single beam per fraction (SBPF), it is observed that SBPF not only helps meet the FLASH dose threshold but also mitigates the uncertainty with beam switching in the FLASH effect. However, SBPF might lead to a higher biological equivalent dose in 2 Gy (EQD2) for normal tissues. PURPOSE: This study aims to develop an EQD2-based integrated optimization framework (EQD2-IOF), encompassing robust dose, delivery efficiency, and beam orientation optimization (BOO) for Bragg peak FLASH plans using the SBPF treatment schedule. The EQD2-IOF aims to enhance both dose sparing and the FLASH effect. METHODS: A superconducting gantry was employed for fast energy switching within 27 ms, while universal range shifters were utilized to improve beam current in the implementation of FLASH plans with five Bragg peak beams. To enhance dose delivery efficiency while maintaining plan quality, a simultaneous dose and spot map optimization (SDSMO) algorithm for single field optimization was incorporated into a Bayesian optimization-based auto-planning algorithm. Subsequently, a BOO algorithm based on Tabu search was developed to select beam angle combinations (BACs) for 10 lung cases. To simultaneously consider dose sparing and FLASH effect, a quantitative model based on dose-dependent dose modification factor (DMF) was used to calculate FLASH-enhanced dose distribution. The EQD2-IOF plan was compared to the plan optimized without SDSMO using BAC selected by a medical physicist (Manual plan) in the SBPF treatment schedule. Meanwhile, the mean EQD2 in the normal tissue was evaluated for the EQD2-IOF plan in both SBPF and ABPF treatment schedules. RESULTS: No significant difference was found in D2% and D98% of the target between EQD2-IOF plans and Manual Plans. When using a minimum DMF of 0.67 and a dose threshold of 4 Gy, EQD2-IOF plans showed a significant reduction in FLASH-enhanced EQD2mean of the ipsilateral lung and normal tissue by 10.5% and 11.5%, respectively, compared to Manual plans. For normal tissues that received a dose greater than 70% of the prescription dose, using a minimum DMF of 0.7 for FLASH sparing compensated for the increase in EQD2mean resulting from replacing ABPF with SBPF schedules. CONCLUSIONS: The EQD2-IOF can automatically optimize SBPF FLASH-RT plans to achieve optimal sparing of normal tissues. With an energy switching time of 27 ms, the loss of fractionate repairing using SBPF schedules in high-dose regions can be compensated for by the FLASH effect. However, when an energy switching time of 500 ms is utilized, the SBPF schedule needs careful consideration, as the FLASH effect diminishes with longer irradiation time.

Feasibility study of multiple-energy Bragg peak proton FLASH on a superconducting gantry with large momentum acceptance.

BACKGROUND: While the Bragg peak proton beam (BP) is capable of superior target conformity and organs-at-risk sparing than the transmission proton beam (TB), its efficacy in FLASH-RT is hindered by both a slow energy switching process and the beam current. A universal range shifter (URS) can pull back the high-energy proton beam while preserving the beam current. Meanwhile, a superconducting gantry with large momentum acceptance (LMA-SC gantry) enables fast energy switching. PURPOSE: This study explores the feasibility of multiple-energy BP FLASH-RT on the LMA-SC gantry. METHOD AND MATERIALS: A simultaneous dose and spot map optimization algorithm was developed for BP FLASH-RT treatment planning to improve the dose delivery efficiency. The URS was designed to be 0-27 cm thick, with 1 cm per step. BP plans using the URS were optimized using single-field optimization (SFO) and multiple-field optimization (MFO) for ten prostate cancer patients and ten lung cancer patients. The plan delivery parameters, dose, and dose rate metrics of BP plans were compared to those of TB plans using the parameters of the LMA-SC gantry. RESULTS: Compared to TB plans, BP plans significantly reduced MUs by 42.7% (P < 0.001) with SFO and 33.3% (P < 0.001) with MFO for prostate cases. For lung cases, the reduction in MUs was 56.8% (P < 0.001) with SFO and 36.4% (P < 0.001) with MFO. BP plans also outperformed TB plans by reducing mean normal tissue doses. BP-SFO plans achieved a reduction of 56.7% (P < 0.001) for prostate cases and 57.7% (P < 0.001) for lung cases, while BP-MFO plans achieved a reduction of 54.2% (P < 0.001) for the prostate case and 40.0% (P < 0.001) for lung cases. For both TB and BP plans, normal tissues in prostate and lung cases received 100.0% FLASH dose rate coverage (>40 Gy/s). CONCLUSIONS: By utilizing the URS and the LMA-SC gantry, it is possible to perform multiple-energy BP FLASH-RT, resulting in better normal tissue sparing, as compared to TB plans.

Comparison and evaluation of different deep learning models of synthetic CT generation from CBCT for nasopharynx cancer adaptive proton therapy.

BACKGROUND: Cone-beam computed tomography (CBCT) scanning is used for patient setup in image-guided radiotherapy. However, its inaccurate CT numbers limit its applicability in dose calculation and treatment planning. PURPOSE: This study compares four deep learning methods for generating synthetic CT (sCT) to determine which method is more appropriate and offers potential for further clinical exploration in adaptive proton therapy for nasopharynx cancer. METHODS: CBCTs and deformed planning CT (dCT) from 75 patients (60/5/10 for training, validation and testing) were used to compare cycle-consistent Generative Adversarial Network (cycleGAN), Unet, Unet+cycleGAN and conditionalGenerative Adversarial Network (cGAN) for sCT generation. The sCT images generated by each method were evaluated against dCT images using mean absolute error (MAE), structural similarity (SSIM), peak signal-to-noise ratio (PSNR), spatial non-uniformity (SNU) and radial averaging in the frequency domain. In addition, dosimetric accuracy was assessed through gamma analysis, differences in water equivalent thickness (WET), and dose-volume histogram metrics. RESULTS: The cGAN model has demonstrated optimal performance in the four models across various indicators. In terms of image quality under global condition, the average MAE has been reduced to 16.39HU, SSIM has increased to 95.24%, and PSNR has increased to 28.98. Regarding dosimetric accuracy, the gamma passing rate (2%/2 mm) has reached 99.02%, and the WET difference is only 1.28 mm. The D95 value of CTVs coverage and Dmax value of spinal cord, brainstem show no significant differences between dCT and sCT generated by cGAN model. CONCLUSIONS: The cGAN model has been shown to be a more suitable approach for generating sCT using CBCT, considering its characteristics and concepts. The resulting sCT has the potential for application in adaptive proton therapy.

Effect of Strain Rates on the Stress-Strain Behavior of FRP-Confined Pre-Damaged Concrete.

There are many studies on fiber-reinforced polymer (FRP)-confined pre-damaged concrete under quasi-static strain rates. However, few studies have focused on FRP-confined pre-damaged concrete under high strain rates. Thus, an experimental and analytical investigation was conducted to obtain the mechanical behavior of FRP-confined pre-damaged concrete under different strain rates. The results show that the stress-strain curves, ultimate stress, and strain values were affected by strain rate and the extent of concrete damage. A stress-strain model of FRP-confined pre-damaged concrete considering the strain rate was developed by modifying a stress-strain model of FRP-confined pre-damaged concrete under quasi-static loading. The proposed model was evaluated by using test data. The evaluation results show that the proposed model can predict the stress-strain behavior of FRP-confined pre-damaged concrete under different strain rates.