Monte Carlo simulation-based patient-specific QA using machine log files for line-scanning proton radiation therapy.

BACKGROUND: Quality assurance (QA) is a prerequisite for safe and accurate pencil-beam proton therapy. Conventional measurement-based patient-specific QA (pQA) can only verify limited aspects of patient treatment and is labor-intensive. Thus, a better method is needed to ensure the integrity of the treatment plan. PURPOSE: Line scanning, which involves continuous and rapid delivery of pencil beams, is a state-of-the-art proton therapy technique. Machine performance in delivering scanning protons is dependent on the complexity of the beam modulations. Moreover, it contributes to patient treatment accuracy. A Monte Carlo (MC) simulation-based QA method that reflects the uncertainty related to the machine during scanning beam delivery was developed and verified for clinical applications to pQA. METHODS: Herein, a tool for particle simulation (TOPAS) for nozzle modeling was used, and the code was commissioned against the measurements. To acquire the beam delivery uncertainty for each plan, patient plans were delivered. Furthermore, log files recorded every 60 µs by the monitors downstream of the nozzle were exported from the treatment control system. The spot positions and monitor unit (MU) counts in the log files were converted to dipole magnet strengths and number of particles, respectively, and entered into the TOPAS. For the 68 clinical cases, MC simulations were performed in a solid water phantom, and two-dimensional (2D) absolute dose distributions at 20-mm depth were measured using an ionization chamber array (Octavius 1500, PTW, Freiburg, Germany). Consequently, the MC-simulated 2D dose distributions were compared with the measured data, and the dose distributions in the pre-treatment QA plan created with RayStation (RaySearch Laboratories, Stockholm, Sweden). Absolute dose comparisons were made using gamma analysis with 3%/3 mm and 2%/2 mm criteria for 47 clinical cases without considering daily machine output variation in the MC simulation and 21 cases with daily output variation, respectively. All cases were analyzed with 90% or 95% of passing rate thresholds. RESULTS: For 47 clinical cases not considering daily output variations, the absolute gamma passing rates compared with the pre-treatment QA plan were 99.71% and 96.97%, and the standard deviations (SD) were 0.70% and 3.78% with the 3%/3 mm or 2%/2 mm criteria, respectively. Compared with the measurements, the passing rate of 2%/2 mm gamma criterion was 96.76% with 3.99% of SD. For the 21 clinical cases compared with pre-treatment QA plan data and measurements considering daily output variations, the 2%/2 mm absolute gamma analysis result was 98.52% with 1.43% of SD and 97.67% with 2.72% of SD, respectively. With a 95% passing rate threshold of 2%/2 mm criterion, the false-positive and false-negative were 21.8% and 8.3% for without and with considering output variation, respectively. With a 90% threshold, the false-positive and false-negative reduced to 11.4% and 0% for without and with considering output variation, respectively. CONCLUSIONS: A log-file-based MC simulation method for patient QA of line-scanning proton therapy was successfully developed. The proposed method exhibited clinically acceptable accuracy, thereby exhibiting a potential to replace the measurement-based dosimetry QA method with a 90% gamma passing rate threshold when applying the 2%/2 mm criterion.

Proposing a Clinical Model for RBE Based on Proton Track-End Counts.

PURPOSE: In proton therapy, the clinical application of linear energy transfer (LET) optimization remains contentious, in part because of challenges associated with the definition and calculation of LET and its exact relationship with relative biological effectiveness (RBE) because of large variation in experimental in vitro data. This has raised interest in other metrics with favorable properties for biological optimization, such as the number of proton track ends in a voxel. In this work, we propose a novel model for clinical calculations of RBE, based on proton track end counts. METHODS AND MATERIALS: We developed an effective dose concept to translate between the total proton track-end count per unit mass in a voxel and a proton RBE value. Dose, track end, and dose-averaged LET (LETd) distributions were simulated using Monte Carlo models for a series of water phantoms, in vitro radiobiological studies, and patient treatment plans. We evaluated the correlation between track ends and regions of elevated biological effectiveness in comparison to LETd-based models of RBE. RESULTS: Track ends were found to correlate with biological effects in in vitro experiments with an accuracy comparable to LETd. In patient simulations, our track end model identified the same biological hotspots as predicted by LETd-based radiobiological models of proton RBE. CONCLUSIONS: These results suggest that, for clinical optimization and evaluation, an RBE model based on proton track end counts may match LETd-based models in terms of information provided while also offering superior statistical properties.

MOQUI: an open-source GPU-based Monte Carlo code for proton dose calculation with efficient data structure.

Objective.Monte Carlo (MC) codes are increasingly used for accurate radiotherapy dose calculation. In proton therapy, the accuracy of the dose calculation algorithm is expected to have a more significant impact than in photon therapy due to the depth-dose characteristics of proton beams. However, MC simulations come at a considerable computational cost to achieve statistically sufficient accuracy. There have been efforts to improve computational efficiency while maintaining sufficient accuracy. Among those, parallelizing particle transportation using graphic processing units (GPU) achieved significant improvements. Contrary to the central processing unit, a GPU has limited memory capacity and is not expandable. It is therefore challenging to score quantities with large dimensions requiring extensive memory. The objective of this study is to develop an open-source GPU-based MC package capable of scoring those quantities.Approach.We employed a hash-table, one of the key-value pair data structures, to efficiently utilize the limited memory of the GPU and score the quantities requiring a large amount of memory. With the hash table, only voxels interacting with particles will occupy memory, and we can search the data efficiently to determine their address. The hash-table was integrated with a novel GPU-based MC code, moqui.Main results.The developed code was validated against an MC code widely used in proton therapy, TOPAS, with homogeneous and heterogeneous phantoms. We also compared the dose calculation results of clinical treatment plans. The developed code agreed with TOPAS within 2%, except for the fall-off and regions, and the gamma pass rates of the results were >99% for all cases with a 2 mm/2% criteria.Significance.We can score dose-influence matrix and dose-rate on a GPU for a 3-field H&N case with 10 GB of memory using moqui, which would require more than 100 GB of memory with the conventionally used array data structure.

A dynamic blood flow model to compute absorbed dose to circulating blood and lymphocytes in liver external beam radiotherapy.

We have developed a novel 4D dynamic liver blood flow model, capable of accurate dose estimation to circulating blood cells during liver-directed external beam radiotherapy, accounting for blood recirculation and radiation delivery time structure. Adult male and adult female liver computational phantoms with detailed vascular trees were developed to include the hepatic arterial, hepatic portal venous, and hepatic venous trees. A discrete time Markov Chain approach was applied to determine the spatiotemporal distribution of 105blood particles (BP) in the human body based on reference values for cardiac output and organ blood volumes. For BPs entering the liver, an explicit Monte Carlo simulation was implemented to track their propagation along ∼2000 distinct vascular pathways through the liver. The model tracks accumulated absorbed dose from time-dependent radiation fields with a 0.1 s time resolution. The computational model was then evaluated for 3 male and 3 female patients receiving photon (VMAT and IMRT) and proton (passive SOBP and active PBS) treatments. The dosimetric impact of treatment modality, delivery time, and fractionation on circulating blood cells was investigated and quantified using the mean dose (µdose,b),V>0Gy,V>0.125Gy,andD2%. Average reductions inµdose,b,V>0Gy,V>0.125GyandD2%of 45%, 6%, 53%, 19% respectively, were observed for proton treatments as compared to photon treatments. Our simulation also showed thatV>0Gy,V>0.125Gy, andD2%were highly sensitive to the beam-on time. BothV>0GyandV>0.125Gyincreased with beam-on time, whereasD2%decreased with increasing beam-on time, demonstrating the tradeoff between low dose to a large fraction of blood cells and high dose to a small fraction of blood cells. Consequently, proton treatments are not necessarily advantageous in terms of dose to the blood simply based on integral dose considerations. Instead, both integral dose and beam-on time can substantially impact relevant dosimetric indices.

DICOM-RT Ion interface to utilize MC simulations in routine clinical workflow for proton pencil beam radiotherapy.

To adopt Monte Carlo (MC) simulations as an independent dose calculation method for proton pencil beam radiotherapy, an interface that converts the plan information in DICOM format into MC components such as geometries and beam source is a crucial element. For this purpose, a DICOM-RT Ion interface (https://github.com/topasmc/dicom-interface) has been developed and integrated into the TOPAS MC code to perform such conversions on-the-fly. DICOM-RT objects utilized in this interface include Ion Plan (RTIP), Ion Beams Treatment Record (RTIBTR), CT image, and Dose. Beamline geometries, gantry and patient coordinate systems, and fluence maps are determined from RTIP and/or RTIBTR. In this interface, DICOM information is processed and delivered to a MC engine in two steps. A MC model, which consists of beamline geometries and beam source, to represent a treatment machine is created by a DICOM parser of the interface. The complexities from different DICOM types, various beamline configurations and source models are handled in this step. Next, geometry information and beam source are transferred to TOPAS on-the-fly via the developed TOPAS extensions. This interface with two treatment machines was successfully deployed into our automated MC workflow which provides simulated dose and LET distributions in a patient or a water phantom automatically when a new plan is identified. The developed interface provides novel features such as handling multiple treatment systems based on different DICOM types, DICOM conversions on-the-fly, and flexible sampling methods that significantly reduce the burden of handling DICOM based plan or treatment record information for MC simulations.

The TOPAS tool for particle simulation, a Monte Carlo simulation tool for physics, biology and clinical research.

PURPOSE: This paper covers recent developments and applications of the TOPAS TOol for PArticle Simulation and presents the approaches used to disseminate TOPAS. MATERIALS AND METHODS: Fundamental understanding of radiotherapy and imaging is greatly facilitated through accurate and detailed simulation of the passage of ionizing radiation through apparatus and into a patient using Monte Carlo (MC). TOPAS brings Geant4, a reliable, experimentally validated MC tool mainly developed for high energy physics, within easy reach of medical physicists, radiobiologists and clinicians. Requiring no programming knowledge, TOPAS provides all of the flexibility of Geant4. RESULTS: After 5 years of development followed by its initial release, TOPAS was subsequently expanded from its focus on proton therapy physics to incorporate radiobiology modeling. Next, in 2018, the developers expanded their user support and code maintenance as well as the scope of TOPAS towards supporting X-ray and electron therapy and medical imaging. Improvements have been achieved in user enhancement through software engineering and a graphical user interface, calculational efficiency, validation through experimental benchmarks and QA measurements, and either newly available or recently published applications. A large and rapidly increasing user base demonstrates success in our approach to dissemination of this uniquely accessible and flexible MC research tool. CONCLUSIONS: The TOPAS developers continue to make strides in addressing the needs of the medical community in applications of ionizing radiation to medicine, creating the only fully integrated platform for four-dimensional simulation of all forms of radiotherapy and imaging with ionizing radiation, with a design that promotes inter-institutional collaboration.

End-of-Range Radiobiological Effect on Rib Fractures in Patients Receiving Proton Therapy for Breast Cancer.

PURPOSE: A prospective trial of proton therapy for breast cancer revealed an increased rib fracture rate of 7%, which is higher than the expected rate based on the literature on photon therapies. We aim to evaluate the hypothesis that the increased relative biological effectiveness (RBE) at the distal edge of proton beams is the cause. METHODS AND MATERIALS: We combined the cohort from the prospective clinical trial and a retrospective cohort from a database. Monte Carlo simulations were performed to recalculate the physical dose and dose-averaged linear energy transfer (LETd). The first 10 ribs and fracture areas in patients with fractures were contoured and deformably registered. The LETd-weighted dose was used as a surrogate for biological effectiveness and compared with the conventional fixed RBE of 1.1. Dose to 0.5 cm3 of the ribs (D0.5) was selected to analyze the dose-response relationship using logistic regression. We chose an alpha/beta ratio of 3 to calculate the biological effective dose in Gy3(RBE). RESULTS: Thirteen of 203 patients in the cohorts exhibited a total of 25 fractures. The LETd in fractured areas is increased (6.1 ± 2.0 keV/µm, mean ± standard deviation), suggesting possible end-of-range radiobiological effects with increased RBE. The D0.5 of the fractured ribs is 80.3 ± 9.4 Gy3(RBE) with a generic factor of 1.1 and is relatively low compared with historical photon results. On the other hand, the D0.5 of the fractured ribs is 100.0 ± 12.5 Gy3(RBE) using the LETd-based model with a dose-response curve that is more consistent with historical photon data. CONCLUSIONS: The increased rib fracture rate seen in our trial is probably associated with the increased LETd and RBE at the distal edge of proton beams. This phenomenon warrants further investigation and possible integration of LETd into treatment planning and optimization in proton therapy.

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy-1 to 1 Gy Gy-1) were generally much higher than those for the intracranial irradiations (2.1 µGy Gy-1 to 0.1 Gy Gy-1), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.

Experimental depth dose curves of a 67.5 MeV proton beam for benchmarking and validation of Monte Carlo simulation.

PURPOSE: To measure depth dose curves for a 67.5 ± 0.1 MeV proton beam for benchmarking and validation of Monte Carlo simulation. METHODS: Depth dose curves were measured in 2 beam lines. Protons in the raw beam line traversed a Ta scattering foil, 0.1016 or 0.381 mm thick, a secondary emission monitor comprised of thin Al foils, and a thin Kapton exit window. The beam energy and peak width and the composition and density of material traversed by the beam were known with sufficient accuracy to permit benchmark quality measurements. Diodes for charged particle dosimetry from two different manufacturers were used to scan the depth dose curves with 0.003 mm depth reproducibility in a water tank placed 300 mm from the exit window. Depth in water was determined with an uncertainty of 0.15 mm, including the uncertainty in the water equivalent depth of the sensitive volume of the detector. Parallel-plate chambers were used to verify the accuracy of the shape of the Bragg peak and the peak-to-plateau ratio measured with the diodes. The uncertainty in the measured peak-to-plateau ratio was 4%. Depth dose curves were also measured with a diode for a Bragg curve and treatment beam spread out Bragg peak (SOBP) on the beam line used for eye treatment. The measurements were compared to Monte Carlo simulation done with geant4 using topas. RESULTS: The 80% dose at the distal side of the Bragg peak for the thinner foil was at 37.47 ± 0.11 mm (average of measurement with diodes from two different manufacturers), compared to the simulated value of 37.20 mm. The 80% dose for the thicker foil was at 35.08 ± 0.15 mm, compared to the simulated value of 34.90 mm. The measured peak-to-plateau ratio was within one standard deviation experimental uncertainty of the simulated result for the thinnest foil and two standard deviations for the thickest foil. It was necessary to include the collimation in the simulation, which had a more pronounced effect on the peak-to-plateau ratio for the thicker foil. The treatment beam, being unfocussed, had a broader Bragg peak than the raw beam. A 1.3 ± 0.1 MeV FWHM peak width in the energy distribution was used in the simulation to match the Bragg peak width. An additional 1.3-2.24 mm of water in the water column was required over the nominal values to match the measured depth penetration. CONCLUSIONS: The proton Bragg curve measured for the 0.1016 mm thick Ta foil provided the most accurate benchmark, having a low contribution of proton scatter from upstream of the water tank. The accuracy was 0.15% in measured beam energy and 0.3% in measured depth penetration at the Bragg peak. The depth of the distal edge of the Bragg peak in the simulation fell short of measurement, suggesting that the mean ionization potential of water is 2-5 eV higher than the 78 eV used in the stopping power calculation for the simulation. The eye treatment beam line depth dose curves provide validation of Monte Carlo simulation of a Bragg curve and SOBP with 4%/2 mm accuracy.

Secondary neutron dose measurement for proton eye treatment using an eye snout with a borated neutron absorber.

BACKGROUND: We measured and assessed ways to reduce the secondary neutron dose from a system for proton eye treatment. METHODS: Proton beams of 60.30 MeV were delivered through an eye-treatment snout in passive scattering mode. Allyl diglycol carbonate (CR-39) etch detectors were used to measure the neutron dose in the external field at 0.00, 1.64, and 6.00 cm depths in a water phantom. Secondary neutron doses were measured and compared between those with and without a high-hydrogen-boron-containing block. In addition, the neutron energy and vertices distribution were obtained by using a Geant4 Monte Carlo simulation. RESULTS: The ratio of the maximum neutron dose equivalent to the proton absorbed dose (H(10)/D) at 2.00 cm from the beam field edge was 8.79 ± 1.28 mSv/Gy. The ratio of the neutron dose equivalent to the proton absorbed dose with and without a high hydrogen-boron containing block was 0.63 ± 0.06 to 1.15 ± 0.13 mSv/Gy at 2.00 cm from the edge of the field at depths of 0.00, 1.64, and 6.00 cm. CONCLUSIONS: We found that the out-of-field secondary neutron dose in proton eye treatment with an eye snout is relatively small, and it can be further reduced by installing a borated neutron absorbing material.