Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to patient setup errors.

PURPOSE: This study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors. METHODS: Multiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription. Setup error was simulated using an in-house tool. Dose to targets was assessed via dose covering 99 % (D99 %) of gross tumour volume (GTV) and 98 % of planning target volume (PTV). Dose to organs at risk was assessed using volume of normal brain receiving 12 Gy and maximum dose covering 0.03 cc of brainstem. Plan complexity was assessed via edge metric, modulation complexity score, mean multi-leaf collimator (MLC) gap, mean MLC speed and plan modulation. RESULTS: Even for small (0.5 mm/°) errors, GTV D99 % was reduced by up to 20 %. The strongest correlation was found between lower complexity plans (larger mean MLC gap and lower edge metric) and higher robustness to setup error. Lower complexity plans had 1 %-20 % fewer targets/scenarios with GTV D99 % falling below the specified tolerance threshold. These complexity metrics correlated with 100 % isodose volume sphericity and dose conformity, though similar conformity was achievable with a range of complexities. CONCLUSIONS: A higher level of importance should be directed towards plan complexity when considering plan robustness. It is recommended when planning multi-target SRS, larger MLC gaps and lower MLC aperture irregularity be considered during plan optimisation due to higher robustness should patient positioning errors occur.

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.

HDR brachytherapy afterloader quality assurance optimization using monolithic silicon strip detectors.

BACKGROUND: There currently exists no widespread high dose-rate (HDR) brachytherapy afterloader quality assurance (QA) tool for simultaneously assessing the afterloader's positional, temporal, transit velocity and air kerma strength accuracy. PURPOSE: The purpose of this study was to develop a precise and rigorous technique for performing daily QA of HDR brachytherapy afterloaders, incorporating QA of: dwell position accuracy, dwell time accuracy, transit velocity consistency and relative air kerma strength (AKS) of an Ir-192 source. METHOD: A Sharp ProGuide 240 mm catheter (Elekta Brachytherapy, Veenendaal, The Netherlands) was fixed 5 mm above a 256 channel epitaxial diode array 'dose magnifying glass' (DMG256) (Centre for Medical and Radiation Physics, University of Wollongong). Three dwell positions, each of 5.0 s dwell times, were spaced 13.0 mm apart along the array with the Flexitron HDR afterloader (Elekta Brachytherapy, Veenendaal, The Netherlands). The DMG256 was connected to a data acquisition system (DAQ) and a computer via USB2.0 link for live readout and post-processing. The outputted data files were analyzed using a Python script to provide positional and temporal localization of the Ir-192 source by tracking the centroid of the detected response. Measurements were repeated on a weekly basis, for a period of 5 weeks to determine the consistency of the measured parameters over an extended period. RESULTS: Using the DMG256 for relative AKS measurements resulted in measured values within 0.6%-3.0% of the expected activity over a 7-week period. The sub-millisecond temporal accuracy of the device allowed for measurements of the transit velocity with an average of (10.88 ± 1.01) cm/s for 13 mm steps. The dwell position localization for 1, 2, 3, 5, and 10 mm steps had an accuracy between 0.1 and 0.3 mm (3σ), with a fixed temporal accuracy of 10 ms. CONCLUSION: The DMG256 silicon strip detector allows for clinics to perform rigorous daily QA of HDR afterloader dwell position and dwell time accuracy with greater precision than the current standard methodology using closed circuit television and a stopwatch. Additionally, DMG256 unlocks the ability to perform measurements of transit velocity/time and relative AKS, which are not possible using current standard techniques.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

Objective.To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy.Approach.Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results.Main results.Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions.Significance.The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

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.

Development of patient and catheter specific error thresholds for high dose rate prostate brachytherapy.

BACKGROUND: In-vivo source tracking has been an active topic of research in the field of high-dose rate brachytherapy in recent years to verify accuracy in treatment delivery. Although detection systems for source tracking are being developed, the allowable threshold of treatment error is still unknown and is likely patient-specific due to anatomy and planning variation. PURPOSE: The purpose of this study was to determine patient and catheter-specific shift error thresholds for in-vivo source tracking during high-dose-rate prostate brachytherapy (HDRPBT). METHODS: A module was developed in the previously described graphical processor unit multi-criteria optimization (gMCO) algorithm. The module generates systematic catheter shift errors retrospectively into HDRPBT treatment plans, performed on 50 patients. The catheter shift model iterates through the number of catheters shifted in the plan (from 1 to all catheters), the direction of shift (superior, inferior, medial, lateral, cranial, and caudal), and the magnitude of catheter shift (1-6 mm). For each combination of these parameters, 200 error plans were generated, randomly selecting the catheters in the plan to shift. After shifts were applied, dose volume histogram (DVH) parameters were re-calculated. Catheter shift thresholds were then derived based on plans where DVH parameters were clinically unacceptable (prostate V100 < 95%, urethra D0.1cc > 118%, and rectum Dmax > 80%). Catheter thresholds were also Pearson correlated to catheter robustness values. RESULTS: Patient-specific thresholds varied between 1 to 6 mm for all organs, in all shift directions. Overall, patient-specific thresholds typically decrease with an increasing number of catheters shifted. Anterior and inferior directions were less sensitive than other directions. Pearson's correlation test showed a strong correlation between catheter robustness and catheter thresholds for the rectum and urethra, with correlation values of -0.81 and -0.74, respectively (p < 0.01), but no correlation was found for the prostate. CONCLUSIONS: It was possible to determine thresholds for each patient, with thresholds showing dependence on shift direction, and number of catheters shifted. Not every catheter combination is explorable, however, this study shows the feasibility to determine patient-specific thresholds for clinical application. The correlation of patient-specific thresholds with the equivalent robustness value indicated the need for robustness consideration during plan optimization and treatment planning.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy.

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages [Formula: see text]B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector's circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target [Formula: see text]B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

The rationale for a carbon ion radiation therapy facility in Australia.

Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in Adelaide, other potential proton centres and an under-evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide-ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.

Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to delivery errors.

BACKGROUND: The use of modulated techniques for intra-cranial stereotactic radiosurgery (SRS) results in highly modulated fields with small apertures, which may be susceptible to uncertainties in the delivery device. PURPOSE: This study aimed to quantify the impact of simulated delivery errors on treatment plan dosimetry and how this is affected by treatment planning system (TPS), plan geometry, delivery technique, and plan complexity. A beam modelling error was also included as context to the dose uncertainties due to treatment delivery errors. METHODS: Delivery errors were assessed for multiple-target brain SRS plans obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets, each with a prescription of 20 Gy. Of the final dataset of 54 plans, 51 were created using the volumetric modulated arc therapy (VMAT) technique and three used intensity modulated arc therapy (IMRT). Thirty-five plans were from the Varian Eclipse TPS, 17 from Elekta Monaco TPS, and one plan each from RayStation and Philips Pinnacle TPS. The errors introduced included: monitor unit calibration errors, multi-leaf collimator (MLC) bank offset, single MLC leaf offset, couch rotations, and collimator rotations. Dosimetric leaf gap (DLG) error was also included as a beam modelling error. Dose to targets was assessed via dose covering 98% of planning target volume (PTV) (D98%), dose covering 2% of PTV (D2%), and dose covering 99% of gross tumor volume (GTV) (D99%). Dose to organs at risk (OARs) was assessed using the volume of normal brain receiving 12 Gy (V12Gy), mean dose to normal brain, and maximum dose covering 0.03cc brainstem (D0.03cc). Plan complexity was also assessed via edge metric, modulation complexity score (MCS), mean MLC gap, mean MLC speed, and plan modulation (PM). RESULTS: PTV D98% showed high robustness on average to most errors with the exception of a bank shift of 1.0 mm and large rotational errors ≥1.0° for either the couch or collimator. However, in some cases, errors close to or within generally accepted machine tolerances resulted in clinically relevant impacts. The greatest impact upon normal brain V12Gy, mean dose to normal brain, and D0.03cc brainstem was found for DLG error in alignment with other recent studies. All delivery errors had on average a minimal impact across these parameters. Comparing plans from the Monaco TPS and the Eclipse TPS, showed a lesser increase to V12Gy, mean dose to normal brain, and D0.03cc brainstem for Monaco plans (p < 0.01) when DLG error was simulated. Monaco plans also correlated to lower plan complexity. Using Spearman's correlation coefficient (r) a strong negative correlation (r ≤ -0.8) was found between the mean MLC gap and dose to OARs for DLG errors. CONCLUSIONS: Reducing MLC complexity and using larger mean MLC gaps is recommended to improve plan robustness and reduce sensitivity to delivery and modelling errors. For cases in which the calculated dose distribution or dose indices are close to the clinically acceptable limits, this is especially important.

A Monte Carlo model of the Dingo thermal neutron imaging beamline.

In this study, we present a validated Geant4 Monte Carlo simulation model of the Dingo thermal neutron imaging beamline at the Australian Centre for Neutron Scattering. The model, constructed using CAD drawings of the entire beam transport path and shielding structures, is designed to precisely predict the in-beam neutron field at the position at the sample irradiation stage. The model's performance was assessed by comparing simulation results to various experimental measurements, including planar thermal neutron distribution obtained in-beam using gold foil activation and [Formula: see text]B[Formula: see text]C-coated microdosimeters and the out-of-beam neutron spectra measured with Bonner spheres. The simulation results demonstrated that the predicted neutron fluence at the field's centre is within 8.1% and 2.1% of the gold foil and [Formula: see text]B[Formula: see text]C-coated microdosimeter measurements, respectively. The logarithms of the ratios of average simulated to experimental fluences in the thermal (E[Formula: see text] 0.414 eV), epithermal (0.414 eV < E[Formula: see text] 11.7 keV) and fast (E[Formula: see text] 11.7 keV) spectral regions were approximately - 0.03 to + 0.1, - 0.2 to + 0.15, and - 0.4 to + 0.2, respectively. Furthermore, the predicted thermal, epithermal and fast neutron components in-beam at the sample stage position constituted approximately 18%, 64% and 18% of the total neutron fluence.

In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment.

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.

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.

Accurate and Fast Deep Learning Dose Prediction for a Preclinical Microbeam Radiation Therapy Study Using Low-Statistics Monte Carlo Simulations.

Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumor diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Monte Carlo (MC) simulations are one of the most used methods at the Imaging and Medical Beamline, Australian Synchrotron to calculate the dose in MRT preclinical studies. The steep dose gradients associated with the 50µm-wide coplanar beamlets present a significant challenge for precise MC simulation of the dose deposition of an MRT irradiation treatment field in a short time frame. The long computation times inhibit the ability to perform dose optimization in treatment planning or apply online image-adaptive radiotherapy techniques to MRT. Much research has been conducted on fast dose estimation methods for clinically available treatments. However, such methods, including GPU Monte Carlo implementations and machine learning (ML) models, are unavailable for novel and emerging cancer radiotherapy options such as MRT. In this work, the successful application of a fast and accurate ML dose prediction model for a preclinical MRT rodent study is presented for the first time. The ML model predicts the peak doses in the path of the microbeams and the valley doses between them, delivered to the tumor target in rat patients. A CT imaging dataset is used to generate digital phantoms for each patient. Augmented variations of the digital phantoms are used to simulate with Geant4 the energy depositions of an MRT beam inside the phantoms with 15% (high-noise) and 2% (low-noise) statistical uncertainty. The high-noise MC simulation data are used to train the ML model to predict the energy depositions in the digital phantoms. The low-noise MC simulations data are used to test the predictive power of the ML model. The predictions of the ML model show an agreement within 3% with low-noise MC simulations for at least 77.6% of all predicted voxels (at least 95.9% of voxels containing tumor) in the case of the valley dose prediction and for at least 93.9% of all predicted voxels (100.0% of voxels containing tumor) in the case of the peak dose prediction. The successful use of high-noise MC simulations for the training, which are much faster to produce, accelerates the production of the training data of the ML model and encourages transfer of the ML model to different treatment modalities for other future applications in novel radiation cancer therapies.

A Geant4 shielding design for the first US carbon multi-ion hybrid synchrotron facility.

The Mayo Clinic Florida Integrated Oncology Building will be the home of the first spot-scanning only carbon/proton hybrid therapy system by Hitachi, Ltd. It will provide proton beams up to kinetic energies of 230 MeV and carbon beams up to 430 MeV n-1for clinical deployment. To provide adequate radiation protection, the Geant4 (v10.6) Monte Carlo toolkit was utilized to quantify the ambient dose equivalent at a 10 mm depth (H*(10)) for photons and neutrons. To perform accurate calculations of the ambient dose equivalent, three-dimensional computer-aided design files of the entire planned facility were imported into Geant4, as well as certain particle system components such as the bending magnets, fast Faraday cup, and gantry. Particle fluence was scored using 60 cm diameter spheres, which were strategically placed throughout areas of interests. Analytical calculations were performed as first-pass design checks. Major shielding slabs were optimized using Geant4 simulations iteratively, with more than 20 alternative designs evaluated within Geant4. The 430 MeV n-1carbon beams played the most significant role in concrete thickness Requirements. The primary wall thickness for the carbon fixed beam room is 4 meters. The presence of the proton gantry structure in the simulation caused the ambient dose equivalent to increase by around 67% at the maze entrance, but a decrease in the high energy beam transport corridor. All shielding primary and secondary goals for clinical operations were met per state regulation and national guidelines.

Feasibility of online adaptive HDR prostate brachytherapy: A novel treatment concept.

PURPOSE: The purpose of this study was to determine the feasibility of online adaptive transrectal ultrasound (TRUS)-based high-dose-rate prostate brachytherapy (HDRPBT) through retrospective simulation of source positioning and catheter swap errors on patient treatment plans. METHOD: Source positioning errors (catheter shifts in 1 mm increments in the cranial/caudal, anterior/posterior, and medial/lateral directions up to ±6 mm) and catheter swap errors (between the most and least heavily weighted) were introduced retrospectively into DICOM treatment plans of 20 patients that previously received TRUS HDRPBT. Dose volume histogram (DVH) indices were monitored as errors were introduced sequentially into individual catheters, simulating potential errors throughout treatment. Whenever DVH indices were outside institution thresholds: prostate V100% <95%, urethra D0.1cc >118% and rectum Dmax >80%, the plan was adapted using remaining catheters (i.e., simulating previous catheters as previously delivered). The final DVH indices were recorded. RESULTS: Prostate coverage (V100% >95%) could be maintained for source position errors up to 6 mm through online plan adaptation. The source position error at which the urethra D0.1cc and rectum Dmax was able to return to clinically acceptable levels using online adaptation varied between 6 mm to 1 mm, depending on the direction of the source position error and patient anatomy. After introduction of catheter swap errors to patient plans, prostate V100% was recoverable using online adaptation to near original plan characteristics. Urethra D0.1cc and rectum Dmax showed less recoverability. CONCLUSION: Online adaptive HDRPBT maintains the prostate V100% to clinically acceptable values for majority of directional shifts. However, the current online adaptive method may not correct for source position errors near organs at risk.

On the measurement uncertainty of microdosimetric quantities using diamond and silicon microdosimeters in carbon-ion beams.

PURPOSE: The purpose of this paper is to compare the response of two different types of solid-state microdosimeters, that is, silicon and diamond, and their uncertainties. A study of the conversion of silicon microdosimetric spectra to the diamond equivalent for microdosimeters with different geometry of the sensitive volumes is performed, including the use of different stopping power databases. METHOD: Diamond and silicon microdosimeters were irradiated under the same conditions, aligned at the same depth in a carbon-ion beam at the MedAustron ion therapy center. In order to estimate the microdosimetric quantities, the readout electronic linearity was investigated with three different methods, that is, the first being a single linear regression, the second consisting of a double linear regression with a channel transition and last a multiple linear regression by splitting the data into odd and even groups. The uncertainty related to each of these methods was estimated as well. The edge calibration was performed using the intercept with the horizontal axis of the tangent through the inflection point of the Fermi function approximation multi-channel analyzer spectrum. It was assumed that this point corresponds to the maximum energy difference of particle traversing the sensitive volume (SV) for which the residual range difference in the continuous slowing down approximation is equal to the thickness of the SV of the microdosimeter. Four material conversion methods were explored, the edge method, the density method, the maximum-deposition energy method and the bin-by-bin transformation method. The uncertainties of the microdosimetric quantities resulting from the linearization, the edge calibration and the detectors thickness were also estimated. RESULTS: It was found that the double linear regression had the lowest uncertainty for both microdosimeters. The propagated standard (k = 1) uncertainties on the frequency-mean lineal energy y ¯ F ${\bar{y}}_{\rm{F}}$ and the dose-mean lineal energy y ¯ D ${\bar{y}}_{\rm{D}}$ values from the marker point, in the spectra, in the plateau were 0.1% and 0.2%, respectively, for the diamond microdosimeter, whilst for the silicon microdosimeter data converted to diamond, the uncertainty was estimated to be 0.1%. In the range corresponding to the 90% of the amplitude of the Bragg Peak at the distal part of the Bragg curve (R90 ) the uncertainty was found to be 0.1%. The uncertainty propagation from the stopping power tables was estimated to be between 5% and 7% depending on the method. The uncertainty on the y ¯ F ${\bar{y}}_{\rm{F}}$ and y ¯ D ${\bar{y}}_{\rm{D}}$ coming from the thickness of the detectors varied between 0.3% and 0.5%. CONCLUSION: This article demonstrate that the linearity of the readout electronics affects the microdosimetric spectra with a difference in y ¯ F ${\bar{y}}_{\rm{F}}$ values between the different linearization methods of up to 17.5%. The combined uncertainty was dominated by the uncertainty of stopping power on the edge.

Microdosimetric investigation for multi-ion therapy by means of silicon on insulator (SOI) microdosimeter.

Objective.Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams.Approach.This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC.Main results.The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system.Significance.The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy.

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.