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.

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.

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.

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.

Quantifying the Dosimetric Impact of Proton Range Uncertainties on RBE-Weighted Dose Distributions in Intensity-Modulated Proton Therapy for Bilateral Head and Neck Cancer.

BACKGROUND: In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. METHODS: The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient's plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. RESULTS: The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (Dmean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (Dmax) values (2.78-10.75 Gy(RBE)). The Dmean and Dmax to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. CONCLUSION: The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans.

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.

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.

3D printed heterogeneous paediatric head and adult thorax phantoms for linear accelerator radiotherapy quality assurance: from fabrication to treatment delivery.

OBJECTIVE: This study aims to design and fabricate a 3D printed heterogeneous paediatric head phantom and to customize a thorax phantom for radiotherapy dosimetry. Approach: This study designed, fabricated, and tested 3D printed radiotherapy phantoms that can simulate soft tissue, lung, brain, and bone. Various polymers were considered in designing the phantoms. Polylactic acid+, nylon, and plaster were used in simulating different tissue equivalence. Dimensional accuracy, and CT number were investigated. The phantoms were subjected to a complete radiotherapy clinical workflow. Several treatment plans were delivered in both the head and the thorax phantom from a simple single 6 MV beam, parallel opposed beams, and five-field intensity modulated radiotherapy (IMRT) beams. Dose measurements using an ionization chamber and radiochromic films were compared with the calculated doses of the Varian Eclipse treatment planning system (TPS). Main results: The fabricated heterogeneous phantoms represent paediatric human head and adult thorax based on its radiation attenuation and anatomy. The measured CT number ranges are within -786.23 ± 10.55, 0.98 ± 3.86, 129.51 ± 12.83, and 651.14 ± 47.76 HU for lung, water/brain, soft tissue, and bone, respectively. It has a good radiological imaging visual similarity relative to a real human head and thorax depicting soft tissue, lung, bone, and brain. The accumulated dose readings for both conformal radiotherapy and IMRT match with the TPS calculated dose within ±2% and ±4% for head and thorax phantom, respectively. The mean pass rate for all the plans delivered are above 90% for gamma analysis criterion of 3% / 3 mm. Significance and conclusion: The fabricated heterogeneous paediatric head and thorax phantoms are useful in Linac end-to-end radiotherapy quality assurance based on its CT image and measured radiation dose. The manufacturing and dosimetry workflow of this study can be utilized by other institutions for dosimetry and trainings. .

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.

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.

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.

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.