Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy.

Purpose. To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS).Methods and materials. A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4-43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC.Results. In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly 'trial-and-error' optimization procedure took only 71.4 s on average for the selected three patients.Conclusion. VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy.

Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 cc with range of 0.4 - 43.3 cc). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC. Results: In the water phantoms, 3D gamma passing rate (2%/2mm/10%) between VPMC and MCsquare was 99.71±0.23%. In the patient geometries, 3D gamma passing rates (3%/2mm/10%) between VPMC/MCsquare and RayStation MC were 97.79±2.21%/97.78±1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45±114.08 seconds (MCsquare) to 8.20±6.42 seconds (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 seconds and the subsequent on-the-fly "trial-and-error" optimization procedure took only 71.4 seconds on average for the selected three patients. Conclusion: VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

GPU-accelerated Monte Carlo-based online adaptive proton therapy: A feasibility study.

PURPOSE: To develop an online graphic processing unit (GPU)-accelerated Monte Carlo-based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS. METHODS AND MATERIALS: A four-step workflow was developed using our in-house developed GPU-accelerated Monte Carlo-based treatment planning system to implement online Monte Carlo-based ART for PBS. The first step conducts diffeomorphic demon-based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two-stage (before and after delivery) patient-specific quality assurance (PSQA) of the reoptimized plan. The before-delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open-source Monte Carlo code, MCsquare. The after-delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS. RESULTS: For all three patients, the propagated contours were found to have good volume conformance [JI (lowest-highest: 0.833-0.983) and DSC (0.909-0.992)] but suboptimal boundary coincidence [HD (2.37-20.76 mm)] for organs-at-risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention. CONCLUSION: The proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.

Technical Note: Multiple energy extraction techniques for synchrotron-based proton delivery systems may exacerbate motion interplay effects in lung cancer treatments.

PURPOSE: The multiple energy extraction (MEE) delivery technique for synchrotron-based proton delivery systems reduces beam delivery time by decelerating the beam multiple times during one accelerator spill, but this might cause additional plan quality degradation due to intrafractional motion. We seek to determine whether MEE causes significantly different plan quality degradation compared to single energy extraction (SEE) for lung cancer treatments due to the interplay effect. METHODS: Ten lung cancer patients treated with IMPT at our institution were nonrandomly sampled based on a representative range of tumor motion amplitudes, tumor volumes, and respiratory periods. Dose-volume histogram (DVH) indices from single-fraction SEE and MEE four-dimensional (4D) dynamic dose distributions were compared using the Wilcoxon signed-rank test. Distributions of monitor units (MU) to breathing phases were investigated for features associated with plan quality degradation. SEE and MEE DVH indices were compared in fractionated deliveries of the worst-case patient treatment scenario to evaluate the impact of fractionation. RESULTS: There were no clinically significant differences in target mean dose, target dose conformity, or dose to organs-at-risk between SEE and MEE in single-fraction delivery. Three patients had significantly worse dose homogeneity with MEE compared to SEE (single-fraction mean D5% -D95% increased by up to 9.6% of prescription dose), and plots of MU distribution to breathing phases showed synchronization patterns with MEE but not SEE. However, after 30 fractions the patient in the worst-case scenario had clinically acceptable target dose homogeneity and coverage with MEE (mean D5% -D95% increased by 1% compared to SEE). CONCLUSIONS: For some patients with breathing periods close to the mean spill duration, MEE resulted in significantly worse single-fraction target dose homogeneity compared to SEE due to the interplay effect. However, this was mitigated by fractionation, and target dose homogeneity and coverage were clinically acceptable after 30 fractions with MEE.

A method for quantitative evaluations of scanning-proton dose distributions.

PURPOSE: Patient-Specific Quality Assurance (PSQA) measurement analysis depends on generating metrics representative of calculation and measurement agreement. Considering the heightened capability of discrete spot scanning protons to modulate individual dose voxels, a dose plane comparison approach that maintained all of the capabilities of the well-established γ test, but that also provided a more intuitive error parameterization, was desired. METHODS: Analysis was performed for 300 dose planes compared by searching all calculated points within a fixed radius around each measured pixel to determine the dose deviation. Dose plane agreement is reported as the dose difference minimum (DDM) within an empirically established search radius: ΔDmin(r). This per-pixel metric is aggregated into a histogram binned by dose deviation. Search-radius criteria were based on a weighted-beamlet 3σ spatial deviation from imaging isocenter. Equipment setup error was mitigated during analysis using tracked image registration, ensuring beamlet deviations to be the dominant source of spatial error. The percentage of comparison points with <3% dose difference determined pass rate. RESULTS: The mean beamlet radial deviation was 0.38mm from x-ray isocenter, with a standard deviation of 0.19mm, such that 99.9% of relevant pencil beams were within 1 mm of nominal. The dose-plane comparison data showed no change in passing rate between a 3%/1mm ΔDmin(r) analysis (97.6 +/- 3.6%) and a 3%/2mm γ test (97.7 +/- 3.2%). CONCLUSIONS: PSQA dose-comparison agreements corresponding to a search radius outside of machine performance limits are likely false positives. However, the elliptical shape of the γ test is too dose-restrictive with a spatial-error threshold set at 1 mm. This work introduces a cylindrical search shape, proposed herein as more relevant to plan quality, as part of the new DDM planar-dose comparison algorithm. DDM accepts all pixels within a given dose threshold inside the search radius, and carries forward plan-quality metrics in a straightforward manner for evaluation.

Clinical Validation of a Ray-Casting Analytical Dose Engine for Spot Scanning Proton Delivery Systems.

PURPOSE: To describe and validate the dose calculation algorithm of an independent second-dose check software for spot scanning proton delivery systems with full width at half maximum between 5 and 14 mm and with a negligible spray component. METHODS: The analytical dose engine of our independent second-dose check software employs an altered pencil beam algorithm with 3 lateral Gaussian components. It was commissioned using Geant4 and validated by comparison to point dose measurements at several depths within spread-out Bragg peaks of varying ranges, modulations, and field sizes. Water equivalent distance was used to compensate for inhomogeneous geometry. Twelve patients representing different disease sites were selected for validation. Dose calculation results in water were compared to a fast Monte Carlo code and ionization chamber array measurements using dose planes and dose profiles as well as 2-dimensional-3-dimensional and 3-dimensional-3-dimensional γ-index analysis. Results in patient geometry were compared to Monte Carlo simulation using dose-volume histogram indices, 3-dimensional-3-dimensional γ-index analysis, and inpatient dose profiles. RESULTS: Dose engine model parameters were tuned to achieve 1.5% agreement with measured point doses. The in-water γ-index passing rates for the 12 patients using 3%/2 mm criteria were 99.5% ± 0.5% compared to Monte Carlo. The average inpatient γ-index analysis passing rate compared to Monte Carlo was 95.8% ± 2.9%. The average difference in mean dose to the clinical target volume between the dose engine and Monte Carlo was -0.4% ± 1.0%. For a typical plan, dose calculation time was 2 minutes on an inexpensive workstation. CONCLUSIONS: Following our commissioning process, the analytical dose engine was validated for all treatment sites except for the lung or for calculating dose-volume histogram indices involving point doses or critical structures immediately distal to target volumes. Monte Carlo simulations are recommended for these scenarios.

Automation of routine elements for spot-scanning proton patient-specific quality assurance.

PURPOSE: At our institution, all proton patient plans undergo patient-specific quality assurance (PSQA) prior to treatment delivery. For intensity-modulated proton beam therapy, quality assurance is complex and time consuming, and it may involve multiple measurements per field. We reviewed our PSQA workflow and identified the steps that could be automated and developed solutions to improve efficiency. METHODS: We used the treatment planning system's (TPS) capability to support C# scripts to develop an Eclipse scripting application programming interface (ESAPI) script and automate the preparation of the verification phantom plan for measurements. A local area network (LAN) connection between our measurement equipment and shared database was established to facilitate equipment control, measurement data transfer, and storage. To improve the analysis of the measurement data, a Python script was developed to automatically perform a 2D-3D γ-index analysis comparing measurements in the plane of a two-dimensional detector array with TPS predictions in a water phantom for each acquired measurement. RESULTS: Device connection via LAN granted immediate access to the plan and measurement information for downstream analysis using an online software suite. Automated scripts applied to verification plans reduced time from preparation steps by at least 50%; time reduction from automating γ-index analysis was even more pronounced, dropping by a factor of 10. On average, we observed an overall time savings of 55% in completion of the PSQA per patient plan. CONCLUSIONS: The automation of the routine tasks in the PSQA workflow significantly reduced the time required per patient, reduced user fatigue, and frees up system users from routine and repetitive workflow steps allowing increased focus on evaluating key quality metrics.

Multiple energy extraction reduces beam delivery time for a synchrotron-based proton spot-scanning system.

PURPOSE: Multiple energy extraction (MEE) is a technology that was recently introduced by Hitachi for its spot-scanning proton treatment system, which allows multiple energies to be delivered in a single synchrotron spill. The purpose of this paper is to investigate how much beam delivery time (BDT) can be reduced with MEE compared with single energy extraction (SEE), in which one energy is delivered per spill. METHODS AND MATERIALS: A recently developed model based on BDT measurements of our synchrotron's delivery performance was used to compute BDT. The total BDT for 2694 beam deliveries in a cohort of 79 patients treated at our institution was computed in both SEE and 9 MEE configurations to determine BDT reduction. The cohort BDT reduction was also calculated for hypothetical accelerators with increased deliverable charge and compared with the results of our current delivery system. RESULTS: A vendor-provided MEE configuration with 4 energy layers per spill reduced the total BDT on average by 35% (41 seconds) compared with SEE, with up to 65% BDT reduction for individual fields. Adding an MEE layer reduced the total BDT by <1% of SEE BDT. However, improving charge recapture efficiency increased BDT savings by up to 42% of SEE BDT. CONCLUSIONS: The MEE delivery technique reduced the total BDT by 35%. Increasing the charge per spill and charge recapture efficiency is necessary to further reduce BDT and thereby take full advantage of our MEE system's potential to improve treatment delivery efficiency and operational throughput.

Technical Note: An efficient daily QA procedure for proton pencil beam scanning.

PURPOSE: The aim of this work was to develop an efficient daily quality assurance (QA) program with strict tolerance levels for pencil beam scanning (PBS) proton radiotherapy featuring simultaneous dosimetric testing on a single, nonuniform field. METHODS: A nonuniform field measuring beam output, proton range, and spot position was designed for delivery onto a Sun Nuclear Daily-QA 3 device. A custom acrylic block permitted simultaneous measurement of low- and high-energy proton ranges in addition to beam output. Sensitivities to output, range, and spot position were evaluated to quantitate the device's response. Reproducibility tests were used to identify and control sources of measurement error as well as to assess the QA procedure's robustness. This procedure was implemented in each of our four treatment rooms independently; 4-6 months of daily QA measurements were collected. RESULTS: The 1% output, 0.5 mm range, and 1.5 mm spot position tolerances derived from preliminary tests were tighter overall than tolerances found in the literature and equivalent to the limits used for proton system commissioning. The simplicity and automation of the procedure reduced the time required for daily QA to 10 min per treatment room, and competition for beam between multiple treatment rooms was minimized. CONCLUSIONS: An efficient daily PBS QA procedure can be performed using a single, nonuniform field on a nondedicated QA device. A thorough quantitation of the device's response and careful control of measurement uncertainties allowed daily tolerances to match commissioning standards.

Use of a radial projection to reduce the statistical uncertainty of spot lateral profiles generated by Monte Carlo simulation.

Monte Carlo (MC) simulation has been used to generate commissioning data for the beam modeling of treatment planning system (TPS). We have developed a method called radial projection (RP) for postprocessing of MC-simulation-generated data. We used the RP method to reduce the statistical uncertainty of the lateral profile of proton pencil beams with axial symmetry. The RP method takes advantage of the axial symmetry of dose distribution to use the mean value of multiple independent scores as the representative score. Using the mean as the representative value rather than any individual score results in substantial reduction in statistical uncertainty. Herein, we present the concept and step-by-step implementation of the RP method, as well as show the advantage of the RP method over conventional measurement methods for generating lateral profile. Lateral profiles generated by both methods were compared to demonstrate the uncertainty reduction qualitatively, and standard error comparison was performed to demonstrate the reduction quantitatively. The comparisons showed that statistical uncertainty was reduced substantially by the RP method. Using the RP method to postprocess MC data, the corresponding MC simulation time was reduced by a factor of 10 without quality reduction in the generated result from the MC data. We concluded that the RP method is an effective technique to increase MC simulation efficiency for generating lateral profiles for axially symmetric pencil beams.

Using field size factors to characterize the in-air fluence of a proton machine with a range shifter.

INTRODUCTION: The range shifter (RS) is used to treat shallow tumors for a proton pencil beam scanning system (PBS). Adding RS certainly complicates the commissioning of the treatment planning system (TPS) because the spot sizes are significantly enlarged with RS. In this work, we present an efficient method to configure a commercial TPS for a PBS system with a fixed RS. METHODS: By combining a spiral delivery with customized control points, we were able to significantly improve measurement efficiency and obtain 250 field size factors (FSF) within three hours. The measured FSFs were used to characterize the proton fluence and fit the parameters for the double-Gaussian fluence model used in the TPS. Extensive validation was performed using FSFs measured in air and in water, absolute doses of spread-out Bragg peak (SOBP) fields, and the dose measurements carried out for patient-specific quality assurance (QA). RESULTS: The measured in-air FSFs agreed with the model's prediction within 3% for all 250 FSFs, and within 2 for 94% of the FSFs. The agreement between model's prediction and measurement was within 2% for the in-air and in-water FSFs and the absolute doses for SOBP beams. The patient-specific QA of 113 fields showed an excellent gamma passing rates (96.95 ± 2.51%) for the absolute dose comparisons with gamma criteria of 2 mm and 2%. CONCLUSION: The excellent agreement between the model's prediction and measurements proved the efficiency and accuracy of the proposed method of using FSFs to characterize the proton fluence and configure the TPS for a PBS system with fixed RS.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer.

PURPOSE: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. METHODS AND MATERIALS: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered. In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. RESULTS: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D95% CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D5%-D95% CTV: 10.3 vs 17.7, respectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D95% CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. CONCLUSIONS: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.

Impact of range shifter material on proton pencil beam spot characteristics.

PURPOSE: To quantitatively investigate the effect of range shifter materials on single-spot characteristics of a proton pencil beam. METHODS: An analytic approximation for multiple Coulomb scattering ("differential Moliere" formula) was adopted to calculate spot sizes of proton spot scanning beams impinging on a range shifter. The calculations cover a range of delivery parameters: six range shifter materials (acrylonitrile butadiene styrene, Lexan, Lucite, polyethylene, polystyrene, and wax) and water as reference material, proton beam energies ranging from 75 to 200 MeV, range shifter thicknesses of 4.5 and 7.0 g/cm(2), and range shifter positions from 5 to 50 cm. The analytic method was validated by comparing calculation results with the measurements reported in the literature. RESULTS: Relative to a water-equivalent reference, the spot size distal to a wax or polyethylene range shifter is 15% smaller, while the spot size distal to a range shifter made of Lexan or Lucite is about 6% smaller. The relative spot size variations are nearly independent of beam energy and range shifter thickness and decrease with smaller air gaps. CONCLUSIONS: Among the six material investigated, wax and polyethylene are desirable range shifter materials when the spot size is kept small. Lexan and Lucite are the desirable range shifter materials when the scattering power is kept similar to water.

Intensity modulated proton therapy for craniospinal irradiation: organ-at-risk exposure and a low-gradient junctioning technique.

PURPOSE: To compare field junction robustness and sparing of organs at risk (OARs) during craniospinal irradiation (CSI) using intensity modulated proton therapy (IMPT) to conventional passively scattered proton therapy (PSPT). METHODS AND MATERIALS: Ten patients, 5 adult and 5 pediatric patients, previously treated with PSPT-based CSI were selected for comparison. Anterior oblique cranial fields, using a superior couch rotation, and posterior spinal fields were used for IMPT planning. To facilitate low-gradient field junctioning along the spine, the inverse-planning IMPT technique was divided into 3 stages. Dose indices describing target coverage and normal tissue dose, in silico error modeling, and film dosimetry were used to assess plan quality. RESULTS: Field junction robustness along the spine was improved using the staged IMPT planning technique, reducing the worst case impact of a 4-mm setup error from 25% in PSPT to <5% of prescription dose. This was verified by film dosimetry for clinical delivery. Exclusive of thyroid dose in adult patients, IMPT plans demonstrated sparing of organs at risk as good or better than PSPT. Coverage of the cribriform plate for pediatric (V95% [percentage of volume of the target receiving at least 95% of the prescribed dose]; 87 ± 11 vs 92 ± 7) and adult (V95%; 94 ± 7 vs 100 ± 1) patients and the clinical target in pediatric (V95%; 98 ± 2 vs 100 ± 1) and adult (V95%; 100 ± 1 vs 100 ± 1) patients for PSPT and IMPT plans, respectively, were comparable or improved. For adult patients, IMPT target dose inhomogeneity was increased, as determined by heterogeneity index (HI) and inhomogeneity coefficient (IC). IMPT lowered maximum spinal cord dose, improved spinal dose homogeneity, and reduced exposure to other OARs. CONCLUSIONS: IMPT has the potential to improve CSI plan quality and the homogeneity of intrafractional dose at match lines. The IMPT approach developed may also simplify treatments and reduce workload per patient relative to PSPT.