Auto-Trending daily quality assurance program for a pencil beam scanning proton system aligned with TG 224.

The Daily Quality Assurance (DQA) for a proton modality is not standardized. The modern pencil beam scanning proton system is becoming a trend and an increasing number of proton centers with PBS are either under construction or in planning. The American Association of Physicists in Medicine has a Task Group 224 report published in 2019 for proton modality routine QA. Therefore, there is a clinical need to explore a DQA procedure to meet the TG 224 guideline. The MatriXX PT and a customized phantom were used for the dosimetry constancy checking. An OBI box was used for imaging QA. The MyQA(TM) software was used for logging the dosimetry results. An in-house developed application was applied to log and auto analyze the DQA results. Another in-house developed program "DailyQATrend" was used to create DQA databases for further analysis. All the functional and easy determined tasks passed. For dosimetry constancy checking, the outputs for four gantry rooms were within ±3% with room to room baseline differences within ±1%. The energy checking was within ±1%. The spot location checking from the baseline was within 0.63 mm and the spot size checking from the baseline was within -1.41 ± 1.27 mm (left-right) and -0.24 ± 1.27 mm (in-out) by averaging all the energies. We have found that there was also a trend for the beam energies of two treatment rooms slowly going down (0.76% per month and 0.48 per month) after analyzing the whole data trend with linear regression. A DQA program for a PBS proton system has been developed and fully implemented into the clinic. The DQA program meets the TG 224 guideline and has web-based logging and auto treading functions. The clinical data show the DQA program is efficient and has the potential to identify the PBS proton system potential issue.

Using patient-specific bolus for pencil beam scanning proton treatment of periorbital disease.

PURPOSE: A unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient-specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity. MATERIALS/METHODS: A blue-wax patient-specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue-wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient-specific bolus plans. An in-house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter-fraction dose accumulation. RESULTS: The patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2-3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient-specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as "very comfortable" by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention. CONCLUSION: Our patient-specific blue-wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient-specific bolus with robustness on both setup and dosimetry.

Validation and clinical implementation of an accurate Monte Carlo code for pencil beam scanning proton therapy.

Monte Carlo (MC)-based dose calculations are generally superior to analytical dose calculations (ADC) in modeling the dose distribution for proton pencil beam scanning (PBS) treatments. The purpose of this paper is to present a methodology for commissioning and validating an accurate MC code for PBS utilizing a parameterized source model, including an implementation of a range shifter, that can independently check the ADC in commercial treatment planning system (TPS) and fast Monte Carlo dose calculation in opensource platform (MCsquare). The source model parameters (including beam size, angular divergence and energy spread) and protons per MU were extracted and tuned at the nozzle exit by comparing Tool for Particle Simulation (TOPAS) simulations with a series of commissioning measurements using scintillation screen/CCD camera detector and ionization chambers. The range shifter was simulated as an independent object with geometric and material information. The MC calculation platform was validated through comprehensive measurements of single spots, field size factors (FSF) and three-dimensional dose distributions of spread-out Bragg peaks (SOBPs), both without and with the range shifter. Differences in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2.2%, with and without a range shifter, indicating an accurate source model. TOPAS was also validated against anthropomorphic lung phantom measurements. Comparison of dose distributions and DVHs for representative liver and lung cases between independent MC and analytical dose calculations from a commercial TPS further highlights the limitations of the ADC in situations of highly heterogeneous geometries. The fast MC platform has been implemented within our clinical practice to provide additional independent dose validation/QA of the commercial ADC for patient plans. Using the independent MC, we can more efficiently commission ADC by reducing the amount of measured data required for low dose "halo" modeling, especially when a range shifter is employed.

A study of the beam-specific interplay effect in proton pencil beam scanning delivery in lung cancer.

BACKGROUND: For lung tumors with large motion amplitudes, the use of proton pencil beam scanning (PBS) can produce large dose errors. In this study, we assess under what circumstances PBS can be used to treat lung cancer patients who exhibit large tumor motion, based on the quantification of tumor motion and the dose interplay. MATERIAL AND METHODS: PBS plans were optimized on average 4DCT datasets using a beam-specific PTV method for 10 consecutive patients with locally advanced non-small-cell-lung-cancer (NSCLC) treated with proton therapy to 6660/180 cGy. End inhalation (CT0) and end exhalation (CT50) were selected as the two extreme scenarios to acquire the relative stopping power ratio difference (Δrsp) for a respiration cycle. The water equivalent difference (ΔWET) per radiological path was calculated from the surface of patient to the iCTV by integrating the Δrsp of each voxel. The magnitude of motion of voxels within the target follows a quasi-Gaussian distribution. A motion index (MI (>5mm WET)), defined as the percentage of target voxels with an absolute integral ΔWET larger than 5 mm, was adopted as a metric to characterize interplay. To simulate the treatment process, 4D dose was calculated by accumulating the spot dose on the corresponding respiration phase to the reference phase CT50 by deformable image registration based on spot timing and patient breathing phase. RESULTS: The study indicated that the magnitude of target underdose in a single fraction plan is proportional to the MI (p < .001), with larger motion equating to greater dose degradation and standard deviations. The target homogeneity, minimum, maximum and mean dose in the 4D dose accumulations of 37 fractions varied as a function of MI. CONCLUSIONS: This study demonstrated that MI can predict the level of dose degradation, which potentially serves as a clinical decision tool to assess whether lung cancer patients are potentially suitable to receive PBS treatment.

A benchmarking method to evaluate the accuracy of a commercial proton monte carlo pencil beam scanning treatment planning system.

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run-time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi-spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid-range depth of multi-energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation.

Use of a novel two-dimensional ionization chamber array for pencil beam scanning proton therapy beam quality assurance.

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard MatriXX(Evolution) but utilizes a smaller 2 mm plate spacing instead of 5mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate Pion from the ratios of charges collected. In comparison with the MatriXX(Evolution), a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the MatriXX(Evolution) can be up to 4%, it is < 1% for the MatriXX PT. Therefore the MatriXX(Evolution) should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of Pion can be > 1%; chambers with an electrode spacing of 2 mm or smaller are recommended.

Beam-specific planning target volumes incorporating 4D CT for pencil beam scanning proton therapy of thoracic tumors.

The purpose of this study is to determine whether organ sparing and target coverage can be simultaneously maintained for pencil beam scanning (PBS) proton therapy treatment of thoracic tumors in the presence of motion, stopping power uncertainties, and patient setup variations. Ten consecutive patients that were previously treated with proton therapy to 66.6/1.8 Gy (RBE) using double scattering (DS) were replanned with PBS. Minimum and maximum intensity images from 4D CT were used to introduce flexible smearing in the determination of the beam specific PTV (BSPTV). Datasets from eight 4D CT phases, using ± 3% uncertainty in stopping power and ± 3 mm uncertainty in patient setup in each direction, were used to create 8 × 12 × 10 = 960 PBS plans for the evaluation of 10 patients. Plans were normalized to provide identical coverage between DS and PBS. The average lung V20, V5, and mean doses were reduced from 29.0%, 35.0%, and 16.4 Gy with DS to 24.6%, 30.6%, and 14.1 Gy with PBS, respectively. The average heart V30 and V45 were reduced from 10.4% and 7.5% in DS to 8.1% and 5.4% for PBS, respectively. Furthermore, the maximum spinal cord, esophagus, and heart doses were decreased from 37.1 Gy, 71.7 Gy, and 69.2 Gy with DS to 31.3 Gy, 67.9 Gy, and 64.6 Gy with PBS. The conformity index (CI), homogeneity index (HI), and global maximal dose were improved from 3.2, 0.08, 77.4 Gy with DS to 2.8, 0.04, and 72.1 Gy with PBS. All differences are statistically significant, with p-values <0.05, with the exception of the heart V45 (p = 0.146). PBS with BSPTV achieves better organ sparing and improves target coverage using a repainting method for the treatment of thoracic tumors. Incorporating motion-related uncertainties is essential.

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.

The Status and Challenges for Prostate Stereotactic Body Radiation Therapy Treatments in United States Proton Therapy Centers: An NRG Oncology Practice Survey.

Purpose: To report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and Methods: A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

Validation and reproducibility of in vivo dosimetry for pencil beam scanned FLASH proton treatment in mice.

PURPOSE: To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber. METHODS AND MATERIALS: 227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector. RESULTS: Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R2 values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ±â€¯3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ±â€¯0.8 Gy/s and mean local average dose rate of 160.6 ±â€¯3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose. CONCLUSION: In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.

NRG Oncology and Particle Therapy Co-Operative Group Patterns of Practice Survey and Consensus Recommendations on Pencil-Beam Scanning Proton Stereotactic Body Radiation Therapy and Hypofractionated Radiation Therapy for Thoracic Malignancies.

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques.

A Novel Inverse Algorithm To Solve the Integrated Optimization of Dose, Dose Rate, and Linear Energy Transfer of Proton FLASH Therapy With Sparse Filters.

PURPOSE: The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for ultra-high dose rate (FLASH) treatment planning. Finding solutions to IPO-IMPT is difficult because of computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biologic dose to organs at risk in patients with cancer as well as reduce the number of animal irradiations needed to derive extra biologic dose models in preclinical studies. METHODS AND MATERIALS: Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human patient with central lung cancer and a minipig. RESULTS: SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the patient with lung cancer, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/µm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies. CONCLUSIONS: The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate subspot proton energy and intensity distributions for clinical and preclinical studies.

Proton Pencil-Beam Scanning Stereotactic Body Radiation Therapy and Hypofractionated Radiation Therapy for Thoracic Malignancies: Patterns of Practice Survey and Recommendations for Future Development from NRG Oncology and PTCOG.

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally-fractionated PBSPT due to concerns of amplified uncertainties at the larger dose per fraction. NRG Oncology and Particle Therapy Cooperative Group (PTCOG) Thoracic Subcommittee surveyed US proton centers to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Amongst other points, the recommendations highlight the need for volumetric image guidance and multiple CT-based robust optimization and robustness tools to minimize further the impact of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques.

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

The status and challenges for prostate SBRT treatments in United States proton therapy centers: An NRG Oncology practice survey.

A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in Feb. 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and IGRT methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited three primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and MRI for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35-40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

Proton liver stereotactic body radiation therapy: Treatment techniques and dosimetry feasibility from a single institution.

Purpose: To assess the resulting dosimetry characteristics of simulation and planning techniques for proton stereotactic body radiation therapy (SBRT) of primary and secondary liver tumors. Methods: Consecutive patients treated under volumetric daily image guidance with liver proton SBRT between September 2019 and March 2022 at Emory Proton Therapy Center were included in this study. Prescriptions ranged from 40 Gy to 60 Gy in 3- or 5-fraction regimens, and motion management techniques were used when target motion exceeded 5 mm. 4D robust optimization was used when necessary. Dosimetry evaluation was conducted for ITV V100, D99, Dmax, and liver-ITV mean dose and D700cc. Statistical analysis was performed using independent-samples Mann-Whitney U tests. Results: Thirty-six tumors from 29 patients were treated. Proton therapy for primary and secondary liver tumors using motion management techniques and robust optimization resulted in high target coverage and low doses to critical organs. The median ITV V100% was 100.0%, and the median ITV D99% was 111.3%. The median liver-ITV mean dose and D700cc were 499 cGy and 5.7 cGy, respectively. The median conformity index (CI) was 1.03, and the median R50 was 2.56. Except for ITV D99% (primary 118.1% vs. secondary 107.2%, p = 0.005), there were no significant differences in age, ITV volume, ITV V100%, ITV maximum dose, liver-ITV mean dose, or D700cc between primary and secondary tumor groups. Conclusion: The study demonstrated that proton therapy with motion management techniques and robust optimization achieves excellent target coverage with low normal liver doses for primary and secondary liver tumors. The results showed high target coverage, high conformality, and low doses to the liver.

Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment.

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.

An Integrated Physical Optimization Framework for Proton Stereotactic Body Radiation Therapy FLASH Treatment Planning Allows Dose, Dose Rate, and Linear Energy Transfer Optimization Using Patient-Specific Ridge Filters.

PURPOSE: Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LETd). METHODS AND MATERIALS: We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT. RESULTS: The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LETd, using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LETd, while maintaining dose coverage within the beam specific planning target volume. CONCLUSIONS: This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LETd simultaneously.

Proton Bragg Peak FLASH Enables Organ Sparing and Ultra-High Dose-Rate Delivery: Proof of Principle in Recurrent Head and Neck Cancer.

Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared dosimetry and dose rate coverage between PBS Bragg peak FLASH and PBS transmission FLASH in head and neck reirradiation. PBS Bragg peak FLASH plans were created via the highest beam single energy, range shifter, and range compensator, and were compared to PBS transmission FLASH plans for 6 GyE/fraction and 10 GyE/fraction in eight recurrent head and neck patients originally treated with quad shot reirradiation (14.8/3.7 CGE). The 6 GyE/fraction and 10 GyE/fraction plans were also created using conventional-rate intensity-modulated proton therapy techniques. PBS Bragg peak FLASH, PBS transmission FLASH, and conventional plans were compared for OAR sparing, FLASH dose rate coverage, and target coverage. All FLASH OAR V40 Gy/s dose rate coverage was 90-100% at 6 GyE and 10 GyE for both FLASH modalities. PBS Bragg peak FLASH generated dose volume histograms (DVHs) like those of conventional therapy and demonstrated improved OAR dose sparing over PBS transmission FLASH. All the modalities had similar CTV coverage. PBS Bragg peak FLASH can deliver conformal, ultra-high dose rate FLASH with a two-millisecond delivery of the minimum MU per spot. PBS Bragg peak FLASH demonstrated similar dose rate coverage to PBS transmission FLASH with improved OAR dose-sparing, which was more pronounced in the 10 GyE/fraction than in the 6 GyE/fraction. This feasibility study generates hypotheses for the benefits of FLASH in head and neck reirradiation and developing biological models.