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

Applications of various range shifters for proton pencil beam scanning radiotherapy

Background A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. Methods Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system. Results A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. Conclusion We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB

Higgs Portal Inflation with Fermionic Dark Matter

We discuss the inflationary model presented in [1], involving a gauge singlet scalar field and fermionic dark matter added to the standard model. Either the Higgs or the singlet scalar could play the role of the inflaton, and slow roll is realized through its non-minimal coupling to gravity. The effective scalar potential is stabilized by the mixing between the scalars as well as the coupling with the fermionic field. Mixing of the two scalars also provides a portal to dark matter. Constraints on the model come from perturbativity and stability, collider searches and dark matter constraints and impose a constraining relationship on the masses of dark matter and scalar fields. Inflationary predictions are generically consistent with current Planck data

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics

Validation and clinical implementation of a full Monte Carlo code for scanned proton pencil beams

Purpose: To present a methodology for commissioning and validating a full Monte Carlo (MC) code (TOPAS/Geant4) for proton pencil beams utilizing a double Gaussian phase space source model and a simplified range shifter implementation. Application of this source model onto an independent fast MC code (MCsquare), and comparison between MC simulations with analytical treatment planning system (TPS) are investigated. Methods: The phase space parameters and protons per MU were extracted and tuned without simulating any components of the nozzle by comparing TOPAS simulations with a series of commissioning measurements. The beam model was validated by comprehensive measurements of single spots, field size factors (FSF) and three dimensional dose distributions of Spread Out Bragg Peaks (SOBPs) both without and with range shifter. To demonstrate the application, this source model was directly implemented into a fast, dedicated PBS MC code, MCsquare. Clinical treatment cases were compared between TOPAS, MCsquare and our commercial treatment planning system. Results: Based on comprehensive comparison with measurements, TOPAS was validated for all aspects. The difference in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2%, indicating an accurate source modeling with and without a range shifter. Comparison of two dimensional dose distributions and DVHs for representative liver case and lung case between MC and analytical calculations (TPS) highlights limitations in the TPS dose calculation in situations of highly heterogeneous geometries. Conclusions: We have proposed a universal method to model a proton PBS dedicated nozzle, with better addressing the halo inherent from nozzle and simplified implementation of a range shifter, using acceptance and commissioning measurements. We compared patient treatments between two MC codes and analytical calculations to show this tool can be implemented clinically to provide an independent dose calculation algorithm for patient specific QA and for benchmarking other dose calculation engines under development

Assessing the clinical impact of TPS dose calculation for proton PBS treatment using fast Monte Carlo algorithm

The impact of approximated analytical dose calculation (ADC), often used in TPS, on the proton PBS treatment plan quality was assessed using an open-source fast Monte Carlo (MC) code, MCsquare. Firstly, MCsquare was commissioned and validated using water and tissue-mimicking phantom measurements as well as benchmarked with the general purpose MC application TOPAS for various representative patient cases. Both MC codes enabled to dramatically improve the dose calculation in the IROC lung phantom with respect to ADC. Indeed, the gamma-index analysis (7%/5mm) passing rate increased from below 85%, to over 93%. Figure1 compares the 1-dimensional dose profiles through the center of the PTV between simulation and film measurements. Second, a total of 50 patients were investigated with 10 patients per site (liver, pelvis, brain, H&N and lung) by comparing dose distributions between ADC and MCsquare. Differences were evaluated using DVH indicators, estimations of tumor control probability (TCP) and a gamma-index analysis as shown in Figure2. Generally, the impact of approximated ADC on the plan quality increases with the tissue heterogeneities. ADC overestimated the target doses on average by up to 1.7% for lung patients. The D95 were predicted within 6.5%, while D02 and V90 within 2.9% of the MC dose. Dose differences can result in large TCP differences for lung (<10.5%), head and neck (<7.5%), and small differences for brain (<2.5%), pelvis and liver (<1.5%). Establishment of fast MC calculation can facilitate patient plan reviews at any institution given the accuracy, speed and availability of the open source dedicated MC

Assessment of Clinical Impact of Analytical Dose Calculation in TPS for Proton PBS Treatment Using Fast Monte Carlo Simulation

Purpose/Objective(s): The limited accuracy of analytical dose calculation algorithms (ADC) currently used in commercial TPS will lead to dose degradation for proton treatment plan. Monte Carlo dose calculation (MDC) is generally superior to ADC to model the dose distribution especially for lung and head/neck patients where high heterogeneity involves. The purpose of this study is to provide a validated and fast Monte Carlo (FMC) code to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites. Materials/Methods: First, FMC was commissioned and validated using water and tissue-mimicking lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS. Then a comparative analysis between FMC and ADC were performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head and neck, lung). Differences between FMC and ADC were evaluated using dosimetric indices (target Dmean, D95, homogeneity index, V90) based on dose-volume histogram analysis, a 3D gamma-index (3%/3mm) analysis, and estimations of tumor control probability (TCP). Results: The FMC significantly reduced the calculation time from tens of hours for TOPAS to less than 15mins based on our workstation resource. Both FMC and TOPAS dramatically improved the gamma-index (7%/5mm) passing rate between simulation and 2D film measurements using the lung phantom from below the passing threshold of 85% for ADC to over 93%. Comparison between FMC and TOPAS for selected 20 patients covering 5 sites showed less than 1.7% difference for all the dosimetric indices/TCP value and larger than 99% for the 3D gamma-index passing rate of the target. Generally, through investigations of the difference between ADC and FMC for 50 patients, we found that the impact of approximations in ADC on the plan quality increases from site liver, pelvis, brain, head and neck, to lung, as the degree of tissue heterogeneity increases. The D95s were predicted within 6.5% of the corresponding FMC statistic, while the V90s were within 2.9%. The median gamma-index passing rate for target volumes decreased from 99.3% for liver to 75.8% for long. Dose differences can result in large TCP differences for lung (<10.5%) and head and neck (<7.5%), with smaller differences seen for brain (<2.5%), pelvis and liver (<1.5%). Conclusions: The establishment of the FMC can facilitate patient plan reviews at any institution and avoiding unbiased comparison in clinical trials given its accuracy, speed and open source availability. Comparison between our FMC and ADC for 50 patients indicates that current ADC lead to under-dosage of the target by as much as 4.2%, resulting in differences in TCP of up to 10%. More accurate dose calculation algorithm like Monte Carlo simulations may be necessary in proton therapy especially for high heterogeneous sites, such as head and neck, lung

Evaluation of Motion Mitigation Using Abdominal Compression in the Clinical Implementation of Pencil Beam Scanning Proton Therapy of Liver Tumors

Purpose: To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion. Methods: Four-dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy-proven motion reduction by AC. For each scan, the motion amplitudes and the motion-induced variation of water equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam-specific planning target volume (BSPTV). M₈₀ and ΔWET₈₀ derived from the 80ᵗʰ percentiles of motion amplitude (M) and ΔWET were compared with and without AC. Proton plans were created on the average CT. 4D dynamic dose calculation was performed post plan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment. Results: AC resulted in reductions in mean Liver-GTV dose, M, ΔWET, and BSPTV volumes and improved dose degradation (ΔD₉₅ and ΔD₁) within the CTV. For small motion (M₈₀ 10 mm or ΔWET₈₀ > 7 mm), AC and/or some other form of mitigation strategies were required. Conclusion: A workflow for screening patients’ motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion