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The presence of artificial implants complicates the delivery of proton therapy due to inaccurate characterization of both the implant and the surrounding tissues. In this work, we describe a method to characterize implant and human tissue mimicking materials in terms of relative stopping power (RSP) using a novel proton counting detector. Each proton is tracked by directly measuring the deposited energy along the proton track using a fast, pixelated spectral detector AdvaPIX-TPX3 (TPX3). We considered three scenarios to characterize the RSPs. First, in-air measurements were made in the presence of metal rods (Al, Ti and CoCr) and bone. Then, measurements of energy perturbations in the presence of metal implants and bone in an anthropomorphic phantom were performed. Finally, sampling of cumulative stopping power (CSP) of the phantom were made at different locations of the anthropomorphic phantom. CSP and RSP information were extracted from energy spectra at each beam path. To quantify the RSP of metal rods we used the shift in the most probable energy (MPE) of CSP from the reference CSP without a rod. Overall, the RSPs were determined as 1.48, 2.06, 3.08, and 5.53 from in-air measurements; 1.44, 1.97, 2.98, and 5.44 from in-phantom measurements, for bone, Al, Ti and CoCr, respectively. Additionally, we sampled CSP for multiple paths of the anthropomorphic phantom ranging from 18.63 to 25.23 cm deriving RSP of soft tissues and bones in agreement within 1.6% of TOPAS simulations. Using minimum error of these multiple CSP, optimal mass densities were derived for soft tissue and bone and they are within 1% of vendor-provided nominal densities. The preliminary data obtained indicates the proposed novel method can be used for the validation of material and density maps, required by proton Monte Carlo Dose calculation, provided by competing multi-energy computed tomography and metal artifact reduction techniques.

Purpose: Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties., Methods: A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm 2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation., Results: The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT., Conclusions: The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement., (© 2020 American Association of Physicists in Medicine.)

Purpose: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites., Methods: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP)., Results: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%)., Conclusions: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability., (© 2018 American Association of Physicists in Medicine.)

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., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

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.

Purpose: In this study, we investigated computationally and experimentally a hexagonal‐pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics. Methods: An optimized minibeam arrangement is one that would produce high peak‐to‐valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal‐pattern array of minibeams by collimating the proton pencil beams through the 1–3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center‐to‐center (c‐t‐c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC). Results: Optimized hexagonal‐pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread‐out‐Bragg‐peak (SOBP) over the depth of 10–14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to ~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c‐t‐c distance, we delivered 1.72 Gy at SOBP for 7.2 × 7.2 × 4 cm3 volume in 48 s. Conclusions: We conclude that it is feasible to implement the optimized hexagonal‐pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable. [ABSTRACT FROM AUTHOR]

Purpose: To commission an open source Monte Carlo (MC) dose engine, "MCsquare" for a synchrotron‐based proton machine, integrate it into our in‐house C++‐based I/O user interface and our web‐based software platform, expand its functionalities, and improve calculation efficiency for intensity‐modulated proton therapy (IMPT). Methods: We commissioned MCsquare using a double Gaussian beam model based on in‐air lateral profiles, integrated depth dose of 97 beam energies, and measurements of various spread‐out Bragg peaks (SOBPs). Then we integrated MCsquare into our C++‐based dose calculation code and web‐based second check platform "DOSeCHECK." We validated the commissioned MCsquare based on 12 different patient geometries and compared the dose calculation with a well‐benchmarked GPU‐accelerated MC (gMC) dose engine. We further improved the MCsquare efficiency by employing the computed tomography (CT) resampling approach. We also expanded its functionality by adding a linear energy transfer (LET)‐related model‐dependent biological dose calculation. Results: Differences between MCsquare calculations and SOBP measurements were <2.5% (<1.5% for ~85% of measurements) in water. The dose distributions calculated using MCsquare agreed well with the results calculated using gMC in patient geometries. The average 3D gamma analysis (2%/2 mm) passing rates comparing MCsquare and gMC calculations in the 12 patient geometries were 98.0 ± 1.0%. The computation time to calculate one IMPT plan in patients' geometries using an inexpensive CPU workstation (Intel Xeon E5‐2680 2.50 GHz) was 2.3 ± 1.8 min after the variable resolution technique was adopted. All calculations except for one craniospinal patient were finished within 3.5 min. Conclusions: MCsquare was successfully commissioned for a synchrotron‐based proton beam therapy delivery system and integrated into our web‐based second check platform. After adopting CT resampling and implementing LET model‐dependent biological dose calculation capabilities, MCsquare will be sufficiently efficient and powerful to achieve Monte Carlo‐based and LET‐guided robust optimization in IMPT, which will be done in the future studies. [ABSTRACT FROM AUTHOR]

Purpose: For pencil‐beam scanning proton therapy systems, in‐air non‐Gaussian halo can significantly impact output at small field sizes and low energies. Since the low‐intensity tail of spot profile (halo) is not necessarily modeled in treatment planning systems (TPSs), this can potentially lead to significant differences in patient dose distribution. In this work, we report such impact for a Varian ProBeam system. Methods: We use a pair magnification technique to measure two‐dimensional (2D) spot profiles of protons from 70 to 242 MeV at the treatment isocenter and 30 cm upstream of the isocenter. Measurements are made with both Gafchromic film and a scintillator detector coupled to a CCD camera (IBA Lynx). Spot profiles are measured down to 0.01% of their maximum intensity. Field size factors (FSFs) are compared among calculation using measured 2D profiles, calculation using a clinical treatment planning algorithm (Raystation 8A clinical Monte Carlo), and a CC04 small‐volume ion chamber. FSFs were measured for square fields of proton energies ranging from 70 to 242 MeV. Results: All film and Lynx measurements agree within 1 mm for full width at half maximum beam intensity. The measured radial spot profiles disagree with simple Gaussian approximations, which are used for modeling in the TPS. FSF measurements show the magnitude of disagreements between beam output in reality and in the TPS without modeling halo. We found that the clinical TPS overestimated output by as much as 6% for small field sizes of 2 cm at the lowest energy of 70 MeV while the film and Lynx measurements agreed within 4% and 1%, respectively, for this FSF. Conclusions: If the in‐air halo for low‐energy proton beams is not fully modeled by the TPS, this could potentially lead to under‐dosing small, shallow treatment volumes in PBS treatment plans. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the glass dosimeter suitability as an external audit program in proton therapy beam. A feasibility test of the glass dosimeter postal dose intercomparison was performed for high-energy proton beam use in radiation oncology with the collaboration of five proton therapy centers (Shizuoka Cancer Center, University of Florida Proton Center, MD Anderson Cancer Center, Loma Linda University Medical Center, and University of Pennsylvania School of Medicine). Material and methods: The dosimetric properties of a GD-301 glass dosimeter were investigated for its potential use for postal dosimetry. Measurements were performed in a water phantom using a stair-like holder specially designed for this study. The depth-dose distribution measured with the glass dosimeter was compared to those from GEANT4 Monte-Carlo simulation. The GEANT4 code was also used to simulate the influence of holder material in the absorbed dose by inserting the glass dosimeter in a water phantom within the stair-like holder. We investigated the methodology of the absorbed dose determination with the glass dosimeter system establishing the calibration factor and various correction factors (non-linearity, fading, energy, holder). The participating proton therapy centers were asked to irradiate the glass dosimeter to 2 Gy with similar setup and conditions. Results: The repeatability and dose rate dependence is within 1.2% and 1.5%, respectively. Depth-dose distributions in the pristine Bragg curve and the spread-out Bragg curve were estimated to be within 3%, compared with depth-dose measured with the ionization chamber. The difference in absorbed dose between the glass dosimeter and ionization chamber was within ±2% as a function of proton beam quality, residual ranges were between 2.1 and 9.0 cm. The influence of the holder material in absorbed doses of the proton beams is less than 1%. In the accuracy evaluation of the glass dosimeter system established in blind test, we obtained within 2.5% agreements with the ionization chamber dosimetry for the proton beam. In this feasibility study, the results on the proton beam output check are relatively good within ±6% for all participating centers. Conclusion: We believe that the glass dosimeter system has considerable potential to be used for a postal dose audit program in proton beam. [ABSTRACT FROM AUTHOR]