Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.

PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center. METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined. RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated. CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.

Characterization of a flat-panel detector for 2D dosimetry in scanned proton and carbon ion beams.

PURPOSE: To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams. MATERIALS AND METHODS: The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and dose rate dependence as well as its proportionality with an increasing number of particles and potential quenching effect. Potential radiation damage was evaluated. Finally, we compared the spot characterization (position and profile FWHM) with our radiochromic EBT3 film baseline. RESULTS: The detector showed a repeatability of 1.7% and 0.9% for single spots of protons and carbon ions, respectively, while for small scanned fields it was inferior to 0.2% for both particles. The response was independent from the dose rate (difference from nominal value < 1.5%). We observed an under-response due to quenching effect for both particles, mostly for carbon ions. No radiation damage effects were observed after two months of weekly use and approximately 1350 Gy delivered to the detector. Good agreement was found between the Sphinx and EBT3 films for the spot position (central-axis deviation within 1 mm). The spot size measured with the Sphinx was larger compared to films. For protons, the average and maximum differences over different energies were 0.4 mm (3%) and 1 mm (7%); for carbon ions they were 0.2 mm (4%) and 0.4 mm (6%). CONCLUSIONS: Despite the quenching effect the Sphinx Compact fulfills the requirements needed for constancy checks and could represent a time-saving tool for daily QA in scanned particle beams.

Implementation of Sphinx/Lynx as daily QA equipment for scanned proton and carbon ion beams.

PURPOSE: Reporting on the first implementation of a proton dedicated commercial device (IBA Sphinx/Lynx) for daily Quality Assurance (QA) of scanned proton and carbon ion beams. METHODS: Daily QA trendlines over more than 3 years for protons and more than 2 years for carbon ions have been acquired. Key daily QA parameters were reviewed, namely the spot size and position, beam range, Bragg peak width, coincidence (between beam and imaging system isocenters), homogeneity and dose. RESULTS: The performance of the QA equipment for protons and carbon ions was evaluated. Daily QA trendlines allowed us to detect machine performance drifts and changes. The definition of tolerances and action levels is provided and compared with levels used in the literature. CONCLUSION: The device has been successfully implemented for routine daily QA activities in a dual particle therapy facility for more than 2 years. It improved the efficiency of daily QA and provides a comprehensive QA process.

Monte Carlo computation of 3D distributions of stopping power ratios in light ion beam therapy using GATE-RTion.

PURPOSE: This paper presents a novel method for the calculation of three-dimensional (3D) Bragg-Gray water-to-detector stopping power ratio (sw,det ) distributions for proton and carbon ion beams. METHODS: Contrary to previously published fluence-based calculations of the stopping power ratio, the sw,det calculation method used in this work is based on the specific way GATE/Geant4 scores the energy deposition. It only requires the use of the so-called DoseActor, as available in GATE, for the calculation of the sw,det at any point of a 3D dose distribution. The simulations are performed using GATE-RTion v1.0, a dedicated GATE release that was validated for the clinical use in light ion beam therapy. RESULTS: The Bragg-Gray water-to-air stopping power ratio (sw,air ) was calculated for monoenergetic proton and carbon ion beams with the default stopping power data in GATE-RTion v1.0 and the new ICRU90 recommendation. The sw,air differences between the use of the default and the ICRU90 configuration were 0.6% and 5.4% at the physical range (R80 - 80% dose level in the distal dose fall-off) for a 70 MeV proton beam and a 120 MeV/u carbon ion beam, respectively. For protons, the sw,det results for lithium fluoride, silicon, gadolinium oxysulfide, and the active layer material of EBT2 (radiochromic film) were compared with the literature and a reasonable agreement was found. For a real patient treatment plan, the 3D distributions of sw,det in proton beams were calculated. CONCLUSIONS: Our method was validated by comparison with available literature data. Its equivalence with Bragg-Gray cavity theory was demonstrated mathematically. The capability of GATE-RTion v1.0 for the sw,det calculation at any point of a 3D dose distribution for simple and complex proton and carbon ion plans was presented.

Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy.

PURPOSE: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations. MATERIALS AND METHODS: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement. RESULTS AND DISCUSSION: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by γ-rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations. CONCLUSION: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies.

Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction.

The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX® does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX® presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.