Evaluation of the EQ-5D-3L and 5L versions in low back pain patients.

BACKGROUND: The EuroQol EQ-5D is one of the most widely researched and applied patient-reported outcome measures worldwide. The original EQ-5D-3L and more recent EQ-5D-5L include three and five response categories respectively. Evidence from healthy and sick populations shows that the additional two response categories improve measurement properties but there has not been a concurrent comparison of the two versions in patients with low back pain (LBP). METHODS: LBP patients taking part in a multicenter randomized controlled trial of lumbar total disc replacement and conservative treatment completed the EQ-5D-3L and 5L in an eight-year follow-up questionnaire. The 3L and 5L were assessed for aspects of data quality including missing data, floor and ceiling effects, response consistency, and based on a priori hypotheses, associations with the Oswestry Disability Index (ODI), Pain-Visual Analogue Scales and Hopkins Symptom Checklist (HSCL-25). RESULTS: At the eight-year follow-up, 151 (87%) patients were available and 146 completed both the 3L and 5L. Levels of missing data were the same for the two versions. Compared to the EQ-5D-5L, the 3L had significantly higher floor (pain discomfort) and ceiling effects (mobility, self-care, pain/discomfort, anxiety/depression). For these patients the EQ-5D-5L described 73 health states compared to 28 for the 3L. Shannon's indices showed the 5L outperformed the 3L in tests of classification efficiency. Correlations with the ODI, Pain-VAS and HSCL-25 were largely as hypothesized, the 5L having slightly higher correlations than the 3L. CONCLUSION: The EQ-5D assesses important aspect of health in LBP patients and the 5L improves upon the 3L in this respect. The EQ-5D-5L is recommended in preference to the 3L version, however, further testing in other back pain populations together with additional measurement properties, including responsiveness to change, is recommended. TRIAL REGISTRATION: retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT01704677 .

Use of Receiver Operating Curve Analysis and Machine Learning With an Independent Dose Calculation System Reduces the Number of Physical Dose Measurements Required for Patient-Specific Quality Assurance.

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.

Complications, reoperations, readmissions, and length of hospital stay in 34 639 surgical cases of lumbar disc herniation.

AIMS: The aims of this study were to determine the rates of surgical complications, reoperations, and readmissions following herniated lumbar disc surgery, and to investigate the impact of sociodemographic factors and comorbidity on the rate of such unfavourable events. PATIENTS AND METHODS: This was a longitudinal observation study. Data from herniated lumbar disc operations were retrieved from a large medical database using a combination of procedure and diagnosis codes from all public hospitals in Norway from 1999 to 2013. The impact of age, gender, geographical affiliation, education, civil status, income, and comorbidity on unfavourable events were analyzed by logistic regression. RESULTS: Of 34 639 operations, 2.7% (95% confidence interval (CI) 2.6 to 2.9) had a surgical complication, 2.1% (95% CI 2.0 to 2.3) had repeat surgery within 90 days, 2.4% (95% CI 2.2 to 2.5) had a non-surgical readmission within 90 days, and 6.7% (95% CI 6.4 to 6.9) experienced at least one of these unfavourable events. Unfavourable events were found to be associated with advanced age and comorbidity. CONCLUSION: The results suggest that surgical complications are less frequent than previously suggested. There are limited associations between sociodemographic patient characteristics and unfavourable events. Cite this article: Bone Joint J 2019;101-B:470-477.

A mathematical framework for virtual IMRT QA using machine learning.

PURPOSE: It is common practice to perform patient-specific pretreatment verifications to the clinical delivery of IMRT. This process can be time-consuming and not altogether instructive due to the myriad sources that may produce a failing result. The purpose of this study was to develop an algorithm capable of predicting IMRT QA passing rates a priori. METHODS: From all treatment, 498 IMRT plans sites were planned in eclipse version 11 and delivered using a dynamic sliding window technique on Clinac iX or TrueBeam Linacs. 3%/3 mm local dose/distance-to-agreement (DTA) was recorded using a commercial 2D diode array. Each plan was characterized by 78 metrics that describe different aspects of their complexity that could lead to disagreements between the calculated and measured dose. A Poisson regression with Lasso regularization was trained to learn the relation between the plan characteristics and each passing rate. RESULTS: Passing rates 3%/3 mm local dose/DTA can be predicted with an error smaller than 3% for all plans analyzed. The most important metrics to describe the passing rates were determined to be the MU factor (MU per Gy), small aperture score, irregularity factor, and fraction of the plan delivered at the corners of a 40 × 40 cm field. The higher the value of these metrics, the worse the passing rates. CONCLUSIONS: The Virtual QA process predicts IMRT passing rates with a high likelihood, allows the detection of failures due to setup errors, and it is sensitive enough to detect small differences between matched Linacs.

Estimates of autozygosity derived from runs of homozygosity: empirical evidence from selected cattle populations.

Using genome-wide SNP data, we calculated genomic inbreeding coefficients (FROH  > 1  Mb , FROH  > 2 Mb , FROH  > 8 Mb and FROH  > 16 Mb ) derived from runs of homozygosity (ROH) of different lengths (>1, >2, >8 and > 16 Mb) as well as from levels of homozygosity (FHOM ). We compared these values of inbreeding coefficients with those calculated from pedigrees (FPED ) of 1422 bulls comprising Brown Swiss (304), Fleckvieh (502), Norwegian Red (499) and Tyrol Grey (117) cattle breeds. For all four breeds, population inbreeding levels estimated by the genomic inbreeding coefficients FROH  > 8 Mb and FROH  > 16 Mb were similar to the levels estimated from pedigrees. The lowest values were obtained for Fleckvieh (FPED  = 0.014, FROH  > 8 Mb  = 0.019 and FROH  > 16 Mb  = 0.008); the highest, for Brown Swiss (FPED  = 0.048, FROH  > 8 Mb  = 0.074 and FROH  > 16 Mb  = 0.037). In contrast, inbreeding estimates based on the genomic coefficients FROH  > 1 Mb and FROH  > 2 Mb were considerably higher than pedigree-derived estimates. Standard deviations of genomic inbreeding coefficients were, on average, 1.3-1.7-fold higher than those obtained from pedigrees. Pearson correlations between genomic and pedigree inbreeding coefficients ranged from 0.50 to 0.62 in Norwegian Red (lowest correlations) and from 0.64 to 0.72 in Tyrol Grey (highest correlations). We conclude that the proportion of the genome present in ROH provides a good indication of inbreeding levels and that analysis based on ROH length can indicate the relative amounts of autozygosity due to recent and remote ancestors.

Commissioning of the Varian TrueBeam linear accelerator: a multi-institutional study.

PURPOSE: Latest generation linear accelerators (linacs), i.e., TrueBeam (Varian Medical Systems, Palo Alto, CA) and its stereotactic counterpart, TrueBeam STx, have several unique features, including high-dose-rate flattening-filter-free (FFF) photon modes, reengineered electron modes with new scattering foil geometries, updated imaging hardware/software, and a novel control system. An evaluation of five TrueBeam linacs at three different institutions has been performed and this work reports on the commissioning experience. METHODS: Acceptance and commissioning data were analyzed for five TrueBeam linacs equipped with 120 leaf (5 mm width) MLCs at three different institutions. Dosimetric data and mechanical parameters were compared. These included measurements of photon beam profiles (6X, 6XFFF, 10X, 10XFFF, 15X), photon and electron percent depth dose (PDD) curves (6, 9, 12 MeV), relative photon output factors (Scp), electron cone factors, mechanical isocenter accuracy, MLC transmission, and dosimetric leaf gap (DLG). End-to-end testing and IMRT commissioning were also conducted. RESULTS: Gantry/collimator isocentricity measurements were similar (0.27-0.28 mm), with overall couch/gantry/collimator values of 0.46-0.68 mm across the three institutions. Dosimetric data showed good agreement between machines. The average MLC DLGs for 6, 10, and 15 MV photons were 1.33 ± 0.23, 1.57 ± 0.24, and 1.61 ± 0.26 mm, respectively. 6XFFF and 10XFFF modes had average DLGs of 1.16 ± 0.22 and 1.44 ± 0.30 mm, respectively. MLC transmission showed minimal variation across the three institutions, with the standard deviation <0.2% for all linacs. Photon and electron PDDs were comparable for all energies. 6, 10, and 15 MV photon beam quality, %dd(10)x varied less than 0.3% for all linacs. Output factors (Scp) and electron cone factors agreed within 0.27%, on average; largest variations were observed for small field sizes (1.2% coefficient of variation, 10 MV, 2 × 2 cm(2)) and small cone sizes (<1% coefficient of variation, 6 × 6 cm(2) cone), respectively. CONCLUSIONS: Overall, excellent agreement was observed in TrueBeam commissioning data. This set of multi-institutional data can provide comparison data to others embarking on TrueBeam commissioning, ultimately improving the safety and quality of beam commissioning.

SU-E-T-551: A Customized Plan Evaluation System for On-Line Adaptive Radiotherapy.

PURPOSE: Treatment plan evaluation based on daily images, to determine whether it is necessary to re-plan the treatment, is an essential element of adaptive radiotherapy. A fully automatic system, incorporating physician preferences and requirements of specific protocols quantified by a series of objective functions, was developed to evaluate treatment plans. METHODS: The evaluation system was developed using IDL 6.1 (ITT Visual Information Solutions, Boulder, CO). Based on customized evaluation guidelines, dosimetric parameters, including maximum dose, minimum dose, uniformity dose, dose coverage, conformity index, heterogeneity index, gEUD, and DVH for the targets and OARs are evaluated as series of cost functions which incorporate specific protocol constraints and physician requirements. The evaluation system was applied to IMRT plans of head/neck cancer patients. The Pinnacle Treatment Planning System (research version 9.0) was used to generate verification treatment plan trials, with image datasets, ROI structures, and dose distributions exported to evaluation system. RESULTS: Results show that the evaluation system can complete evaluation of a dose plan within 2∼8 seconds. The system is capable of displaying and comparing dose distributions among different plans. It also demonstrates great flexibility in customizing cost functions based on physician preferences. This system is supported with various user-friendly options, graphical displays, and feasibly structure in adding new modules. CONCLUSIONS: This evaluation system is capable of quantifying specific protocols and preferences of physicians and completing automatic evaluation almost in real-time. It is an essential a platform for adaptive radiation therapy and also valuable for initial treatment planning. This research is supported by CPRIT Individual Investigator Award RP110329.

SU-E-J-127: An Initial Application of Evaluating Lung Tumor Motion Throughout Radiotherapy.

PURPOSE: We present a novel method for evaluating lung tumor motion incorporating planning CT scan, imaging for patient localization, and during treatment delivery. METHODS: Tumor motion is evaluated at three stages of the treatment process. Following the acquisition of 4D CT scans for treatment planning, tumors are contoured at one phase and registered to other phases to obtain tumor motion patterns. Tumor motion prior to each treatment is evaluated by identifying tumors directly on every raw projection of the daily localization CBCT scans. Finally, tumor motion during treatment is evaluated by analyzing MV treatment beam images. Every frame of image is evaluated as three components, each with separate DRRs: all non-moving structures, the tumor, and other moving structures. The locations of three components are determined though a registration process. In order to quantify tumor motion, the cumulated probability, the percentage of time when the tumor motion is equal to or smaller than a given range, is evaluated at every stage. RESULTS: This methodology has been applied to five lung cancer patients undergoing radiotherapy. More than 5400 frames from MV treatment beam images and 24 CBCT scans were acquired from 12 fractions. Both the average tumor position and the cumulated probability with the range were evaluated. The tumor motion ranges are generally larger than those obtained from 4D CT. Significant variation in motion patterns was observed as well. CONCLUSIONS: Information obtained from 4DCT is insufficient for motion assessment. In contrast, our novel methodology is capable of accurately characterizing lung tumor motion on a daily basis, without the need for implanted fiducial markers and without additional imaging dose. It provides daily verification that the tumor range is within prior estimates and covered by the treatment planning volume. This research is supported by CPRIT Individual Investigator Award RP110329.

SU-E-J-112: A Splatting Method to Generate DRRs for Deformed CT Volume.

PURPOSE: To develop an efficient algorithm for generating high-quality digitally reconstructed radiographs (DRRs) for regularly and irregularly sampled volumes based on a splatting method with dynamic elliptical Gaussian kernels, and to evaluate this method using ray tracing. METHODS: The traditional ray tracing method, which takes every intersected voxel into account, produces high quality DRRs but is very time consuming. Additionally, it is not suitable for handling irregularly-sampled volumes since it always requires image re-sampling, which leads to inaccuracy. We present a splatting approach to compute the 'footprint function', facilitating efficient perspective projection of elliptical Gaussian kernels at very low cost. This reported framework allows dealing with both regularly and irregularly sampled volumes effectively and efficiently. An XCAT digital phantom was used to generate 3D chest volumes at different respiratory phases, and CT projections are generated using ray tracing and the splatting method, respectively. Normalized cross correlation (NCC) is applied to evaluate the DRR similarity of two methods. RESULTS: Respiratory Phases one and four are used as volume datasets from the 4D XCAT digital phantom as they represent the lung at end inhale and end exhale, respectively. The dataset of Phase one is the basic regularly-sampled volume while the dataset of Phase four is deformed from that of Phase one, and resampled to a regularly sampled dataset for the ray tracing method. NCC between splatting and ray tracing DRRs are 0.9980 and 0.9977 for Phase one and Phase four, respectively. The calculation speed of the splatting method is 3 times faster than that of ray tracing. CONCLUSIONS: Our splatting approach can generate high-quality DRRs efficiently, and is a good alternative for current DRR generation techniques for deformed volume datasets. This research is supported by CPRIT Individual Investigator Award RP110329.

SU-E-T-386: Gamma Analysis of Normalized and Un-Normalized Dose Distributions.

PURPOSE: The gamma index method, as currently implemented in all commercial QA software, calls for selection of a normalization point to evaluate agreement between two dose distributions. The implication of this is that there is an infinite number of possible solutions! Which one to pick? A unique and more relevant solution is obtained only if no normalization point is used. METHODS AND MATERIALS: The set of test cases suggested by the AAPM TG1 19 were planned using Pinnacle 8.0m and delivered on a Varian 21EX linac for 6 and 18 MV photons. The recommended point and planar dose measurements were obtained using a Pinpoint ion chamber, EDR2 film and MatriXX. The gamma index method using typical 3%, 3 mm criteria with and without a normalization point was used to assess the agreement between calculated and delivered planar dose distributions. The analysis was extended to a set of data for clinically treated patients. RESULTS: The comparison with the TG119 benchmark data showed that all point dose and planar measurements for 6 MV were within the published range. Similar results, although without published data to compare with, were obtained for 18 MV as well. For all complex tests, the percentage of points passing the gamma criteria of 3%, 3 mm was (95.8±1.6)% and (95.6±1.0)% for 6 MV and 18 MV, respectively. Without a normalization point, however, the same gamma analysis fell to (20.7±6.7)% and (13.9±4.0)% for 6 MV and 18 MV, respectively. The clinical data set showed the same trend, with the gamma passing rate declining from (98.9±0.7)% to (33.4±13.1)%. CONCLUSION: The gamma index method provides a unique answer for gamma passing rate only without normalizing dose distributions to any particular point. The common gamma criteria of 3%, 3 mm, however, is a very poor metric in that case.

SU-E-T-414: Clinical Implementation of Anthropomorphic Lung Phantom for Patient-Specific SAbR QA.

PURPOSE: Dose calculations for lung stereotactic ablative radiotherapy (SAbR) are challenged by the presence of extremely heterogeneous tissue and small treatment volumes. In this work, an anthropomorphic chest phantom has been constructed for the purpose of commissioning treatment planning systems (TPS) and for patient-specific SAbR QA. METHODS: A CT scan of a realistic chest phantom containing tissue equivalent materials for the spine, ribs, and lungs was imported into a Pinnacle TPS (CCC dose algorithm) where treatment plans were created for right and left-sided lung lesions. The phantom lungs are unique in that they contain embedded unit density spherical targets (2 and 4cm in diameter) that represent lung lesions. Plans directed to both tumors were designed for PTVs ranging from 2-5cm in diameter using 6, 10, and 15MV beams while passing RTOG 0813 dose and conformality criteria. Each plan was then exported to an Eclipse TPS (AAA dose algorithm) for dose calculation. Plans were delivered with a TrueBeam LINAC corrected for machine output. Point dose measurementswere verified with a 0.015 cc air ionization chamber placed in the center of each tumor. RESULTS: While the majority of plans developed in Pinnacle passed conformality criteria, the dose distribution as calculated in Eclipse failed to meet the RTOG guidelines, particularly for the small tumor at higher photon energies. All point dose measurements matched both TPS within 4%. Both TPS calculated a lower point dose than measured for large PTVs at all energies, improving as PTV size decreased. CONCLUSIONS: After comparing TPS and validating calculations with point dose measurements, the phantom was clinically implemented for patient-specific conformal SAbR QA.

SU-E-T-274: Monte Carlo Simulations of Output Factors for a Small Animal Irradiator.

PURPOSE: Measurement of dosimetric parameters of small photon beams, with field sizes as small 1 mm in diameter, is particularly challenging. This work utilizes Monte Carlo techniques to calculate percent depth dose (PDD) and output factors for small photon fields from a kV x-ray based small animal irradiator. METHODS: Absolute dose calibration of a commercial small animal stereotactic irradiator (XRAD225, Precision X-ray) was performed in accordance with the recommendations of AAPM TG-61 protocol. Both in-air and in-water calibrations were performed at a 30.4 cm source-to-surface distance (SSD) for a reference collimator 50 mm in diameter. The BEAM/EGS was used to model 225 kV photon beams used for most therapeutic applications. The Monte Carlo model was provided good agreement with measured beam characteristics, e.g. PDD and off-axis ratios. Subsequently, output factors for various square and circular applicators were measured using an ionization chamber and radiochromic film, and compared with MC simulations. Directional Bremsstrahlung splitting (DBS) was utilized for variance reduction to improve efficiency of the output factor simulations. The statistical uncertainty on the MC- calculated results is between 0.5% and 1% for most points. RESULTS: The absolute dose measured for reference collimator at 30.4 cm SSD in water and in air is 4.1 and 4.12 Gy/min. The agreement between simulated and measured output factors was excellent, ranging from 1% to 2.84%. The MC- simulated and measured depth dose data, normalized at the surface, show excellent agreement, with a maximum deviation is approximately 2.5 %. CONCLUSIONS: Monte Carlo simulation provides an indispensible tool for validating measurements of the smallest field sizes used in preclinical small animal irradiation.

SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac in a Low-Energy Vault.

PURPOSE: To design and quantify the shielding efficacy of an inner Borated Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. METHODS: A Varian TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller, preexisting vault. This vault originally housed a low-energy machine and did not havesufficient maze length recommended for neutron attenuation. Effective dose rate calculationswere performed using the Modified Kersey's Method as detailed in NCRP Report No. 151 andfound to be unacceptably high. An initial survey following the machine installation confirmedthese calculations. Rather than restrict the linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition. An inner wall and door were planned and constructed using4'×8'×1″ thick 5% BPE sheets. The resulting door and wall had 2″ of BPE; conduits and ductwork were also redesigned and shielded. A survey was conducted following construction of thewall. RESULTS: The vault modification reduced the expected effective dose at the vault door from 36.23to 0.010 mSv/week. CONCLUSION: As specific guidelines for vault modification are lacking, this project quantitativelydemonstrates the potential use of BPE for vault modification. Such modifications may provide alow-cost shielding solution to allow for the use of high energy modes in smaller treatment vaults.

SU-E-T-451: Optimization of Normalized Prescription Isodose Selection for Stereotactic Radiation Therapy: Conventional Vs. Robotic Linac.

PURPOSE: To determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic radiation therapy comparing conventional linear accelerator and robotic delivery. METHODS: A computer based digital torso phantom which has the capability to simulate respiratory and cardiac motion were used in this study. Spherical targets were constructed in lung and liver, with diameter of 20mm, 30mm, and 40mm. Two concentric 5mm shells, from the target surface extending 5mm radially and from 5mm to 10mm, were identified/contoured. Non-coplanar, non- opposing 3D conformal beams were designed for linac planning. Variable prescription isodose lines were achieved by varying the block margin. 4D dose calculation was used for moving target and surrounding tissue. After linac planning, the CT images and contours were transferred for Cyberknife® planning. Variable prescription isodose lines were achieved by inverse planning technique. Doses of 60Gy in 3 fractions were prescribed to cover exactly 95% of target tumor with each technology. gEUD (generalized effective uniform dose) with different formulations for parallel and serial tissues was used for comparison between different plans. RESULTS: For linac plans, the optimal prescription isodose line yielding maximum normal tissue sparing occurs between 50% and 70% for the lung tumor and 60% and 90% for liver tumor. The gEUD difference between plans with optimum and arbitrarily chosen prescription isodose line may be up to 20% of prescription dose. For Cyberknife plans, the optimal prescription isodose line is approximately 50% for tissues displaying either parallel or serial behavior. These results are similar for different tumor sizes. CONCLUSIONS: Both conventional linac and Cyberknife® delivery can provide conformal tumor coverage with normal tissue sparing. By carefully choosing the optimal prescription isodose line, the gEUD of the surrounding normal tissue can be reduced by up to 20% of prescription dose.

Dosimetric characterization of an image-guided stereotactic small animal irradiator.

Small animal irradiation provides an important tool used by preclinical studies to assess and optimize new treatment strategies such as stereotactic ablative radiotherapy. Characterization of radiation beams that are clinically and geometrically scaled for the small animal model is uniquely challenging for orthovoltage energies and minute field sizes. The irradiator employs a commercial x-ray device (XRAD 320, Precision x-ray, Inc.) with a custom collimation system to produce 1-10 mm diameter beams and a 50 mm reference beam. Absolute calibrations were performed using the AAPM TG-61 methodology. Beam's half-value layer (HVL) and timer error were measured with an ionization chamber. Percent depth dose (PDD), output factors (OFs) and off-axis ratios were measured using radiochromic film, a diode and a pinpoint ionization chamber at 19.76 and 24.76 cm source-to-surface distance (SSD). PDD measurements were also compared with Monte Carlo (MC) simulations. In-air and in-water absolute calibrations for the reference 50 mm diameter collimator at 19.76 cm SSD were measured as 20.96 and 20.79 Gy min(-1), respectively, agreeing within 0.8%. The HVL at 250 kVp and 15 mAs was measured to be 0.45 mm Cu. The reference field PDD MC simulation results agree with measured data within 3.5%. PDD data demonstrate typical increased penetration with increasing field size and SSD. For collimators larger than 5 mm in diameter, OFs measured using film, an ion chamber and a diode were within 3% agreement.

An x-ray image guidance system for small animal stereotactic irradiation.

An x-ray image-guided small animal stereotactic irradiator was developed and characterized to enable tumor visualization and accurate target localization for small field, high dose irradiation. The system utilizes a custom collimation system, a motorized positioning system (x, y, θ), a digital imaging panel and operating software, and is integrated with a commercial x-ray unit. The essential characteristics of the irradiator include small radiation fields (1-10 mm), high dose rate (>10 Gy min(-1)) and submillimeter target localization. The software enables computer-controlled image acquisition, stage motion and target localization providing simple and precise automated target localization. The imaging panel was characterized in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution. Overall localization accuracy and precision were assessed. SNR, CNR and spatial resolution are 24 dB, 21 dB and 2.8 lp mm(-1), respectively, and localization accuracy is approximately 65 µm with 6 µm precision. With the aid of image guidance, system performance was subsequently used to evaluate radiation response in a rat orthotopic lung tumor effectively sparing normal tissues and in a mouse normal lung. The capabilities of 3D treatment and cone-beam computed tomography are presented for 3D localization and delivery as a work in progress.

Genomic selection using different marker types and densities.

With the availability of high-density marker maps and cost-effective genotyping, genomic selection methods may provide faster genetic gain than can be achieved by current selection methods based on phenotypes and the pedigree. Here we investigate some of the factors driving the accuracy of genomic selection, namely marker density and marker type (i.e., microsatellite and SNP markers), and the use of marker haplotypes versus marker genotypes alone. Different densities were tested with marker densities equivalent to 2, 1, 0.5, and 0.25N(e) markers/morgan using microsatellites and 8, 4, 2, and 1N(e) markers/morgan using SNP, where 1N(e) markers/morgan means 100 markers per morgan, if effective size (N(e)) is 100. Marker characteristics and linkage disequilibria were obtained by simulating a population over 1,000 generations to achieve a mutation drift balance. The marker designs were evaluated for their accuracy of predicting breeding values from either estimating marker effects or estimating effects of haplotypes based upon combining 2 markers. Using microsatellites as direct marker effects, the accuracy of selection increased from 0.63 to 0.83 as the density increased from 0.25N(e)/morgan to 2N(e)/morgan. Using SNP markers as direct marker effects, the accuracy of selection increased from 0.69 to 0.86 as the density increased from 1N(e)/morgan to 8N(e)/morgan. The SNP markers required a 2 to 3 times greater density compared with using microsatellites to achieve a similar accuracy. The biases that genomic selection EBV often show are due to the prediction of marker effects instead of QTL effects, and hence, genomic selection EBV may need rescaling for practical use. Using haplotypes resulted in similar or reduced accuracies compared with using direct marker effects. In practical situations, this means that it is advantageous to use direct marker effects, because this avoids the estimation of marker phases with the associated errors. In general, the results showed that the accuracy remained responsive with small bias to increasing marker density at least up to 8N(e) SNP/morgan, where the effective population size was 100 and with the genomic model assumed. For a 30-morgan genome and N(e) = 100, this implies that about approximately 24,000 SNP are needed.

Cone-beam CT using a mobile C-arm: a registration solution for IGRT with an optical tracking system.

A method for registering images acquired from a prototype flat panel mobile C-arm, capable of kilovoltage (kV) cone-beam computed tomography (CT), to a linear accelerator (LINAC) isocenter is presented. A calibration procedure is performed which involves locating reflective markers placed on the C-arm and a phantom in two coordinate systems. A commercial optical tracking system locates the markers relative to the LINAC isocenter (room coordinates). The cone-beam imaging capabilities of the C-arm provide the location of the markers on the calibration phantom in image coordinates. A singular value decomposition (SVD) algorithm is used to determine the relationship between the C-arm, image coordinates and room coordinates. Once the calibration is completed, the position of the C-arm at any arbitrary location is accurately determined from the tracking system. A final transformation is calculated capable of mapping voxels in the reconstructed image set to their corresponding position in room coordinates. An evaluation to determine the accuracy of this method was performed by locating markers on a phantom. The position of the phantom markers in room coordinates was obtained directly using the optical tracking system and compared with that using the described method above. A mean absolute distance of 1.4+/-0.5 was observed for a completely transformed image set. This is comparable to that of systems routinely used for image-guided radiation therapy (IGRT).

Stereotactic radiotherapy for the treatment of pituitary adenomas.

PURPOSE: The aim of this study was to retrospectively review local control and morbidity following stereotactic radiotherapy (SRT) for pituitary adenoma. METHODS: Between 1997 and 2004, 39 patients with pituitary adenomas received SRT. Median age was 56 years (range: 13 to 90 years). Thirty-three patients underwent incomplete transsphenoidal surgery prior to SRT and six had unresectable tumors. The largest tumor dimension varied from 1.7 to 6 cm (median: 3 cm). Tumor volume varied from 1.2 to 56 mL (median 10.5 mL). Thirty-five tumors were < or = 1 mm from the optic chiasm/nerve. Thirty-three tumors were non-functional. SRT was delivered by a dedicated linear accelerator (Novalis, Heimstetten, Germany). Beam collimation was achieved by a fixed circular collimator (five patients) or a micro-multileaf collimator (34 patients). Total dose varied from 4500 to 5040 cGy (median: 4860 cGy) and was prescribed at the 90 % isodose line. RESULTS: After a median follow-up of 32 months (range: 12 to 94 months), the local control rate was 100 %. Tumor size was stable in 26 patients and decreased in 13 patients. Hormone normalization did not occur following SRT. New endocrine deficiency occurred in six patients. No patient developed cranial nerve injury or second malignancy following treatment. CONCLUSIONS: SRT achieves a high rate of local control and a low rate of treatment-induced morbidity. SRT is applicable to pituitary adenomas in close proximity to the optic apparatus and tumors in excess of three centimeters in the greatest dimension. Further follow-up is necessary to establish the long-term outcome following SRT for pituitary adenomas.

Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma.

PURPOSE: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. METHODS: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. CONCLUSIONS: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.