Treatment Head Research Articles

Development of an EGSnrc multi-leaf collimator component module and treatment head model for a low-field MRI linear accelerator.

Monte Carlo (MC) modeling of MR-guided radiotherapy (MRgRT) treatment machines enables the characterization of photon/electron interactions in the presence of a magnetic field. The EGSnrc MC code system is a well-established system for radiation dose calculations. The multi-leaf collimator (MLC) component modules presently available within the EGSnrc MC code system do not include a model of the double-focused MLC available on a low-field (0.35T) MRI linear accelerator (MR linac). Here we developed and validated a new component module (CM) for the low-field MRgRT MLC using the EGSnrc/BEAMnrc/DOSXYZnrc code system. We performed detailed modeling of the treatment head and validated the model using measurements and calculations from the vendor-specific treatment planning system (TPS). The detailed geometry of the low-field MR linac MLC and other treatment head structures were modeled using BEAMnrc. Comparisons of DOSXYZnrc simulated dose against measurements and the low-field MR linac TPS for a variety of AAPM TG-53 task group report suggested square and shaped fields, as well as a step-and-shoot intensity-modulated radiotherapy (IMRT) plan, are presented. Our model agrees with both measured and TPS calculated data on average within 2%/2mm (dose/DTA) criterion for square field profiles. Output factors agreed within 1% for field sizes down to 2.49×2.49cm2 and within 2% of TPS data for the smallest field size of 0.83×0.83cm2. Shaped field and IMRT MC calculations agreed with measured and TPS data such that the gamma pass rates (3%/2mm) were 99.5% and (3%/3mm) 96.2%, respectively. We developed and validated an MLC CM (SYNCVRMLC) for the low-field MR linac using the EGSnrc MC code systems. This new CM will facilitate MC computation of fluence and dose distributions using BEAMnrc/DOSXYZnrc for patients treated on the low-field MR linac.

“Comparative Evaluation Of The Pre And Post Treatment Head Postural Change In Completely Edentulous Patients Rehabilitated With Complete Dentures - An In Vivo Prospective Study”

“Comparative Evaluation Of The Pre And Post Treatment Head Postural Change In Completely Edentulous Patients Rehabilitated With Complete Dentures - An In Vivo Prospective Study”

Transcutaneous Transmission of Light of Photobiomodulation Therapy Wavelengths at 808 nm, 915 nm, 975 nm, and 1064 nm to the Spinal Canal of Cadaver Dogs

This study compared the transcutaneous target level irradiances from the thoracic to lumbar segments of the interior spinal canal in three cadaver dogs, measured for light at four wavelengths (808 nm, 915 nm, 975 nm, and 1064 nm), common in photobiomodulation therapy (PBMT). Intra-spinal irradiances at nine sites spanning approximately 8 cm in length were measured using a flexible intra-spinal probe under surface application of continuous-wave (CW) light with powers ranging from 0.5 W to 2 W. Surface illumination was applied using an acupuncture treatment head in three modes: non-contact with skin removed, non-contact with skin intact, and contact with skin intact. During surface application, the treatment head was positioned over the spinal canal near the 13th vertebrae (T13, surface site 1), and approximately 4 cm (surface site 5) and 8 cm (surface site 9) caudal to T13. At each position of the treatment head, the light was multiplexed among the four wavelengths at the same power setting. In all three modes of surface application, the target level irradiance at the 1064 nm wavelength was significantly greater than that at the other three wavelengths (p ≤ 0.0017). At a surface irradiance of ~157 mW/cm2, corresponding to 0.5 W light applied with the treatment head directly in contact with the skin, the intra-spinal irradiance at 1064 nm reached 0.137 ± 0.095 mW/cm2. Obtaining a dosage of PBMT-associative wavelengths of this magnitude at the level of the spinal canal may guide focused research into the transcutaneous applicability of PBMT for spinal cord injuries.

Monte Carlo Simulation for the Radixact™ Tomotherapy Linac Using EGSnrc.

When exact information regarding the treatment head and initial electron beam is available, the Monte Carlo (MC) approach can properly simulate any linear accelerator. However, manufacturers seldom offer information such as the incident electron beam's energy, radial intensity (spot size), or angular spread. This research aims to forecast these features and verify an MC-simulated linear accelerator model using measurements. The BEAMnrc code simulated a 6 MV photon beam from a Radixact™ Tomotherapy Linac. Percentage depth dose and beam profile calculations were conducted using DOSYXZnrc by various electron energies and spot sizes and compared to measurements using a Gamma index with two distinct criterion sets. Furthermore, the fine-tuned electron energy and spot size profiles were created to minimize any disparities using distinct angle spreads. Finally, the output factors (OFs) for various field sizes were compared. The MC model's fine-tuned electron energy was determined to be 5.8 MeV, with 88.6% of the calculation points passing the 1%/1 mm γ test. A circular radial intensity of 1.4 mm best represented the 6 MV photon beam regarding spot size. Furthermore, a mean angular spread of 0.05 reduced the disparity in cross-field profile between computation and measurement. The most considerable disparities between the MC model OFs and observations were 1.5%. Using the BEAMnrc code, a reliable MC model of the Radixact™ Tomotherapy Linac can be created, as shown in this paper. This model can be used to compute dose distributions with confidence.

Development and verification of a Geant4 model of the electron beam mode in a clinical linear accelerator

At present, a significant number of studies are focused on the development of novel methodologies for the fabrication of dosimetry phantoms. One of these methods is to produce heterogeneous samples by 3D printing. In order to select the most appropriate parameters for such products, it is necessary to conduct numerical simulations. In this work, we developed the model of a beam-forming system using a medical linear accelerator as a reference. This model was used to determine simulation parameters and corresponding dose distributions of an electron beam with nominal energies of 6, 12, and 15 MeV in a homogeneous water phantom. These parameters were, in fact, adapted to provide maximum agreement between simulated distributions and those experimentally obtained with the clinical linear accelerator. The beam simulation was performed using the Geant4 Monte Carlo toolkit. The simulation geometry of the accelerator treatment head includes scattering foil and a flattening filter, which are designed for electron beam broadening. Additionally, the beam-forming system was incorporated to collimate the beam to the required size. A metal applicator was included to reduce the contribution of electron scattering in air. The main simulation parameters were iteratively tuned by comparing simulation results with experimentally obtained data. It is shown that the simulated percentage depth dose and transverse profiles for electron beams in water phantom are in good agreement with the experimental data obtained with a cylindrical ionization chamber. This demonstrates that the methodology employed in the development of the numerical model of the medical linear accelerator is vendor-independent, readily implementable, and allows for rapid calculations. Furthermore, the model can be applied for a variety of purposes, including the selection of parameters for the fabrication of heterogeneous dosimetry phantoms.

Acetabular coverage exerts minimal influence on femoral head collapse and the necessity for surgical intervention in patients with osteonecrosis of femoral head

PurposeThe acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse.MethodsThe study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated.ResultsThere were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse.ConclusionsAcetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.

Determination of kilovoltage x-ray therapy depth doses with open-ended applicators.

The purpose of this work was to determine percentage depth dose (PDD) curves for kilovoltage x-rays from the WOmed-T105 unit, with open-ended steel applicators and beam qualities ranging from 0.5 to 4.2mm Al. Measurements were made with parallel plate chambers in a water phantom, with extrapolation based on a fifth order polynomial used to estimate the surface dose. Measurements were also made with parallel plate chambers in a plastic water phantom, with thin plastic sheets used to obtain detailed measurements at shallow depths (less than 1mm). Monte Carlo simulations were performed using the EGSnrc package, with two different sources as input: a SpekPy simulation of the x-ray beam and a full simulation of the x-ray tube, treatment head and applicators. Results showed that all four methods (two measurements and two simulations) agreed within the measurement uncertainty at depths greater than 2mm. At shallow depths, significant differences were noted. At depths less than 0.1mm, the full Monte Carlo simulation and the solid water measurements showed a sharp spike in surface dose which is attributed to electron contamination, which was not seen in the SpekPy Monte Carlo simulation or the extrapolated water measurements. At depths between 0.1mm and 2mm, beyond the range of contaminant electrons, the extrapolated water measurements underestimate the dose by up to 13% compared to the full Monte Carlo simulation and the solid water measurements, attributed to fluorescent photons generated in the applicators. This work demonstrates that for open-ended applicators, measurement of depth doses in water with extrapolation of surface dose has the potential to significantly underestimate the dose at shallow depths between the surface and 2mm, even after eliminating electron contamination from the beam.

Research Photon Energy Spectrum of Medical Linear Accelerator by Monte Carlo Method

The distribution of the photon energy spectrum in isocenter plane of the medical linear accelerator and the influence of secondary collimator on the photon energy spectrum are studied. Methods Use the BEAMnrc program to simulate the transmission of the 6 MeV electrons and photons in 5 cm×5 cm,10 cm×10 cm,15 cm×15 cm and 20 cm×20 cm fields in treatment head of the medical linear accelerator, where a phase space file was set up at the isocenter plane to record the particle information passing through this plane. The BEAMdp program is used to analyze the phase space file, in order to obtain the distribution of the photon energy spectrum in isocenter plane and the influence of secondary collimator on the photon energy spectrum. By analyzing the photon energy spectrum of a medical linear accelerator with a nominal energy of 6 MV, it is found that the secondary collimator has little effect on the photon energy spectrum; different fields have different photon energy spectrum distributions; the photon energy spectrum in different central regions of the same field have the same normalized distribution. In the dose calculation of radiation therapy, the influence of photon energy spectrum should be carefully considered.

Extended in-field and out-of-field validation of a compact Monte Carlo model of an IBA PROTEUS®ONE proton beam in TOPAS/GEANT4

Objective: This study evaluates a compact Monte Carlo (MC) model of a pencil beam scanning clinical proton beam using TOPAS to estimate the dose out-of-field (OOF). Compact modelling means that the model starts from a pristine proton beam at the nozzle exit, customised based on acceptance and commissioning data, instead of modelling the full treatment head and room. Approach: First, in-field validation tests were performed. Then, the OOF dose was validated in an RW3 phantom with bubble detectors for personal neutron dosimetry (measuring the neutron dose equivalent) and thermoluminiescent detectors (measuring the absorbed dose by protons and gammas). Measurements were performed at 15 and 35 cm from the distal edge of the field for five different irradiation plans, covering different beam orientations, proton energies and a 40 mm range shifter. TOPAS simulations were performed with QGSP Binary Cascade HP (BIC) and QGSP Bertini HP (Bertini) hadron physics lists. Main results: In-field validation shows that MC simulations agree with point dose measurements within −2.5 % and +1.5 % at locations on- and off-axis and before, in and after the Bragg peak or plateau. The gamma passing rate 2%/3mm of four simulated treatment plans compared to the dose distribution calculated by the TPS exceeds 97 % agreement score. OOF dose simulations showed an average overestimation of 27 % of the neutron dose equivalent for the BIC hadron physics list and an average underestimation of 20 % for the Bertini hadron physics list. The simulated absorbed dose of protons and gammas showed a systematic underestimation which was on average 21 % and 51 % for BIC and Bertini respectively. Significance: Our study demonstrates that a compact MC model can reliably produce in-field data, while out-of-field dose data are within the uncertainties of the detector systems and MC simulations nuclear models, and do so with shorter modelling and faster calculation time.

Clinical Characterization of a Novel Robotic IORT Unit

A novel mobile robotically-guided low-energy intra-operative radiation therapy device was characterized for clinical use. The compact system offers flexible positioning with treatment delivery up to 70 kV energy and 10 Gy/min dose rate with radially collimated emission, and underwent characterization for its dosimetric performance, positioning accuracy and overall clinical suitability. The Morpheus system (Empyrean Medical Systems) consists of a miniature electron esource and a partitioned partial-transmission tungsten target capable of producing 50, 60, and 70 kVp x-rays, mounted on a robotic arm and supported by a motorized mobile base. The radially collimated beam is partitioned in six segments with three radial positions per segment for selective emission, target irradiation and tissue sparing. The beam characteristics were assessed with ion chamber and film dosimetry, both in-air and in a water tank. Radiation levels were assessed for safety and shielding requirements. The absolute dose rate at the surface of a 2 cm radius sterilizable treatment balloon is 8 Gy/min for the 70 kV beam using the AAPM TG-61 formalism. The six treatments sectors emit radially in 60 degrees wedges to within +/- 15% of each other, which can be simply corrected for treatment delivery. The dose falls off to 50% of its initial value within 8 mm from the surface of a treatment balloon for a 70 kV beam. The robotic arm enables a free-hand positioning of the X-ray treatment head to within 1 mm. All interlocks and sterility requirements for operation within an operating room environment were found to be satisfactory. Radiation levels require mobile shielding or a shielded room to be within permissible public radiation levels. The clinical characterization shows the new unit provides a stable and flexible beam delivery platform suitable for IORT treatments. The simplified docking and collimated beam emission provides enhanced capabilities for patient treatment.

Shielding Analysis of a Preclinical Bremsstrahlung X-ray FLASH Radiotherapy System within a Clinical Radiation Therapy Vault.

A preclinical radiotherapy system producing FLASH dose rates with 12 MV bremsstrahlung x rays is being developed at Stanford University and SLAC National Accelerator Laboratory. Because of the high expected workload of 6,800 Gy w -1 at the isocenter, an efficient shielding methodology is needed to protect operators and the public while the preclinical system is operated in a radiation therapy vault designed for 6 MV x rays. In this study, an analysis is performed to assess the shielding of the local treatment head and radiation vault using the Monte Carlo code FLUKA and the empirical methodology given in the National Council on Radiation Protection and Measurements Report 151. Two different treatment head shielding designs were created to compare single-layer and multilayer shielding methodologies using high-Z and low-Z materials. The multilayered shielding methodology produced designs with a 17% reduction in neutron fluence leaking from the treatment head compared to the single layered design of the same size, resulting in a decreased effective dose to operators and the public. The conservative assumptions used in the empirical methods can lead to over-shielding when treatment heads use polyethylene or multilayered shielding. High-Z/Low-Z multilayered shielding optimized via Monte Carlo is shown to be effective in the case of treatment head shielding and provide more effective shielding design for external beam radiotherapy systems that use 12 MV bremsstrahlung photons. Modifications to empirical methods used in the assessment of MV radiotherapy systems may be warranted to capture the effects of polyethylene in treatment head shielding.

Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells.

Despite the relative effectiveness of standard cancer treatment strategies, head and neck cancer (HNC) is still considered one of the leading causes of mortality and morbidity. While selected bioactive compounds of plant origin reveal a pro-apoptotic effect, kaempferol and fisetin flavonols have been reported as potential anti-cancer agents against malignant neoplasms. To date, their exact role in signaling pathways of head and neck cancer cells is largely unknown. Based on the various methods of cytotoxicity testing, we elucidated that kaempferol and fisetin inhibit proliferation, reduce the capacity of cell migration, and induce apoptosis in SCC-9, SCC-25, and A-253 HNC cells in a dose-dependent manner in vitro (p < 0.05, fisetin IC50 values of 38.85 µM, 62.34 µM, and 49.21 µM, and 45.03 µM, 49.90 µM, and 47.49 µM for kaempferol-SCC-9, SCC-25, and A-253, respectively). The obtained results showed that exposure to kaempferol and fisetin reduces Bcl-2 protein expression, simultaneously leading to the arrest in the G2/M and S phases of the cell cycle. Kaempferol and fisetin inhibit cell proliferation by interfering with the cell cycle, which is strongly associated with the induction of G2/M arrest, and induce apoptosis by activating caspase-3 and releasing cytochrome c in human HNC cells. In addition, investigating flavonols, by inhibiting anti-apoptotic proteins from the Bcl-2 family and damaging the mitochondrial transmembrane potential, increased the level of cytochrome c. While flavonols selectively induce apoptosis of head and neck cancer cells, they may support oncological therapy as promising agents. The discovery of new derivatives may be a breakthrough in the search for effective chemotherapeutic agents with less toxicity and thus fewer side effects.

Monte Carlo modeling of Halcyon and Ethos radiotherapy beam using CAD geometry: validation and IAEA-compliant phase space

Objective. A Monte Carlo (MC) model of a Halcyon and Ethos (Varian Medical Systems, a Siemens Healthineers Company) radiotherapy beam was validated and field-independent phase space (PHSP) files were recorded above the dual-layer multileaf collimators (MLC). Approach. The treatment head geometry was modeled according to engineering drawings and the dual-layer MLC was imported from CAD (computer-aided design) files. The information for the incident electron beam was achieved from an iterative electromagnetic solver. The validation of the model was performed by comparing the dose delivered by the square MLC fields as well as complex field measurements. Main results. An electron phase space was generated from linac simulations and achieved improved MC results. The output factors for square fields were within 1% and the largest differences of 5% were found in the build-up region of PDDs and the penumbra region of profiles. With the more complicated MLC-shaped field (Fishbone), the largest differences of up to 8% were found in the MLC leaf tip region due to the uncertainty of the MLC positioning and the mechanical leaf gap value. The impact of the collimator rotation on the PHSP solution has been assessed with both small and large fields, confirming negligible effects on in-field and out-of-field dose distributions. Significance. A computational model of the Halcyon and Ethos radiotherapy beam with a high accuracy implementation of the MLC was shown to be able to reproduce the radiation beam characteristics with square fields and more complex MLC-shaped fields. The field-independent PHSP files that were produced can be used as an accurate treatment head model above the MLC, and reduce the time to simulate particle transport through treatment head components.

Sensitivity Analysis of a 6 MeV Photon Beam Monte Carlo Model.

This study aimed to optimize efficiency in Monte Carlo (MC) simulation using sensitivity analysis of a beam model. The BEAMnrc-based model of 6 MV beam of a Siemens Primus linac was developed. For sensitivity analysis, the effect of the electron source, treatment head, and virtual phantom specifications on calculated percent depth dose (PDD) and lateral dose profiles was evaluated. The optimum mean energy (E) and the full width at half maximum (FWHM) of the intensity distribution of the electron beam were calculated as 6.7 MeV and 3 mm, respectively. Increasing E from 6.1 to 6.7 MeV, increased the PDD in the fall-off region by 4.70% and decreased the lateral profile by 8.76%. Changing the FWHM had a significant effect on the buildup region of PDD and the horns and out-of-field regions of the lateral profile. Increasing the collimators opening by 0.5 mm, PDD increased by 2.13% and the central and penumbra regions of profiles decreased by 1.98% and 11.40% respectively. Collimator properties such as thickness and density were effective in changing the penumbra (11.32% for 0.25 cm increment) and the out-of-field (22.82% for 3 g/cm3) regions of the lateral profiles. Analysis of a 6 MV model showed that PDD profiles were more sensitive to changes in energy than to FWHM of the electron source. The lateral profiles were sensitive to E, FWHM, and collimator opening. The density of the collimator affected only the out-of-field region of lateral profiles. The findings of this study may be used to make benchmarking of an MC beam model more efficient.

Costs of Newly Funded Proton Therapy Using Time-Driven Activity-Based Costing in The Netherlands.

Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended.

Dosimetric characterization of a mobile accelerator dedicated for intraoperative radiation therapy: Monte Carlo simulations and experimental validation

PurposeThis Technical Note validates previously published data about the dosimetry of the electron beams produced by a mobile accelerator dedicated for intraoperative radiation therapy (IORT). The evaluation of the directional response of a PTW microDiamond detector is presented together with a detailed analysis of the output factors (OFs) for bevelled applicators. MethodsThe OFs of the 6, 8, 10 and 12 MeV electron beams produced by a light intraoperative accelerator (LIAC, SIT, Italy) were measured in a commercial water phantom using the microDiamond. A set of flat and bevelled applicators with sizes ranging from 4 to 10 cm was characterized. For bevelled applicators, a correction for the angular dependence of the microDiamond was calculated using a home-made spherical phantom. Correction factors were obtained through measurements performed rotating the accelerator treatment head at 0°, 15°, 30° and 45°. ResultsFor flat applicators, the average deviation between measured and simulated OFs was (−1.1 ± 0.7)%. The microDiamond showed a higher angular dependence for the 6 MeV beam (∼8% for angles up to 45°, range 92 % ÷ 100 %), while the variations for 8, 10 and 12 MeV beams were ∼ 4 % (range 97 % ÷ 101 %). Correcting for this dependence, the average deviation of the OFs for bevelled applicators was (-0.9 ± 1.6)%. ConclusionsThe presented results were in very good agreement with those reported in literature. Very similar deviations were found between flat and bevelled applicators confirming the suitability of our method to determine the angular dependence correction factors of the microDiamond detector.

Clinical and Treatment Characteristics of Infants and Toddlers Less Than Two Years of Age with Hemophilia: A Report from the Community Counts Registry

Introduction: Congenital hemophilia is an X-linked bleeding disorder often diagnosed in infants and toddlers (ITs) <2 years of age. Intracranial hemorrhage (ICH) in ITs with hemophilia remains a major complication, with a 7% occurrence, leading to disability and in some cases death. ICH in ITs may be preventable through delivery practices which avoid head trauma, especially when there is a family history (FH) of a bleeding disorder, and by early initiation of prophylaxis. The objective of this study was to examine the role of FH on mode of delivery, delivery practices, and initiation of prophylaxis, all within the context of the new treatment product emicizumab, which is approved for prophylaxis in individuals with hemophilia A (HA) of any age. We hypothesized that a FH of hemophilia would be associated with lower proportion of vaginal deliveries and instrumentation at birth and earlier age of prophylaxis initiation. Methods: We included ITs who were <2 years of age and enrolled in Community Counts, a US based Registry for Bleeding Disorders Surveillance that collects data from individuals who receive care at federally funded hemophilia treatment centers. The analysis was limited to initial surveillance visits through 2021 for ITs born ≥2011 and diagnosed with congenital HA or hemophilia B (HB), with a clotting factor activity level of <50%. Analyzed data included socio-demographics, FH of hemophilia (defined as parent report of one or more blood relative), mode of delivery (including the presence or absence of instrumentation), diagnosis type, age at diagnosis, ICH, treatment product usage, head trauma, and age at prophylaxis initiation. Summary statistics were used to characterize demographic and clinical information by FH. Differences between FH, demographic and clinical information, as well as differences between birth cohorts (2011-2015, 2015-2018, and 2019-2021) and treatment product usage were assessed for statistical significance using chi-square or parametric or non-parametric tests of differences between means as appropriate. Results: Of the 883 ITs in the analysis, most were male (98%), White (73%), non-Hispanic (78%), with HA (78%), severe disease (62%), and a known FH (70%). ITs with a FH had a lower proportion of vaginal deliveries than those with no FH (67% vs. 80%, p = 0.0006) and less instrumentation with vaginal delivery (4% vs. 9%; p = 0.02). ITs with a FH were also diagnosed earlier than those without a FH (p = <0.0001); however, age of prophylaxis initiation was not significantly different between ITs with vs without a FH (10.0 mo ± 6.2 versus 11.2 mo ± 6.0; p = 0.17) [Table 1]. Sixty-eight (8%) ITs had one or more ICH during the first two years of life. ITs with a FH were slightly less likely to have an ICH than those with no FH, but the difference was not statistically significant (7% vs 11%, p=0.08). Among all ITs with an ICH, 8 (12%) were on continuous prophylaxis at the time of ICH and 24 (35%) experienced ICH within the first month of life. Of the 24 with ICH in the first month of life, 17 (71%) had vaginal delivery and 8 (33%) reported head trauma. Regarding prophylaxis, 205 (30%) ITs with HA were on continuous prophylaxis within the first two years of life, 91% with severe HA. Thirty-five (18%) with HB were on continuous prophylaxis, 88% with severe HB. Prophylaxis with extended half-life (EHL) clotting factor and emicizumab increased over the study period for ITs with HB and HA respectively. Additionally, ITs with HA born after 2018 started prophylaxis sooner than those born in earlier years (Table 2). Conclusions: The ICH rate of 8% in ITs in this study is substantial and similar to prior reports. This study showed that a known FH of hemophilia was associated with earlier age of diagnosis and decreased rate of vaginal delivery. Nonetheless, the proportion of ICH was only slightly lower among ITs with a FH than those with no FH, and the difference did not reach statistical significance. EHL clotting factor and emicizumab use for prophylaxis increased across the birth cohorts reflecting the addition of new treatment options. The age of prophylaxis initiation decreased in ITs with HA, perhaps reflecting easier mode of administration and national guidelines supporting early initiation to prevent ICH. In ITs with hemophilia there remains opportunity to further reduce ICH by identifying at risk fetuses, optimizing delivery plans to minimize head trauma, and initiating prophylaxis even within the first month of life. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Validation of Monte Carlo multithreading TOpas 3.6 software in order to simulate the 6 MV Elekta Synergy MLCi2 platform linac.

Monte Carlo simulation is generally appreciated as an extraordinary technique to investigate particle physics processes and interactions in nuclear medicine and Radiation Therapy. The present task validates a new methodology of Monte Carlo simulation based on the Multithreading technique to reduce CPU time to simulate a 6 MV photon beam provided by the Elekta Synergy MLCi2 platform medical linear accelerator treatment head utilizing TOpas version 3.6 Monte Carlo software and the Slurm Marwan cluster. The simulation includes the linear accelerator (LINAC) major components. Calculations are performed for the photon beam with several treatment field sizes varying from 3 × 3 to 10 × 10 cm2 at a 100 cm of distance from the source to the surface of the IBA dosimetry water box. The simulation was wholly approved by comparison with experimental distributions. To evaluate simulation accuracy, gamma index formalism for (2%/2mm) and (3%/2mm) criteria, Distance To Agreement DTA, and the estimator standard error ɛ and ɛ max are used. Good agreement between simulations and measurements was observed for depth doses and lateral dose profiles, respectively. The gamma index comparisons also highlighted this agreement; more than 97% of the points for all simulations satisfy the quality assurance criteria of (2%/2mm). Regarding calculation performance, the event processing speed is faster using Gate-[mp] compared to TOpas-[mt] mode when running the identical simulation code for both. Consequently, according to the achieved results, the proposed methodology shows the first validation of TOpas in radiotherapy linacs simulations and a reduction in calculation time, capping simulation accuracy as much as possible. For this reason, this software is recommended to be serviceable for Treatment Planning Systems (TPS) purposes.

A phantom-based experimental and Monte Carlo study of the suitability of in-vivo diodes and TLD for entrance in-vivo dosimetry in small-to-medium sized 6 MV photon fields

In-vivo dosimetry is recommended for radiotherapy treatment verification. The main purpose of the study is to investigate the suitability of various dosimeters for performing in-vivo measurements in small 6 MV photon fields by measurement as well as Monte Carlo simulation. Two types of diode dosimeters designed for placement on skin for the purpose of in-vivo dosimetry (EDD-5 and EDP-10), 3.1 × 3.1 × 0.89 mm3 LiF TLDs, and an electron field diode (EFD) were used for dosimetric measurements in a custom-made PMMA phantom. An Elekta accelerator’s treatment head was Monte Carlo modeled in detail, which was used together with validated Monte Carlo models of the diodes. Dose perturbation effects of the dosimeters and their suitability for in-vivo measurements were investigated. In fields ≥2 × 2 cm2, differences in the measured response of EDD-5, EDP-10 and TLD from the Monte Carlo gold-standard were <2%. For the 1 × 1 cm2 field, however, the differences from the Monte Carlo gold-standard were all greater than 2% due to the influence of dosimeter size as well as any misalignment and set-up uncertainties. In fields ≥1 × 1 cm2, EDD-5, EDP-10, and TLD produced 2.2%–3.2%, 5.3%–6.6% and 0.8–1.1% dose perturbation (≤10 cm depths), respectively. A better than 2% dosimetric accuracy was not achieved by these diodes for field sizes smaller than 2 × 2 cm2. Routine patient in-vivo dosimetry is feasible with the EDD-5 diode and TLD for field sizes down to 2 × 2 cm2 without exceeding the 5% tolerance level for overall uncertainty. But the EDP-10 diode produces a higher perturbation making it much less suitable for this purpose.

A Review of Proton Therapy - Current Status and Future Directions.

The original rationale for proton therapy was the highly conformal depth-dose distributions that protons are able to produce, compared to photons, which allow greater sparing of normal tissues and escalation of tumor doses, thus potentially improving outcomes. Additionally, recent research, which is still ongoing, has revealed previously unrecognized advantages of proton therapy. For instance, the higher relative biological effectiveness (RBE) near the end of the proton range can be exploited to increase the difference in biologically effective dose in tumors vs. normal tissues. Moreover, the smaller "dose bath", i.e., the compact nature of proton dose distributions has been found to reduce exposure of circulating lymphocytes and the immune organs at risk. There is emerging evidence that the resulting sparing of the immune system has the potential to improve outcomes. Protons, accelerated to therapeutic energies ranging from 70 to 250 MeV, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initially narrow beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanically for "passively-scattered proton therapy' (PSPT); or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique is used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton therapy modality, which is rapidly supplanting PSPT. Treatment planning and plan evaluation for proton therapy require different techniques compared to photon therapy due, in part, to the greater vulnerability of protons to uncertainties, especially those introduced by inter- and intra-fractional variations in anatomy. In addition to anatomic variations, other sources of uncertainty in the treatments delivered include the approximations and assumptions of models used for computing dose distributions and the current practice of proton therapy of assuming the RBE to have a constant value of 1.1. In reality, the RBE is variable and a complex function of proton energy, dose per fraction, tissue and cell type, end point, etc. Despite the high theoretical potential of proton therapy, the clinical evidence supporting its broad use has so far been mixed. The uncertainties and approximations mentioned above, and the technological limitations of proton therapy may have diminished its true clinical potential. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Promising results have been and continue to be reported for many other types of cancers as well; however, they are based on small studies. At the same time, there have been reports of unforeseen toxicities. Furthermore, because of the high cost of establishing and operating proton therapy centers, questions are often raised about the value of proton therapy. The general consensus is that there is a need for continued improvement in the state of the art of proton therapy. There is also a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to generate high level evidence of the advantages of protons. Fortuitously, such efforts are taking currently place. Ongoing research is aimed at better understanding the biological and immunomodulatory effects of proton therapy and the consequences of the physical uncertainties on proton therapy and reducing them through image-guidance and adaptive radiotherapy. Since residual uncertainties will remain despite our best efforts, in order to increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented and continue to be perfected. Such research and continuing technological advancements in planning and delivery methods are likely to help demonstrate the superiority of protons.