LITE SABR M1: Planning design and dosimetric endpoints for a phase I trial of lattice SBRT.

PURPOSE: Lattice stereotactic body radiation therapy (SBRT) is a form of spatially fractionated radiation therapy (SFRT) using SBRT methods. This study reports clinical dosimetric endpoints achieved for Lattice SBRT plans delivering 20 Gy in 5 fractions to the periphery of a tumor with a simultaneous integrated boost (SIB) of 66.7 Gy, as part of a prospective Phase I clinical trial (NCT04133415). Additionally, it updates previously reported planning and delivery techniques based on extended experience with a broader patient population. METHODS: Patients were enrolled on a single-arm phase I trial conducted between November 2019 and August 2020. Eligibility was restricted to tumors >4.5 cm in the largest dimension. Characteristic SFRT dose gradients were achieved using a lattice of 1.5 cm diameter spheres spaced within the GTV in a regular pattern, with peak-to-valley dose varying from 66.7 Gy to 20 Gy within 1.5 cm. Organ-at-risk (OAR) sparing followed AAPM TG101 recommendations for 5-fraction SBRT. RESULTS: Twenty patients (22 plans) were enrolled on study, with one additional plan treated off study. All OAR and target coverage planning objectives were achieved, with the exception of a single small bronchus. Conformity of the 20 Gy isodose line significantly improved over the course of the study. The majority (85.2%) of treatment fractions were delivered in a 30 minutes timeslot, with 4 (3.5%) exceeding a total treatment time of 40 minutes. CONCLUSION: Lattice SBRT planning techniques produce consistent and efficient treatment plans. Refined techniques described here further improve the quality of the planning technique.

Evaluation of Motion Compensation Methods for Noninvasive Cardiac Radioablation of Ventricular Tachycardia.

PURPOSE: Noninvasive cardiac radioablation is increasingly used for treatment of refractory ventricular tachycardia. Attempts to limit normal tissue exposure are important, including managing motion of the target. An interplay between cardiac and respiratory motion exists for cardiac radioablation, which has not been studied in depth. The objectives of this study were to estimate target motion during abdominal compression free breathing (ACFB) and respiratory gated (RG) deliveries and to investigate the quality of either implanted cardioverter defibrillator lead tip or the diaphragm as a gating surrogate. METHODS AND MATERIALS: Eleven patients underwent computed tomography (CT) simulation with an ACFB 4-dimensional CT (r4DCT) and an exhale breath-hold cardiac 4D-CT (c4DCT). The target, implanted cardioverter defibrillator lead tip and diaphragm trajectories were measured for each patient on the r4DCT and c4DCT using rigid registration of each 4D phase to the reference (0%) phase. Motion ranges for ACFB and exhale (40%-60%) RG delivery were estimated from the target trajectories. Surrogate quality was estimated as the correlation with the target motion magnitudes. RESULTS: Mean (range) target motion across patients from r4DCT was as follows: left/right (LR), 3.9 (1.7-6.9); anteroposterior (AP), 4.1 (2.2-5.4); and superoinferior (SI), 4.7 (2.2-7.9) mm. Mean (range) target motion from c4DCT was as follows: LR, 3.4 (1.0-4.8); AP, 4.3 (2.6-6.5); and SI, 4.1 (1.4-8.0) mm. For an ACFB, treatment required mean (range) margins to be 4.5 (3.1-6.9) LR, 4.8 (3-6.5) AP, and 5.5 (2.3-8.0) mm SI. For RG, mean (range) internal target volume motion would be 3.6 (1.1-4.8) mm LR, 4.3 (2.6-6.5) mm AP, and 4.2 (2.2-8.0) mm SI. The motion correlations between the surrogates and target showed a high level of interpatient variability. CONCLUSIONS: In ACFB patients, a simulated exhale-gated approach did not lead to large projected improvements in margin reduction. Furthermore, the variable correlation between readily available gating surrogates could mitigate any potential advantage to gating and should be evaluated on a patient-specific basis.

A Monte Carlo based analytic model of the in-room neutron ambient dose equivalent for a Mevion gantry-mounted passively scattered proton system.

The goal of this study was to develop a Monte Carlo (MC)-based analytical model that can predict the in-room ambient dose equivalent from a Mevion gantry-mounted passively scattered proton system. The Mevion S250 and treatment vault were simulated using the MCNPX MC code. The results of the in-room neutron dose measurements, using an FHT 762 WENDI-II detector, were employed to benchmark the MC-derived values. After tuning the MCNPX MC code, for the same beam delivery parameters, the code was used to calculate the neutron spectra and ambient dose equivalent in the vault and at varying angles from the isocenter. Then, based on the calculations, an analytical model was reconstructed and data were fitted to derive the model parameters at 95% confidence intervals (CI). The MCNPX codes were tuned to within about 19% of the measured values for most of the measurements in the vault. For the maze, up to 0.08 mSv Gy-1 discrepancies were found between the experimental measurements and MCNPX calculated results. The analytical model showed up to 18% discrepancy for distances between 100 and 600 cm from the isocenter compared to the MC calculations. The model may underestimate the neutron ambient dose equivalent up to 21% for distances less than 100 cm from the isocenter. The proposed analytical model can be used to estimate the contribution of the secondary neutron dose from the Mevion S250 for the design of local shielding inside the proton therapy treatment vault.

A Monte Carlo-based analytic model of neutron dose equivalent for a mevion gantry-mounted passively scattered proton system for craniospinal irradiation.

PURPOSE: To calculate in- and out-of-field neutron spectra and dose equivalent, using Monte Carlo (MC) simulation, for a Mevion gantry-mounted passively scattered proton system in craniospinal irradiation. An analytical model based on the MC calculations that estimates in- and out-of-field neutron dose equivalent from proton Craniospinal irradiation (CSI) was also developed. METHODS: The MCNPX MC code was used to simulate a Mevion S250 proton therapy system. The simulated proton depth doses and profiles for pristine and spread-out Bragg peaks were benchmarked against the measured data. Previous measurements using extended-range Bonner spheres were used to verify the calculated neutron spectra and dose equivalent. Using the benchmarked results as a reference condition, a correction-based analytical model was reconstructed by fitting the data to derive model parameters at 95% confidence interval. Sensitivity analysis of brass aperture opening, thickness of the Lucite (PMMA) range compensator, and modulation width was performed to obtain correction parameters for nonreference conditions. RESULTS: For the neutron dose equivalent per therapeutic proton dose, the MCNPX calculated dose equivalent matched the measured values to within 8%. The benchmarked neutron dose equivalent at the isocenter was 41.2 and 20.8 mSv/Gy, for cranial and spinal fields, respectively. For in- and out-of-field neutron dose calculations, the correction-based analytical model showed up to 17% discrepancy compared to the MC calculations. The correction factors may provide a conservative estimation of neutron dose, especially for depth ≤ 5 cm and regions underneath the brass aperture. CONCLUSION: The proposed analytical model can be used to estimate the contribution of the neutron dose to the overall CSI treatment dose. Moreover, the model can be employed to estimate the neutron dose to the implantable cardiac electronic devices.

Evaluation of a new secondary dose calculation software for Gamma Knife radiosurgery.

Current available secondary dose calculation software for Gamma Knife radiosurgery falls short in situations where the target is shallow in depth or when the patient is positioned with a gamma angle other than 90°. In this work, we evaluate a new secondary calculation software which utilizes an innovative method to handle nonstandard gamma angles and image thresholding to render the skull for dose calculation. 800 treatment targets previously treated with our GammaKnife Icon system were imported from our treatment planning system (GammaPlan 11.0.3) and a secondary dose calculation was conducted. The agreement between the new calculations and the TPS were recorded and compared to the original secondary dose calculation agreement with the TPS using a Wilcoxon Signed Rank Test. Further comparisons using a Mann-Whitney test were made for targets treated at a 90° gamma angle against those treated with either a 70 or 110 gamma angle for both the new and commercial secondary dose calculation systems. Correlations between dose deviations from the treatment planning system against average target depth were evaluated using a Kendall's Tau correlation test for both programs. The Wilcoxon Signed Rank Test indicated a significant difference in the agreement between the two secondary calculations and the TPS, with a P-value < 0.0001. With respect to patients treated at nonstandard gamma angles, the new software was largely independent of patient setup, while the commercial software showed a significant dependence (P-value < 0.0001). The new secondary dose calculation software showed a moderate correlation with calculation depth, while the commercial software showed a weak correlation (Tau = -.322 and Tau = -.217 respectively). Overall, the new secondary software has better agreement with the TPS than the commercially available secondary calculation software over a range of diverse treatment geometries.

Sensitivity analysis of Monte Carlo model of a gantry-mounted passively scattered proton system.

PURPOSE: This study aimed to present guidance on the correlation between treatment nozzle and proton source parameters, and dose distribution of a passive double scattering compact proton therapy unit, known as Mevion S250. METHODS: All 24 beam options were modeled using the MCNPX MC code. The calculated physical dose for pristine peak, profiles, and spread out Bragg peak (SOBP) were benchmarked with the measured data. Track-averaged LET (LETt ) and dose-averaged LET (LETd ) distributions were also calculated. For the sensitivity investigations, proton beam line parameters including Average Energy (AE), Energy Spread (ES), Spot Size (SS), Beam Angle (BA), Beam Offset (OA), and Second scatter Offset (SO) from central Axis, and also First Scatter (FS) thickness were simulated in different stages to obtain the uncertainty of the derived results on the physical dose and LET distribution in a water phantom. RESULTS: For the physical dose distribution, the MCNPX MC model matched measurements data for all the options to within 2 mm and 2% criterion. The Mevion S250 was found to have a LETt between 0.46 and 8.76 keV.µm-1 and a corresponding LETd between 0.84 and 15.91 keV.µm-1 . For all the options, the AE and ES had the greatest effect on the resulting depth of pristine peak and peak-to-plateau ratio respectively. BA, OA, and SO significantly decreased the flatness and symmetry of the profiles. The LETs were found to be sensitive to the AE, ES, and SS, especially in the peak region. CONCLUSIONS: This study revealed the importance of considering detailed beam parameters, and identifying those that resulted in large effects on the physical dose distribution and LETs for a compact proton therapy machine.

A complete workflow for utilizing Monte Carlo toolkits in clinical cases for a double-scattering proton therapy system.

The methods described in this paper allow end users to utilize Monte Carlo (MC) toolkits for patient-specific dose simulation and perform analysis and plan comparisons for double-scattering proton therapy systems. The authors aim to fill two aspects of this process previously not explicitly published. The first one addresses the modeling of field-specific components in simulation space. Patient-specific compensator and aperture models are exported from treatment planning system and converted to STL format using a combination of software tools including Matlab and Autodesk's Netfabb. They are then loaded into the MC geometry for simulation purpose. The second details a method for easily visualizing and comparing simulated doses with the dose calculated from the treatment planning system. This system is established by utilizing the open source software 3D Slicer. The methodology was demonstrated with a two-field proton treatment plan on the IROC lung phantom. Profiles and two-dimensional (2D) dose planes through the target isocenter were analyzed using our in-house software tools. This present workflow and set of codes can be easily adapted by other groups for their clinical practice.

Shielding verification and neutron dose evaluation of the Mevion S250 proton therapy unit.

For passive scattering proton therapy systems, neutron contamination is the main concern both from an occupational and patient safety perspective. The Mevion S250 compact proton therapy system is the first of its kind, offering an in-room cyclotron design which prompts more concern for shielding assessment. The purpose of this study was to accomplish an in-depth evaluation of both the shielding design and in-room neutron production at our facility using both Monte Carlo simulation and measurement. We found that the shielding in place at our facility is adequate, with simulated annual neutron ambient dose equivalents at 30 cm outside wall/door perimeter ranging from background to 0.07 mSv and measured dose equivalents ranging from background to 0.06 mSv. The in-room measurements reveal that the H*/D decreases when the distance from isocenter and field size increases. Furthermore, the H*/D generally increases when the angle around isocenter increases. Our results from in-room measurements show consistent trends with our Monte Carlo model of the Mevion system.

Investigation on Patient/Compensator Scatter Factor for Monitor Unit Calculation in Proton Therapy.

PURPOSE: It is the goal of this study to use both Monte Carlo (MC) simulation and the pencil beam dose algorithm (PBA) in the treatment planning system to investigate Patient scatter factor (PSF) and Compensator scatter factor (CSF) for calibrating the dose per monitor unit (DMU) for a passive scattering proton therapy system. MATERIALS AND METHODS: PSFs and CSFs for brain, lung, pancreas, and prostate treatment sites were calculated by using MC simulation and PBA from the treatment planning software to evaluate the agreement between the two. RESULTS: This study shows that the CSF values are always greater than 1, with some reaching nearly 4% above unity, and depending strongly on the shape of the compensator. Monte Carlo and PBA-calculated CSF factors agree very well, with average differences below 1%. PSF values calculated in this study ranged from 0.919 to 1.023 and are largely dependent on the type of tissue heterogeneities in the treatment field. Monte Carlo and PBA-calculated PSF factors show differences, with the largest discrepancies seen in lung cases, with an average difference of 1.9%. It is also shown that dense bone will drive a PSF to values greater than unity, while large quantities of air decrease the PSF to below unity. CONCLUSION: We have showed that the compensator and patient anatomy can have a significant impact on clinical proton dose distribution. It is recommended that both Monte Carlo and treatment planning system should be used to take these factors into account in the final DMU calculation.

TOPAS Simulation of the Mevion S250 compact proton therapy unit.

As proton therapy becomes increasingly popular, so does the need for Monte Carlo simulation studies involving accurate beam line modeling of proton treatment units. In this study, the 24 beam configurations of the Mevion S250 proton therapy system installed recently at our institution were modeled using the TOolkit for PArticle Simulation (TOPAS) code. Pristine Bragg peak, spread out Bragg peak (SOBP), and lateral beam profile dose distributions were simulated and matched to the measurements taken during commissioning of the unit. Differences in the range for all Percent Depth Dose (PDD) curves between measured and simulated data agreed to within 0.1 cm. For SOBP scans, the SOBP widths all agreed to within 0.3 cm. With regards to lateral beam profile comparisons between the measured and simulated data, the penumbras differed by less than 1 mm and the flatness differed by less than 1% in nearly all cases. This study shows that Monte Carlo simulation studies involving the Mevion S250 proton therapy unit can be a viable tool in commissioning and verification of the proton treatment planning system.