Machine performance and stability of the first clinical self-shielded stereotactic radiosurgery system: Initial 2-year experience.

This study provides insight into the overall system performance, stability, and delivery accuracy of the first clinical self-shielded stereotactic radiosurgery (SRS) system. Quality assurance procedures specifically developed for this unit are discussed, and trends and variations over the course of 2-years for beam constancy, targeting and dose delivery are presented. Absolute dose calibration for this 2.7 MV unit is performed to deliver 1 cGy/MU at dmax  = 7 mm at a source-to-axis-distance (SAD) of 450 mm for a 25 mm collimator. Output measurements were made with 2-setups: a device that attaches to a fixed position on the couch (daily) and a spherical phantom that attaches to the collimating wheel (monthly). Beam energy was measured using a cylindrical acrylic phantom at depths of 100 (D10 ) and 200 (D20 ) mm. Beam profiles were evaluated using Gafchromic film and compared with TPS beam data. Accuracy in beam targeting was quantified with the Winston-Lutz (WL) and end-to-end (E2E) tests. Delivery quality assurance (DQA) was performed prior to clinical treatments using Gafchromic EBT3/XD film. Net cumulative output adjustments of 15% (pre-clinical), 9% (1st year) and 3% (2nd year) were made. The mean output was 0.997 ± 0.010 cGy/MU (range: 0.960-1.046 cGy/MU) and 0.993 ± 0.029 cGy/MU (range: 0.884-1.065 cGy/MU) for measurements with the daily and monthly setups, respectively. The mean relative beam energy (D10 /D20 ) was 0.998 ± 0.004 (range: 0.991-1.006). The mean total targeting error was 0.46 ± 0.17 mm (range: 0.06-0.98 mm) for the WL and 0.52 ± 0.28 mm (range: 0.11-1.27 mm) for the E2E tests. The average gamma pass rates for DQA measurements were 99.0% and 90.5% for 2%/2 mm and 2%/1 mm gamma criteria, respectively. This SRS unit meets tolerance limits recommended by TG-135, MPPG 9a., and TG-142 with a treatment delivery accuracy similar to what is achieved by other SRS systems.

Technical note: Absolute dose measurements of a vault-free radiosurgery system.

BACKGROUND: Methods for accurate absolute dose (AD) calibration are essential for the proper functioning of radiotherapy treatment machines. Many systems do not conform to TG-51 calibration standards, and modifications are required. TG-21 calibration is also a viable methodology for these situations with the appropriate setup, equipment, and factors. It has been shown that both these methods result in minimal errors. A similar approach has been taken in calibrating the dose for a recent vault-free radiosurgery system. PURPOSE: To evaluate modified TG-21 and TG-51 protocols for AD calibrations of the ZAP-X radiosurgery system using ion chambers, film, and thermoluminescent dosimeters (TLDs). METHODS: The current treatment planning system for ZAP-X requires AD calibration at dmax (7 mm) and 450 mm source-to-axis distance. Both N D , w 60 C o [ G y / C ] $N_{D,w}^{{60}Co}[ {Gy/C} ]$ and Nx [R/C] calibration coefficients were provided by an accredited dosimetry calibration laboratory for a physikalisch technische werkstatten (PTW) 31010 chamber (0.125 cc). The vendor provides an f-bracket that can be mounted on the collimator. Various phantoms can then be attached to the f-bracket. A custom acrylic phantom was designed based on recommendations from TG-21 and technical report series-398 that places the chamber at 500 mm from the source with a depth of 44-mm acrylic and 456-mm SSD. Nx along with other TG-21 parameters was used to calculate the AD. Measurements using a PTW MP3-XS water tank and the same chamber were used to calculate AD using N D , w 60 C o $N_{D,w}^{{60}Co}$ and TG-51 factors. Dose verification was performed using Gafchromic film and 3rd party TLDs. RESULTS: Measurements from TG-51, TG-21 (utilizing the custom acrylic phantom), film, and TLDs agreed to within ± 2%. CONCLUSIONS: A modified TG-51 AD calculation in water is preferred but may not be practical due to the difficulty in tank setup. The TG-21 modified protocol using a custom acrylic phantom is an accurate alternative option for dose calibration. Both of these methods are within acceptable agreement and provide confidence in the system's AD calibration.

Dosimetric Impacts of Source Migration, Radioisotope Type, and Decay with Permanent Implantable Collagen Tile Brachytherapy for Brain Tumors.

Introduction: Brachytherapy using permanently implantable collagen tiles containing cesium-131 (Cs-131) is indicated for treatment of malignant intracranial neoplasms. We quantified Cs-131 source migration and modeled the resulting dosimetric impact for Cs-131, iodine-125 (I-125), and palladium-103 (Pd-103). Methods and Materials: This was a retrospective analysis of a subgroup of patients enrolled in a prospective, single-center, nonrandomized, clinical trial (NCT03088579) of Cs-131 collagen tile brachytherapy. Postimplant Cs-131 plans and hypothetical I-125 and Pd-103 calculations were compared for 20 glioblastoma patients for a set seed geometry. Dosimetric impact of decay and seed migration was calculated for 2 hypothetical scenarios: Scenario 1, assuming seed positions on a given image set were unchanged until acquisition of the subsequent set; Scenario 2, assuming any change in seed positions occurred the day following acquisition of the prior images. Seed migration over time was quantified for a subset of 7 patients who underwent subsequent image-guided radiotherapy. Results: Mean seed migration was 1.7 mm (range: 0.7-3.1); maximum seed migration was 4.3 mm. Mean dose to the 60 Gy volume differed by 0.4 Gy (0.6%, range 0.1-1.0) and 0.9 Gy (1.5%, range 0.2-1.7) for Cs-131, 1.2 Gy (2.0%, range 0.1-2.1) and 1.6 Gy (2.6%, range 1.2-2.6) for I-125, and 0.8 Gy (1.3%, range 0.2-1.5) and 1.4 Gy (2.3%, range 0.3-1.9) for Pd-103, for Scenarios 1 and 2, respectively, compared with the postimplant plan. For a set seed geometry mean implant dose was higher for Pd-103 (1.3 times) and I-125 (1.1 times) versus Cs-131. Dose fall-off was steepest for Pd-103: gradient index 1.88 versus 2.23 (I-125) and 2.40 (Cs-131). Conclusions: Dose differences due to source migration were relatively small, suggesting robust prevention of seed migration from Cs-131-containing collagen tiles. Intratarget heterogeneity was greater with Pd-103 and I-125 than Cs-131. Dose fall-off was fastest with Pd-103 followed by I-125 and then Cs-131.

Small-field beam data acquisition, detector dependency, and film-based validation for a novel self-shielded stereotactic radiosurgery system.

PURPOSE: This study reports a single-institution experience with beam data acquisition and film-based validation for a novel self-shielded sterotactic radiosurgery unit and investigates detector dependency on field output factors (OFs), off-axis ratios (OARs), and percent depth dose (PDD) measurements within the context of small-field dosimetry. METHODS: The delivery platform for this unit consists of a 2.7-MV S-band linear accelerator mounted on coupled gimbals that rotate around a common isocenter (source-to-axis distance [SAD] = 450 mm), allowing for more than 260 noncoplanar beam angles. Beam collimation is achieved via a tungsten collimator wheel with eight circular apertures ranging from 4 mm to 25 mm in diameter. Three diodes (PTW 60012 Diode E, PTW 60018 SRS Diode, and Sun Nuclear EDGE) and a synthetic diamond detector (PTW 60019 micro Diamond [µD] detector) were used for OAR, PDD, and OF measurements. OFs were also acquired with a PTW 31022 PinPoint ionization chamber. Beam scanning was performed using a 3D water tank at depths of 7, 50, 100, 200, and 250 mm with a source-to-surface distance of 450 mm. OFs were measured at the depth of maximum dose (dmax  = 7 mm) with the SAD at 450 mm. Gafchromic EBT3 film was used to validate OF and profile measurements and as a reference detector for estimating correction factors for active detector OFs. Deviations in field size, penumbra, and PDDs across the different detectors were quantified. RESULTS: Relative OFs (ROFs) for the diodes were within 1.4% for all collimators except for 5 and 7.5 mm, for which SRS Diode measurements were higher by 1.6% and 2.6% versus Diode E. The µD ROFs were within 1.4% of the diode measurements. PinPoint ROFs were lower by >10% for the 4-mm and 5-mm collimators versus the Diode E and µD. Corrections to OFs using EBT3 film as a reference were within 1.2% for all diodes and the µD detector for collimators 10 mm and greater and within 2.0%, 2.8%, and 1.1% for the 7.5-, 5-, and 4-mm collimators, respectively. The maximum difference in full width at half maximum (FWHM) between the Diode E and the other active detectors was for the 25-mm collimator and was 0.09 mm (µD), 0.16 mm (SRS Diode), and 0.65 mm (EDGE). Differences seen in PDDs beyond the depth of dmax were <1% across the three diodes and the µD. FWHM and penumbra measurements made using EBT3 film were within 1.34% and 3.26%, respectively, of the processed profile data entered into the treatment planning system. CONCLUSIONS: Minimal differences were seen in OAR and PDD measurements acquired with the diodes and the µD. ROFs measured with the three diodes were within 2.6% and within 1.4% versus the µD. Gafchromic Film measurements provided independent verification of the OAR and OF measurements. Estimated corrections to OFs using film as a reference were <1.6% for the Diode E, EDGE, and µD detector.

Treatment planning system and beam data validation for the ZAP-X: A novel self-shielded stereotactic radiosurgery system.

PURPOSE: To evaluate the treatment planning system (TPS) performance of the ZAP-X stereotactic radiosurgery (SRS) system through nondosimetric, dosimetric, and end-to-end (E2E) tests. METHODS: A comprehensive set of TPS commissioning and validation tests was developed using published guidelines. Nondosimetric validation tests included information transfer, computed tomography-magnetic resonance (CT-MR) image registration, structure/contouring, geometry, dose tools, and CT density. Dosimetric validation included comparisons between TPS and water tank/Solid Water measurements for various geometries and beam arrangements and end-to-end (E2E) tests. Patient-specific quality assurance was performed with an ion chamber in the Lucy phantom and with Gafchromic EBT3 film in the CyberKnife head phantom. RadCalc was used for independent verification of monitor units. Additional E2E tests were performed using the RPC Gamma Knife thermoluminescent dosimeter (TLD) phantom, MD Anderson SRS head phantom, and PseudoPatient gel phantom for independent absolute dose verification. RESULTS: CT-MR image registrations with known translational and rotational offsets were within tolerance (<0.5 × maximum voxel dimension). Slice thickness and distance accuracy were within 0.1 mm, and volume accuracy was within 0 to 0.11 cm3 . Treatment planning system volume measurement uncertainty was within 0.1 to 0.4 cm3 . Ion chamber point-dose measurements for a single beam in a water phantom agreed to TPS-calculated values within ±4% for collimator diameters 10 to 25 mm, and ±6% for 7.5 mm, for all measured depths (7, 50, 100, 150, and 200 mm). In homogeneous Solid Water, point-dose measurements agreed to within ±4% for cones sizes 7.5 to 25 mm. With 1-cm high/low density inserts, measurements were within ±4.2% for cone sizes 10 to 25 mm. Film-based E2E using 4/5-mm cones resulted in a gamma passing rate (%GP) of 99.8% (2%/1.5 mm). Point-dose measurements in a Lucy phantom with an ion chamber using 36 beams distributed along three noncoplanar arcs agreed to within ±4% for cone sizes 10 to 25 mm. The RPC Gamma Knife TLD phantom yielded passing results with a measured-to-expected TLD dose ratio of 1.02. The MD Anderson SRS head phantom yielded passing results, with 4% TLD agreement and %GP of 95%/93% (5%/3 mm) for coronal/sagittal film planes. The RTsafe gel phantom gave %GP of >95% (5%/2 mm) for all four targets. For our first 58 patients, film-based patient-specific quality assurance has resulted in an average %GP of 98.7% (range, 94-100%) at 2%/2 mm. CONCLUSIONS: Core ZAP-X features were found to be functional. On the basis of our results, point-dose and planar measurements were in agreement with TPS calculations using multiple phantoms and setup geometries, validating the ZAP-X TPS beam model for clinical use.

CyberKnife radiosurgery for acoustic neuromas: Tumor control and clinical outcomes.

Fractionated CyberKnife radiosurgery (CKRS) treatment for acoustic neuromas may reduce the risk of long-term radiation toxicity to nearby critical structures compared to that of single-fraction radiosurgery. However, tumor control rates and clinical outcomes after CKRS for acoustic neuromas are not well described. We retrospectively reviewed all acoustic neuroma patients treated with CKRS (2004-2011) in a prospectively maintained clinical and radiographic database. Treatment failure, the need for additional surgical intervention, was evaluated using Kaplan-Meier analysis. For 119 treated patients, median values were 49 months (range, 6-133 months) of follow-up, 1.6 cm3 (range, 0.02-17 cm3) tumor volume, and 18 Gy (range, 13-25 Gy) prescribed dose delivered in 3 fractions (range, 1-5 fractions). Thirty-five of 59 patients (59%) with pre-radiosurgery serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery class A or B) maintained serviceable hearing at the last audio follow-up (median, 21 months). Two of 111 patients (2%) with facial nerve function House-Brackmann (HB) grade ≤3 progressed to HB grade >3 after radiosurgery. Koos grade IV was predictive of radiographic tumor growth after radiosurgery compared to grades I to III (p = 0.02). Treatment failure occurred in 9 of 119 patients (8%); median time to failure was 29 months (range, 4-70 months). The actuarial rates of tumor control at 1, 3, 5, and 7 years were 96%, 94%, 88%, and 88%, respectively. CKRS affords effective tumor control for acoustic neuromas with an acceptable rate of hearing preservation. Further studies are needed to compare CKRS to single-fraction radiosurgery for acoustic neuromas.

Resection and permanent intracranial brachytherapy using modular, biocompatible cesium-131 implants: results in 20 recurrent, previously irradiated meningiomas.

OBJECTIVE: Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas. METHODS: Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression. RESULTS: Nineteen patients (median age 64.5 years, range 50-78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1-3) and 2 (range 1-4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9-92.0 cm3). The median radiation dose from BT was 63 Gy (range 54-80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03-47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9-321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically. CONCLUSIONS: R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

A mathematical model of comprehensive test-and-treat services and HIV incidence among men who have sex with men in the United States.

BACKGROUND: Early diagnosis and treatment of HIV infection and suppression of viral load are potentially powerful interventions for reducing HIV incidence. A test-and-treat strategy may have long-term effects on the epidemic among urban men who have sex with men (MSM) in the United States and may achieve the 5-year goals of the 2010 National AIDS Strategy that include: 1) lowering to 25% the annual number of new infections, 2) reducing by 30% the HIV transmission rate, 3) increasing to 90% the proportion of persons living with HIV infection who know their HIV status, 4) increasing to 85% the proportion of newly diagnosed patients linked to clinical care, and 5) increasing by 20% the proportion of HIV-infected MSM with an undetectable HIV RNA viral load. METHODS AND FINDINGS: We constructed a dynamic compartmental model among MSM in an urban population (based on New York City) that projects new HIV infections over time. We compared the cumulative number of HIV infections in 20 years, assuming current annual testing rate and treatment practices, with new infections after improvements in the annual HIV testing rate, notification of test results, linkage to care, initiation of antiretroviral therapy (ART) and viral load suppression. We also assessed whether five of the national HIV prevention goals could be met by the year 2015. Over a 20-year period, improvements in test-and-treat practice decreased the cumulative number of new infections by a predicted 39.3% to 69.1% in the urban population based on New York City. Institution of intermediate improvements in services would be predicted to meet at least four of the five goals of the National HIV/AIDS Strategy by the 2015 target. CONCLUSIONS: Improving the five components of a test-and-treat strategy could substantially reduce HIV incidence among urban MSM, and meet most of the five goals of the National HIV/AIDS Strategy.

The cost-effectiveness of routine office-based identification and subsequent medical treatment of primary open-angle glaucoma in the United States.

OBJECTIVE: To estimate the incremental cost-effectiveness of routine glaucoma assessment and treatment under current eye care visit and treatment patterns and different levels of treatment effectiveness (from randomized trials). DESIGN: We compared the costs and benefits of routine glaucoma assessment and treatment compared with no treatment using conservative and optimistic assumptions regarding treatment efficacy and including and excluding prediagnostic assessment costs. PARTICIPANTS AND CONTROLS: Computer simulation of 20 million people followed from age 50 years to death or age 100 years. METHODS: With the use of a computer model, we simulated glaucoma incidence, natural progression, diagnosis, and treatment. We defined glaucoma incidence conservatively as a mean deviation of -4 decibels (dB) on visual field testing in either eye for all diagnoses to be both clinically meaningful and unambiguous. We simulated the annual probability of subsequent progression and the quantity of visual field lost when progression occurred. MAIN OUTCOME MEASURES: Visual field loss, ophthalmologic and nursing home costs, quality-adjusted life years (QALYs), cost per QALY gained, and cost per year of sight gained. Costs and QALYs were discounted to 2005 values using a 3% rate. RESULTS: Compared with no treatment and when including diagnostic assessment costs, the incremental cost-effectiveness of routine assessment and treatment was $46,000 per QALY gained, assuming conservative treatment efficacy, and $28,000 per QALY gained, assuming optimistic treatment efficacy. Compared with no treatment and when excluding diagnostic assessment costs, the incremental cost-effectiveness of routine assessment and treatment was $20,000 per QALY gained, assuming conservative treatment efficacy, and $11,000 per QALY gained, assuming optimistic treatment efficacy. The cost-effectiveness was most sensitive to the treatment costs and the value of QALY losses assigned to visual field losses. CONCLUSIONS: Glaucoma treatment was highly cost-effective when the costs of diagnostic assessments were excluded or when we assumed optimistic treatment efficacy. The cost was reasonable and in line with other health interventions even when diagnostic assessment costs were included and assuming conservative efficacy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cost-effectiveness of screening for pre-diabetes among overweight and obese U.S. adults.

OBJECTIVE: To estimate the cost-effectiveness of screening overweight and obese individuals for pre-diabetes and then modifying their lifestyle based on the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS: A Markov simulation model was used to estimate disease progression, costs, and quality of life. Cost-effectiveness was evaluated from a health care system perspective. We considered two screening/treatment strategies for pre-diabetes. Strategy 1 included screening overweight subjects and giving them the lifestyle intervention included in the DPP if they were diagnosed with both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Strategy 2 included screening followed by lifestyle intervention for subjects diagnosed with either IGT or IFG or both. Each strategy was compared with a program of no screening. RESULTS: Screening for pre-diabetes and treating those identified as having both IGT and IFG with the DPP lifestyle intervention had a cost-effectiveness ratio of $8,181 per quality-adjusted life-year (QALY) relative to no screening. If treatment was also provided to subjects with only IGT or only IFG (strategy 2), the cost-effectiveness ratio increased to $9,511 per QALY. Changes in screening-related parameters had small effects on the cost-effectiveness ratios; the results were more sensitive to changes in intervention-related parameters. CONCLUSIONS: Screening for pre-diabetes in the overweight and obese U.S. population followed by the DPP lifestyle intervention has a relatively attractive cost-effectiveness ratio.

Cost-effectiveness of vitamin therapy for age-related macular degeneration.

OBJECTIVE: To determine the cost-effectiveness of vitamin therapy (antioxidants plus zinc) for all indicated patients diagnosed with age-related macular degeneration (AMD). DESIGN: We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized, stochastic, agent-based model. The model simulated the natural history of AMD and patterns of ophthalmic service use in the United States in a cohort from age 50 years until 100 or death. PARTICIPANTS AND/OR CONTROLS: The model created 20 million simulated individuals. These individuals each received both the intervention (vitamin therapy after diagnosis) and the control (no vitamin therapy). Expected outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes generated when they were not. METHODS: The model created individuals representative of patients in the U.S. Incidence of early AMD was based on published studies, as was vision loss and response to choroidal neovascularization therapies. Post-incident disease progression was governed by previously unpublished data drawn from the Age-Related Eye Disease Study. MAIN OUTCOME MEASURES: Extent of disease progression, years and severity of visual impairment, cost of ophthalmic care and nursing home services, and quality-adjusted life years (QALYs). Costs and benefits were considered from the health care perspective and discounted using a 3% rate. The analysis was run for 50 years starting in 2003. RESULTS: Compared with no therapy, vitamin therapy yielded a cost-effectiveness ratio of $21,387 per QALY gained and lowered the percentage of patients with AMD who ever developed visual impairment in the better-seeing eye from 7.0% to 5.6%. CONCLUSIONS: Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable cost.

An evaluation of cost sharing to finance a diet and physical activity intervention to prevent diabetes.

OBJECTIVE: The Diabetes Prevention Program (DPP) lifestyle intervention is a cost-effective strategy to prevent type 2 diabetes, but it is unclear how this intervention could be financed. We explored whether this intervention could be offered in a way that allows return on investment for private health insurers while remaining attractive for consumers, employers, and Medicare. RESEARCH DESIGN AND METHODS: We used the DPP and other published reports to build a Markov simulation model to estimate the lifetime progression of disease, costs, and quality of life for adults with impaired glucose tolerance. The model assumed a health-payer perspective and compared DPP lifestyle and placebo interventions. Primary outcomes included cumulative incidence of diabetes, direct medical costs, quality-adjusted life-years (QALYs), and cost per QALY gained. RESULTS: Compared with placebo, providing the lifestyle intervention at age 50 years could prevent 37% of new cases of diabetes before age 65, at a cost of $1,288 per QALY gained. A private payer could reimburse $655 (24%) of the $2,715 in total discounted intervention costs during the first 3 intervention years and still recover all of these costs in the form of medical costs avoided. If Medicare paid up to $2,136 in intervention costs over the 15-year period before participants reached age 65, it could recover those costs in the form of future medical costs avoided beginning at age 65. CONCLUSIONS: Cost-sharing strategies to offer the DPP lifestyle intervention for eligible people between ages 50 and 64 could provide financial return on investment for private payers and long-term benefits for Medicare.

Image-guided radiotherapy using a mobile kilovoltage x-ray device.

A mobile isocentric C-arm kilovoltage imager has been evaluated as a potential tool for image-guided radiotherapy. The C-arm is equipped with an amorphous silicon flat panel for high-quality image acquisition. Additionally, the device is capable of cone beam computed tomography (CT) and volumetric reconstruction. This is achieved through the application of a modified Feldkamp algorithm with acquisition over a 180 degrees scan arc. The number of projections can be varied from 100 to 1000, resulting in a reconstructed volume 20 cm in diameter by 15-cm long. While acquisition time depends upon number of projections, acceptable quality images can be obtained in less than 60 seconds. Image resolution and contrast of cone-beam phantom images have been compared with images from a conventional CT scanner. The system has a spatial resolution of > or = 10 lp/cm and resolution is approximately equal in all 3 dimensions. Conversely, subject contrast is poorer than conventional CT, compromised by the increased scatter and underlying noise inherent in cone beam reconstruction, as well as the absence of filtering prior to reconstruction. The mobility of the C-arm makes it necessary to determine the C-arm position relative to the linear accelerator isocenter. Two solutions have been investigated: (1) the use of fiducial markers, embedded in the linac couch, that can subsequently be registered in the image sets; and (2), a navigation approach for infrared tracking of the C-arm relative to the linac isocenter. Observed accuracy in phantom positioning ranged from 1.0 to 1.5 mm using the navigation approach and 1.5 to 2.5 mm using the fiducial-based approach. As part of this work, the impact of respiratory motion on cone-beam image quality was evaluated, and a scheme for retrospective gating was devised. Results demonstrated that kilovoltage cone beam CT provides spatial integrity and resolution comparable to conventional CT. Cone-beam CT studies of patients undergoing radiotherapy have demonstrated acceptable soft tissue contrast, allowing assessment of daily changes in target anatomy. Of the 2 approaches developed to register images to the linac isocenter, the navigation method demonstrated superior accuracy for daily patient positioning relative to the fiducial-based method. Finally, significant image degradation due to respiratory motion was observed. It was demonstrated that this could be improved by correlating the acquisition of individual 2D projections with respiration for retrospective reconstruction of phase-based volumetric datasets.

Respiratory correlated cone-beam computed tomography on an isocentric C-arm.

A methodology for 3D image reconstruction from retrospectively gated cone-beam CT projection data has been developed. A mobile x-ray cone-beam device consisting of an isocentric C-arm equipped with a flat panel detector was used to image a moving phantom. Frames for reconstruction were retrospectively selected from complete datasets based on the known rotation of the C-arm and a signal from a respiratory monitor. Different sizes of gating windows were tested. A numerical criterion for blur on the reconstructed image was suggested. The criterion is based on minimization of an Ising energy function, similar to approaches used in image segmentation or restoration. It is shown that this criterion can be used for the determination of the optimal gating window size. Images reconstructed from the retrospectively gated projection sequences using the optimal gating window data showed a significant improvement compared to images reconstructed from the complete projection datasets.

The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance.

BACKGROUND: The Diabetes Prevention Program (DPP) demonstrated that interventions can delay or prevent the development of type 2 diabetes. OBJECTIVE: To estimate the lifetime cost-utility of the DPP interventions. DESIGN: Markov simulation model to estimate progression of disease, costs, and quality of life. DATA SOURCES: The DPP and published reports. TARGET POPULATION: Members of the DPP cohort 25 years of age or older with impaired glucose tolerance. TIME HORIZON: Lifetime. PERSPECTIVES: Health system and societal. INTERVENTIONS: Intensive lifestyle, metformin, and placebo interventions as implemented in the DPP. OUTCOME MEASURES: Cumulative incidence of diabetes, microvascular and neuropathic complications, cardiovascular complications, survival, direct medical and direct nonmedical costs, quality-adjusted life-years (QALYs), and cost per QALY. RESULTS OF BASE-CASE ANALYSIS: Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per QALY was approximately 1100 dollars for the lifestyle intervention and $31 300 for the metformin intervention. From a societal perspective, the interventions cost approximately 8800 dollars and 29,900 dollars per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness improved when the interventions were implemented as they might be in routine clinical practice. The lifestyle intervention was cost-effective in all age groups. The metformin intervention did not represent good use of resources for persons older than 65 years of age. LIMITATIONS: Simulation results depend on the accuracy of the underlying assumptions, including participant adherence. CONCLUSIONS: Health policy should promote diabetes prevention in high-risk individuals.

Combination pharmacotherapy for cardiovascular disease prevention: threat or opportunity for public health?

In a series of three papers in the British Medical Journal (June 28, 2003), Wald et al. proposed that the Polypill can reduce the incidence of coronary heart disease by 88%, and stroke by 80%, if taken by all people aged > or = 55, as well as people of any age with existing cardiovascular disease or diabetes. We review the rationale and uniqueness behind this idea, identify the concerns and questions that need to be addressed, discuss whether this strategy is a threat or an opportunity for public health, and hope that this will stimulate further debate.

Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus.

OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical trials have shown ACE inhibitors can affect the development of nephropathy when initiated prior to the onset of microalbuminuria. Our objective is to examine the cost effectiveness of treating adults aged over 20 years with an ACE inhibitor (captopril) immediately following diagnosis of type 1 diabetes versus treating them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we calculated four main outcome measures: lifetime direct medical costs (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars. SETTING: All analyses were from the viewpoint of a single US payer responsible for all direct medical costs, including screening for microalbuminuria, ACE inhibitor treatment (captopril), management of major diabetic complications, and routine annual medical costs not specific to diabetes. METHODS: We applied the model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1 diabetes. Distribution of sex and race/ethnicity within the cohort is representative of the general US population. RESULTS: We estimated that the incremental cost of early use of captopril for the average adult with type 1 diabetes is USD 27,143 per QALY. This level varies considerably with age and glycaemic level. When the age at onset of diabetes is 20 years and glycosylated haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost-effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its underlying assumptions and data, suggests that early treatment with captopril provides modest benefit at reasonable cost effectiveness, from the US single-payer perspective, in the prevention of ESRD compared with delaying treatment until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors will provide similar cost effectiveness if they have equivalent efficacy, compliance and price per dose. Treatment may be considered among patients at age 20 years with new onset of type 1 diabetes. This conclusion is sensitive to the extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as the patient's age and glycaemic level must be considered when deciding to initiate early treatment.