Beam Scanning Proton Therapy System Research Articles

Stochastic model for predicting the temporal structure of the plan delivery in a synchrotron-based pencil beam scanning proton therapy system

Accurately predicting dose delivery is crucial for achieving fully personalized treatments in external beam radiation therapy. However, this task remains challenging in some current technologies. In the case of Proton Therapy, for example, current systems employ complex strategies where a pencil beam is scanned in the tumor for treatment delivery. Some parameters in these treatments fluctuate and cannot be fully controlled. Therefore, a stochastic model that accounts for temporal uncertainties can be the best approach to describe these behaviors, particularly when the time-dependent beam interacts with other processes such as moving tumors or organs at risk.This paper aims to provide medical physicists with a tool for accurately predicting the temporal structure of beam delivery. To achieve this, we followed a two-step process. First, we characterized the probability distributions for all relevant times in dose delivery. Second, we developed a model based on the measured data. This model serves as a starting point to improve treatment planning performance by providing a range of expected times for dose delivery. While the process was carried out using a compact synchrotron at our university, it can be easily adapted to other technologies.

Lines-based rotating beam profiling algorithm using pixel ionization chamber with dead pixels

In a pencil beam scanning proton therapy system, critical beam parameters, including the spot size, spot center position, and tilt angle, are monitored for security by beam profile detectors such as two-dimensional (2D) pixel-segmented ionization chambers. A method, named lines-based beam profiling (LBBP), is proposed to identify the five geometric parameters μx,μy,σx,σy,θ of rotating elliptical beam profiles using several lines (rows and columns) in the 2D detector data. The method provides solid results even in the presence of dead pixels, which can be located using a wavelet analysis. Simulation experiments were used to define the number of lines used by the LBBP method and to characterize its performance as a function of the signal-to-noise (SNR). For SNR greater than 30, the root mean square errors (RMSEs) of the beam spot size, spot center position, and rotation angle obtained with the LBBP method are less than 0.16 mm, 0.05 mm, and 0.78 degrees, respectively. The LBBP method was applied to the data collected by a pixel chamber illuminated by an X-ray source, demonstrating the capability of identifying dead pixels and providing more accurate measurements of the beam spot size and center position than the standard Gaussian fitting.

Characterization of penumbra sharpening and scattering by adaptive aperture for a compact pencil beam scanning proton therapy system.

To quantitatively access penumbra sharpening and scattering by adaptive aperture (AA) under various beam conditions and clinical cases for a Mevion S250i compact pencil beam scanning proton therapy system. First, in-air measurements were performed using a scintillation detector for single spot profile and lateral penumbra for five square field sizes (3×3 to 18×18cm2 ), three energies (33.04, 147.36, and 227.16MeV), and three snout positions (5, 15, and 33.6cm) with Open and AA field. Second, treatment plans were generated in RayStation treatment planning system (TPS) for various combination of target size (3- and 10-cm cube), target depth (5, 10, and 15cm) and air gap (5-20cm) for both Open and AA field. These plans were delivered to EDR2 films in the solid water and penumbra reduction by AA was quantified. Third, the effect of the AA scattered protons on the surface dose was studied at 5mm depth by EDR2 film and the RayStation TPS computation. Finally, dosimetric advantage of AA over Open field was studied for five brain and five prostate cases using the TPS simulation. The spot size changed dramatically from 3.8mm at proton beam energy of 227.15MeV to 29.4mm at energy 33.04MeV. In-air measurements showed that AA substantially reduced the lateral penumbra by 30% to 60%. The EDR2 film measurements in solid water presented the maximum penumbra reduction of 10 to 14mm depending on the target size. The maximum increase of 25% in field edge dose at 5mm depth as compared to central axis was observed. The substantial penumbra reduction by AA produced less dose to critical structures for all the prostate and brain cases. Adaptive aperture sharpens the penumbra by factor of two to three depending upon the beam condition. The absolute penumbra reduction with AA was more noticeable for shallower target, smaller target, and larger air gap. The AA-scattered protons contributed to increase in surface dose. Clinically, AA reduced the doses to critical structures.

Performance evaluation of adaptive aperture's static and dynamic collimation in a compact pencil beam scanning proton therapy system: A dosimetric comparison study for multiple disease sites

A compact pencil beam scanning (PBS) proton therapy system, Mevion S250i with Hyperscan, is equipped with adaptive aperture (AA) to collimate the beam with 2 different techniques: Static aperture (SA) and dynamic aperture (DA). SA (single aperture) collimates the outermost contour of the target and DA (multi-layer aperture) collimates each energy layer of the proton beam. This study evaluates dosimetric performance of SA and DA for different disease sites. This study includes 5 disease sites (brain, head and neck (HN), partial breast, lung, and prostate), and 8 patients for each. A total of 80 patient treatment plans (5 sites × 8 patients per site × 2 collimation techniques) were created using 2 to 4 proton beams. Both SA and DA plans were made using the same plan and optimization parameters calculated by a Monte Carlo dose algorithm. Multi-field optimization (MFO) was used for HN treatment plans, whereas treatment plans for the other sites were made with single-field optimization (SFO). All plans were robustly optimized with 3 mm (brain and HN) or 5 mm (breast, lung, and prostate) position uncertainty along with 3.5% range uncertainty. Treatment plans were normalized such that 99% of the clinical target volume (CTV) received 100% of the prescribed dose. Dose volume histogram (DVH) parameters were evaluated for CTV and organs at risk (OARs). The CTV was also evaluated for dose homogeneity, dose conformity, and dose gradient. In general, the DA plan made CTV hotter, while it saved OARs better. DA produced better conformity with sharper dose falloff around CTV, while SA generated better homogenous target coverage. DA decreased Dmax to brainstem (1.2% = [(SA-DA)/DA × 100%]) for brain, Dmax to the spinal cord (137.3%) for HN, D1% of the ipsilateral lung (50.5%) for breast, and Dmax to the spinal cord (74.0%) for lung. The dose reduction in bladder and rectum for prostate plans with DA was less than 2.5%. The DA plans reduced the dose to OARs for all disease sites but escalated the target maximum dose for the same target coverage than the SA plans. The OAR saving and dose escalation depended on CTV size, proximity of the OARs to CTV, and the plan complexity.

Parametrization of in-air spot size as a function of energy and air gap for the ProteusPLUS pencil beam scanning proton therapy system.

The purpose of this study was to parametrize the in-air one sigma spot size for various energies and air gaps in pencil beam scanning (PBS) proton therapy. The current study included range shifters with a water equivalent thickness (WET) of 40mm (RS40) and 75mm (RS75). For RS40, the spot sizes were measured for energies ranging from 80 to 225MeV in increments of 2.5MeV, whereas the air gap was varied from 5 to 25cm in increments of 2.5cm. For RS75, the spot sizes were measured for energies ranging from 120 to 225MeV in increments of 2.5MeV, whereas the air gap was varied from 5 to 35cm in increments of 2.5cm. For both RS40 and RS75, all measurements (n = 1090) were acquired at the isocenter using a Lynx 2D scintillation detector. For RS40, the spot sizes increased from 3.1mm to 10.4mm, whereas the variation in spot sizes for RS75 ranged from 3.3mm to 13.1mm. For each range shifter, an analytical equation demonstrating the relationship of the spot size with the proton energy and air gap was obtained. The best parametrization results were obtained with the 3rd degree polynomial fits of the energy and air gap parameters. The average difference between the modeled and measured spot sizes was 0.0 ± 0.1mm (range, -0.24-0.21mm) for RS40, and 0.0 ± 0.1mm (range, -0.23-0.15mm) for RS75. In conclusion, the analytical model agrees within ± 0.25mm of the measured spot sizes on a ProteusPLUS PBS proton system with a PBS dedicated nozzle.

Developing a Monte Carlo model for MEVION S250i with HYPERSCAN and Adaptive Aperture™ pencil beam scanning proton therapy system

AbstractAim:As the number of proton therapy facilities has steadily increased, the need for the tool to provide precise dose simulation for complicated clinical and research scenarios also increase. In this study, the treatment head of Mevion HYPERSCAN pencil beam scanning (PBS) proton therapy system including energy modulation system (EMS) and Adaptive Aperture™ (AA) was modelled using TOPAS (TOolkit for PArticle Simulation) Monte Carlo (MC) code and was validated during commissioning process.Materials and methods:The proton beam characteristics including integral depth doses (IDDs) of pristine Bragg peak and in-air beam spot sizes were simulated and compared with measured beam data. The lateral profiles, with and without AA, were also verified against calculation from treatment planning system (TPS).Results:All beam characteristics for IDDs and in-air spot size agreed well within 1 mm and 10% separately. The full width at half maximum and penumbra of lateral dose profile also agree well within 2 mm.Finding:The TOPAS MC simulation of the MEVION HYPERSCAN PBS proton therapy system has been modelled and validated; it could be a viable tool for research and verification of the proton treatment in the future.

A Monte-Carlo-based and GPU-accelerated 4D-dose calculator for a pencil beam scanning proton therapy system.

The presence of respiratory motion during radiation treatment leads to degradation of the expected dose distribution, both for target coverage and healthy tissue sparing, particularly for techniques like pencil beam scanning proton therapy which have dynamic delivery systems. While tools exist to estimate this degraded four-dimensional (4D) dose, they typically have one or more deficiencies such as not including the particular effects from a dynamic delivery, using analytical dose calculations, and/or using nonphysical dose-accumulation methods. This work presents a clinically useful 4D-dose calculator that addresses each of these shortcomings. To quickly compute the 4D dose, the three main tasks of the calculator were run on graphics processing units (GPUs). These tasks were (a) simulating the delivery of the plan using measured delivery parameters to distribute the plan amongst 4DCT phases characterizing the patient breathing, (b) using an in-house Monte Carlo simulation (MC) dose calculator to determine the dose delivered to each breathing phase, and (c) accumulating the doses from the various breathing phases onto a single phase for evaluation. The accumulation was performed by individually transferring the energy and mass of dose-grid subvoxels, a technique that models the transfer of dose in a more physically realistic manner. The calculator was run on three test cases, with lung, esophagus, and liver targets, respectively, to assess the various uncertainties in the beam delivery simulation as well as to characterize the dose-accumulation technique. Four-dimensional doses were successfully computed for the three test cases with computation times ranging from 4-6min on a server with eight NVIDIA Titan X graphics cards; the most time-consuming component was the MC dose engine. The subvoxel-based dose-accumulation technique produced stable 4D-dose distributions at subvoxel scales of 0.5-1.0mm without impairing the total computation time. The uncertainties in the beam delivery simulation led to moderate variations of the dose-volume histograms for these cases; the variations were reduced by implementing repainting or phase-gating motion mitigation techniques in the calculator. A MC-based and GPU-accelerated 4D-dose calculator was developed to estimate theeffects of respiratory motion on pencil beam scanning proton therapy treatments. After future validation, the calculator could be used to assess treatment plans and its quick runtime would make it easily usable in a future 4D-robust optimization system.

Proton Radioprotection of Fanconi Anemia (Fanca-/-) Mouse Marrow Stromal Cell Lines by Mitochondrial Targeted GS-Nitroxide JP-4-039

The increasing incidence of oral cavity squamous cell carcinomas in radiosensitive Fanconi Anemia (FA) patients suggested that protons might minimize normal tissue toxicity. We tested the radiation protector/mitigator, JP4-039, with Proton irradiated mesenchymal stem cell lines derived from Fanca-/- mouse marrow. Fanca-/- and control Fanca+/+ bone marrow stromal cell lines were irradiated to doses of 0 – 10 Gy via pencil beam scanning proton therapy system. Subgroups of cultures were treated with 100uM JP4-039 for 12 h prior to irradiation and after plating for clonogenic survival curves. Parallel cultures were irradiated using a JL Shepherd Model 68A cesium irradiator at 340 cGy per minute, subgroups treated with JP4-039 in a similar protocol. Cells were plated in 4 well limbro plates and incubated for 10 days in a CO2 tissue culture incubator. Colonies of greater than 50 cells were stained with crystal violet and counted. Data from triplicate experiments was analyzed using Linear Quadratic and Single Hit, Multiple Target model. Cultures irradiated to 5 or 10 Gy using proton or gamma irradiation were plated in T25 flasks and stained 10 days later for β-Galactosidase. Proton irradiation revealed radiosensitivity of Fanca-/- bone marrow stromal cell lines compared to Fanca+/+ cell lines (D0 = 2.11 ± 0.17, vs D0 = 3.28 ± 0.10 p = 0.0027, ñ = 1.1 ± 0.1, vs ñ = 1.0 ± 0.1, respectively). Fanca-/- cells were also radiosensitive to gamma irradiation, (D0 = 2.08 ± 0.17, vs D0 = 3.36 ± 0.05 p = 0.0017, ñ = 2.0 ± 0.5, ñ = 1.3 ± 0.3, respectively). JP4-039 provided significant radiation protection for both Fanca-/- and Fanca+/+ cell lines against both proton irradiation (D0 = 3.01 ± 0.19 p = 0.0125, ñ = 1.0 ± 0.1, vs D0 = 3.84 ± 0.11 p = 0.0196, ñ = 1.0 ± 0.1), and gamma irradiation ((D0 = 3.81 ± 0.72 p = 0.0423, ñ = 1.2 ± 0.2; D0 = 3.70 ± 0.06 p = 0.0133 p = 0.0133, ñ = 1.7 ± 0.7). Following proton irradiation, Fanca+/+ cells showed greater senescence compared to Fanca-/- cells: 28% vs 10% β-galactosidase positive (p < 0.05). In contrast, gamma irradiation of Fanca+/+ compared to Fanca-/- cells showed decreased senescence (7% compared to 17% (p < 0.05). Fanca-/- bone marrow stromal cell lines are radiosensitive to proton and gamma irradiation, but significantly protected by JP4-039. The data support intra-oral JP4-039 for Fanconi Anemia patients receiving proton radiotherapy for oral squamous cell carcinoma.

TU-A-108-02: A 4D Monte Carlo Study Quantifying Changes in the Interplay Effect as a Function of Treatment Delivery Parameters in Proton Beam Scanning for Lung

Purpose: To assess the impact of delivery parameters of a pencil beam scanning proton therapy system on the dosimetric interplay effect during lung treatments. Methods: 4D Monte Carlo simulations were performed using TOPAS for 5 lung cancer patients with varying tumor sizes (50.4–167.1cc) and superior‐inferior (SI) motion amplitudes (2.9–30.1mm). Each patient was planned based on a 4DCT scan. The complete time structure of the proton fields was incorporated into the simulation framework by including the time required to deposit dose, scan the beam laterally, change the beam energy and the time required for magnet settling. Changes in the 4D dose distribution resulting from altering the spot size, energy switch time, magnet settling time, initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and breathing period were determined using deformable image registration. The metrics used for analysis were mean dose, minimum dose, maximum dose, dose homogeneity, equivalent uniform dose (EUD), lung V 5, V 20 and mean lung dose. Results: In general, longer delivery times led to less interplay and the interplay effect could not be predicted using motion amplitude alone. Larger spot sizes (σ ∼9–16mm) gave a EUD of 99.0% + 4.4% (1 standard deviation) of the prescription dose in 1 fraction compared to 86.1% + 13.1% for smaller spots (σ ∼2–4mm). Smaller spot sizes gave EUD values as low as 65.3% in 1 fraction. Target dose homogeneity improved with reduced spot spacing. The interplay effect can vary significantly with initial breathing phase. No definitive benefit was observed when scanning predominantly parallel or perpendicular to the SI axis. Conventional fractionation reduced interplay, giving EUD values of at least 84.7% and 100.0% for the small and larger spot sizes respectively. Conclusion: The interplay effect is highly patient specific and varies based on the motion amplitude, tumor location and various delivery parameters. This project was supported by the National Cancer Institute Grant No. R01 CA111590