Continuous real time 3D motion reproduction using dynamic MRI and precomputed 4DCT deformation fields.

Radiotherapy of mobile tumors requires specific imaging tools and models to reduce the impact of motion on the treatment. Online continuous nonionizing imaging has become possible with the recent development of magnetic resonance imaging devices combined with linear accelerators. This opens the way to new guided treatment methods based on the real-time tracking of anatomical motion. In such devices, 2D fast MR-images are well-suited to capture and predict the real-time motion of the tumor. To be used effectively in an adaptive radiotherapy, these MR images have to be combined with X-ray images such as CT, which are necessary to compute the irradiation dose deposition. We therefore developed a method combining both image modalities to track the motion on MR images and reproduce the tracked motion on a sequence of 3DCT images in real-time. It uses manually placed navigators to track organ interfaces in the image, making it possible to select anatomical object borders that are visible on both MRI and CT modalities and giving the operator precise control of the motion tracking quality. Precomputed deformation fields extracted from the 4DCT acquired in the planning phase are then used to deform existing 3DCT images to match the tracked object position, creating a new set of 3DCT images encompassing irregularities in the breathing pattern for the complete duration of the MRI acquisition. The final continuous reconstructed 4DCT image sequence reproduces the motion captured by the MRI sequence with high precision (difference below 2 mm).

Dosimetric evaluation of synthetic CT generated with GANs for MRI-only proton therapy treatment planning of brain tumors.

PURPOSE: The purpose of this study was to address the dosimetric accuracy of synthetic computed tomography (sCT) images of patients with brain tumor generated using a modified generative adversarial network (GAN) method, for their use in magnetic resonance imaging (MRI)-only treatment planning for proton therapy. METHODS: Dose volume histogram (DVH) analysis was performed on CT and sCT images of patients with brain tumor for plans generated for intensity-modulated proton therapy (IMPT). All plans were robustly optimized using a commercially available treatment planning system (RayStation, from RaySearch Laboratories) and standard robust parameters reported in the literature. The IMPT plan was then used to compute the dose on CT and sCT images for dosimetric comparison, using RayStation analytical (pencil beam) dose algorithm. We used a second, independent Monte Carlo dose calculation engine to recompute the dose on both CT and sCT images to ensure a proper analysis of the dosimetric accuracy of the sCT images. RESULTS: The results extracted from RayStation showed excellent agreement for most DVH metrics computed on the CT and sCT for the nominal case, with a mean absolute difference below 0.5% (0.3 Gy) of the prescription dose for the clinical target volume (CTV) and below 2% (1.2 Gy) for the organs at risk (OARs) considered. This demonstrates a high dosimetric accuracy for the generated sCT images, especially in the target volume. The metrics obtained from the Monte Carlo doses mostly agreed with the values extracted from RayStation for the nominal and worst-case scenarios (mean difference below 3%). CONCLUSIONS: This work demonstrated the feasibility of using sCT generated with a GAN-based deep learning method for MRI-only treatment planning of patients with brain tumor in intensity-modulated proton therapy.

Effect of continuous positive airway pressure administration during lung stereotactic ablative radiotherapy: a comparative planning study.

PURPOSE: By increasing lung volume and decreasing respiration-induced tumour motion amplitude, administration of continuous positive airway pressure (CPAP) during stereotactic ablative radiotherapy (SABR) could allow for better sparing of the lungs and heart. In this study, we evaluated the effect of CPAP on lung volume, tumour motion amplitude and baseline shift, as well as the dosimetric impact of the strategy. METHODS: Twenty patients with lung tumours referred for SABR underwent 4D-computed tomography (CT) scans with and without CPAP (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP and noCPAP treatment plans were computed and compared for lung dose parameters (mean lung dose (MLD), lung volume receiving 20 Gy (V20Gy), 13 Gy (V13Gy), and 5 Gy (V5Gy)) and mean heart dose (MHD). RESULTS: On average, CPAP increased lung volume by 8.0% (p < 0.001) and 6.3% (p < 0.001) at T0 and T1, respectively, but did not change tumour motion amplitude or baseline shift. As a result, CPAP administration led to an absolute decrease in MLD, lung V20Gy, V13Gy and V5Gy of 0.1 Gy (p = 0.1), 0.4% (p = 0.03), 0.5% (p = 0.04) and 0.5% (p = 0.2), respectively, while having no significant influence on MHD. CONCLUSIONS: In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.

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.

Monte Carlo simulation of initial and volume ion recombination correction factor in plane parallel ionization chambers exposed to ion beams.

Objective.Accurate reference dosimetry with ionization chambers (ICs) relies on correcting for various influencing factors, including ion recombination. Theoretical frameworks, such as the Boag and Jaffe theories, are conventionally used to describe the ion recombination correction factors. Experimental methods are time consuming, the applicability may be limited and, in some cases, impractical to be used in clinical routine. The development of simulation tools becomes necessary to enhance the understanding of recombination under circumstances that may differ from conventional use. Before progressing, it is crucial to benchmark novel approaches to calculate ion recombination losses under known conditions. In this study, we introduce and validate a versatile simulation tool based on a Monte Carlo scheme for calculating initial and volume ion recombination correction factors in air-filled ICs exposed to ion beams with clinical dose rates.Approach. The simulation includes gaussian distribution of ion positions to model the distribution of charge carriers along the chamber volume. It accounts for various physical transport effects, including drift, diffusion, space charge screening and free electron fraction. To compute ion recombination, a Monte Carlo scheme is used due to its versatility in multiple geometries, without exhibiting convergence problems associated with numerically solved procedures.Main results. The code is validated in conventional dose rates against Jaffe's theory for initial recombination and Boag's theory for volume recombination based on parameters derived from experimental data including proton, helium and carbon ion beams measured with a plane parallel IC.Significance. The simulation demonstrates excellent agreement, typically 0.05% or less relative difference with the theoretical and experimental data. The current code successfully predicts ion recombination correction factors, in a large variety of ion beams, including different temporal beam structures.

Technical note: Beamlet-free optimization for Monte-Carlo-based treatment planning in proton therapy.

BACKGROUND: Dose calculation and optimization algorithms in proton therapy treatment planning often have high computational requirements regarding time and memory. This can hinder the implementation of efficient workflows in clinics and prevent the use of new, elaborate treatment techniques aiming to improve clinical outcomes like robust optimization, arc, and adaptive proton therapy. PURPOSE: A new method, namely, the beamlet-free algorithm, is presented to address the aforementioned issue by combining Monte Carlo dose calculation and optimization into a single algorithm and omitting the calculation of the time-consuming and costly dose influence matrix. METHODS: The beamlet-free algorithm simulates the dose in proton batches of randomly chosen spots and evaluates their relative impact on the objective function at each iteration. Based on the approximated gradient, the spot weights are then updated and used to generate a new spot probability distribution. The beamlet-free method is compared against a conventional, beamlet-based treatment planning algorithm on a brain case and a prostate case. RESULTS: The beamlet-free algorithm maintained a comparable plan quality while largely reducing the dependence of computation time and memory usage on the number of spots. CONCLUSION: The implementation of a beamlet-free treatment planning algorithm for proton therapy is feasible and capable of achieving treatment plans of comparable quality to conventional methods. Its efficient usage of computational resources and low spot dependence makes it a promising method for large plans, robust optimization, and arc proton therapy.

Technical note: development of a simulation framework, enabling the investigation of locally tuned single energy proton radiography.

Range uncertainties remain a limitation for the confined dose distribution that proton therapy can offer. The uncertainty stems from the ambiguity when translating CT Hounsfield Units (HU) into proton stopping powers. Proton Radiography (PR) can be used to verify the proton range. Specifically, PR can be used as a quality-control tool for CBCT-based synthetic CTs. An essential part of the work illustrating the potential of PR has been conducted using multi-layer ionization chamber (MLIC) detectors and mono-energetic PR. Due to the dimensions of commercially available MLICs, clinical adoption is cumbersome. Here, we present a simulation framework exploring locally-tuned single energy (LTSE) proton radiography and corresponding potential compact PR detector designs. Based on a planning CT data set, the presented framework models the water equivalent thickness. Subsequently, it analyses the proton energies required to pass through the geometry within a defined ROI. In the final step, an LTSE PR is simulated using the MCsquare Monte Carlo code. In an anatomical head phantom, we illustrate that LTSE PR allows for a significantly shorter longitudinal dimension of MLICs. We compared PR simulations for two exemplary 30 × 30 mm2proton fields passing the phantom at a 90° angle at an anterior and a posterior location in an iso-centric setup. The longitudinal distance over which all spots per field range out is significantly reduced for LTSE PR compared to mono-energetic PR. In addition, we illustrate the difference in shape of integral depth dose (IDD) when using constrained PR energies. Finally, we demonstrate the accordance of simulated and experimentally acquired IDDs for an LTSE PR acquisition. As the next steps, the framework will be used to investigate the sensitivity of LTSE PR to various sources of errors. Furthermore, we will use the framework to systematically explore the dimensions of an optimized MLIC design for daily clinical use.

Efficient proton arc optimization and delivery through energy layer pre-selection and post-filtering.

BACKGROUND: Proton arc therapy (PAT) has emerged as a promising approach for improving dose distribution, but also enabling simpler and faster treatment delivery in comparison to conventional proton treatments. However, the delivery speed achievable in proton arc relies on dedicated algorithms, which currently do not generate plans with a clear speed-up and sometimes even result in increased delivery time. PURPOSE: This study aims to address the challenge of minimizing delivery time through a hybrid method combining a fast geometry-based energy layer (EL) pre-selection with a dose-based EL filtering, and comparing its performance to a baseline approach without filtering. METHODS: Three methods of EL filtering were developed: unrestricted, switch-up (SU), and switch-up gap (SU gap) filtering. The unrestricted method filters the lowest weighted EL while the SU gap filtering removes the EL around a new SU to minimize the gantry rotation braking. The SU filtering removes the lowest weighted group of EL that includes a SU. These filters were combined with the RayStation dynamic proton arc optimization framework energy layer selection and spot assignment (ELSA). Four bilateral oropharyngeal and four lung cancer patients' data were used for evaluation. Objective function values, target coverage robustness, organ-at-risk doses and normal tissue complication probability evaluations, as well as comparisons to intensity-modulated proton therapy (IMPT) plans, were used to assess plan quality. RESULTS: The SU gap filtering algorithm performed best in five out of the eight cases, maintaining plan quality within tolerance while reducing beam delivery time, in particular for the oropharyngeal cohort. It achieved up to approximately 22% and 15% reduction in delivery time for oropharyngeal and lung treatment sites, respectively. The unrestricted filtering algorithm followed closely. In contrast, the SU filtering showed limited improvement, suppressing one or two SU without substantial delivery time shortening. Robust target coverage was kept within 1% of variation compared to the PAT baseline plan while organs-at-risk doses slightly decreased or kept about the same for all patients. CONCLUSIONS: This study provides insights to accelerate PAT delivery without compromising plan quality. These advancements could enhance treatment efficiency and patient throughput.

Real-time image-guided treatment of mobile tumors in proton therapy by a library of treatment plans: a simulation study.

PURPOSE: To improve target coverage and reduce the dose in the surrounding organs-at-risks (OARs), we developed an image-guided treatment method based on a precomputed library of treatment plans controlled and delivered in real-time. METHODS: A library of treatment plans is constructed by optimizing a plan for each breathing phase of a four dimensional computed tomography (4DCT). Treatments are delivered by simulation on a continuous sequence of synthetic computed tomographies (CTs) generated from real magnetic resonance imaging (MRI) sequences. During treatment, the plans for which the tumor are at a close distance to the current tumor position are selected to deliver their spots. The study is conducted on five liver cases. RESULTS: We tested our approach under imperfect knowledge of the tumor positions with a 2 mm distance error. On average, compared to a 4D robustly optimized treatment plan, our approach led to a dose homogeneity increase of 5% (defined as 1 - D 5 - D 95 prescription $1-\frac{D_5-D_{95}}{\text{prescription}}$ ) in the target and a mean liver dose decrease of 23%. The treatment time was roughly increased by a factor of 2 but remained below 4 min on average. CONCLUSIONS: Our image-guided treatment framework outperforms state-of-the-art 4D-robust plans for all patients in this study on both target coverage and OARs sparing, with an acceptable increase in treatment time under the current accuracy of the tumor tracking technology.

A spot-specific range uncertainty framework for robust optimization of proton therapy treatments.

PURPOSE: An accurate estimation of range uncertainties is essential to exploit the potential of proton therapy. According to Paganetti's study, a value of 2.4% (1.5 standard deviation) is currently recommended for planning robust treatments with Monte Carlo dose engines. This number is based on a dominant contribution from the mean excitation energy of tissues. However, it was recently shown that expressing tissues as a mixture of water and "dry" material in the CT calibration process allowed for a significant reduction of this uncertainty. We thus propose an adapted framework for pencil beam scanning robust optimization. First, we move towards a spot-specific range uncertainty (SSRU) determination. Second, we use the water-based formalism to reduce range uncertainties and, potentially, to spare better the organs at risk. METHODS: The stoichiometric calibration was adapted to provide a molecular decomposition (including water) of each voxel of the CT. The SSRU calculation was implemented in MCsquare, a fast Monte Carlo dose engine dedicated to proton therapy. For each spot, a ray-tracing method was used to propagate molecular I-values uncertainties and obtain the corresponding effective range uncertainty. These were then combined with other sources of range uncertainties, according to Paganetti's study of 2012. The method was then assessed on three head-and-neck patients. Two plans were optimized for each patient: the first one with the classical 2.4% flat range uncertainty (FRU), the second one with the variable range uncertainty. Both plans were then compared in terms of target coverage and OAR mean dose reduction. Robustness evaluations were also performed, using the SSRU for both plans in order to simulate errors as realistically as possible. RESULTS: For patient 1, it was found that the median SSRU was 1.04% (1.5 standard deviation), yielding, therefore, a very large reduction from the 2.4% FRU. All three SSRU plans were found to have a very good robustness level at a 90% confidence interval while sparing OAR better than the classical plan. For instance, in nominal cases, average reductions in the mean dose of 15.7, 8.4, and 13.2% were observed in the left parotid, right parotid, and pharyngeal constrictor muscle, respectively. As expected, the classical plans showed a higher but unnecessary level of robustness. CONCLUSIONS: Promising results of the SSRU framework were observed on three head-and-neck cases, and more patients should now be considered. The method could also benefit to other tumor sites and, in the long run, the variable part of the range uncertainty could be generalized to other sources of uncertainty in order to move towards more and more patient-specific treatments.

Advances in treatment planning and management for the safety and accuracy of lung stereotactic body radiation therapy using proton pencil beam scanning: Simulation, planning, quality assurance, and delivery recommendations.

This study presents the clinical experiences of the New York Proton Center in employing proton pencil beam scanning (PBS) for the treatment of lung stereotactic body radiation therapy. It encompasses a comprehensive examination of multiple facets, including patient simulation, delineation of target volumes and organs at risk, treatment planning, plan evaluation, quality assurance, and motion management strategies. By sharing the approaches of the New York Proton Center and providing recommendations across simulation, treatment planning, and treatment delivery, it is anticipated that the valuable experience will be provided to a broader proton therapy community, serving as a useful reference for future clinical practice and research endeavors in the field of stereotactic body proton therapy for lung tumors.

Improved healthy tissue sparing in proton therapy of lung tumors using statistically sound robust optimization and evaluation.

INTRODUCTION: Robust planning is essential in proton therapy for ensuring adequate treatment delivery in the presence of uncertainties. For both robust optimization and evaluation, commonly-used techniques can be overly conservative in selecting error scenarios and lack in providing quantified confidence levels. In this study, established techniques are compared to comprehensive alternatives to assess the differences in target coverage and organ at risk (OAR) dose. METHOD: Thirteen lung cancer patients were planned. Two robust optimization methods were used: scenario selection from marginal probabilities (SSMP) based on using maximum setup and range error values and scenario selection from joint probabilities (SSJP) that selects errors on a predefined 90% hypersurface. Two robust evaluation methods were used: conventional evaluation (CE) based on generating error scenarios from combinations of maximum errors of each uncertainty source and statistical evaluation (SE) via the Monte Carlo dose engine MCsquare which considers scenario probabilities. RESULTS: Plans optimized using SSJP had, on average, 0.5 Gy lower dose in CTV D98(worst-case) than SSMP-optimized plans. When evaluated using SE, 92.3% of patients passed our clinical threshold in both optimization methods. Average gains in OAR sparing were recorded when transitioning from SSMP to SSJP: esophagus (0.6 Gy D2(nominal), 0.9 Gy D2(worst-case)), spinal cord (3.9 Gy D2(nominal), 4.1 Gy D2(worst-case)) heart (1.1 Gy Dmean, 1.9% V30), lungs-GTV (1.0 Gy Dmean , 1.9% V30). CONCLUSION: Optimization using SSJP yielded significant OAR sparing in all recorded metrics with a target robustness within our clinical objectives, provided that a more statistically sound robustness evaluation method was used.

Bi-criteria Pareto optimization to balance irradiation time and dosimetric objectives in proton arc therapy.

Objective. Proton arc therapy (PAT) is a new delivery technique that exploits the continuous rotation of the gantry to distribute the therapeutic dose over many angular windows instead of using a few static fields, as in conventional (intensity-modulated) proton therapy. Although coming along with many potential clinical and dosimetric benefits, PAT has also raised a new optimization challenge. In addition to the dosimetric goals, the beam delivery time (BDT) needs to be considered in the objective function. Considering this bi-objective formulation, the task of finding a good compromise with appropriate weighting factors can turn out to be cumbersome.Approach. We have computed Pareto-optimal plans for three disease sites: a brain, a lung, and a liver, following a method of iteratively choosing weight vectors to approximate the Pareto front with few points. Mixed-integer programming (MIP) was selected to state the bi-criteria PAT problem and to find Pareto optimal points with a suited solver.Main results. The trade-offs between plan quality and beam irradiation time (staticBDT) are investigated by inspecting three plans from the Pareto front. The latter are carefully picked to demonstrate significant differences in dose distribution and delivery time depending on their location on the frontier. The results were benchmarked against IMPT and SPArc plans showing the strength of degrees of freedom coming along with MIP optimization.Significance. This paper presents for the first time the application of bi-criteria optimization to the PAT problem, which eventually permits the planners to select the best treatment strategy according to the patient conditions and clinical resources available.

Treatment planning in arc proton therapy: Comparison of several optimization problem statements and their corresponding solvers.

Arc proton therapy (ArcPT) is an emerging modality in cancer treatments. It delivers the proton beams following a sequence of irradiation angles while the gantry is continuously rotating around the patient. Compared to conventional proton treatments (intensity modulated proton therapy, IMPT), the number of beams is significantly increased bringing new degrees of freedom that leads to potentially better cancer care. However, the optimization of such treatment plans becomes more complex and several alternative statements of the problem can be considered and compared in order to solve the ArcPT problem. Three such problem statements, distinct in their mathematical formulation and properties, are investigated and applied to solving the ArcPT optimization problem. They make use of (i) fast iterative shrinkage-thresholding algorithm (FISTA), (ii) local search (LS) and (iii) mixed-integer programming (MIP). The treatment plans obtained with those methods are compared among them, but also with IMPT and an existing state-of-the-art method: Spot-Scanning Proton Arc (SPArc). MIP stands out at low scale problems both in terms of dose quality and time delivery efficiency. FISTA shows high dose quality but experiences difficulty to optimize the energy sequence while LS is mostly the antagonist. This detailed study describes independent approaches to solve the ArcPT problem and depending on the clinical case, one should be cautiously picked rather than the other. This paper gives the first formal definition of the problem at stake, as well as a first reference benchmark. Finally, empirical conclusions are drawn, based on realistic assumptions.

Towards a safe and efficient clinical implementation of machine learning in radiation oncology by exploring model interpretability, explainability and data-model dependency.

The interest in machine learning (ML) has grown tremendously in recent years, partly due to the performance leap that occurred with new techniques of deep learning, convolutional neural networks for images, increased computational power, and wider availability of large datasets. Most fields of medicine follow that popular trend and, notably, radiation oncology is one of those that are at the forefront, with already a long tradition in using digital images and fully computerized workflows. ML models are driven by data, and in contrast with many statistical or physical models, they can be very large and complex, with countless generic parameters. This inevitably raises two questions, namely, the tight dependence between the models and the datasets that feed them, and the interpretability of the models, which scales with its complexity. Any problems in the data used to train the model will be later reflected in their performance. This, together with the low interpretability of ML models, makes their implementation into the clinical workflow particularly difficult. Building tools for risk assessment and quality assurance of ML models must involve then two main points: interpretability and data-model dependency. After a joint introduction of both radiation oncology and ML, this paper reviews the main risks and current solutions when applying the latter to workflows in the former. Risks associated with data and models, as well as their interaction, are detailed. Next, the core concepts of interpretability, explainability, and data-model dependency are formally defined and illustrated with examples. Afterwards, a broad discussion goes through key applications of ML in workflows of radiation oncology as well as vendors' perspectives for the clinical implementation of ML.

Denoising proton therapy Monte Carlo dose distributions in multiple tumor sites: A comparative neural networks architecture study.

INTRODUCTION: Monte Carlo (MC) algorithms provide accurate modeling of dose calculation by simulating the delivery and interaction of many particles through patient geometry. Fast MC simulations using large number of particles are desirable as they can lead to reliable clinical decisions. In this work, we assume that faster simulations with fewer particles can approximate slower ones by denoising them with deep learning. MATERIALS AND METHODS: We use mean squared error (MSE) as loss function to train networks (sNet and dUNet), with 2.5D and 3D setups considering volumes of 7 and 24 slices. Our models are trained on proton therapy MC dose distributions of six different tumor sites acquired from 50 patients. We provide networks with input MC dose distributions simulated using 1 × 106 particles while keeping 1 × 109 particles as reference. RESULTS: On average over 10 new patients with different tumor sites, in 2.5D and 3D, our models recover relative residual error on target volume, ΔD95TV of 0.67 ± 0.43% and 1.32 ± 0.87% for sNet vs. 0.83 ± 0.53% and 1.66 ± 0.98% for dUNet, compared to the noisy input at 12.40 ± 4.06%. Moreover, the denoising time for a dose distribution is: < 9s and  < 1s for sNet vs. < 16s and  < 1.5s for dUNet in 2.5D and 3D, in comparison to about 100 min (MC simulation using 1 × 109 particles). CONCLUSION: We propose a fast framework that can successfully denoise MC dose distributions. Starting from MC doses with 1 × 106 particles only, the networks provide comparable results as MC doses with1 × 109 particles, reducing simulation time significantly.

Introducing a probabilistic definition of the target in a robust treatment planning framework.

The 'clinical target distribution' (CTD) has recently been introduced as a promising alternative to the binary clinical target volume (CTV). However, a comprehensive study that considers the CTD, together with geometric treatment uncertainties, was lacking. Because the CTD is inherently a probabilistic concept, this study proposes a fully probabilistic approach that integrates the CTD directly in a robust treatment planning framework. First, the CTD is derived from a reported microscopic tumor infiltration model such that it explicitly features the probability of tumor cell presence in its target definition. Second, two probabilistic robust optimization methods are proposed that evaluate CTD coverage under uncertainty. The first method minimizes the expected-value (EV) over the uncertainty scenarios and the second method minimizes the sum of the expected value and standard deviation (EV-SD), thereby penalizing the spread of the objectives from the mean. Both EV and EV-SD methods introduce the CTD in the objective function by using weighting factors that represent the probability of tumor presence. The probabilistic methods are compared to a conventional worst-case approach that uses the CTV in a worst-case optimization algorithm. To evaluate the treatment plans, a scenario-based evaluation strategy is implemented that combines the effects of microscopic tumor infiltrations with the other geometric uncertainties. The methods are tested for five lung tumor patients, treated with intensity-modulated proton therapy. The results indicate that for the studied patient cases, the probabilistic methods favor the reduction of the esophagus dose but compensate by increasing the high-dose region in a low conflicting organ such as the lung. These results show that a fully probabilistic approach has the potential to obtain clinical benefits when tumor infiltration uncertainties are taken into account directly in the treatment planning process.

Artificial intelligence supported single detector multi-energy proton radiography system.

Proton radiography imaging was proposed as a promising technique to evaluate internal anatomical changes, to enable pre-treatment patient alignment, and most importantly, to optimize the patient specific CT number to stopping-power ratio conversion. The clinical implementation rate of proton radiography systems is still limited due to their complex bulky design, together with the persistent problem of (in)elastic nuclear interactions and multiple Coulomb scattering (i.e. range mixing). In this work, a compact multi-energy proton radiography system was proposed in combination with an artificial intelligence network architecture (ProtonDSE) to remove the persistent problem of proton scatter in proton radiography. A realistic Monte Carlo model of the Proteus®One accelerator was built at 200 and 220 MeV to isolate the scattered proton signal in 236 proton radiographies of 80 digital anthropomorphic phantoms. ProtonDSE was trained to predict the proton scatter distribution at two beam energies in a 60%/25%/15% scheme for training, testing, and validation. A calibration procedure was proposed to derive the water equivalent thickness image based on the detector dose response relationship at both beam energies. ProtonDSE network performance was evaluated with quantitative metrics that showed an overall mean absolute percentage error below 1.4% ± 0.4% in our test dataset. For one example patient, detector dose to WET conversions were performed based on the total dose (ITotal), the primary proton dose (IPrimary), and the ProtonDSE corrected detector dose (ICorrected). The determined WET accuracy was compared with respect to the reference WET by idealistic raytracing in a manually delineated region-of-interest inside the brain. The error was determined 4.3% ± 4.1% forWET(ITotal),2.2% ± 1.4% forWET(IPrimary),and 2.5% ± 2.0% forWET(ICorrected).

openPR - A computational tool for CT conversion assessment with proton radiography.

PURPOSE: One of the main sources of uncertainty in proton therapy is the conversion of the Hounsfield Units of the planning CT to (relative) proton stopping powers. Proton radiography provides range error maps but these can be affected by other sources of errors as well as the CT conversion (e.g., residual misalignment). To better understand and quantify range uncertainty, it is desirable to measure the individual contributions and particularly those associated to the CT conversion. METHODS: A workflow is proposed to carry out an assessment of the CT conversion solely on the basis of proton radiographs of real tissues measured with a multilayer ionization chamber (MLIC). The workflow consists of a series of four stages: (a) CT and proton radiography acquisitions, (b) CT and proton radiography registration in postprocessing, (c) sample-specific validation of the semi-empirical model both used in the registration and to estimate the water equivalent path length (WEPL), and (d) WEPL error estimation. The workflow was applied to a pig head as part of the validation of the CT calibration of the proton therapy center PARTICLE at UZ Leuven, Belgium. RESULTS: The CT conversion-related uncertainty computed based on the well-established safety margin rule of 1.2 mm + 2.4% were overestimated by 71% on the pig head. However, the range uncertainty was very much underestimated where cavities were encountered by the protons. Excluding areas with cavities, the overestimation of the uncertainty was 500%. A correlation was found between these localized errors and HUs between -1000 and -950, suggesting that the underestimation was not a consequence of an inaccurate conversion but was probably rather due to the resolution of the CT leading to material mixing at interfaces. To reduce these errors, the CT calibration curve was adapted by increasing the HU interval corresponding to the air up to -950. CONCLUSION: The application of the workflow as part of the validation of the CT conversion to RSPs showed an overall overestimation of the expected uncertainty. Moreover, the largest WEPL errors were found to be related to the presence of cavities which nevertheless are associated with low WEPL values. This suggests that the use of this workflow on patients or in a generalized study on different types of animal tissues could shed sufficient light on how the contributions to the CT conversion-related uncertainty add up to potentially reduce up to several millimeters the uncertainty estimations taken into account in treatment planning. All the algorithms required to perform the workflow were implemented in the computational tool named openPR which is part of openREGGUI, an open-source image processing platform for adaptive proton therapy.

Linear Energy Transfer Incorporated Spot-Scanning Proton Arc Therapy Optimization: A Feasibility Study.

PURPOSE: To integrate dose-averaged linear energy transfer (LETd) into spot-scanning proton arc therapy (SPArc) optimization and to explore its feasibility and potential clinical benefits. METHODS: An open-source proton planning platform (OpenREGGUI) has been modified to incorporate LETd into optimization for both SPArc and multi-beam intensity-modulated proton therapy (IMPT) treatment planning. SPArc and multi-beam IMPT plans with different beam configurations for a prostate patient were generated to investigate the feasibility of LETd-based optimization using SPArc in terms of spatial LETd distribution and plan delivery efficiency. One liver and one brain case were studied to further evaluate the advantages of SPArc over multi-beam IMPT. RESULTS: With similar dose distributions, the efficacy of spatially optimizing LETd distributions improves with increasing number of beams. Compared with multi-beam IMPT plans, SPArc plans show substantial improvement in LETd distributions while maintaining similar delivery efficiency. Specifically, for the liver case, the average LETd in the GTV was increased by 124% for the SPArc plan, and only 9.6% for the 2-beam IMPT plan compared with the 2-beam non-LETd optimized IMPT plan. In case of LET optimization for the brain case, the SPArc plan could effectively increase the average LETd in the CTV and decrease the values in the critical structures while smaller improvement was observed in 3-beam IMPT plans. CONCLUSION: This work demonstrates the feasibility and significant advantages of using SPArc for LETd-based optimization, which could maximize the LETd distribution wherever is desired inside the target and averts the high LETd away from the adjacent critical organs-at-risk.