Design, construction, and dosimetry of 3D printed heterogeneous phantoms for synchrotron brain cancer radiation therapy quality assurance.

Objective.This study aims to design, manufacture, and test 3D printed quality assurance (QA) dosimetry phantoms for synchrotron brain cancer radiation therapy at the Australian synchrotron.Approach.Fabricated 3D printed phantoms from simple slab phantoms, a preclinical rat phantom, and an anthropomorphic head phantom were fabricated and characterized. Attenuation measurements of various polymers, ceramics and metals were acquired using synchrotron monochromatic micro-computed tomography (CT) imaging. Polylactic acid plus, VeroClear, Durable resin, and tricalcium phosphate were used in constructing the phantoms. Furthermore, 3D printed bone equivalent materials were compared relative to ICRU bone and hemihydrate plaster. Homogeneous and heterogeneous rat phantoms were designed and fabricated using tissue-equivalent materials. Geometric accuracy, CT imaging, and consistency were considered. Moreover, synchrotron broad-beam x-rays were delivered using a 3 Tesla superconducting multipole wiggler field for four sets of synchrotron radiation beam qualities. Dose measurements were acquired using a PinPoint ionization chamber and compared relative to a water phantom and a RMI457 Solid Water phantom. Experimental depth doses were compared relative to calculated doses using a Geant4 Monte Carlo simulation.Main results.Polylactic acid (PLA+) shows to have a good match with the attenuation coefficient of ICRU water, while both tricalcium phosphate and hydroxyapatite have good attenuation similarity with ICRU bone cortical. PLA+ material can be used as substitute to RMI457 slabs for reference dosimetry with a maximum difference of 1.84%. Percent depth dose measurement also shows that PLA+ has the best match with water and RMI457 within ±2.2% and ±1.6%, respectively. Overall, PLA+ phantoms match with RMI457 phantoms within ±3%.Significance and conclusion.The fabricated phantoms are excellent tissue equivalent equipment for synchrotron radiation dosimetry QA measurement. Both the rat and the anthropomorphic head phantoms are useful in synchrotron brain cancer radiotherapy dosimetry, experiments, and future clinical translation of synchrotron radiotherapy and imaging.

Characterization of selected additive manufacturing materials for synchrotron monochromatic imaging and broad-beam radiotherapy at the Australian synchrotron-imaging and medical beamline.

Objective.This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline.Approach.Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities.Main results.Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments.Significance and conclusion.These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study.

Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy.

PURPOSE: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs). METHODS AND MATERIALS: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil. RESULTS: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 109 n/cm2/Gy (relative biological effectiveness) for the carbon beam and 5.8 × 109 n/cm2/Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions. CONCLUSIONS: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.

Assessment of cross-dose contributions from tumors within computational phantoms using a Geant4 radiation dosimetry tool exploiting hybrid analytical/voxelised geometries.

BACKGROUND: Dosimetry software tools developed for Radiopharmaceutical Therapy, such as OLINDA/EXM or IDAC-Dose, account only for radiation dose to organs from radiopharmaceutical taken up in other organs. PURPOSE: The aim of this study is to present a methodology, that can be applied to any voxelised computational model, able to account for cross-dose to organs from tumors of any shape and number enclosed within an organ. METHODS: A Geant4 application using hybrid analytical/voxelised geometries has been developed as an extension to the ICRP110_HumanPhantom Geant4 advanced example and validated against ICRP publication 133. In this new Geant4 application, tumors are defined using the Geant4 Parallel Geometry functionality, which allows the co-existence of two independent geometries in the same Monte Carlo simulation. The methodology was validated by estimating total dose to healthy tissue from 90 Y and from 177 Lu distributed within tumors of various sizes localized within the liver of the ICRP110 adult male phantom. RESULTS: Agreement of the Geant4 application with ICRP133 was within 5% when masses were adjusted for blood content. Total dose to healthy liver and to tumors was found to agree within 1% when compared to the ground truth. CONCLUSIONS: The methodology presented in this work can be extended to investigate total dose to healthy tissue from systemic uptake of radiopharmaceuticals in tumors of different sizes using any voxelised computational dosimetric model.

An inception network for positron emission tomography based dose estimation in carbon ion therapy.

Objective. We aim to evaluate a method for estimating 1D physical dose deposition profiles in carbon ion therapy via analysis of dynamic PET images using a deep residual learning convolutional neural network (CNN). The method is validated using Monte Carlo simulations of12C ion spread-out Bragg peak (SOBP) profiles, and demonstrated with an experimental PET image.Approach. A set of dose deposition and positron annihilation profiles for monoenergetic12C ion pencil beams in PMMA are first generated using Monte Carlo simulations. From these, a set of random polyenergetic dose and positron annihilation profiles are synthesised and used to train the CNN. Performance is evaluated by generating a second set of simulated12C ion SOBP profiles (one 116 mm SOBP profile and ten 60 mm SOBP profiles), and using the trained neural network to estimate the dose profile deposited by each beam and the position of the distal edge of the SOBP. Next, the same methods are used to evaluate the network using an experimental PET image, obtained after irradiating a PMMA phantom with a12C ion beam at QST's Heavy Ion Medical Accelerator in Chiba facility in Chiba, Japan. The performance of the CNN is compared to that of a recently published iterative technique using the same simulated and experimental12C SOBP profiles.Main results. The CNN estimated the simulated dose profiles with a mean relative error (MRE) of 0.7% ± 1.0% and the distal edge position with an accuracy of 0.1 mm ± 0.2 mm, and estimate the dose delivered by the experimental12C ion beam with a MRE of 3.7%, and the distal edge with an accuracy of 1.7 mm.Significance. The CNN was able to produce estimates of the dose distribution with comparable or improved accuracy and computational efficiency compared to the iterative method and other similar PET-based direct dose quantification techniques.

Characterizing magnetically focused contamination electrons by off-axis irradiation on an inline MRI-Linac.

PURPOSE: The aim of this study is to investigate off-axis irradiation on the Australian MRI-Linac using experiments and Monte Carlo simulations. Simulations are used to verify experimental measurements and to determine the minimum offset distance required to separate electron contamination from the photon field. METHODS: Dosimetric measurements were performed using a microDiamond detector, Gafchromic® EBT3 film, and MOSkinTM . Three field sizes were investigated including 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2 . Each field was offset a maximum distance, approximately 10 cm, from the central magnetic axis (isocenter). Percentage depth doses (PDDs) were collected at a source-to-surface distance (SSD) of 1.8 m for fields collimated centrally and off-axis. PDD measurements were also acquired at isocenter for each off-axis field to measure electron contamination. Monte Carlo simulations were used to verify experimental measurements, determine the minimum field offset distance, and demonstrate the use of a spoiler to absorb electron contamination. RESULTS: Off-axis irradiation separates the majority of electron contamination from an x-ray beam and was found to significantly reduce in-field surface dose. For the 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2 field, surface dose was reduced from 120.9% to 24.9%, 229.7% to 39.2%, and 355.3% to 47.3%, respectively. Monte Carlo simulations generally were within experimental error to MOSkinTM and microDiamond, and used to determine the minimum offset distance, 2.1 cm, from the field edge to isocenter. A water spoiler 2 cm thick was shown to reduce electron contamination dose to near zero. CONCLUSIONS: Experimental and simulation data were acquired for a range of field sizes to investigate off-axis irradiation on an inline MRI-Linac. The skin sparing effect was observed with off-axis irradiation, a feature that cannot be achieved to the same extent with other methods, such as bolusing, for beams at isocenter.

Quantitative analysis of dose-averaged linear energy transfer (LETd ) robustness in pencil beam scanning proton lung plans.

PURPOSE: The primary objective of our study was to perform a quantitative robustness analysis of the dose-averaged linear energy transfer (LETd ) and related RBE-weighted dose in robustly optimized (in terms of the range and set up uncertainties) pencil beam scanning (PBS) proton lung cancer plans. METHODS: In this study, we utilized the 4DCT dataset of six anonymized lung patients. PBS lung plans were generated using a robust optimization technique (range uncertainty: ±3.5% and setup errors: ±5 mm) on the CTV for a total dose of 5000 cGy (RBE) in five fractions using the RBE of 1.1. For each patient, the LETd distributions were calculated for the nominal plan and three groups. Group 1: two plan robustness scenarios for range uncertainties of ±3.5%; Group 2: twelve plan robustness scenarios (range uncertainty (±3.5%) in conjunction with setup errors (±5 mm)); and Group 3: ten different breathing phases of the 4DCT dataset. The RBE-weighted dose to the OARs was evaluated for all robustness scenarios and breathing phases. The variation (∆) in the mean LETd and mean RBE-weighted dose from each group was recorded. RESULTS: The mean LETd in the CTV of nominal PBS lung plans among six patients ranged from 2.2 to 2.6 keV/µm. On average, for the combined range and setup uncertainties, the ∆ in the mean LETd among 12 scenarios of all six patients was 0.6 keV/µm, which is slightly higher than when only the range uncertainties were considered (0.4 keV/µm). The ∆ in the mean LETd in a patient was ≤1.7 keV/µm in the heart and ≤1.2 keV/µm in the esophagus and total lung. The ∆ in the mean RBE-weighted dose in a patient was up to 79 cGy for the total lung, 165 cGy for the heart, and 258 cGy for the esophagus. For ten breathing phases, the ∆ in the mean LETd in a patient was ≤0.3 keV/µm in the CTV, ≤0.5 keV/µm in the heart, ≤0.4 keV/µm in the esophagus, and ≤0.7 keV/µm in the total lung. CONCLUSION: The addition of setup errors to the range uncertainties resulted in slightly less homogeneous LETd distributions. The variations in the mean LETd among the ten breathing phases were slightly larger in the total lung than in the heart and esophagus. The combination of setup and range uncertainties had a greater impact than the effect of breathing phases on the variations in the mean RBE-weighted dose to the OARs. Overall, the LETd distributions in the CTV were less sensitive than those in the OARs to setup errors, range uncertainties, and breathing phases for robustly optimized (in terms of range and setup uncertainities) PBS proton lung cancer plans.

A portable magnet for radiation biology and dosimetry studies in magnetic fields.

BACKGROUND AND PURPOSE: In the current and rapidly evolving era of real-time MRI-guided radiotherapy, our radiation biology and dosimetry knowledge is being tested in a novel way. This paper presents the successful design and implementation of a portable device used to generate strong localized magnetic fields. These are ideally suited for small-scale experiments that mimic the magnetic field environment inside an MRI-linac system, or more broadly MRI-guided particle therapy as well. MATERIALS AND METHODS: A portable permanent magnet-based device employing an adjustable steel yoke and magnetic field focusing cones has been designed, constructed, and tested. The apparatus utilizes two banks of Nd 2 $_{2}$ Fe 14 $_{14}$ B permanent magnets totaling around 50 kg in mass to generate a strong magnetic field throughout a small volume between two pole tips. The yoke design allows adjustment of the pole tip gap and exchanging of the focusing cones. Further to this, beam portal holes are present in the yoke and focusing cones, allowing for radiation beams of up to 5 × $\times$ 5 cm 2 $^{2}$ to pass through the region of high magnetic field between the focusing cone tips. Finite element magnetic modeling was performed to design and characterize the performance of the device. Automated physical measurements of the magnetic field components at various locations were measured to confirm the performance. The adjustable pole gap and interchangeable cones allows rapid changing of the experimental set-up to allow different styles of measurements to be performed. RESULTS: A mostly uniform magnetic field of 1.2 T can be achieved over a volume of at least 3 × $\times$ 3 × $\times$ 3 cm 3 $^{3}$ . This can be reduced in strength to 0.3 T but increased in volume to 10 × $\times$ 10 × $\times$ 10 cm 3 $^{3}$ via removal of the cone tips and/or adjustment of the steel yoke. Although small, these volumes are sufficient to house radiation detectors, cell culture dishes, and various phantom arrangements targeted at examining small radiation field dosimetry inside magnetic field strengths that can be changed with ease. Most important is the ability to align the magnetic field both perpendicular to, or inline with, the radiation beam. To date, the system has been successfully used to conduct published research in the areas of radiation detector performance, lung phantom dosimetry, and how small clinical electron beams behave in these strong magnetic fields. CONCLUSIONS: A portable, relatively inexpensive, and simple to operate device has successfully been constructed and used for performing radiation oncology studies around the theme of MRI-guided radiotherapy. This can be in either inline and perpendicular magnetic fields of up to 1.2 T with x-ray and particle beams.

Small spot size versus large spot size: Effect on plan quality for lung cancer in pencil beam scanning proton therapy.

PURPOSE: The purpose of the current study was to evaluate the impact of spot size on the interplay effect, plan robustness, and dose to the organs at risk for lung cancer plans in pencil beam scanning (PBS) proton therapy METHODS: The current retrospective study included 13 lung cancer patients. For each patient, small spot (∼3 mm) plans and large spot (∼8 mm) plans were generated. The Monte Carlo algorithm was used for both robust plan optimization and final dose calculations. Each plan was normalized, such that 99% of the clinical target volume (CTV) received 99% of the prescription dose. Interplay effect was evaluated for treatment delivery starting in two different breathing phases (T0 and T50). Plan robustness was investigated for 12 perturbed scenarios, which combined the isocenter shift and range uncertainty. The nominal and worst-case scenario (WCS) results were recorded for each treatment plan. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were evaluated for the total lung, heart, and esophagus. RESULTS: In comparison to large spot plans, the WCS values of small spot plans at CTV D95% , D96% , D97% , D98% , and D99% were higher with the average differences of 2.2% (range, 0.3%-3.7%), 2.3% (range, 0.5%-4.0%), 2.6% (range, 0.6%-4.4%), 2.7% (range, 0.9%-5.2%), and 2.7% (range, 0.3%-6.0%), respectively. The nominal and WCS mean dose and EUD for the esophagus, heart, and total lung were higher in large spot plans. The difference in NTCP between large spot and small spot plans was up to 1.9% for the total lung, up to 0.3% for the heart, and up to 32.8% for the esophagus. For robustness acceptance criteria of CTV D95% ≥ 98% of the prescription dose, seven small spot plans had all 12 perturbed scenarios meeting the criteria, whereas, for 13 large spot plans, there were ≥2 scenarios failing to meet the criteria. Interplay results showed that, on average, the target coverage in large spot plans was higher by 1.5% and 0.4% in non-volumetric and volumetric repainting plans, respectively. CONCLUSION: For robustly optimized PBS lung cancer plans in our study, a small spot machine resulted in a more robust CTV against the setup and range errors when compared to a large spot machine. In the absence of volumetric repainting, large spot PBS lung plans were more robust against the interplay effect. The use of a volumetric repainting technique in both small and large spot PBS lung plans led to comparable interplay target coverage.

Response of SOI microdosimeter in fast neutron beams: experiment and Monte Carlo simulations.

In this study, Monte Carlo codes, Geant4 and MCNP6, were used to characterize the fast neutron therapeutic beam produced at iThemba LABS in South Africa. Experimental and simulation results were compared using the latest generation of Silicon on Insulator (SOI) microdosimeters from the Centre for Medical Radiation Physics (CMRP). Geant4 and MCNP6 were able to successfully model the neutron gantry and simulate the expected neutron energy spectrum produced from the reaction by protons bombarding a 9Be target. The neutron beam was simulated in a water phantom and its characteristics recorded by the silicon microdosimeters; bare and covered by a 10B enriched boron carbide converter, at different positions. The microdosimetric quantities calculated using Geant4 and MCNP6 are in agreement with experimental measurements. The thermal neutron sensitivity and production of 10B capture products in the p+ boron-implanted dopant regions of the Bridge microdosimeter is investigated. The obtained results are useful for the future development of dedicated SOI microdosimeters for Boron Neutron Capture Therapy (BNCT). This paper provides a benchmark comparison of Geant4 and MCNP6 capabilities in the context of further applications of these codes for neutron microdosimetry.

On the evaluation of edgeless diode detectors for patient-specific QA in high-dose stereotactic radiosurgery.

PURPOSE: In this work, the potential of an innovative "edgeless" silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain. METHODS: The edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly. RESULTS: The reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV. CONCLUSIONS: The angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities.

Impact of errors in spot size and spot position in robustly optimized pencil beam scanning proton-based stereotactic body radiation therapy (SBRT) lung plans.

PURPOSE: The purpose of the current study was threefold: (a) investigate the impact of the variations (errors) in spot sizes in robustly optimized pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans, (b) evaluate the impact of spot sizes and position errors simultaneously, and (c) assess the overall effect of spot size and position errors occurring simultaneously in conjunction with either setup or range errors. METHODS: In this retrospective study, computed tomography (CT) data set of five lung patients was selected. Treatment plans were regenerated for a total dose of 5000 cGy(RBE) in 5 fractions using a single-field optimization (SFO) technique. Monte Carlo was used for the plan optimization and final dose calculations. Nominal plans were normalized such that 99% of the clinical target volume (CTV) received the prescription dose. The analysis was divided into three groups. Group 1: The increasing and decreasing spot sizes were evaluated for ±10%, ±15%, and ±20% errors. Group 2: Errors in spot size and spot positions were evaluated simultaneously (spot size: ±10%; spot position: ±1 and ±2 mm). Group 3: Simulated plans from Group 2 were evaluated for the setup (±5 mm) and range (±3.5%) errors. RESULTS: Group 1: For the spot size errors of ±10%, the average reduction in D99% for -10% and +10% errors was 0.7% and 1.1%, respectively. For -15% and +15% spot size errors, the average reduction in D99% was 1.4% and 1.9%, respectively. The average reduction in D99% was 2.1% for -20% error and 2.8% for +20% error. The hot spot evaluation showed that, for the same magnitude of error, the decreasing spot sizes resulted in a positive difference (hotter plan) when compared with the increasing spot sizes. Group 2: For a 10% increase in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the average reduction in D99% was 1.5% (1.8%). For a 10% decrease in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the reduction in D99% was 0.8% (0.9%). For the spot size errors of ±10% and spot position errors of ±2 mm, the average reduction in D99% was 2.4%. Group 3: Based on the results from 160 plans (4 plans for spot size [±10%] and position [±1 mm] errors × 8 scenarios × 5 patients), the average D99% was 4748 cGy(RBE) with the average reduction of 5.0%. The isocentric shift in the superior-inferior direction yielded the least homogenous dose distributions inside the target volume. CONCLUSION: The increasing spot sizes resulted in decreased target coverage and dose homogeneity. Similarly, the decreasing spot sizes led to a loss of target coverage, overdosage, and degradation of dose homogeneity. The addition of spot size and position errors to plan robustness parameters (setup and range uncertainties) increased the target coverage loss and decreased the dose homogeneity.

Impact of proton dose calculation algorithms on the interplay effect in PBS proton based SBRT lung plans.

Purpose. The purpose of the current study was to investigate the impact of RayStation analytical pencil beam (APB) and Monte Carlo (MC) algorithms on the interplay effect in pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans.Methods. The currentin-silicoplanning study was designed for a total dose of 5000 cGy(RBE) with a fractional dose of 1000 cGy(RBE). First, three sets of nominal plans were generated for each patient: (a) APB optimization followed by APB dose calculation (PB-PB), (b) APB optimization followed by MC dose calculation (PB-MC), and (c) MC optimization followed by MC dose calculation (MC-MC). Second, for each patient, two sets of volumetric repainting plans (five repaintings) - PB-MCVR5and MC-MCVR5were generated based on PB-MC and MC-MC, respectively. Dosimetric differences between APB and MC algorithms were calculated on the nominal and interplay dose-volume-histograms (DVHs).Results. Interplay evaluation in non-volumetric repainting plans showed that APB algorithm overestimated the target coverage by up to 8.4% for D95%and 10.5% for D99%, whereas in volumetric repainting plans, APB algorithm overestimated by up to 5.3% for D95%and 7.0% for D99%. Interplay results for MC calculations showed a decrease in D95%and D99%by average differences of 3.5% and 4.7%, respectively, in MC-MC plans and by 1.8% and 3.0% in MC-MCVR5plans.Conclusion. In PBS proton-based SBRT lung plans, the combination of APB algorithm and interplay effect reduced the target coverage. This may result in inferior local control. The use of MC algorithm for both optimization and final dose calculations in conjunction with the volumetric repainting technique yielded superior target coverage.

In-field and out-of-field microdosimetric characterisation of a 62 MeV proton beam at CATANA.

PURPOSE: A 5 and 10 µm thin silicon on insulator (SOI) 3D mushroom microdosimeter was used to characterize both the in-field and out-of-field of a 62 MeV proton beam. METHODS: The SOI mushroom microdosimeter consisted of an array of cylindrical sensitive volumes (SVs), developed by the Centre for Medical Radiation Physics, University of Wollongong, was irradiated with 62 MeV protons at the CATANA (Centro di AdroTerapia Applicazioni Nucleari Avanzate) facility in Catania, Italy, a facility dedicated to the radiation treatment of ocular melanomas. Dose mean lineal energy, ( y D ¯ ), values were obtained at various depths in PMMA along a pristine and spread out Bragg peak (SOBP). The measured microdosimetric spectra at each position were then used as inputs into the modified Microdosimetric Kinetic Model (MKM) to derive the RBE for absorbed dose in a middle of the SOBP 2Gy (RBED ). Microdosimetric spectra were obtained with both the 5 and 10 µm 3D SOI microdosimeters, with a focus on the distal part of the BP. The in-field and out-of-field measurement configurations along the Bragg curve were modeled in Geant4 for comparison with experimental results. Lateral out-of-field measurements were performed to study secondary particles' contribution to normal tissue's dose, up to 12 mm from the edge of the beam field, and quality factor and dose equivalent results were obtained. RESULTS: Comparison between experimental and simulation results showed good agreement between one another for both the pristine and SOBP beams in terms of y D ¯ and RBED. Though a small discrepancy between experiment and simulation was seen at the entrance of the Bragg curve, where experimental results were slightly lower than Geant4. The dose equivalent value measured 12 mm from the edge of the target volume was 1.27 ± 0.15 mSv/Gy with a Q ¯ value of 2.52 ± 0.30, both of which agree within uncertainty with Geant4 simulation. CONCLUSIONS: These results demonstrate that SOI microdosimeters are an effective tool to predict RBED in-field as well as dose equivalent monitoring out-of-field to provide insight to probability of second cancer generation.

Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy.

PURPOSE: The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order ("down" and "up" directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. METHOD: The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst-case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. RESULTS: The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95%  ≥ 98% and D99%  ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1%  < 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI < 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 3 to 10, whereas for the high-dose region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation. CONCLUSION: The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion < 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient-specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment.

Consistency of small-field dosimetry, on and off axis, in beam-matched linacs used for stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) can be delivered with a standard linear accelerator (linac). At institutions having more than one linac, beam matching is common practice. In the literature, there are indications that machine central axis (CAX) matching for broad fields does not guarantee matching of small fields with side ≤2 cm. There is no indication on how matching for broad fields on axis translates to matching small fields off axis. These are of interest to multitarget single-isocenter (MTSI) SRS planning and the present work addresses that gap in the literature. METHODS: We used 6 MV flattening filter free (FFF) beams from four Elekta VersaHD® linacs equipped with an Agility™ multileaf collimator (MLC). The linacs were strictly matched for broad fields on CAX. We compared output factors (OPFs) and effective field size, measured concurrently using a novel 2D solid-state dosimeter "Duo" with a spatial resolution of 0.2 mm, in square and rectangular static fields with sides from 0.5 to 2 cm, either on axis or away from it by 5 to 15 cm. RESULTS: Among the four linacs, OPF for fields ≥1 × 1 cm2 ranged 1.3% on CAX, whereas off axis a maximum range of 1.9% was observed at 15 cm. A larger variability in OPF was noted for the 0.5 × 0.5 cm2 field, with a range of 5.9% on CAX, which improved to a maximum of 2.3% moving off axis. Two linacs showed greater consistency with a range of 1.4% on CAX and 2.2% at 15 cm off axis. Between linacs, the effective field size varied by <0.04 cm in most cases, both on and off axis. Tighter matching was observed for linacs with a similar focal spot position. CONCLUSIONS: Verification of small-field consistency for matched linacs used for SRS is an important task for dosimetric validation. A significant benefit of concurrent measurement of field size and OPF allowed for a comprehensive assessment using a novel diode array. Our study showed the four linacs, strictly matched for broad fields on CAX, were still matched down to a field size of 1 x 1 cm2 on and off axis.

Estimating the biological effects of helium, carbon, oxygen, and neon ion beams using 3D silicon microdosimeters.

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm3, treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

Dose quantification in carbon ion therapy using in-beam positron emission tomography.

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

Impact of magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and beam range in pencil beam scanning proton therapy.

PURPOSE: The objective of this study was to evaluate the impact of the magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and range in pencil beam scanning proton therapy. METHODS: "Field regulation" - a feature to reduce the switching time between layers by applying a magnetic field setpoint (instead of a current setpoint) has been implemented on the proton beam delivery system at the Miami Cancer Institute. To investigate the impact of field regulation for the volumetric repainting technique, several spot maps were generated with beam delivery sequence in both directions, that is, irradiating from the deepest layer to the most proximal layer ("down" direction) as well as irradiating from the most proximal layer to the deepest layer ("up" direction). Range measurements were performed using a multi-layer ionization chamber array. Spot positions were measured using two-dimensional and three-dimensional scintillation detectors. For range and central-axis spot position, spot maps were delivered for energies ranging from 70-225 MeV. For off-axis spot positions, the maps were delivered for high-, medium, and low-energies at eight different gantry angles. The results were then compared between the "up" and "down" directions. RESULTS: The average difference in range for given energy between "up" and "down" directions was 0.0 ± 0.1 mm. The off-axis spot position results showed that 846/864 of the spots were within ±1 mm, and all off-axis spot positions were within ±1.2 mm. For spots (n = 126) at the isocenter, the evaluation between "up" and "down" directions for given energy showed the spot position difference within ±0.25 mm. At the nozzle entrance, the average differences in X and Y positions for given energy were 0.0 ± 0.2 mm and -0.0 ± 0.4 mm, respectively. At the nozzle exit, the average differences in X and Y positions for given energy were 0.0 ± 0.1 mm and -0.1 ± 0.1 mm, respectively. CONCLUSION: The volumetric repainting technique in magnetic field regulation mode resulted in acceptable spot position and range differences for our beam delivery system. The range differences were found to be within ±1 mm (TG224). For the spot positions (TG224: ±1 mm), the central axis measurements were within ±1 mm, whereas for the off-axis measurements, 97.9% of the spots were within ±1 mm, and all spots were within ±1.2 mm.

eXaSkin: A novel high-density bolus for 6MV X-rays radiotherapy.

PURPOSE: To evaluate eXaSkin, a novel high-density bolus alternative to commercial tissue-equivalent Superflab, for 6MV photon-beam radiotherapy. MATERIALS AND METHODS: We delivered a 10 × 10 cm2 open field at 90° and head-and-neck clinical plan, generated with the volumetric modulated arc therapy (VMAT) technique, to an anthropomorphic phantom in three scenarios: with no bolus on the phantom's surface, with Superflab, and with eXaSkin. In each scenario, we measured dose to a central planning target volume (PTV) in the nasopharynx region with an ionization chamber, and we measured dose to the skin, at three different positions within the vicinity of a neck lymph node PTV, with MOSkin™, a semiconductor dosimeter. Measurements were compared against calculations with the treatment planning system (TPS). RESULTS: For the static field, MOSkin results underneath the eXaSkin were in agreement with calculations to within 1.22%; for VMAT, to within 5.68%. Underneath Superflab, those values were 3.36% and 11.66%. The inferior agreement can be explained by suboptimal adherence of Superflab to the phantom's surface as well as difficulties in accurately reproducing its placement between imaging and treatment session. In all scenarios, dose measured at the central target agreed to within 1% with calculations. CONCLUSIONS: eXaSkin was shown to have superior adaptation to the phantom's surface, producing minimal air gaps between the skin surface and bolus, allowing for accurate positioning and reproducibility of set-up conditions. eXaSkin with its high density material provides sufficient build-up to achieve full skin dose with less material thickness than Superflab.