Feasibility of a Tungsten-181 HDR brachytherapy source: Analysis of isotope production and source dosimetry.

BACKGROUND: Interest in Intensity Modulated Brachytherapy (IMBT) for High Dose Rate Brachytherapy (HDR) treatments has steadily increased in recent years. However, intensity modulation is not best optimized for currently used HDR sources since they emit high energy photons. To that end, the focus on IMBT has moved to middle energy sources, such as Ytterbium-169; yet even Yb-169 emits some high energy photons at a low yield. We present an alternative isotope, Tungsten-181 (T1/2 = 121 days) that is interesting due to its complete lack of high energy photon emissions. (Eavg = 58.9 keV, Emed = 57.5 keV) making it potentially favorable as high dose rate brachytherapy source from both a medical physics and health physics perspective. PURPOSE: The purpose of this study was to determine the feasibility of using W-181 as an HDR brachytherapy source; in this study we focused on W-181's production, dosimetric properties, and intensity modulation capabilities. METHODS: We determined the isotope production kinetics, its Dose Rate Constant, Radial Dose Function, photon self-absorption, and the shielding intensity modulation capabilities for a W-181 pellet source geometry using the MCNP6.2 Computer Simulations Code. All simulations were performed using a personal computer running an AMD Ryzen 5 3600 6-Core Processor 3.59 GHz. The number of histories run for each study were selected to produce relative simulation convergence errors in the MCNP tally output of less than 2%. Dosimetric calculations were made using the MCNP6.2 computer simulations code and activation analyses were determined mathematically using a Catenary kinetics analysis (also known as a Bateman Analysis) of W-181 and Tantlum-182 production from the neutron activation of a pure Tungsten-180 stable target. Since W-181 emits middle energy photons and has a high density, we also assessed the effects of photon self-absorption within a tungsten pellet. RESULTS: From our analysis, we determined that a 3.5 mm long and 0.6 mm in diameter is feasible for clinical applications. Our activation analyses found that these pellets can achieve W-181 activities up to 7.9Ci and 13Ci using neutron fluence rates of 4E14 cm-2 s-1 and 1E15 cm-2 s-1 respectively, which then would provide a dose rate of 1.84 ± 0.01 cG y/Ci/min at a depth of 1 cm from the source. Using our resulting Monte Carlo simulated Dose Rate Constant of 1.24 ± 0.02 cGy h-1∙U-1, a W-181 source in this geometry would require a source activity upwards of 10Ci for use in HDR treatments. In the intensity modulation analysis, only 0.1 mm of gold shielding was found to reduce a pellet's absorbed dose by over 50% while 0.3 mm of gold shielding, which is thin enough to theoretically fit between an HDR pellet and the inner catheter wall, was found to reduce the pellet's absorbed dose by over 85%. CONCLUSIONS: While W-181 has a lower specific activity than Ir-192 and Yb-169, it shows great promise as an isotope for use in Intensity Modulated Brachytherapy due to its easily shielded photons. We therefore expect that W-181 may lend itself best for use as a multi-pellet configuration in IMBT.

Intensity modulated high dose rate ocular brachytherapy using Se-75.

PURPOSE: We propose an alternative to LDR brachytherapy for the treatment of ocular melanomas by coupling intensity modulation, through the use of a gold shielded ring applicator, with a middle energy HDR brachytherapy source, Se-75. In this study, we computationally test this proposed design using MCNP6. METHODS AND MATERIALS: An array of discrete Se-75 sources is formed into a ring configuration within a gold shielded applicator, which collimates the beam to a conical shape. Varying this angle of collimation allows for the prescription dose to be delivered to the apex of various sized targets. Simulations in MCNP6 were performed to calculate the dosimetric output of the Se-75 ring source for various sized applicators, collimators, and target sizes. RESULTS: The prescription dose was delivered to a range of target apex depths 3.5-8 mm in the eye covering targets 10-15 mm in diameter by using various sized applicators and collimators. For a 16 mm applicator with a collimator opening that delivers the prescription dose to a depth of 5 mm in the eye, the maximum percent dose rate to critical structures was 30.5% to the cornea, 35.7% to the posterior lens, 33.3% to the iris, 20.1% to the optic nerve, 278.0% to the sclera, and 267.3% to the tumor. CONCLUSIONS: When using Se-75 in combination with the proposed gold shielded ring applicator, dose distributions are appropriate for ocular brachytherapy. The use of a collimator allows for the dose to more easily conform to the tumor volume. This method also reduces treatment time and cost, and it eliminates hand dose to the surgeon through the use of a remote afterloader device.

Shielded high dose rate ocular brachytherapy using Yb-169.

Purpose.We propose an approach for treating ocular melanoma using a new type of brachytherapy treatment device. This device couples Yb-169, a middle-energy high dose rate (HDR) brachytherapy source, with a gold shielded ring applicator to better conform radiation exposures to the tumor. In this study, we computationally test the dosimetric output of our proposed shielded ring applicator design using MCNP6 and validate it against an I-125 COMS plaque.Methods.The proposed Yb-169 ring applicator consists of an assembly of discrete sources delivered into an applicator with a conical collimated opening; this opening is tangent to the outside of the source tube. Using MCNP6, we simulated the dosimetric output of a ring of Yb-169 pellets placed within the collimator at various conical diameters and angles to demonstrate the dosimetric distribution for various prescription dose depths and target sizes using static intensity modulation.Results.Using various angles of collimation, the prescription dose was delivered to target apex depths of 3.5-8.0 mm into the eye covering target sizes ranging from 10 to 15 mm in diameter. This proposed device reduced the maximum absorbed dose to critical structures relative to I-125 by 5.2% to the posterior lens, 9.3% to the iris, 13.8% to the optic nerve, and 1.3% to the sclera.Conclusions.This proposed eye plaque design provides a more conformal dose distribution to the ocular tumor while minimizes dose to healthy ocular structures. In addition, the use of a middle-energy HDR brachytherapy source allows the use of a remote afterloader to expose the tumor after the plaque is sutured in place. This system is inherently safer and eliminates dose to the surgeon's hands.

Classroom Promotion of Oral Language (CPOL): protocol for a cluster randomised controlled trial of a school-based intervention to improve children's literacy outcomes at grade 3, oral language and mental health.

INTRODUCTION: Oral language and literacy competence are major influences on children's developmental pathways and life success. Children who do not develop the necessary language and literacy skills in the early years of school then go on to face long-term difficulties. Improving teacher effectiveness may be a critical step in lifting oral language and literacy outcomes. The Classroom Promotion of Oral Language trial aims to determine whether a specifically designed teacher professional learning programme focusing on promoting oral language can lead to improved teacher knowledge and practice, and advance outcomes in oral language and literacy for early years school children, compared with usual practice. METHODS AND ANALYSIS: This is a two-arm cluster multisite randomised controlled trial conducted within Catholic and Government primary schools across Victoria, Australia. The intervention comprises 4 days of face-to-face professional learning for teachers and ongoing implementation support via a specific worker. The primary outcome is reading ability of the students at grade 3, and the secondary outcomes are teacher knowledge and practice, student mental health, reading comprehension and language ability at grade 1; and literacy, writing and numeracy at grade 3. Economic evaluation will compare the incremental costs of the intervention to the measured primary and secondary outcomes. ETHICS AND DISSEMINATION: This trial was approved by the Monash University Human Research Ethics Committee #CF13/2634-2013001403 and later transferred to the University of Melbourne #1545540. The investigators (including Government and Catholic partners) will communicate trial results to stakeholders, collaborators and participating schools and teachers via appropriate presentations and publications. TRIAL REGISTRATION NUMBER: ISRCTN77681972; Pre-results.

32P brachytherapy conformal source model RIC-100 for high-dose-rate treatment of superficial disease: Monte Carlo calculations, diode measurements, and clinical implementation.

PURPOSE: A novel (32)P brachytherapy source has been in use at our institution intraoperatively for temporary radiation therapy of the spinal dura and other localized tumors. We describe the dosimetry and clinical implementation of the source. METHODS AND MATERIALS: Dosimetric evaluation for the source was done with a complete set of MCNP5 Monte Carlo calculations preceding clinical implementation. In addition, the depth dose curve and dose rate were measured by use of an electron field diode to verify the Monte Carlo calculations. Calibration procedures using the diode in a custom-designed phantom to provide an absolute dose calibration and to check dose uniformity across the source area for each source before treatment were established. RESULTS: Good agreement was established between the Monte Carlo calculations and diode measurements. Quality assurance measurements results are provided for about 100 sources used to date. Clinical source calibrations were usually within 10% of manufacturer specifications. Procedures for safe handling of the source are described. DISCUSSION: Clinical considerations for using the source are discussed.

Oral language supports early literacy: a pilot cluster randomized trial in disadvantaged schools.

This study examined the impact of teacher professional development aimed at improving the capacity of primary teachers in disadvantaged schools to strengthen children's expressive and receptive oral language skills and early literacy success in the first 2 years of school. Fourteen low-SES schools in Victoria, Australia were randomly allocated to a research (n = 8) or control arm (n = 6), resulting in an initial sample of 1254 students, (n = 602 in research arm and n = 652 in control arm). The intervention comprised 6 days of teacher and principal professional development (delivered by language and literacy experts), school-based continuing contact with the research team and completion by one staff member of each research school of a postgraduate unit on early language and literacy. Schools in the control arm received standard teaching according to state auspiced curriculum guidelines. Full data were available on 979 students at follow-up (time 2). Students in the research arm performed significantly better on Test of Language Development: Primary (Fourth Edition) sub-tests (p ≤ .002) and the Reading Progress Test (F = 10.4(1); p = .001) than students in the control arm at time 2. Narrative scores were not significantly different at time 2, although students in research schools showed greater gains. Findings provide "proof of concept" for this approach, and are discussed with respect to implications for teacher professional development and pre-service education concerning the psycholinguistic competencies that underpin the transition to literacy.

Dosimetric characterization of the GammaClip™ 169Yb low dose rate permanent implant brachytherapy source for the treatment of nonsmall cell lung cancer postwedge resection.

PURPOSE: A novel (169)Yb low dose rate permanent implant brachytherapy source, the GammaClip™, was developed by Source Production & Equipment Co. (New Orleans, LA) which is designed similar to a surgical staple while delivering therapeutic radiation. In this report, the brachytherapy source was characterized in terms of "Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: Report of the AAPM and ESTRO" by Perez-Calatayud et al. [Med. Phys. 39, 2904-2929 (2012)] using the updated AAPM Task Group Report No. 43 formalism. METHODS: Monte Carlo calculations were performed using Monte Carlo N-Particle 5, version 1.6 in water and air, the in-air photon spectrum filtered to remove photon energies below 10 keV in accordance with TG-43U1 recommendations and previously reviewed (169)Yb energy cutoff levels [D. C. Medich, M. A. Tries, and J. M. Munro, "Monte Carlo characterization of an Ytterbium-169 high dose rate brachytherapy source with analysis of statistical uncertainty," Med. Phys. 33, 163-172 (2006)]. TG-43U1 dosimetric data, including SK, D(r,θ), Λ, gL(r), F(r, θ), φan(r), and φan were calculated along with their statistical uncertainties. Since the source is not axially symmetric, an additional set of calculations were performed to assess the resulting axial anisotropy. RESULTS: The brachytherapy source's dose rate constant was calculated to be (1.22±0.03) cGy h(-1) U(-1). The uncertainty in the dose to water calculations, D(r,θ), was determined to be 2.5%, dominated by the uncertainties in the cross sections. The anisotropy constant, φan, was calculated to be 0.960±0.011 and was obtained by integrating the anisotropy factor between 1 and 10 cm using a weighting factor proportional to r(-2). The radial dose function was calculated at distances between 0.5 and 12 cm, with a maximum value of 1.20 at 5.15±0.03 cm. Radial dose values were fit to a fifth order polynomial and dual exponential regression. Since the source is not axially symmetric, angular Monte Carlo calculations were performed at 1 cm which determined that the maximum azimuthal anisotropy was less than 8%. CONCLUSIONS: With a higher photon energy, shorter half-life and higher initial dose rate 169Yb is an interesting alternative to 125I for the treatment of nonsmall cell lung cancer.

Selection of an appropriate air kerma rate constant for 75Se sources.

Monte Carlo simulation techniques using a Monte Carlo N-Particle code (MCNP5) analyzed six Source Production & Equipment Co., Inc., Se industrial radiography sources to determine an appropriate air kerma rate constant for Se, factoring in source encapsulation and compared to a theoretical approximation. Based on this study, an air kerma rate constant was calculated to be 17.7 Gy cm h Ci (0.203 R m h Ci), which was found to be five times lower than values published in the 1992 Edition of the Radiological Health Handbook and Oak Ridge National Laboratory RISC-45. Simulations were also employed to determine the effects of self-attenuation with the SPEC sources, the relationship between photon transmission values, and the thickness of various shielding materials in reducing exposure rates from a (75)Se source.

A novel ytterbium-169 brachytherapy source and delivery system for use in conjunction with minimally invasive wedge resection of early-stage lung cancer.

PURPOSE: To describe a novel source-delivery system for intraoperative brachytherapy in patients with early-stage lung cancer that is readily adaptable to a video-assisted thoracoscopic surgery approach and can be precisely delivered to achieve optimal dose distribution. METHODS AND MATERIALS: Radioactive ytterbium-169 ((169)Yb) was sealed within a titanium tube 0.28 mm in diameter and then capped and resealed by titanium wires laser welded to the tube to serve as the legs of a tissue-fastening system. Dose simulations were performed using Monte Carlo computer code (Los Alamos National Laboratory, Los Alamos, NM) to mimic the geometric and elemental compositions of the source, fastening apparatus, and surroundings. RESULTS: Five test source capsules were subjected to a tensile load to failure. Failure in each capsule occurred in the wire of the fastener leg; there were no weld failures. Monte Carlo simulations and subsequent dose measurement showed the perturbation by the source legs in the deployed (bent over) position to be small (4-5%) for (169)Yb and much less than that for iodine-125 (32%). CONCLUSION: We have developed a (169)Yb brachytherapy source-delivery system that can be used in conjunction with commercially available surgical stapling instruments, facilitates the precise placement of brachytherapy sources relative to the surgical margin, assures the seeds remain fixed in their precise position for the duration of the treatment, overcomes the technical difficulties of manipulating the seeds through the narrow surgical incision associated with video-assisted thoracoscopic surgery, and reduces the radiation dose to the clinicians.

Effects of breast-air and breast-lung interfaces on the dose rate at the planning target volume of a MammoSite catheter for Yb-169 and Ir-192 HDR sources.

PURPOSE: To study the effects of the breast-air and breast-lung interfaces on the absorbed dose within the planning target volume (PTV) of a MammoSite balloon dose delivery system as well as the effect of contrast material on the dose rate in the PTV. METHODS: The Monte Carlo MCNP5 code was used to simulate dose rate in the PTV of a 2 cm radius MammoSite balloon dose delivery system. The simulations were carried out using an average female chest phantom (AFCP) and a semi-infinite water phantom for both Yb-169 and Ir-192 high dose rate sources for brachytherapy application. Gastrografin was introduced at varying concentrations to study the effect of contrast material on the dose rate in the PTV. RESULTS: The effect of the density of the materials surrounding the MammoSite balloon containing 0% contrast material on the calculated dose rate at different radial distances in the PTV was demonstrated. Within the PTV, the ratio of the calculated dose rate for the AFCP and the semi-infinite water phantom for the point closest to the breast-air interface (90 degrees) is less than that for the point closest to the breast-lung interface (270 degrees) by 11.4% and 4% for the HDR sources of Yb-169 and Ir-192, respectively. When contrast material was introduced into the 2 cm radius MammoSite balloon at varying concentrations, (5%, 10%, 15%, and 20%), the dose rate in the AFCP at 3.0 cm radial distance at 90 degrees was decreased by as much as 14.8% and 6.2% for Yb-169 and Ir-192, respectively, when compared to that of the semi-infinite water phantom with contrast concentrations of 5%, 10%, 15%, and 20%, respectively. CONCLUSIONS: Commercially available software used to calculate dose rate in the PTV of a MammoSite balloon needs to account for patient anatomy and density of surrounding materials in the dosimetry analyses in order to avoid patient underdose.

Dependence of Yb-169 absorbed dose energy correction factors on self-attenuation in source material and photon buildup in water.

PURPOSE: Absorbed dose energy correction factors, used to convert the absorbed dose deposited in a LiF thermoluminescent dosimeter (TLD) into the clinically relevant absorbed dose to water, were obtained for both spherical volumetric sources and for the model 4140 HDR Yb-169 source. These correction factors have a strong energy dependence below 200 keV; therefore, spectral changes were quantified as Yb-169 photons traveled through both source material (Yb2O3) and water with the corresponding absorbed dose energy correction factors, f(r, theta), calculated as a function of location in a phantom. METHODS: Using the MCNP5 Monte Carlo radiation transport simulation program, the Yb-169 spectrum emerging from spherical Yb2O3 sources (density 6.9 g/cm3) with radii between 0.2 and 0.9 mm were analyzed and their behavior compared against those for a point-source. The absorbed dose deposited to both LiF and H2O materials was analyzed at phantom depths of 0.1-10 cm for each source radius and the absorbed dose energy correction factor calculated as the ratio of the absorbed dose to water to that of LiF. Absorbed dose energy correction factors for the Model 4140 Yb-169 HDR brachytherapy source similarly were obtained and compared against those calculated for the Model M-19 Ir-192 HDR source. RESULTS: The Yb-169 average spectral energy, emerging from Yb2O3 spherical sources 0.2-0.9 mm in radius, was observed to harden from 7% to 29%; as these photons traveled through the water phantom, the photon average energy softened by as much as 28% at a depth of 10 cm. Spectral softening was dependent on the measurement depth in the phantom. Energy correction factors were found to vary both as a function of source radius and phantom depth by as much as 10% for spherical Yb2O3 sources. The Model 4140 Yb-169 energy correction factors depended on both phantom depth and reference angle and were found to vary by more than 10% between depths of 1 and 10 cm and angles of 0 degrees and 180 degrees. This was in contrast to that of the Model M-19 Ir-192 source which exhibited approximately 3.5%-4.4% variation in its energy correction factors from phantom depths of 0.5-10 cm. The absorbed dose energy correction factor for the Ir-192 source, on the other hand, was independent of angle to within 1%. CONCLUSIONS: The application of a single energy correction factor for Yb-169 TLD based dosimetry would introduce a high degree of measurement uncertainty that may not be reasonable for the clinical characterization of a brachytherapy source; rather, an absorbed dose energy correction function will need to be developed for these sources. This correction function should be specific to each source model, type of TLD used, and to the experimental setup to obtain accurate and precise dosimetric measurements.

Monte Carlo characterization of a new Yb-169 high dose rate source for brachytherapy application.

PURPOSE: The objective was to characterize a new Yb-169 high dose rate source for brachytherapy application. METHODS: Monte Carlo simulations were performed using the MCNP5 F6 energy deposition tallies placed around the Yb-169 source at different radial distances in both air-vacuum and water environments. The calculations were based on a spherical water phantom with a radius of 50 cm. The output from the simulations was converted into radial dose rate distribution in polar coordinates surrounding the brachytherapy source. RESULTS: The results from Monte Carlo simulations were used to calculate the AAPM Task Group 43 dosimetric parameters: Anisotropy function, radial dose function, air kerma strength, and dose rate constant. The results indicate a dose rate constant of 1.12 +/- 0.04 cGy h(-1) U(-1), anisotropy function ranging from 0.44 to 1.00 for radial distances of 0.5-10 cm and polar angles of 0 degrees-180 degrees. CONCLUSIONS: The data from the Yb-169 HDR source, Model M42, presented in this study show that this source compares favorably with another source of Yb-169, Model 4140, already approved for brachytherapy treatment.

The use of new GAFCHROMIC EBT film for 125I seed dosimetry in Solid Water phantom.

Radiochromic film dosimetry has been extensively used for intravascular brachytherapy applications for near field within 1 cm from the sources. With the recent introduction of new model of radiochromic films, GAFCHROMIC EBT, with higher sensitivity than earlier models, it is promising to extend the distances out to 5 cm for low dose rate (LDR) source dosimetry. In this study, the use of new model GAFCHROMIC EBT film for 125I seed dosimetry in Solid Water was evaluated for radial distances from 0.06 cm out to 5 cm. A multiple film technique was employed for four 125I seeds (Implant Sciences model 3500) with NIST traceable air kerma strengths. Each experimental film was positioned in contact with a 125I seed in a Solid Water phantom. The products of the air kerma strength and exposure time ranged from 8 to 3158 U-h, with the initial air kerma strength of 6 U in a series of 25 experiments. A set of 25 calibration films each was sequentially exposed to one 125I seed at about 0.58 cm distance for doses from 0.1 to 33 Gy. A CCD camera based microdensitometer, with interchangeable green (520 nm) and red (665 nm) light boxes, was used to scan all the films with 0.2 mm pixel resolution. The dose to each 125I calibration film center was calculated using the air kerma strength of the seed (incorporating decay), exposure time, distance from seed center to film center, and TG43U1S1 recommended dosimetric parameters. Based on the established calibration curve, dose conversion from net optical density was achieved for each light source. The dose rate constant was determined as 0.991 cGy U(-1)h(-1) (+/-6.9%) and 1.014 cGy U(-1)h(-1) (+/-6.8%) from films scanned using green and red light sources, respectively. The difference between these two values was within the uncertainty of the measurement. Radial dose function and 2D anisotropy function were also determined. The results obtained using the two light sources corroborated each other. We found good agreement with the TG43U1S1 recommended values of radial dose function and 2D anisotropy function, to within the uncertainty of the measurement. We also verified the dosimetric parameters in the near field calculated by Rivard using Monte Carlo method. The radial dose function values in Solid Water were lower than those in water recommended by TG43U1S1, by about 2%, 3%, 7%, and 14% at 2, 3, 4, and 5 cm, respectively, partially due to the difference in the phantom material composition. Radiochromic film dosimetry using GAFCHROMIC EBT model is feasible in determining 2D dose distributions around low dose rate 125I seed. It is a viable alternative to TLD dosimetry for 125I seed dose characterization.

Monte Carlo characterization of the M-19 high dose rate Iridium-192 brachytherapy source.

The MCNP5 Monte Carlo code was used to simulate the dosimetry of an M-19 iridium-192 high dose rate brachytherapy source in both air/vacuum and water environments with the in-air photon spectrum filtered to remove low-energy photons below delta=10 keV. Dosimetric data was organized into an away-along table and was used to derive the updated AAPM Task Group Report No. 43 (TG-43U1) parameters including S(K), D(r, theta), lamda, gL(r), F(r, theta), phi an(r), and phi an, and their respective statistical uncertainties.

Monte Carlo characterization of an ytterbium-169 high dose rate brachytherapy source with analysis of statistical uncertainty.

An ytterbium-169 high dose rate brachytherapy source, distinguished by an intensity-weighted average photon energy of 92.7 keV and a 32.015 +/- 0.009 day half-life, is characterized in terms of the updated AAPM Task Group Report No. 43 specifications using the MCNP5 Monte Carlo computer code. In accordance with these specifications, the investigation included Monte Carlo simulations both in water and air with the in-air photon spectrum filtered to remove low-energy photons below 10 keV. TG-43 dosimetric data including S(K), D(r, lamda), lambda, gL(r), F(r, lamda), phi an(r), and phi(an) were calculated and statistical uncertainties in these parameters were derived and calculated in the appendix.

Experimental determination of the dosimetric characteristics for the I-Plant model 3600 125I brachytherapy source.

The dosimetric characteristics for a new brachytherapy seed source (I-Plant model 3600) were measured using LiF thermoluminescent dosimeters and appropriate phantom materials in conformance with the methodology and guidance provided by the AAPM Task Group 43. The I-Plant model 3600 is the successor to the I-Plant model 3500. The major difference between these sources is that the model 3600 contains a leaded-glass core to provide radio-opacity (while the model 3500 contains a silver core), which does not produce spectral contamination upon neutron activation. The dose rate constant lambda for the model 3600 was determined to be 1.00 Gy h(-1) U(-1) (with a 6% overall relative standard deviation), compared to 1.01 cGy h(-1) U(-1) reported for the model 3500 in previous studies. The remaining dosimetric characteristics also are similar for both sources.

Detection and frequency estimation of rare variants in pools of genomic DNA from large populations using mutational spectrometry.

DNA variants underlying the inheritance of risk for common diseases are expected to have a wide range of population allele frequencies. The detection and scoring of the rare alleles (at frequencies of <0.01) presents significant practical problems, including the requirement for large sample sizes and the limitations inherent in current methodologies for allele discrimination. In the present report, we have applied mutational spectrometry based on constant denaturing capillary electrophoresis (CDCE) to DNA pools from large populations in order to improve the prospects of testing the role of rare variants in common diseases on a large scale. We conducted a pilot study of the cytotoxic T lymphocyte-associated antigen-4 gene (CTLA4) in type 1 diabetes (T1D). A total of 1228 bp, comprising 98% of the CTLA4 coding sequence, all adjacent intronic mRNA splice sites, and a 3' UTR sequence were scanned for unknown point mutations in pools of genomic DNA from a control population of 10,464 young American adults and two T1D populations, one American (1799 individuals) and one from the United Kingdom (2102 individuals). The data suggest that it is unlikely that rare variants in the scanned regions of CTLA4 represent a significant proportion of T1D risk and illustrate that CDCE-based mutational spectrometry of DNA pools offers a feasible and cost-effective means of testing the role of rare variants in susceptibility to common diseases.

Monte Carlo calculated TG-43 dosimetry parameters for the SeedLink 125Iodine brachytherapy system.

The SeedLink brachytherapy system is comprised from an assembly of I-Plant 3500 interstitial brachytherapy seeds and bioresorbable spacers joined together by a 6-mm-long titanium sleeve centered over each seed. This device is designed to maintain specified spacing between seeds during treatment thereby decreasing implant preparation time and reducing radionuclide migration within the prostate and periprostatic region. Reliable clinical treatment and planning applications necessitate accurate dosimetric data for source evaluation, therefore the authors report the results of a Monte Carlo study designed to calculate the AAPM Task Group Report No. 43 dosimetric parameters for the SeedLink brachytherapy source and compare these values against previously published Monte Carlo study results of the I-Plant 3500 brachytherapy seed. For this investigation, a total of 1 x 10(9) source photon histories were processed for each set of in-water and in-air calculations using the MCNP4C2 Monte Carlo radiation transport code (RSICC). Statistically, the radial dose function, g(r), and the dose-rate constant, lambda, were identical to the values calculated previously for the Model 3500 with the dose-rate constant evaluated to be lambda = 1.000+/-0.026 cGyh(-1) U(-1). The titanium sleeve used in SeedLink to bind together Model 3500 seeds and spacers resulted in slightly greater dosimetric anisotropy as exhibited in the anisotropy function, F(r, theta), the anisotropy factor, phi(an) (r), and the anisotropy constant, phi(an), which was calculated to be phi(an) = 0.91 +/- 0.01, or roughly 2% lower than the value calculated previously for the Model 3500. These results indicate that the radiological characteristics of the SeedLink dosimetry system are comparable to those obtained for previously characterized single seeds such as the Implant Sciences Model 3500 I-Plant seed.

Intraoperative dural irradiation by customized 192iridium and 90yttrium brachytherapy plaques.

PURPOSE: After vertebral or paravertebral tumor resection, tumor cells may remain on the dura. Because a tumoricidal dose is difficult to achieve using external beam radiotherapy without exceeding the spinal cord tolerance, we developed intraoperative applicators to deliver additional dose to the dura. METHODS AND MATERIALS: Eight patients with vertebral or paravertebral tumor underwent conformal external beam radiotherapy, tumor resection, and intraoperative radiotherapy to the dura involved by tumor. At surgery, vertebra, soft tissue, and epidural tumor were resected. A radioactive applicator plaque was placed on the dura to deliver 7.5-15 Gy, and then removed. Vertebral reconstruction and stabilization was completed. Chemotherapy was administered for large, high-grade sarcomas. RESULTS: We progressed through three plaque designs, initially (192)Ir, subsequently liquid (90)Y, and finally (90)Y foil in a semicylindrical polycarbonate plaque, in the treatment of 8 patients. The low-energy (90)Y beta-emissions provided a more attractive depth dose profile than that achievable with iridium and gave negligible staff radiation exposure. The (90)Y depth dose measured 29% at 2 mm and 9% at 4 mm from the surface of the foil plaque, with acceptable surface dose homogeneity. The average surface dose rate ranged from 18.7 to 47.6 cGy/min for the iridium plaques and 45.2 to 187.5 cGy/min for the (90)Y plaques. The treatments have been without acute or late neurologic complications. The disease of 6 of 8 patients was locally controlled at median potential follow-up of 24 months. CONCLUSIONS: The (90)Y foil applicator is technically elegant, easy to use, and superior to the earlier models. It has been incorporated into a protocol for spinal tumor treatment.