Design and characterization of a new high-dose-rate brachytherapy Valencia applicator for larger skin lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Candela-Juan, C., E-mail: ccanjuan@gmail.com; Niatsetski, Y.; Laarse, R. van der

Purpose: The aims of this study were (i) to design a new high-dose-rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a {sup 192}Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water. Methods: The PENELOPE2008 MC code was used to optimize dwell positions and dwell times.more » Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a {sup 192}Ir mHDR-v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber. Results: The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off-axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%. Conclusions: The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.« less

TU-F-CAMPUS-I-02: Validation of a CT X-Ray Source Characterization Technique for Dose Computation Using An Anthropomorphic Thorax Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sommerville, M; Tambasco, M; Poirier, Y

2015-06-15

Purpose: To experimentally validate a rotational kV x-ray source characterization technique by computing CT dose in an anthropomorphic thorax phantom using an in-house dose computation algorithm (kVDoseCalc). Methods: The lateral variation in incident energy spectra of a GE Optima big bore CT scanner was found by measuring the HVL along the internal, full bow-tie filter axis. The HVL and kVp were used to generate the x-ray spectra using Spektr software, while beam fluence was derived by dividing the integral product of the spectra and in-air mass-energy absorption coefficients by in-air dose measurements along the bow-tie filter axis. Beams produced bymore » the GE Optima scanner were modeled at 80 and 140 kVp tube settings. kVDoseCalc calculates dose by solving the linear Boltzmann transport equation using a combination of deterministic and stochastic methods. Relative doses in an anthropomorphic thorax phantom (E2E SBRT Phantom) irradiated by the GE Optima scanner were measured using a (0.015 cc) PTW Freiburg ionization chamber, and compared to computations from kVDoseCalc. Results: The agreement in relative dose between dose computation and measurement for points of interest (POIs) within the primary path of the beam was within experimental uncertainty for both energies, however points outside the primary beam were not. The average absolute percent difference for POIs within the primary path of the beam was 1.37% and 5.16% for 80 and 140 kVp, respectively. The minimum and maximum absolute percent difference for both energies and all POIs within the primary path of the beam was 0.151% and 6.41%, respectively. Conclusion: The CT x-ray source characterization technique based on HVL measurements and kVp can be used to accurately compute CT dose in an anthropomorphic thorax phantom.« less

SU-G-BRB-15: Verifications of Absolute and Relative Dosimetry of a Novel Stereotactic Breast Device: GammaPodTM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, S; Mossahebi, S; Yi, B

Purpose: A dedicated stereotactic breast radiotherapy device, GammaPod, was developed to treat early stage breast cancer. The first clinical unit was installed and commissioned at University of Maryland. We report our methodology of absolute dosimetry in multiple calibration conditions and dosimetric verifications of treatment plans produced by the system. Methods: GammaPod unit is comprised of a rotating hemi-spherical source carrier containing 36 Co-60 sources and a concentric tungsten collimator providing beams of 15 and 25 mm. Absolute dose calibration formalism was developed with modifications to AAPM protocols for unique geometry and different calibration medium (acrylic, polyethylene or liquid water). Breastmore » cup-size specific and collimator output factors were measured and verified with respect to Monte-Carlo simulations for single isocenter plans. Multiple isocenter plans were generated for various target size, location and cup-sizes in phantoms and 20 breast cancer patients images. Stereotactic mini-farmer chamber, OSL and TLD detectors as well as radio-chromic films were used for dosimetric measurements. Results: At the time of calibration (1/14/2016), absolute dose rate of the GammaPod was established to be 2.10 Gy/min in acrylic for 25 mm for sources installed in March 2011. Output factor for 15 mm collimator was measured to be 0.950. Absolute dose calibration was independently verified by IROC-Houston with a TLD/Institution ratio of 0.99. Cup size specific output measurements in liquid water for single isocenter were found to be within 3.0% of MC simulations. Point-dose measurements of multiple isocenter treatment plans were found to be within −1.0 ± 1.2 % of treatment planning system while 2-dimensional gamma analysis yielded a pass rate of 97.9 ± 2.2 % using gamma criteria of 3% and 2mm. Conclusion: The first GammaPod treatment unit for breast stereotactic radiotherapy was successfully installed, calibrated and commissioned for patient treatments. An absolute dosimetry and dosimetric verification protocols were successfully created.« less

Poster — Thur Eve — 76: Dosimetric Comparison of Pinnacle and iPlan Algorithms with an Anthropomorphic Lung Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, P.; Tambasco, M.; LaFontaine, R.

2014-08-15

Our goal is to compare the dosimetric accuracy of the Pinnacle-3 9.2 Collapsed Cone Convolution Superposition (CCCS) and the iPlan 4.1 Monte Carlo (MC) and Pencil Beam (PB) algorithms in an anthropomorphic lung phantom using measurement as the gold standard. Ion chamber measurements were taken for 6, 10, and 18 MV beams in a CIRS E2E SBRT Anthropomorphic Lung Phantom, which mimics lung, spine, ribs, and tissue. The plan implemented six beams with a 5×5 cm{sup 2} field size, delivering a total dose of 48 Gy. Data from the planning systems were computed at the treatment isocenter in the leftmore » lung, and two off-axis points, the spinal cord and the right lung. The measurements were taken using a pinpoint chamber. The best results between data from the algorithms and our measurements occur at the treatment isocenter. For the 6, 10, and 18 MV beams, iPlan 4.1 MC software performs the best with 0.3%, 0.2%, and 4.2% absolute percent difference from measurement, respectively. Differences between our measurements and algorithm data are much greater for the off-axis points. The best agreement seen for the right lung and spinal cord is 11.4% absolute percent difference with 6 MV iPlan 4.1 PB and 18 MV iPlan 4.1 MC, respectively. As energy increases absolute percent difference from measured data increases up to 54.8% for the 18 MV CCCS algorithm. This study suggests that iPlan 4.1 MC computes peripheral dose and target dose in the lung more accurately than the iPlan 4.1 PB and Pinnicale CCCS algorithms.« less

TU-F-BRF-03: Effect of Radiation Therapy Planning Scan Registration On the Dose in Lung Cancer Patient CT Scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunliffe, A; Contee, C; White, B

Purpose: To characterize the effect of deformable registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Methods: Eighteen patients who received curative doses (≥60Gy, 2Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pre-therapy (4–75 days) CT scan and a treatment planning scan with an associated dose map calculated in Pinnacle were collected. To establish baseline correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pre-therapy scans were co-registered with planning scans (and associated dose maps)more » using the Plastimatch demons and Fraunhofer MEVIS deformable registration algorithms. Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from both registration algorithms. The absolute difference in planned dose (|ΔD|) between manually and automatically mapped landmark points was calculated. Using regression modeling, |ΔD| was modeled as a function of the distance between manually and automatically matched points (registration error, E), the dose standard deviation (SD-dose) in the eight-pixel neighborhood, and the registration algorithm used. Results: 52–92 landmark point pairs (median: 82) were identified in each patient's scans. Average |ΔD| across patients was 3.66Gy (range: 1.2–7.2Gy). |ΔD| was significantly reduced by 0.53Gy using Plastimatch demons compared with Fraunhofer MEVIS. |ΔD| increased significantly as a function of E (0.39Gy/mm) and SD-dose (2.23Gy/Gy). Conclusion: An average error of <4Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration. Dose differences following registration were significantly increased when the Fraunhofer MEVIS registration algorithm was used, spatial registration errors were larger, and dose gradient was higher (i.e., higher SD-dose). To our knowledge, this is the first study to directly compute dose errors following deformable registration of lung CT scans.« less

Characterization of the Exradin W1 scintillator for use in radiotherapy.

PubMed

Carrasco, P; Jornet, N; Jordi, O; Lizondo, M; Latorre-Musoll, A; Eudaldo, T; Ruiz, A; Ribas, M

2015-01-01

To evaluate the main characteristics of the Exradin W1 scintillator as a dosimeter and to estimate measurement uncertainties when used in radiotherapy. We studied the calibration procedure, energy and modality dependence, short-term repeatability, dose-response linearity, angular dependence, temperature dependence, time to reach thermal equilibrium, dose-rate dependence, water-equivalent depth of the effective measurement point, and long-term stability. An uncertainty budget was derived for relative and absolute dose measurements in photon and electron beams. Exradin W1 showed a temperature dependence of -0.225% °C(-1). The loss of sensitivity with accumulated dose decreased with use. The sensitivity of Exradin W1 was energy independent for high-energy photon and electron beams. All remaining dependencies of Exradin W1 were around or below 0.5%, leading to an uncertainty budget of about 1%. When a dual channel electrometer with automatic trigger was not used, timing effects became significant, increasing uncertainties by one order of magnitude. The Exradin W1 response is energy independent for high energy x-rays and electron beams, and only one calibration coefficient is needed. A temperature correction factor should be applied to keep uncertainties around 2% for absolute dose measurements and around 1% for relative measurements in high-energy photon and electron beams. The Exradin W1 scintillator is an excellent alternative to detectors such as diodes for relative dose measurements.

SU-E-T-117: Analysis of the ArcCHECK Dosimetry Gamma Failure Using the 3DVH System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, S; Choi, W; Lee, H

2015-06-15

Purpose: To evaluate gamma analysis failure for the VMAT patient specific QA using ArcCHECK cylindrical phantom. The 3DVH system(Sun Nuclear, FL) was used to analyze the dose difference statistic between measured dose and treatment planning system calculated dose. Methods: Four case of gamma analysis failure were selected retrospectively. Our institution gamma analysis indexes were absolute dose, 3%/3mm and 90%pass rate in the ArcCHECK dosimetry. The collapsed cone convolution superposition (CCCS) dose calculation algorithm for VMAT was used. Dose delivery was performed with Elekta Agility. The A1SL(standard imaging, WI) and cavity plug were used for point dose measurement. Delivery QA plansmore » and images were used for 3DVH Reference data instead of patient plan and image. The measured data of ‘.txt’ file was used for comparison at diodes to acquire a global dose level. The,.acml’ file was used for AC-PDP and to calculated point dose. Results: The global dose of 3DVH was calculated as 1.10 Gy, 1.13, 1.01 and 0.2 Gy respectively. The global dose of 0.2 Gy case was induced by distance discrepancy. The TPS calculated point dose of was 2.33 Gy to 2.77 Gy and 3DVH calculated dose was 2.33 Gy to 2.68 Gy. The maximum dose differences were −2.83% and −3.1% for TPS vs. measured dose and TPS vs. 3DVH calculated respectively in the same case. The difference between measured and 3DVH was 0.1% in that case. The 3DVH gamma pass rate was 98% to 99.7%. Conclusion: We found the TPS calculation error by 3DVH calculation using ArcCHECK measured dose. It seemed that our CCCS algorithm RTP system over estimated at the central region and underestimated scattering at the peripheral diode detector point. The relative gamma analysis and point dose measurement would be recommended for VMAT DQA in the gamma failure case of ArcCHECK dosimetry.« less

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

PubMed

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

PubMed

Liu, Haisong; Li, Jun; Pappas, Evangelos; Andrews, David; Evans, James; Werner-Wasik, Maria; Yu, Yan; Dicker, Adam; Shi, Wenyin

2016-09-08

An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the treatment delivery accuracy as well. © 2016 The Authors.

Practical dose point-based methods to characterize dose distribution in a stationary elliptical body phantom for a cone-beam C-arm CT system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jang-Hwan, E-mail: jhchoi21@stanford.edu; Constantin, Dragos; Ganguly, Arundhuti

2015-08-15

Purpose: To propose new dose point measurement-based metrics to characterize the dose distributions and the mean dose from a single partial rotation of an automatic exposure control-enabled, C-arm-based, wide cone angle computed tomography system over a stationary, large, body-shaped phantom. Methods: A small 0.6 cm{sup 3} ion chamber (IC) was used to measure the radiation dose in an elliptical body-shaped phantom made of tissue-equivalent material. The IC was placed at 23 well-distributed holes in the central and peripheral regions of the phantom and dose was recorded for six acquisition protocols with different combinations of minimum kVp (109 and 125 kVp)more » and z-collimator aperture (full: 22.2 cm; medium: 14.0 cm; small: 8.4 cm). Monte Carlo (MC) simulations were carried out to generate complete 2D dose distributions in the central plane (z = 0). The MC model was validated at the 23 dose points against IC experimental data. The planar dose distributions were then estimated using subsets of the point dose measurements using two proposed methods: (1) the proximity-based weighting method (method 1) and (2) the dose point surface fitting method (method 2). Twenty-eight different dose point distributions with six different point number cases (4, 5, 6, 7, 14, and 23 dose points) were evaluated to determine the optimal number of dose points and their placement in the phantom. The performances of the methods were determined by comparing their results with those of the validated MC simulations. The performances of the methods in the presence of measurement uncertainties were evaluated. Results: The 5-, 6-, and 7-point cases had differences below 2%, ranging from 1.0% to 1.7% for both methods, which is a performance comparable to that of the methods with a relatively large number of points, i.e., the 14- and 23-point cases. However, with the 4-point case, the performances of the two methods decreased sharply. Among the 4-, 5-, 6-, and 7-point cases, the 7-point case (1.0% [±0.6%] difference) and the 6-point case (0.7% [±0.6%] difference) performed best for method 1 and method 2, respectively. Moreover, method 2 demonstrated high-fidelity surface reconstruction with as few as 5 points, showing pixelwise absolute differences of 3.80 mGy (±0.32 mGy). Although the performance was shown to be sensitive to the phantom displacement from the isocenter, the performance changed by less than 2% for shifts up to 2 cm in the x- and y-axes in the central phantom plane. Conclusions: With as few as five points, method 1 and method 2 were able to compute the mean dose with reasonable accuracy, demonstrating differences of 1.7% (±1.2%) and 1.3% (±1.0%), respectively. A larger number of points do not necessarily guarantee better performance of the methods; optimal choice of point placement is necessary. The performance of the methods is sensitive to the alignment of the center of the body phantom relative to the isocenter. In body applications where dose distributions are important, method 2 is a better choice than method 1, as it reconstructs the dose surface with high fidelity, using as few as five points.« less

Proton dose distribution measurements using a MOSFET detector with a simple dose‐weighted correction method for LET effects

PubMed Central

Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-01-01

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors. PACS number: 87.56.‐v

Evaluation of single-point sampling strategies for the estimation of moclobemide exposure in depressive patients.

PubMed

Ignjatovic, Anita Rakic; Miljkovic, Branislava; Todorovic, Dejan; Timotijevic, Ivana; Pokrajac, Milena

2011-05-01

Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC(0-6)) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC(0-6). The best estimation of AUC(0-6) was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations.

Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

PubMed Central

Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

2015-01-01

Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

Evaluation of six TPS algorithms in computing entrance and exit doses.

PubMed

Tan, Yun I; Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun; Elliott, Alex

2014-05-08

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%-3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison.

Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunliffe, Alexandra R.; Armato, Samuel G.; White, Bradley

2015-01-15

Purpose: To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Methods: Eighteen patients who received curative doses (≥60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4–75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps)more » using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm (“Fast” and “EMPIRE10”). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (d{sub E}) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of d{sub E}, dose (D), dose standard deviation (SD{sub dose}) in an eight-pixel neighborhood, and the registration algorithm used. Results: Over 1400 landmark point pairs were identified, with 58–93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9–10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average d{sub E} across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of d{sub E} (0.42 Gy/mm), D (0.05 Gy/Gy), SD{sub dose} (1.4 Gy/Gy), and the algorithm used (≤1 Gy). Conclusions: An average error of <4 Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration, with the majority of points yielding dose-mapping error <2 Gy (approximately 3% of the total prescribed dose). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, resulting in the smallest errors in mapped dose. Dose differences following registration increased significantly with increasing spatial registration errors, dose, and dose gradient (i.e., SD{sub dose}). This model provides a measurement of the uncertainty in the radiation dose when points are mapped between serial CT scans through deformable registration.« less

SU-F-T-76: Total Skin Electron Therapy: An-End-To-End Examination of the Absolute Dosimetry with a Rando Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, G; Ha, J; Zhou, S

Purpose: To examine and validate the absolute dose for total skin electron therapy (TSET) through an end-to-end test with a Rando phantom using optically stimulated luminescent dosimeters (OSLDs) and EBT3 radiochromic films. Methods: A Varian Trilogy linear accelerator equipped with the special procedure 6 MeV HDTSe- was used to perform TSET irradiations using a modified Stanford 6-dual-field technique. The absolute dose was calibrated using a Markus ion chamber at a reference depth of 1.3cm at 100 cm SSD with a field size of 36 × 36 cm at the isocenter in solid water slabs. The absolute dose was cross validatedmore » by a farmer ion chamber. Then the dose rate in the unit of cGy/Mu was calibrated using the Markus chamber at the treatment position. OSLDs were used to independently verify the dose using the calibrated dose rate. Finally, a patient treatment plan (200 cGy/cycle) was delivered in the QA mode to a Rando phantom, which had 16 pairs of OSLDs and EBT3 films taped onto its surface at different anatomical positions. The doses recorded were read out to validate the absolute dosimetry for TSET. Results: The OSLD measurements were within 7% agreement with the planned dose except the shoulder areas, where the doses recorded were 23% lower on average than those of the planned. The EBT3 film measurements were within 10% agreement with the planned dose except the shoulder and the scalp vertex areas, where the respective doses recorded were 18% and 14% lower on average than those of the planned. The OSLDs gave more consistent dose measurements than those of the EBT3 films. Conclusion: The absolute dosimetry for TSET was validated by an end-to-end test with a Rando phantom using the OSLDs and EBT3 films. The beam calibration and monitor unit calculations were confirmed.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, R; Bai, W

Purpose: Because of statistical noise in Monte Carlo dose calculations, effective point doses may not be accurate. Volume spheres are useful for evaluating dose in Monte Carlo plans, which have an inherent statistical uncertainty.We use a user-defined sphere volume instead of a point, take sphere sampling around effective point make the dose statistics to decrease the stochastic errors. Methods: Direct dose measurements were made using a 0.125cc Semiflex ion chamber (IC) 31010 isocentrically placed in the center of a homogeneous Cylindric sliced RW3 phantom (PTW, Germany).In the scanned CT phantom series the sensitive volume length of the IC (6.5mm) weremore » delineated and defined the isocenter as the simulation effective points. All beams were simulated in Monaco in accordance to the measured model. In our simulation using 2mm voxels calculation grid spacing and choose calculate dose to medium and request the relative standard deviation ≤0.5%. Taking three different assigned IC over densities (air electron density(ED) as 0.01g/cm3 default CT scanned ED and Esophageal lumen ED 0.21g/cm3) were tested at different sampling sphere radius (2.5, 2, 1.5 and 1 mm) statistics dose were compared with the measured does. Results: The results show that in the Monaco TPS for the IC using Esophageal lumen ED 0.21g/cm3 and sampling sphere radius 1.5mm the statistical value is the best accordance with the measured value, the absolute average percentage deviation is 0.49%. And when the IC using air electron density(ED) as 0.01g/cm3 and default CT scanned EDthe recommented statistical sampling sphere radius is 2.5mm, the percentage deviation are 0.61% and 0.70%, respectivly. Conclusion: In Monaco treatment planning system for the ionization chamber 31010 recommend air cavity using ED 0.21g/cm3 and sampling 1.5mm sphere volume instead of a point dose to decrease the stochastic errors. Funding Support No.C201505006.« less

Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials

PubMed Central

Correa, Candace; Duane, Frances K.; Aznar, Marianne C.; Anderson, Stewart J.; Bergh, Jonas; Dodwell, David; Ewertz, Marianne; Gray, Richard; Jagsi, Reshma; Pierce, Lori; Pritchard, Kathleen I.; Swain, Sandra; Wang, Zhe; Wang, Yaochen; Whelan, Tim; Peto, Richard; McGale, Paul

2017-01-01

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk. PMID:28319436

Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials.

PubMed

Taylor, Carolyn; Correa, Candace; Duane, Frances K; Aznar, Marianne C; Anderson, Stewart J; Bergh, Jonas; Dodwell, David; Ewertz, Marianne; Gray, Richard; Jagsi, Reshma; Pierce, Lori; Pritchard, Kathleen I; Swain, Sandra; Wang, Zhe; Wang, Yaochen; Whelan, Tim; Peto, Richard; McGale, Paul

2017-05-20

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.

Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg in subjects aged 12 years with moderate to severe seasonal allergic rhinitis: a pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies.

PubMed

Berkowitz, Robert B; McCafferty, Frank; Lutz, Cheryl; Bazelmans, Donna; Godfrey, Penny; Meeves, Suzanne; Liao, Yuning; Georges, George

2006-10-01

The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR). This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR. Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol. A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively). In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

PubMed

Staerk, L; Gerds, T A; Lip, G Y H; Ozenne, B; Bonde, A N; Lamberts, M; Fosbøl, E L; Torp-Pedersen, C; Gislason, G H; Olesen, J B

2018-01-01

Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, Jennifer L., E-mail: peterson.jennifer2@mayo.edu; Buskirk, Steven J.; Heckman, Michael G.

2014-04-01

Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminologymore » Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.« less

On the sensitivity of TG-119 and IROC credentialing to TPS commissioning errors.

PubMed

McVicker, Drew; Yin, Fang-Fang; Adamson, Justus D

2016-01-08

We investigate the sensitivity of IMRT commissioning using the TG-119 C-shape phantom and credentialing with the IROC head and neck phantom to treatment planning system commissioning errors. We introduced errors into the various aspects of the commissioning process for a 6X photon energy modeled using the analytical anisotropic algorithm within a commercial treatment planning system. Errors were implemented into the various components of the dose calculation algorithm including primary photons, secondary photons, electron contamination, and MLC parameters. For each error we evaluated the probability that it could be committed unknowingly during the dose algorithm commissioning stage, and the probability of it being identified during the verification stage. The clinical impact of each commissioning error was evaluated using representative IMRT plans including low and intermediate risk prostate, head and neck, mesothelioma, and scalp; the sensitivity of the TG-119 and IROC phantoms was evaluated by comparing dosimetric changes to the dose planes where film measurements occur and change in point doses where dosimeter measurements occur. No commissioning errors were found to have both a low probability of detection and high clinical severity. When errors do occur, the IROC credentialing and TG 119 commissioning criteria are generally effective at detecting them; however, for the IROC phantom, OAR point-dose measurements are the most sensitive despite being currently excluded from IROC analysis. Point-dose measurements with an absolute dose constraint were the most effective at detecting errors, while film analysis using a gamma comparison and the IROC film distance to agreement criteria were less effective at detecting the specific commissioning errors implemented here.

Experimental verification of a commercial Monte Carlo-based dose calculation module for high-energy photon beams.

PubMed

Künzler, Thomas; Fotina, Irina; Stock, Markus; Georg, Dietmar

2009-12-21

The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (gamma) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% +/- 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 x 10 cm(2) field at the first density interface from tissue to lung equivalent material. Small fields (2 x 2 cm(2)) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% +/- 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D gamma-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for gamma(>1) was 4.7% +/- 3.7%, the average gamma(1%) value was 1.19 +/- 0.16 and the mean 2D gamma-value was 0.44 +/- 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

Cytogenetic, cytotoxic and GC-MS studies on concrete and absolute oils from Taif rose, Saudi Arabia.

PubMed

Hagag, Heba A; Bazaid, Salih A; Abdel-Hameed, El-Sayed S; Salman, Mahmood

2014-12-01

Taif rose (Rosa damascena trigintipetala Dieck) is a sort of damask rose, which is considered as one of the most important economic products of Taif. In this study, the authors investigated the possible cytotoxic, genotoxic, antimutagenic and anticancer effect of concrete and absolute rose oils. The results showed that both concrete and absolute rose oils were cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. Also, the results showed significant antimutagenic activity at p < 0.001 for absolute rose oil at the same dose level when tested on cultures of normal human blood lymphocytes supplemented with 300 ng/ml mitomycin C (MMC). On the other hand, concrete and absolute oils exerted a cytotoxic activity against two kinds of human cancer cell lines: HepG2 and MCF7. Concrete oil showed cytotoxic activity against HepG2 and MCF7 with a half maximal inhibitory concentration (IC50) of 16.28 and 18.09 μg/ml, respectively, whereas absolute rose oil showed its cytotoxic activity against HepG2 and MCF7 with an IC50 of 24.94 and 19.69, respectively. From this study, it is concluded that concrete and absolute rose oils are cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. In addition, absolute oil has an antimutagenic activity at the same dose. Further investigations are needed to study the activity of higher doses of both oils in vitro and in vivo in experimental animals in order to evaluate the capability of using these oils as therapeutic for treatment of some kinds of cancers.

Accurate dosimetry with GafChromic EBT film of a 6 MV photon beam in water: what level is achievable?

PubMed

van Battum, L J; Hoffmans, D; Piersma, H; Heukelom, S

2008-02-01

This paper focuses on the accuracy, in absolute dose measurements, with GafChromicTM EBT film achievable in water for a 6 MV photon beam up to a dose of 2.3 Gy. Motivation is to get an absolute dose detection system to measure up dose distributions in a (water) phantom, to check dose calculations. An Epson 1680 color (red green blue) transmission flatbed scanner has been used as film scanning system, where the response in the red color channel has been extracted and used for the analyses. The influence of the flatbed film scanner on the film based dose detection process was investigated. The scan procedure has been optimized; i.e. for instance a lateral correction curve was derived to correct the scan value, up to 10%, as a function of optical density and lateral position. Sensitometric curves of different film batches were evaluated in portrait and landscape scan mode. Between various batches important variations in sensitometric curve were observed. Energy dependence of the film is negligible, while a slight variation in dose response is observed for very large angles between film surface and incident photon beam. Improved accuracy in absolute dose detection can be obtained by repetition of a film measurement to tackle at least the inherent presence of film inhomogeneous construction. We state that the overall uncertainty is random in absolute EBT film dose detection and of the order of 1.3% (1 SD) under the condition that the film is scanned in a limited centered area on the scanner and at least two films have been applied. At last we advise to check a new film batch on its characteristics compared to available information, before using that batch for absolute dose measurements.

SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lalonde, R; Heron, D; Huq, M

2015-06-15

Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimatesmore » and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.« less

Intensity- and energy-modulated electron radiotherapy by means of an xMLC for head and neck shallow tumors

NASA Astrophysics Data System (ADS)

Salguero, Francisco Javier; Arráns, Rafael; Atriana Palma, Bianey; Leal, Antonio

2010-03-01

The purpose of this paper is to assess the feasibility of delivering intensity- and energy-modulated electron radiation treatment (MERT) by a photon multileaf collimator (xMLC) and to evaluate the improvements obtained in shallow head and neck (HN) tumors. Four HN patient cases covering different clinical situations were planned by MERT, which used an in-house treatment planning system that utilized Monte Carlo dose calculation. The cases included one oronasal, two parotid and one middle ear tumors. The resulting dose-volume histograms were compared with those obtained from conventional photon and electron treatment techniques in our clinic, which included IMRT, electron beam and mixed beams, most of them using fixed-thickness bolus. Experimental verification was performed with plane-parallel ionization chambers for absolute dose verification, and a PTW ionization chamber array and radiochromic film for relative dosimetry. A MC-based treatment planning system for target with compromised volumes in depth and laterally has been validated. A quality assurance protocol for individual MERT plans was launched. Relative MC dose distributions showed a high agreement with film measurements and absolute ion chamber dose measurements performed at a reference point agreed with MC calculations within 2% in all cases. Clinically acceptable PTV coverage and organ-at-risk sparing were achieved by using the proposed MERT approach. MERT treatment plans, based on delivery of intensity-modulated electron beam using the xMLC, for superficial head and neck tumors, demonstrated comparable or improved PTV dose homogeneity with significantly lower dose to normal tissues. The clinical implementation of this technique will be able to offer a viable alternative for the treatment of shallow head and neck tumors.

Spline-based procedures for dose-finding studies with active control

PubMed Central

Helms, Hans-Joachim; Benda, Norbert; Zinserling, Jörg; Kneib, Thomas; Friede, Tim

2015-01-01

In a dose-finding study with an active control, several doses of a new drug are compared with an established drug (the so-called active control). One goal of such studies is to characterize the dose–response relationship and to find the smallest target dose concentration d*, which leads to the same efficacy as the active control. For this purpose, the intersection point of the mean dose–response function with the expected efficacy of the active control has to be estimated. The focus of this paper is a cubic spline-based method for deriving an estimator of the target dose without assuming a specific dose–response function. Furthermore, the construction of a spline-based bootstrap CI is described. Estimator and CI are compared with other flexible and parametric methods such as linear spline interpolation as well as maximum likelihood regression in simulation studies motivated by a real clinical trial. Also, design considerations for the cubic spline approach with focus on bias minimization are presented. Although the spline-based point estimator can be biased, designs can be chosen to minimize and reasonably limit the maximum absolute bias. Furthermore, the coverage probability of the cubic spline approach is satisfactory, especially for bias minimal designs. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:25319931

Evaluation of six TPS algorithms in computing entrance and exit doses

PubMed Central

Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun P.; Elliott, Alex

2014-01-01

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%‐3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.N‐, 87.53.Bn PMID:24892349

Agreement between gamma passing rates using computed tomography in radiotherapy and secondary cancer risk prediction from more advanced dose calculated models

PubMed Central

Balosso, Jacques

2017-01-01

Background During the past decades, in radiotherapy, the dose distributions were calculated using density correction methods with pencil beam as type ‘a’ algorithm. The objectives of this study are to assess and evaluate the impact of dose distribution shift on the predicted secondary cancer risk (SCR), using modern advanced dose calculation algorithms, point kernel, as type ‘b’, which consider change in lateral electrons transport. Methods Clinical examples of pediatric cranio-spinal irradiation patients were evaluated. For each case, two radiotherapy treatment plans with were generated using the same prescribed dose to the target resulting in different number of monitor units (MUs) per field. The dose distributions were calculated, respectively, using both algorithms types. A gamma index (γ) analysis was used to compare dose distribution in the lung. The organ equivalent dose (OED) has been calculated with three different models, the linear, the linear-exponential and the plateau dose response curves. The excess absolute risk ratio (EAR) was also evaluated as (EAR = OED type ‘b’ / OED type ‘a’). Results The γ analysis results indicated an acceptable dose distribution agreement of 95% with 3%/3 mm. Although, the γ-maps displayed dose displacement >1 mm around the healthy lungs. Compared to type ‘a’, the OED values from type ‘b’ dose distributions’ were about 8% to 16% higher, leading to an EAR ratio >1, ranged from 1.08 to 1.13 depending on SCR models. Conclusions The shift of dose calculation in radiotherapy, according to the algorithm, can significantly influence the SCR prediction and the plan optimization, since OEDs are calculated from DVH for a specific treatment. The agreement between dose distribution and SCR prediction depends on dose response models and epidemiological data. In addition, the γ passing rates of 3%/3 mm does not translate the difference, up to 15%, in the predictions of SCR resulting from alternative algorithms. Considering that modern algorithms are more accurate, showing more precisely the dose distributions, but that the prediction of absolute SCR is still very imprecise, only the EAR ratio could be used to rank radiotherapy plans. PMID:28811995

Marvin: an anatomical phantom for dosimetric evaluation of complex radiotherapy of the head and neck.

PubMed

Aitkenhead, A H; Rowbottom, C G; Mackay, R I

2013-10-07

We report on the design of Marvin, a Model Anatomy for Radiotherapy Verification and audit In the head and Neck and present results demonstrating its use in the development of the Elekta volumetric modulated arc therapy (VMAT) technique at the Christie, and in the audit of TomoTherapy and Varian RapidArc at other institutions. The geometry of Marvin was generated from CT datasets of eight male and female patients lying in the treatment position, with removable inhomogeneities modelling the sinuses and mandible. A modular system allows the phantom to be used with a range of detectors, with the locations of the modules being based on an analysis of a range of typical treatment plans (27 in total) which were mapped onto the phantom geometry. Results demonstrate the use of Gafchromic EBT2/EBT3 film for measurement of relative dose in a plane through the target and organs-at-risk, and the use of a small-volume ionization chamber for measurement of absolute dose in the target and spinal cord. Measurements made during the development of the head and neck VMAT protocol at the Christie quantified the improvement in plan delivery resulting from the installation of the Elekta Integrity upgrade (which permits an effectively continuously variable dose rate), with plans delivered before and after the upgrade having 88.5 ± 9.4% and 98.0 ± 2.2% respectively of points passing a gamma analysis (at 4%, 4 mm, global). Audits of TomoTherapy and Varian RapidArc neck techniques at other institutions showed a similar quality of plan delivery as for post-Integrity Elekta VMAT: film measurements for both techniques had >99% of points passing a gamma analysis at the clinical criteria of 4%, 4 mm, global, and >95% of points passing at tighter criteria of 3%, 3 mm, global; and absolute dose measurements in the PTV and spinal cord were within 1.5% and 3.5% of the planned doses respectively for both techniques. The results demonstrate that Marvin is an efficient and effective means of assessing the quality of delivery of complex radiotherapy in the head and neck, and is a useful tool to assist development and audit of these techniques.

Marvin: an anatomical phantom for dosimetric evaluation of complex radiotherapy of the head and neck

NASA Astrophysics Data System (ADS)

Aitkenhead, A. H.; Rowbottom, C. G.; Mackay, R. I.

2013-10-01

We report on the design of Marvin, a Model Anatomy for Radiotherapy Verification and audit In the head and Neck and present results demonstrating its use in the development of the Elekta volumetric modulated arc therapy (VMAT) technique at the Christie, and in the audit of TomoTherapy and Varian RapidArc at other institutions. The geometry of Marvin was generated from CT datasets of eight male and female patients lying in the treatment position, with removable inhomogeneities modelling the sinuses and mandible. A modular system allows the phantom to be used with a range of detectors, with the locations of the modules being based on an analysis of a range of typical treatment plans (27 in total) which were mapped onto the phantom geometry. Results demonstrate the use of Gafchromic EBT2/EBT3 film for measurement of relative dose in a plane through the target and organs-at-risk, and the use of a small-volume ionization chamber for measurement of absolute dose in the target and spinal cord. Measurements made during the development of the head and neck VMAT protocol at the Christie quantified the improvement in plan delivery resulting from the installation of the Elekta Integrity upgrade (which permits an effectively continuously variable dose rate), with plans delivered before and after the upgrade having 88.5 ± 9.4% and 98.0 ± 2.2% respectively of points passing a gamma analysis (at 4%, 4 mm, global). Audits of TomoTherapy and Varian RapidArc neck techniques at other institutions showed a similar quality of plan delivery as for post-Integrity Elekta VMAT: film measurements for both techniques had >99% of points passing a gamma analysis at the clinical criteria of 4%, 4 mm, global, and >95% of points passing at tighter criteria of 3%, 3 mm, global; and absolute dose measurements in the PTV and spinal cord were within 1.5% and 3.5% of the planned doses respectively for both techniques. The results demonstrate that Marvin is an efficient and effective means of assessing the quality of delivery of complex radiotherapy in the head and neck, and is a useful tool to assist development and audit of these techniques.

Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data

PubMed Central

Sand, Salomon; Parham, Fred; Portier, Christopher J.; Tice, Raymond R.; Krewski, Daniel

2016-01-01

Background: The National Research Council’s vision for toxicity testing in the 21st century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on in vitro high-throughput screening (HTS) data. Objectives: The aim of this study was to compare different PODs for HTS data. Specifically, benchmark doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD), which has been suggested as the lowest dose applicable as a POD. Methods: Hill models were fit to > 10,000 in vitro concentration–response curves, obtained for > 1,400 chemicals tested as part of the U.S. Tox21 Phase I effort. BMDs and lower confidence limits on the BMDs (BMDLs) corresponding to extra effects (i.e., changes in response relative to the maximum response) of 5%, 10%, 20%, 30%, and 40% were estimated for > 8,000 curves, along with BMDs and BMDLs corresponding to additional effects (i.e., absolute changes in response) of 5%, 10%, 15%, 20%, and 25%. The SNCD, defined as the dose where the ratio between the additional effect and the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute effect was 1, 0.67, and 0.5, respectively, was also calculated and compared with the BMDLs. Results: The BMDL40, BMDL25, and BMDL18, defined in terms of extra effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Similarly, the BMDL25, BMDL17, and BMDL13, defined in terms of additional effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Conclusions: The SNCD may serve as a reference level that guides the determination of standardized BMDs for risk assessment based on HTS concentration–response data. The SNCD may also have application as a POD for low-dose extrapolation. Citation: Sand S, Parham F, Portier CJ, Tice RR, Krewski D. 2017. Comparison of points of departure for health risk assessment based on high-throughput screening data. Environ Health Perspect 125:623–633; http://dx.doi.org/10.1289/EHP408 PMID:27384688

Impact of grid size on uniform scanning and IMPT plans in XiO treatment planning system for brain cancer

PubMed Central

Zheng, Yuanshui

2015-01-01

The main purposes of this study are to: 1) evaluate the accuracy of XiO treatment planning system (TPS) for different dose calculation grid size based on head phantom measurements in uniform scanning proton therapy (USPT); and 2) compare the dosimetric results for various dose calculation grid sizes based on real computed tomography (CT) dataset of pediatric brain cancer treatment plans generated by USPT and intensity‐modulated proton therapy (IMPT) techniques. For phantom study, we have utilized the anthropomorphic head proton phantom provided by Imaging and Radiation Oncology Core (IROC). The imaging, treatment planning, and beam delivery were carried out following the guidelines provided by the IROC. The USPT proton plan was generated in the XiO TPS, and dose calculations were performed for grid size ranged from 1 to 3 mm. The phantom containing thermoluminescent dosimeter (TLDs) and films was irradiated using uniform scanning proton beam. The irradiated TLDs were read by the IROC. The calculated doses from the XiO for different grid sizes were compared to the measured TLD doses provided by the IROC. Gamma evaluation was done by comparing calculated planar dose distribution of 3 mm grid size with measured planar dose distribution. Additionally, IMPT plan was generated based on the same CT dataset of the IROC phantom, and IMPT dose calculations were performed for grid size ranged from 1 to 3 mm. For comparative purpose, additional gamma analysis was done by comparing the planar dose distributions of standard grid size (3 mm) with that of other grid sizes (1, 1.5, 2, and 2.5 mm) for both the USPT and IMPT plans. For patient study, USPT plans of three pediatric brain cancer cases were selected. IMPT plans were generated for each of three pediatric cases. All patient treatment plans (USPT and IMPT) were generated in the XiO TPS for a total dose of 54 Gy (relative biological effectiveness [RBE]). Treatment plans (USPT and IMPT) of each case was recalculated for grid sizes of 1, 1.5, 2, and 2.5 mm; these dosimetric results were then compared with that of 3 mm grid size. Phantom study results: There was no distinct trend exhibiting the dependence of grid size on dose calculation accuracy when calculated point dose of different grid sizes were compared to the measured point (TLD) doses. On average, the calculated point dose was higher than the measured dose by 1.49% and 2.63% for the right and left TLDs, respectively. The gamma analysis showed very minimal differences among planar dose distributions of various grid sizes, with percentage of points meeting gamma index criteria 1% and 1 mm to be from 97.92% to 99.97%. The gamma evaluation using 2% and 2 mm criteria showed both the IMPT and USPT plans have 100% points meeting the criteria. Patient study results: In USPT, there was no very distinct relationship between the absolute difference in mean planning target volume (PTV) dose and grid size, whereas in IMPT, it was found that the decrease in grid size slightly increased the PTV maximum dose and decreased the PTV mean dose and PTV D50%. For the PTV doses, the average differences were up to 0.35 Gy (RBE) and 1.47 Gy (RBE) in the USPT and IMPT plans, respectively. Dependency on grid size was not very clear for the organs at risk (OARs), with average difference ranged from −0.61 Gy (RBE) to 0.53 Gy (RBE) in the USPT plans and from −0.83 Gy (RBE) to 1.39 Gy (RBE) in the IMPT plans. In conclusion, the difference in the calculated point dose between the smallest grid size (1 mm) and the largest grid size (3 mm) in phantom for USPT was typically less than 0.1%. Patient study results showed that the decrease in grid size slightly increased the PTV maximum dose in both the USPT and IMPT plans. However, no distinct trend was obtained between the absolute difference in dosimetric parameter and dose calculation grid size for the OARs. Grid size has a large effect on dose calculation efficiency, and use of 2 mm or less grid size can increase the dose calculation time significantly. It is recommended to use grid size either 2.5 or 3 mm for dose calculations of pediatric brain cancer plans generated by USPT and IMPT techniques in XiO TPS. PACS numbers: 87.55.D‐, 87.55.ne, 87.55.dk PMID:26699310

Dosimetric validation and clinical implementation of two 3D dose verification systems for quality assurance in volumetric-modulated arc therapy techniques.

PubMed

Clemente-Gutiérrez, Francisco; Pérez-Vara, Consuelo

2015-03-08

A pretreatment quality assurance program for volumetric techniques should include redundant calculations and measurement-based verifications. The patient-specific quality assurance process must be based in clinically relevant metrics. The aim of this study was to show the commission, clinical implementation, and comparison of two systems that allow performing a 3D redundant dose calculation. In addition, one of them is capable of reconstructing the dose on patient anatomy from measurements taken with a 2D ion chamber array. Both systems were compared in terms of reference calibration data (absolute dose, output factors, percentage depth-dose curves, and profiles). Results were in good agreement for absolute dose values (discrepancies were below 0.5%) and output factors (mean differences were below 1%). Maximum mean discrepancies were located between 10 and 20 cm of depth for PDDs (-2.7%) and in the penumbra region for profiles (mean DTA of 1.5 mm). Validation of the systems was performed by comparing point-dose measurements with values obtained by the two systems for static, dynamic fields from AAPM TG-119 report, and 12 real VMAT plans for different anatomical sites (differences better than 1.2%). Comparisons between measurements taken with a 2D ion chamber array and results obtained by both systems for real VMAT plans were also performed (mean global gamma passing rates better than 87.0% and 97.9% for the 2%/2 mm and 3%/3 mm criteria). Clinical implementation of the systems was evaluated by comparing dose-volume parameters for all TG-119 tests and real VMAT plans with TPS values (mean differences were below 1%). In addition, comparisons between dose distributions calculated by TPS and those extracted by the two systems for real VMAT plans were also performed (mean global gamma passing rates better than 86.0% and 93.0% for the 2%/2 mm and 3%/ 3 mm criteria). The clinical use of both systems was successfully evaluated.

SU-F-T-174: Patient-Specific Point Dose Measurement Using Fiber Optic Radiation Sensor Using Cerenkov Radiation for Proton Therapeutic Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, J; National Cancer Center, Goyang-si; Kim, M

Purpose: A fiber-optic radiation sensor using Cerenkov radiation (FOCR) has been widely studied for use as a dosimeter for proton therapeutic beam. We developed the FOCR, and it applied to patient-specific point dose measurement in order to evaluate the effectiveness of the FOCR system for proton therapy QA. Methods: Calibration of FOCR was performed with an ionization chamber whose absolute doses were determined according to the IAEA TRS-398 protocol. To determine the calibration curve, the FOCR was irradiated perpendicularly to the proton beam at the 13 dose levels steps. We selected five actual patient treatment plans performed at proton therapymore » center and compared the resulting FOCR measurements with the ionization chamber measurements. Results: The Cerenkov light yield of the FOCR increases linearly with as the dose measured using the ionization chamber increases from 0 cGy to 500 cGy. The results indicate that the fitting curve is linear, suggesting that dose measurement based on the light yield of the FOCR is possible. The results of proton radiation dose QA performed using the FOCR for 10 proton fields and five patients are good agreement with an ionization chamber. Conclusion: We carried out the patient QA using the FOCR for proton therapeutic beam and evaluated the effectiveness of the FOCR as a proton therapy QA tool. Our results indicate that the FOCR is suitable for use in patient QA of clinical proton beams.« less

Pharmacokinetics of isochlorgenic acid C in rats by HPLC-MS: Absolute bioavailability and dose proportionality.

PubMed

Huang, Li Hua; Xiong, Xiao Hong; Zhong, Yun Ming; Cen, Mei Feng; Cheng, Xuan Ge; Wang, Gui Xiang; Zang, Lin Quan; Wang, Su Jun

2016-06-05

Isochlorgenic acid C (IAC), one of the bioactive compounds of Lonicera japonica, exhibited diverse pharmacological effects. However, its pharmacokinetic properties and bioavailability remained unresolved. To determine the absolute bioavailability in rats and the dose proportionality on the pharmacokinetics of single oral dose of IAC. A validated HPLC-MS method was developed for the determination of IAC in rat plasma. Plasma concentration versus time data were generated following oral and intravenous dosing. The pharmacokinetic analysis was performed using DAS 3.0 software analysis. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (5, 10 and 25mgkg(-1)) and intravenous (5mgkg(-1)) doses of IAC. The dose proportionality of AUC(0-∞) and Cmax were analyzed by linear regression. Experimental data showed that absolute oral bioavailability of IAC in rats across the doses ranged between 14.4% and 16.9%. The regression analysis of AUC(0-∞) and Cmax at the three doses (5, 10 and 25mgkg(-1)) indicated that the equations were y=35.23x+117.20 (r=0.998) and y=121.03x+255.74 (r=0.995), respectively. A new HPLC-MS method was developed to determine the bioavailability and the dose proportionality of IAC. Bioavailability of IAC in rats was poor and both Cmax and AUC(0-∞) of IAC had a positive correlation with dose. Evaluation of the pharmacokinetics of IAC will be useful in assessing concentration-effect relationships for the potential therapeutic applications of IAC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-491: Importance of Energy Dependent Protons Per MU Calibration Factors in IMPT Dose Calculations Using Monte Carlo Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randeniya, S; Mirkovic, D; Titt, U

2014-06-01

Purpose: In intensity modulated proton therapy (IMPT), energy dependent, protons per monitor unit (MU) calibration factors are important parameters that determine absolute dose values from energy deposition data obtained from Monte Carlo (MC) simulations. Purpose of this study was to assess the sensitivity of MC-computed absolute dose distributions to the protons/MU calibration factors in IMPT. Methods: A “verification plan” (i.e., treatment beams applied individually to water phantom) of a head and neck patient plan was calculated using MC technique. The patient plan had three beams; one posterior-anterior (PA); two anterior oblique. Dose prescription was 66 Gy in 30 fractions. Ofmore » the total MUs, 58% was delivered in PA beam, 25% and 17% in other two. Energy deposition data obtained from the MC simulation were converted to Gy using energy dependent protons/MU calibrations factors obtained from two methods. First method is based on experimental measurements and MC simulations. Second is based on hand calculations, based on how many ion pairs were produced per proton in the dose monitor and how many ion pairs is equal to 1 MU (vendor recommended method). Dose distributions obtained from method one was compared with those from method two. Results: Average difference of 8% in protons/MU calibration factors between method one and two converted into 27 % difference in absolute dose values for PA beam; although dose distributions preserved the shape of 3D dose distribution qualitatively, they were different quantitatively. For two oblique beams, significant difference in absolute dose was not observed. Conclusion: Results demonstrate that protons/MU calibration factors can have a significant impact on absolute dose values in IMPT depending on the fraction of MUs delivered. When number of MUs increases the effect due to the calibration factors amplify. In determining protons/MU calibration factors, experimental method should be preferred in MC dose calculations. Research supported by National Cancer Institute grant P01CA021239.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ricketts, Kate, E-mail: k.ricketts@ucl.ac.uk; Department of Radiotherapy Physics, Royal Berkshire NHS Foundation Trust, Reading; Navarro, Clara

2016-08-01

Purpose: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Methods and Materials: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. Themore » deviation of the results was used to inform future action levels. Results: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of Δ{sub D} of 0 ± 5 cGy or %Δ{sub D} of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (−2 ± 5 cGy) or summed field percentage dose difference (−6% ± 7%). Conclusions: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.« less

Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience.

PubMed

Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Jörgen; Nyholm, Tufve; Ahnesjö, Anders; Karlsson, Mikael

2007-08-21

Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm(3) ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 +/- 1.2% and 0.5 +/- 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 +/- 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach. The physical effects modelled in the dose calculation software MUV allow accurate dose calculations in individual verification points. Independent calculations may be used to replace experimental dose verification once the IMRT programme is mature.

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter.

PubMed

Ricketts, Kate; Navarro, Clara; Lane, Katherine; Blowfield, Claire; Cotten, Gary; Tomala, Dee; Lord, Christine; Jones, Joanne; Adeyemi, Abiodun

2016-08-01

To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups. Copyright © 2016 Elsevier Inc. All rights reserved.

TH-E-BRE-09: TrueBeam Monte Carlo Absolute Dose Calculations Using Monitor Chamber Backscatter Simulations and Linac-Logged Target Current

DOE Office of Scientific and Technical Information (OSTI.GOV)

A, Popescu I; Lobo, J; Sawkey, D

2014-06-15

Purpose: To simulate and measure radiation backscattered into the monitor chamber of a TrueBeam linac; establish a rigorous framework for absolute dose calculations for TrueBeam Monte Carlo (MC) simulations through a novel approach, taking into account the backscattered radiation and the actual machine output during beam delivery; improve agreement between measured and simulated relative output factors. Methods: The ‘monitor backscatter factor’ is an essential ingredient of a well-established MC absolute dose formalism (the MC equivalent of the TG-51 protocol). This quantity was determined for the 6 MV, 6X FFF, and 10X FFF beams by two independent Methods: (1) MC simulationsmore » in the monitor chamber of the TrueBeam linac; (2) linac-generated beam record data for target current, logged for each beam delivery. Upper head MC simulations used a freelyavailable manufacturer-provided interface to a cloud-based platform, allowing use of the same head model as that used to generate the publicly-available TrueBeam phase spaces, without revealing the upper head design. The MC absolute dose formalism was expanded to allow direct use of target current data. Results: The relation between backscatter, number of electrons incident on the target for one monitor unit, and MC absolute dose was analyzed for open fields, as well as a jaw-tracking VMAT plan. The agreement between the two methods was better than 0.15%. It was demonstrated that the agreement between measured and simulated relative output factors improves across all field sizes when backscatter is taken into account. Conclusion: For the first time, simulated monitor chamber dose and measured target current for an actual TrueBeam linac were incorporated in the MC absolute dose formalism. In conjunction with the use of MC inputs generated from post-delivery trajectory-log files, the present method allows accurate MC dose calculations, without resorting to any of the simplifying assumptions previously made in the TrueBeam MC literature. This work has been partially funded by Varian Medical Systems.« less

Metallic artifacts from internal scaphoid fracture fixation screws: comparison between C-arm flat-panel, cone-beam, and multidetector computed tomography.

PubMed

Finkenstaedt, Tim; Morsbach, Fabian; Calcagni, Maurizio; Vich, Magdalena; Pfirrmann, Christian W A; Alkadhi, Hatem; Runge, Val M; Andreisek, Gustav; Guggenberger, Roman

2014-08-01

The aim of this study was to compare image quality and extent of artifacts from scaphoid fracture fixation screws using different computed tomography (CT) modalities and radiation dose protocols. Imaging of 6 cadaveric wrists with artificial scaphoid fractures and different fixation screws was performed in 2 screw positions (45° and 90° orientation in relation to the x/y-axis) using multidetector CT (MDCT) and 2 flat-panel CT modalities, C-arm flat-panel CT (FPCT) and cone-beam CT (CBCT), the latter 2 with low and standard radiation dose protocols. Mean cartilage attenuation and metal artifact-induced absolute Hounsfield unit changes (= artifact extent) were measured. Two independent radiologists evaluated different image quality criteria using a 5-point Likert-scale. Interreader agreements (Cohen κ) were calculated. Mean absolute Hounsfield unit changes and quality ratings were compared using Friedman and Wilcoxon signed-rank tests. Artifact extent was significantly smaller for MDCT and standard-dose FPCT compared with CBCT low- and standard-dose acquisitions (all P < 0.05). No significant differences in artifact extent among different screw types and scanning positions were noted (P > 0.05). Both MDCT and FPCT standard-dose protocols showed equal ratings for screw bone interface, fracture line, and trabecular bone evaluation (P = 0.06, 0.2, and 0.2, respectively) and performed significantly better than FPCT low- and CBCT low- and standard-dose acquisitions (all P < 0.05). Good interreader agreement was found for image quality comparisons (Cohen κ = 0.76-0.78). Both MDCT and FPCT standard-dose acquisition showed comparatively less metal-induced artifacts and better overall image quality compared with FPCT low-dose and both CBCT acquisitions. Flat-panel CT may provide sufficient image quality to serve as a versatile CT alternative for postoperative imaging of internally fixated wrist fractures.

A new lunar absolute control point: established by images from the landing camera on Chang'e-3

NASA Astrophysics Data System (ADS)

Wang, Fen-Fei; Liu, Jian-Jun; Li, Chun-Lai; Ren, Xin; Mu, Ling-Li; Yan, Wei; Wang, Wen-Rui; Xiao, Jing-Tao; Tan, Xu; Zhang, Xiao-Xia; Zou, Xiao-Duan; Gao, Xing-Ye

2014-12-01

The establishment of a lunar control network is one of the core tasks in selenodesy, in which defining an absolute control point on the Moon is the most important step. However, up to now, the number of absolute control points has been very sparse. These absolute control points have mainly been lunar laser ranging retroreflectors, whose geographical location can be observed by observations on Earth and also identified in high resolution lunar satellite images. The Chang'e-3 (CE-3) probe successfully landed on the Moon, and its geographical location has been monitored by an observing station on Earth. Since its positional accuracy is expected to reach the meter level, the CE-3 landing site can become a new high precision absolute control point. We use a sequence of images taken from the landing camera, as well as satellite images taken by CE-1 and CE-2, to identify the location of the CE-3 lander. With its geographical location known, the CE-3 landing site can be established as a new absolute control point, which will effectively expand the current area of the lunar absolute control network by 22%, and can greatly facilitate future research in the field of lunar surveying and mapping, as well as selenodesy.

On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy.

PubMed

Peppa, Vasiliki; Pappas, Eleftherios; Major, Tibor; Takácsi-Nagy, Zoltán; Pantelis, Evaggelos; Papagiannis, Panagiotis

2016-07-01

To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Commissioning of a 3D image‐based treatment planning system for high‐dose‐rate brachytherapy of cervical cancer

PubMed Central

Kim, Yongbok; Modrick, Joseph M.; Pennington, Edward C.

2016-01-01

The objective of this work is to present commissioning procedures to clinically implement a three‐dimensional (3D), image‐based, treatment‐planning system (TPS) for high‐dose‐rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8‐1.0 mm on MRI when compared with X‐rays. In‐house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose‐volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image‐based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End‐to‐end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image‐based TPS for HDR BT for GYN cancer. PACS number(s): 87.55.D‐ PMID:27074463

Absolute bioavailability and safety of a novel rivastigmine nasal spray in healthy elderly individuals.

PubMed

Morgan, Timothy M; Soh, Bob

2017-03-01

To test the feasibility of a novel rivastigmine nasal spray as prospective treatment for dementia. A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58-75 years. Absolute bioavailability (F) of the nasal spray was significant at 0.62 (0.15) for F > 0 (P < 0.001, n = 8). The systemic dose absorbed was 2.0 (0.6) mg, time to maximum plasma concentration was 1.1 (0.5) h and maximum plasma concentration was 6.9 (2.0) ng ml -1 . The NAP226-90 to rivastigmine AUC 0-∞ ratio was 0.78 (0.19). The single dose safety was good with two of five mild adverse events related to the nasal spray. Nasal and throat irritation were perceived as mild and transient, and both had resolved at 20 min post-nasal dose. An estimated dose of two or three sprays twice-daily with nasal spray would deliver comparable rivastigmine exposure and efficacy as a 6-9.7 mg day -1 oral dose and a 10 cm 2 transdermal patch, respectively. The rivastigmine nasal spray had superior absolute bioavailability compared to historical values for oral capsule and transdermal patch determined by other researchers. It had rapid onset of action, low NAP226-90 to rivastigmine exposure ratio and a favourable safety and tolerability profile. The ability to achieve adjustable, individual, twice-daily dosing during waking hours has good potential to minimise undesirable cholinergic burden and sleep disturbances whilst delivering an effective dose for the treatment of dementia associated with Alzheimer's and Parkinson's disease. © 2016 The British Pharmacological Society.

Error Analysis of non-TLD HDR Brachytherapy Dosimetric Techniques

NASA Astrophysics Data System (ADS)

Amoush, Ahmad

The American Association of Physicists in Medicine Task Group Report43 (AAPM-TG43) and its updated version TG-43U1 rely on the LiF TLD detector to determine the experimental absolute dose rate for brachytherapy. The recommended uncertainty estimates associated with TLD experimental dosimetry include 5% for statistical errors (Type A) and 7% for systematic errors (Type B). TG-43U1 protocol does not include recommendation for other experimental dosimetric techniques to calculate the absolute dose for brachytherapy. This research used two independent experimental methods and Monte Carlo simulations to investigate and analyze uncertainties and errors associated with absolute dosimetry of HDR brachytherapy for a Tandem applicator. An A16 MicroChamber* and one dose MOSFET detectors† were selected to meet the TG-43U1 recommendations for experimental dosimetry. Statistical and systematic uncertainty analyses associated with each experimental technique were analyzed quantitatively using MCNPX 2.6‡ to evaluate source positional error, Tandem positional error, the source spectrum, phantom size effect, reproducibility, temperature and pressure effects, volume averaging, stem and wall effects, and Tandem effect. Absolute dose calculations for clinical use are based on Treatment Planning System (TPS) with no corrections for the above uncertainties. Absolute dose and uncertainties along the transverse plane were predicted for the A16 microchamber. The generated overall uncertainties are 22%, 17%, 15%, 15%, 16%, 17%, and 19% at 1cm, 2cm, 3cm, 4cm, and 5cm, respectively. Predicting the dose beyond 5cm is complicated due to low signal-to-noise ratio, cable effect, and stem effect for the A16 microchamber. Since dose beyond 5cm adds no clinical information, it has been ignored in this study. The absolute dose was predicted for the MOSFET detector from 1cm to 7cm along the transverse plane. The generated overall uncertainties are 23%, 11%, 8%, 7%, 7%, 9%, and 8% at 1cm, 2cm, 3cm, and 4cm, 5cm, 6cm, and 7cm, respectively. The Nucletron Freiburg flap applicator is used with the Nucletron remote afterloader HDR machine to deliver dose to surface cancers. Dosimetric data for the Nucletron 192Ir source were generated using Monte Carlo simulation and compared with the published data. Two dimensional dosimetric data were calculated at two source positions; at the center of the sphere of the applicator and between two adjacent spheres. Unlike the TPS dose algorithm, The Monte Carlo code developed for this research accounts for the applicator material, secondary electrons and delta particles, and the air gap between the skin and the applicator. *Standard Imaging, Inc., Middleton, Wisconsin USA † OneDose MOSFET, Sicel Technologies, Morrisville NC ‡ Los Alamos National Laboratory, NM USA

Dosimetric effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, Omar; Williamson, Jeffrey F.; Todor, Dorin

2005-08-15

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKSmore » versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.« less

Dosimetry of 192Ir sources used for endovascular brachytherapy

NASA Astrophysics Data System (ADS)

Reynaert, N.; Van Eijkeren, M.; Taeymans, Y.; Thierens, H.

2001-02-01

An in-phantom calibration technique for 192Ir sources used for endovascular brachytherapy is presented. Three different source lengths were investigated. The calibration was performed in a solid phantom using a Farmer-type ionization chamber at source to detector distances ranging from 1 cm to 5 cm. The dosimetry protocol for medium-energy x-rays extended with a volume-averaging correction factor was used to convert the chamber reading to dose to water. The air kerma strength of the sources was determined as well. EGS4 Monte Carlo calculations were performed to determine the depth dose distribution at distances ranging from 0.6 mm to 10 cm from the source centre. In this way we were able to convert the absolute dose rate at 1 cm distance to the reference point chosen at 2 mm distance. The Monte Carlo results were confirmed by radiochromic film measurements, performed with a double-exposure technique. The dwell times to deliver a dose of 14 Gy at the reference point were determined and compared with results given by the source supplier (CORDIS). They determined the dwell times from a Sievert integration technique based on the source activity. The results from both methods agreed to within 2% for the 12 sources that were evaluated. A Visual Basic routine that superimposes dose distributions, based on the Monte Carlo calculations and the in-phantom calibration, onto intravascular ultrasound images is presented. This routine can be used as an online treatment planning program.

Overview of Global, Regional, and National Routine Vaccination Coverage Trends and Growth Patterns From 1980 to 2009: Implications for Vaccine-Preventable Disease Eradication and Elimination Initiatives

PubMed Central

Wallace, Aaron S.; Ryman, Tove K.; Dietz, Vance

2015-01-01

Background Review of the historical growth in annual vaccination coverage across countries and regions can better inform decision makers’ development of future goals and strategies to improve routine vaccination services. Methods Using the World Health Organization (WHO) and the United Nations Children's Fund estimates of annual national third dose of diphtheria-tetanus-pertussis–containing vaccine (DTP3) and third dose of polio vaccine (POL3) coverage for 1980–2009, we calculated the mean absolute annual rate of change in national DTP3 coverage among all countries (globally) and among countries within each WHO region, as well as the number of years taken by each region to reach specific regional coverage levels. Last, we assessed differences in mean absolute annual rate of change in DTP3 coverage, stratified by baseline level of DTP3 coverage. Results During the 1980s, global DTP3 coverage increased a mean of 5.3 percentage points/year. Annual rate of change decreased to 0.5 percentage points/year in the 1990s and then increased to 0.9 percentage points/year during the 2000s. Mean annual rate of change in coverage across all countries was highest (9.2 percentage points) when national coverage levels were 26%–30% and lowest (−0.9 percentage points) when national coverage levels were 96%–100%. Regional differences existed as both WHO South-East Asia Region and WHO African Region countries experienced mean negative DTP3 coverage growth at lower coverage levels (81%–85%) than other regions. The regions that have achieved 95% DTP3 coverage (Americas, Western Pacific, and European) took 25–29 years to reach that level from a level of 50% DTP3 coverage. POL3 coverage change trends were similar to described DTP3 coverage change trends. Conclusions Mean national coverage growth patterns across all regions are nonlinear as coverage levels increase. Saturation points of mean 0 percentage-point growth in annual coverage varies by region and require further investigation. The achievement of >90% routine coverage is observed to take decades, which has implications for disease eradication and elimination initiatives. PMID:25316875

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carver, R; Popple, R; Benhabib, S

Purpose: To evaluate the accuracy of electron dose distribution calculated by the Varian Eclipse electron Monte Carlo (eMC) algorithm for use with recent commercially available bolus electron conformal therapy (ECT). Methods: eMC-calculated electron dose distributions for bolus ECT have been compared to those previously measured for cylindrical phantoms (retromolar trigone and nose), whose axial cross sections were based on the mid-PTV CT anatomy for each site. The phantoms consisted of SR4 muscle substitute, SR4 bone substitute, and air. The bolus ECT treatment plans were imported into the Eclipse treatment planning system and calculated using the maximum allowable histories (2×10{sup 9}),more » resulting in a statistical error of <0.2%. Smoothing was not used for these calculations. Differences between eMC-calculated and measured dose distributions were evaluated in terms of absolute dose difference as well as distance to agreement (DTA). Results: Results from the eMC for the retromolar trigone phantom showed 89% (41/46) of dose points within 3% dose difference or 3 mm DTA. There was an average dose difference of −0.12% with a standard deviation of 2.56%. Results for the nose phantom showed 95% (54/57) of dose points within 3% dose difference or 3 mm DTA. There was an average dose difference of 1.12% with a standard deviation of 3.03%. Dose calculation times for the retromolar trigone and nose treatment plans were 15 min and 22 min, respectively, using 16 processors (Intel Xeon E5-2690, 2.9 GHz) on a Varian Eclipse framework agent server (FAS). Results of this study were consistent with those previously reported for accuracy of the eMC electron dose algorithm and for the .decimal, Inc. pencil beam redefinition algorithm used to plan the bolus. Conclusion: These results show that the accuracy of the Eclipse eMC algorithm is suitable for clinical implementation of bolus ECT.« less

Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

PubMed

Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

2015-09-01

Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically significant increase in their absolute number in the MSC group compared to their diluent controls. Investigation of behavior in another cohort of animals showed that delayed administration of a high-dose of bone marrow-derived MSCs, at one week after neonatal rat hypoxia-ischemia, improved motor function on the cylinder test. Thus, delayed therapy with a high- or low-dose of adult MSCs, at one week after injury, is effective in restoring the loss of striatal medium-spiny projection neurons after neonatal rat hypoxia-ischemia and a high-dose of MSCs improved motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer.

PubMed

Murray, Louise; Mason, Joshua; Henry, Ann M; Hoskin, Peter; Siebert, Frank-Andre; Venselaar, Jack; Bownes, Peter

2016-08-01

To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-188: Commission of World 1st Commercial Compact PBS Proton System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Patel, B; Song, X

2015-06-15

Purpose: ProteusONE is the 1st commercial compact PBS proton system with an upstream scanning gantry and C230 cyclotron. We commissioned XiO and Raystation TPS simultaneously. This is a summary of beam data collection, modeling, and verification and comparison without range shiter for this unique system with both TPS. Methods: Both Raystation and XiO requires the same measurements data: (i) integral depth dose(IDDs) of single central spot measured in water tank; (ii) absolute dose calibration measured at 2cm depth of water with mono-energetic 10×10 cm2 field with spot spacing 4mm, 1MU per spot; and (iii) beam spot characteristics in air atmore » 0cm and ± 20cm away from ISO. To verify the beam model for both TPS, same 15 cube plans were created to simulate different treatment sites, target volumes and positions. PDDs of each plan were measured using a Multi-layer Ionization Chamber(MLIC), absolute point dose verification were measured using PPC05 in water tank and patient-specific QA were measured using MatriXX PT, a 2D ion chamber array. Results: All the point dose measurements at midSOBP were within 2% for both XiO and Raystation. However, up to 5% deviations were observed in XiO’s plans at shallow depth while within 2% in Raystation plans. 100% of the ranges measured were within 1 mm with maximum deviation of 0.5 mm. 20 patient specific plan were generated and measured in 3 planes (distal, proximal and midSOBP) in Raystation. The average of gamma index is 98.7%±3% with minimum 94% Conclusions: Both TPS were successfully commissioned and can be safely deployed for clinical use for ProteusONE. Based on our clinical experience in PBS planning, user interface, function and workflow, we preferably use Raystation as our main clinical TPS. Gamma Index >95% at 3%/3 mm criteria is our institution action level for patient specific plan QAs.« less

Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma.

PubMed

Cho, Oyeon; Chun, Mison; Oh, Young-Taek; Noh, O Kyu; Chang, Suk-Joon; Ryu, Hee-Sug; Lee, Eun Ju

2017-10-01

Radioresistance often leads to poor survival in concurrent chemoradiotherapy-treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan-Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067). Patients with both anemia and lymphopenia during concurrent chemoradiotherapy showed poor survival, independent of mid-squamous cell carcinoma antigen, and escalating high-dose-rate intracavitary brachytherapy ratio might improve survival.

SU-F-T-36: Dosimetric Comparison of Point Based Vs. Target Based Prescription for Intracavitary Brachytherapy in Cancer of the Cervix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashenafi, M; McDonald, D; Peng, J

Purpose: Improved patient imaging used for planning the treatment of cervical cancer with Tandem and Ovoid (T&O) Intracavitary high-dose-rate brachytherapy (HDR) now allows for 3D delineation of target volumes and organs-at-risk. However, historical data relies on the conventional point A-based planning technique. A comparative dosimetric study was performed by generating both target-based (TBP) and point-based (PBP) plans for ten clinical patients. Methods: Treatment plans created using Elekta Oncentra v. 4.3 for ten consecutive cervical cancer patients were analyzed. All patients were treated with HDR using the Utrecht T&O applicator. Both CT and MRI imaging modalities were utilized to delineate clinicalmore » target volume (CTV) and organs-at-risk (rectum, sigmoid, bladder, and small bowel). Point A (left and right), vaginal mucosa, and ICRU rectum and bladder points were defined on CT. Two plans were generated for each patient using two prescription methods (PBP and TBP). 7Gy was prescribed to each point A for each PBP plan and to the target D90% for each TBP plan. Target V90%, V100%, and V200% were evaluated. In addition, D0.1cc and D2cc were analyzed for each organ-at-risk. Differences were assessed for statistical significance (p<0.05) by use of Student’s t-test. Results: Target coverage was comparable for both planning methods, with each method providing adequate target coverage. TBP showed lower absolute dose to the target volume than PBP (D90% = 7.0Gy vs. 7.4Gy, p=0.028), (V200% = 10.9cc vs. 12.8cc, p=0.014), (ALeft = 6.4Gy vs. 7Gy, p=0.009), and (ARight = 6.4Gy vs. 7Gy, p=0.013). TBP also showed a statistically significant reduction in bladder, rectum, small bowel, and sigmoid doses compared to PBP. There was no statistically significant difference in vaginal mucosa or ICRU-defined rectum and bladder dose. Conclusion: Target based prescription resulted in substantially lower dose to delineated organs-at-risk compared to point based prescription, while maintaining similar target coverage.« less

Absolute bioavailability and pharmacokinetics of avosentan in man.

PubMed

Dieterle, W; Hengelage, T

2009-09-01

Avosentan is a potent, selective endothelin A receptor blocker. The pharmacokinetics of avosentan were investigated in healthy male and female volunteers, following oral and i.v. administration of single doses of avosentan and its absolute bioavailability was determined. In a randomized, balanced open-label, three-period oral crossover study, 26 healthy subjects (19 males and 7 females) received Treatments A, B and C. Treatment A consisted of a single dose of a 25 mg film-coated tablet of avosentan, Treatment B of a single dose of a 50 mg film-coated tablet of avosentan and Treatment C of 10 mg avosentan in 20 ml solution for infusion for 20 minutes (10 mg avosentan in 20 ml phosphate buffer pH 9.0 containing 1% polysorbate 20). Plasma concentrations of avosentan and its hydroxymethyl metabolite Ro 68-5925 were measured by liquid chromatography-tandem mass spectrometry. The absolute bioavailability values (compared with i.v. infusion) for the 25 and 50 mg film-coated tablets were 81% and 72%, respectively. The extent of absorption, as measured by partial and total AUC, increased almost proportionally with the dose. The estimated proportionality coefficient for AUC0- yen was 1.12 (90% CI 1.06, 1.18). For the rate of absorption (Cmax) strict dose-proportionality was not demonstrated (proportionality coefficient 1.13 (90% CI 1.0, 1.28)). No relevant gender differences in the pharmacokinetic characteristics were evident after a single i.v. dose and at an oral dose of 25 mg, whereas after oral administration of 50 mg of avosentan differences were seen in Cmax and t1/2. The absolute bioavailability of avosentan film-coated tablets is high, i.e. 70 - 80%.

Phase I trial of sargramostim in pediatric Crohn's disease.

PubMed

Kelsen, Judith R; Rosh, Joel; Heyman, Mel; Winter, Harland S; Ferry, George; Cohen, Stanley; Mamula, Petar; Baldassano, Robert N

2010-07-01

Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 microg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant corticosteroids (CS). The primary endpoint was identification of a safe and tolerable dose in children. The secondary endpoint was establishment of the pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from baseline of > or =12.5 points and remission as absolute PCDAI of < or =10. In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg, respectively; 19 completed the course. Both doses were found to be safe and well tolerated. Mild injection-site reactions occurred in 90% of patients. Three patients required dose reductions due to elevated absolute neutrophil counts. Following 4 microg/kg the mean area under the curve (AUC) was 2.64 and 2.80 ngh/mL for the 6-11- and 12-16-year-old groups, respectively. The mean half-life (t(1/2)) was 1.22 and 1.59 hours, respectively. Following 6 microg/kg, the mean AUC was 5.01 ngh/mL for the 12-16-year-old group, a 1.8-fold increase. A total of 16/18 patients (88%) achieved remission or response. Sargramostim at both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality unaffected by CS exposure. Remission and response data are encouraging, but further trials are needed to assess efficacy.

Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [(13) C8 ]-evacetrapib as a tracer.

PubMed

Cannady, Ellen A; Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G; Royalty, Jane; Ortega, Demetrio; Pack, Brian W; Begum, Syeda L; Annes, William F; Lin, Qun; Small, David S

2016-05-30

This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration-time curve (AUC) from zero to infinity (AUC[0-∞]) and to the last measureable concentration (AUC[0-tlast ]), were calculated. Bioavailability was calculated as the ratio of least-squares geometric mean of dose-normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2-47.6%) for AUC(0-∞) and 44.3% (90% CI: 41.8-46.9%) for AUC(0-tlast ). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a (13) C-labeled IV microdose tracer at about 1/1000(th) the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. © 2015 The Authors Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons Ltd.

Dosimetric evaluation of a MOSFET detector for clinical application in photon therapy.

PubMed

Kohno, Ryosuke; Hirano, Eriko; Nishio, Teiji; Miyagishi, Tomoko; Goka, Tomonori; Kawashima, Mitsuhiko; Ogino, Takashi

2008-01-01

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

Clinical analysis of speculum-based vaginal packing for high-dose-rate intracavitary tandem and ovoid brachytherapy in cervical cancer

PubMed Central

Sud, Shivani; Roth, Toni

2018-01-01

Purpose Intra-vaginal packing is used to fix the applicator and displace organs at risk (OAR) during high-dose-rate intracavitary tandem and ovoid brachytherapy (HDR-ICB). We retain the speculum from applicator placement as a dual-function bladder and rectum retractor during treatment. Our objective is to review salient techniques for OAR displacement, share our packing technique, and determine the reduction in dose to OAR and inter-fraction variability of dose to OAR, associated with speculum-based vaginal packing (SBVP) in comparison to conventional gauze packing during HDR-ICB. Material and methods We reviewed HDR-ICB treatment plans for 45 patients, including 10 who underwent both conventional gauze packing and SBVP. Due to institutional inter-provider practice differences, patients non-selectively received either packing procedure. Packing was performed under conscious sedation, followed by cone beam computed tomography used for dosimetric planning. Maximum absolute and percent-of-prescription dose to the International Commission of Radiation Units bladder and rectal points in addition to D0.1cc, D1.0cc, and D2.0cc volumes of the bladder and rectum were analyzed and compared for each packing method using an independent sample t-test. Results Of the 179 fractions included, 73% and 27% used SBVP and gauze packing, respectively. For patients prescribed 6 Gy to point A, SBVP was associated with reduced mean D0.1cc bladder dose, inter-fraction variability in D0.1cc bladder dose by 9.3% (p = 0.026) and 9.0%, respectively, and statistically equivalent rectal D0.1cc, D1.0cc, and D2.0cc. Patients prescribed 5.5 Gy or 5 Gy to point A after dose optimization, were less likely to benefit from SBVP. In the intra-patient comparison, 80% of patients had reduction in at least one rectum or bladder parameter. Conclusions In patients with conducive anatomy, SBVP is a cost-efficient packing method that is associated with improved bladder sparing and comparable rectal sparing relative to gauze packing during HDR-ICB without general anesthesia. PMID:29619054

Unwrapping 3D complex hollow organs for spatial dose surface analysis.

PubMed

Witztum, A; George, B; Warren, S; Partridge, M; Hawkins, M A

2016-11-01

Toxicity dose-response models describe the correlation between dose delivered to an organ and a given toxic endpoint. Duodenal toxicity is a dose limiting factor in the treatment of pancreatic cancer with radiation but the relationship between dose and toxicity in the duodenum is not well understood. While there have been limited studies into duodenal toxicity through investigations of the volume of the organ receiving dose over a specific threshold, both dose-volume and dose-surface histograms lack spatial information about the dose distribution, which may be important in determining normal tissue response. Due to the complex geometry of the duodenum, previous methods for unwrapping tubular organs for spatial modeling of toxicity are insufficient. A geometrically robust method for producing 2D dose surface maps (DSMs), specifically for the duodenum, has been developed and tested in order to characterize the spatial dose distribution. The organ contour is defined using Delaunay triangulation. The user selects a start and end coordinate in the structure and a path is found by regulating both length and curvature. This path is discretized and rays are cast from each point on the plane normal to the vector between the previous and the next point on the path and the dose at the closest perimeter point recorded. These angular perimeter slices are "unwrapped" from the edge distal to the pancreas to ensure the high dose region (proximal to the tumor) falls in the centre of the dose map. Gamma analysis is used to quantify the robustness of this method and the effect of overlapping planes. This method was used to extract DSMs for 15 duodena, with one esophagus case to illustrate the application to simpler geometries. Visual comparison indicates that a 30 × 30 map provides sufficient resolution to view gross spatial features of interest. A lookup table is created to store the area (cm 2 ) represented by each pixel in the DSMs in order to allow spatial descriptors in absolute size. The method described in this paper is robust, requires minimal human interaction, has been shown to be generalizable to simpler geometries, and uses readily available commercial software. The difference seen in DSMs due to overlapping planes is large and justifies the need for a solution that removes such planes. This is the first time 2D dose surface maps have been produced for the duodenum and provide spatial dose distribution information which can be explored to create models that may improve toxicity prediction in treatments for locally advanced pancreatic cancer.

SU-G-TeP2-08: Evaluation of Plastic Scintillator Detector for Small Field Stereotactic Patient-Specific Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Y; Gardner, S; Huang, Y

Purpose: To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance using flattening-filter-free (FFF) beams. Methods: A total of ten spherical targets (volume range:[0.03cc–2cc]) were planned using Dynamic Conformal Arc(DCA-10 plans) and Volumetric Modulated Arc Therapy(VMAT-10 plans) techniques in Eclipse(AAA v.11, 1mm dose calculation grid size). Additionally, 15 previously-treated cranial and spine SRS plans were evaluated (6 DCA, 9 VMAT, volume range:[0.04cc–119.02cc]). All measurements were acquired using Varian Edge equipped with HDMLC. Three detectors were used: PinPoint ion chamber (PTW;active volume 0.015cc), Exradin W1 PSD (Standard Imaging;active volume 0.002cc), and Gafchromic EBT3 filmmore » (Ashland). PinPoint and PSD were positioned perpendicular to beam axis in a Lucy phantom (Standard Imaging). Films were placed at isocenter in solid water. Calibration films were delivered for absolute dose analysis. Results: For large spherical targets(>1.5cc) with DCA, all detectors agreed within 1% of AAA calculations. As target volume decreased, PSD measured higher doses than AAA (maximum difference: 3.3% at 0.03cc target), while PinPoint chamber measured lower doses (maximum difference:-3.8% at 0.03cc target). Inter-detector differences between pinpoint and PSD increased with decreasing target size; differences>5% were observed for targets<0.09cc. Similar trends for inter-detector behavior were observed for clinical plans. For target sizes<0.08cc, PSD measured>5% higher dose than PinPoint chamber (maximum difference: 9.25% at 0.04cc target). Film demonstrated agreement of −0.19±1.47% with PSD for all spherical targets, and agreement within −0.98±2.25% for all 15 clinical targets. Unlike DCA, VMAT plans did not show improved AAA-to-detector agreements for large targets. Conclusion: For all targets, the PSD measurements agreed with film within 1.0%, on average. For small volume targets (<0.10cc), PSD agreed with film but measured significantly higher doses (>5%) compared with the pin point ion chamber. The plastic scintillator detector appears to be suitable for accurate measurements of small SRS targets.« less

Statistical variability and confidence intervals for planar dose QA pass rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, Daniel W.; Nelms, Benjamin E.; Attwood, Kristopher

Purpose: The most common metric for comparing measured to calculated dose, such as for pretreatment quality assurance of intensity-modulated photon fields, is a pass rate (%) generated using percent difference (%Diff), distance-to-agreement (DTA), or some combination of the two (e.g., gamma evaluation). For many dosimeters, the grid of analyzed points corresponds to an array with a low areal density of point detectors. In these cases, the pass rates for any given comparison criteria are not absolute but exhibit statistical variability that is a function, in part, on the detector sampling geometry. In this work, the authors analyze the statistics ofmore » various methods commonly used to calculate pass rates and propose methods for establishing confidence intervals for pass rates obtained with low-density arrays. Methods: Dose planes were acquired for 25 prostate and 79 head and neck intensity-modulated fields via diode array and electronic portal imaging device (EPID), and matching calculated dose planes were created via a commercial treatment planning system. Pass rates for each dose plane pair (both centered to the beam central axis) were calculated with several common comparison methods: %Diff/DTA composite analysis and gamma evaluation, using absolute dose comparison with both local and global normalization. Specialized software was designed to selectively sample the measured EPID response (very high data density) down to discrete points to simulate low-density measurements. The software was used to realign the simulated detector grid at many simulated positions with respect to the beam central axis, thereby altering the low-density sampled grid. Simulations were repeated with 100 positional iterations using a 1 detector/cm{sup 2} uniform grid, a 2 detector/cm{sup 2} uniform grid, and similar random detector grids. For each simulation, %/DTA composite pass rates were calculated with various %Diff/DTA criteria and for both local and global %Diff normalization techniques. Results: For the prostate and head/neck cases studied, the pass rates obtained with gamma analysis of high density dose planes were 2%-5% higher than respective %/DTA composite analysis on average (ranging as high as 11%), depending on tolerances and normalization. Meanwhile, the pass rates obtained via local normalization were 2%-12% lower than with global maximum normalization on average (ranging as high as 27%), depending on tolerances and calculation method. Repositioning of simulated low-density sampled grids leads to a distribution of possible pass rates for each measured/calculated dose plane pair. These distributions can be predicted using a binomial distribution in order to establish confidence intervals that depend largely on the sampling density and the observed pass rate (i.e., the degree of difference between measured and calculated dose). These results can be extended to apply to 3D arrays of detectors, as well. Conclusions: Dose plane QA analysis can be greatly affected by choice of calculation metric and user-defined parameters, and so all pass rates should be reported with a complete description of calculation method. Pass rates for low-density arrays are subject to statistical uncertainty (vs. the high-density pass rate), but these sampling errors can be modeled using statistical confidence intervals derived from the sampled pass rate and detector density. Thus, pass rates for low-density array measurements should be accompanied by a confidence interval indicating the uncertainty of each pass rate.« less

Performance Evaluation of sUAS Equipped with Velodyne HDL-32E LiDAR Sensor

NASA Astrophysics Data System (ADS)

Jozkow, G.; Wieczorek, P.; Karpina, M.; Walicka, A.; Borkowski, A.

2017-08-01

The Velodyne HDL-32E laser scanner is used more frequently as main mapping sensor in small commercial UASs. However, there is still little information about the actual accuracy of point clouds collected with such UASs. This work evaluates empirically the accuracy of the point cloud collected with such UAS. Accuracy assessment was conducted in four aspects: impact of sensors on theoretical point cloud accuracy, trajectory reconstruction quality, and internal and absolute point cloud accuracies. Theoretical point cloud accuracy was evaluated by calculating 3D position error knowing errors of used sensors. The quality of trajectory reconstruction was assessed by comparing position and attitude differences from forward and reverse EKF solution. Internal and absolute accuracies were evaluated by fitting planes to 8 point cloud samples extracted for planar surfaces. In addition, the absolute accuracy was also determined by calculating point 3D distances between LiDAR UAS and reference TLS point clouds. Test data consisted of point clouds collected in two separate flights performed over the same area. Executed experiments showed that in tested UAS, the trajectory reconstruction, especially attitude, has significant impact on point cloud accuracy. Estimated absolute accuracy of point clouds collected during both test flights was better than 10 cm, thus investigated UAS fits mapping-grade category.

Effect of γ-irradiation on the temperature coefficient of surface resistivity of two-dimensional island platinum films

NASA Astrophysics Data System (ADS)

Bishay, A. G.; El-Gamal, S.

2011-05-01

Three sets (A, B and C) of two-dimensional island platinum films (2D-I(Pt)Fs) were prepared via the thermal evaporation technique, where the substrates are corning 7059 glass slides. The mass thickness ( d m) of the films of different sets is 5, 10 and 20 Å, respectively. The Pt films were exposed to γ-rays from 137Cs (0.662 MeV) radiation source of dose rate 0.5 Gy/min. and the different doses are 100, 200, 300, 500 and 700 Gy. The dependence of the surface resistivity ( ρ) on temperature over the range of 100-300 K was undertaken at different d m and doses then the temperature coefficient of surface resistivity ( α) was deduced. It was found that; (i) for particular d m and T, the absolute value of α decreases as the dose increases (ii) for particular dose and T, the absolute value of α decreases as d m increases (iii) for particular dose and d m, the absolute value of α decreases as T increases. Qualitative interpretation for the results was offered on the ground that the electrons transfer among islands takes place by the activated tunneling mechanism and the γ-irradiation has changed the shape of islands from spherical to prolate spheroid.

Absolute bioavailability and safety of a novel rivastigmine nasal spray in healthy elderly individuals

PubMed Central

Soh, Bob

2016-01-01

Aims To test the feasibility of a novel rivastigmine nasal spray as prospective treatment for dementia. Methods A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58–75 years. Results Absolute bioavailability (F) of the nasal spray was significant at 0.62 (0.15) for F > 0 (P < 0.001, n = 8). The systemic dose absorbed was 2.0 (0.6) mg, time to maximum plasma concentration was 1.1 (0.5) h and maximum plasma concentration was 6.9 (2.0) ng ml−1. The NAP226–90 to rivastigmine AUC0–∞ ratio was 0.78 (0.19). The single dose safety was good with two of five mild adverse events related to the nasal spray. Nasal and throat irritation were perceived as mild and transient, and both had resolved at 20 min post‐nasal dose. An estimated dose of two or three sprays twice‐daily with nasal spray would deliver comparable rivastigmine exposure and efficacy as a 6–9.7 mg day–1 oral dose and a 10 cm2 transdermal patch, respectively. Conclusions The rivastigmine nasal spray had superior absolute bioavailability compared to historical values for oral capsule and transdermal patch determined by other researchers. It had rapid onset of action, low NAP226–90 to rivastigmine exposure ratio and a favourable safety and tolerability profile. The ability to achieve adjustable, individual, twice‐daily dosing during waking hours has good potential to minimise undesirable cholinergic burden and sleep disturbances whilst delivering an effective dose for the treatment of dementia associated with Alzheimer's and Parkinson's disease. PMID:27639640

Efficacy of alternate day versus daily dosing of rosuvastatin

PubMed Central

Dulay, Daisy; LaHaye, Stephen A; Lahey, Karen A; Day, Andrew G

2009-01-01

BACKGROUND: Compared with other statins, rosuvastatin has a relatively long half-life, which may allow for the administration of this medication on an alternate day basis. OBJECTIVE: To compare the efficacy of administering rosuvastatin on a daily basis versus on an alternate day basis for the treatment of dyslipidemia. METHODS: In the present crossover study, 45 patients with documented hypercholesterolemia requiring pharmacotherapy were administered either 20 mg of rosuvastatin on alternate days or 10 mg of rosuvastatin daily for six weeks. After a four-week washout period, patients were then switched to the other regimen for another six weeks. The primary end point was the percentage reduction of low-density lipoprotein cholesterol (LDL-C). RESULTS: LDL-C decreased by 48.5% versus 40.9% with daily and alternate day dosing, respectively. This represented an additional absolute reduction of LDL-C of 7.6% (95% CI 1.8% to 13.4%, P=0.012) with the daily dosing regimen. Both dosing regimens provided similar improvements in high-density lipoprotein cholesterol and triglycerides. CONCLUSIONS: Compared with alternate day dosing, daily dosing of rosuvastatin provides a statistically significant advantage in LDL-C reduction. However, the alternate day regimen may be a viable option for those patients in whom cost is a limitation to compliance. PMID:19214297

Poster — Thur Eve — 58: Dosimetric validation of electronic compensation for radiotherapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gräfe, James; Khan, Rao; Meyer, Tyler

2014-08-15

In this study we investigate the deliverability of dosimetric plans generated by the irregular surface compensator (ISCOMP) algorithm for 6 MV photon beams in Eclipse (Varian Medical System, CA). In contrast to physical tissue compensation, the electronic ISCOMP uses MLCs to dynamically modulate the fluence of a photon beam in order to deliver a uniform dose at a user defined plane in tissue. This method can be used to shield critical organs that are located within the treatment portal or improve dose uniformity by tissue compensation in inhomogeneous regions. Three site specific plans and a set of test fields weremore » evaluated using the γ-metric of 3%/ 3 mm on Varian EPID, MapCHECK, and Gafchromic EBT3 film with a clinical tolerance of >95% passing rates. Point dose measurements with an NRCC calibrated ionization chamber were also performed to verify the absolute dose delivered. In all cases the MapCHECK measured plans met the gamma criteria. The mean passing rate for the six EBT3 film field measurements was 96.2%, with only two fields at 93.4 and 94.0% passing rates. The EPID plans passed for fields encompassing the central ∼10 × 10 cm{sup 2} region of the detector; however for larger fields and greater off-axis distances discrepancies were observed and attributed to the profile corrections and modeling of backscatter in the portal dose calculation. The magnitude of the average percentage difference for 21 ion chamber point dose measurements and 17 different fields was 1.4 ± 0.9%, and the maximum percentage difference was −3.3%. These measurements qualify the algorithm for routine clinical use subject to the same pre-treatment patient specific QA as IMRT.« less

Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability.

PubMed

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Houston, Brian; Oosterhuis, Berend; Bjerrum, Ole J; Rowland, Malcolm; Garner, Colin

2010-05-12

A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine was collected and analysed for total (14)C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL(R) 4.1L/h, V(ss) 54L, t(1/2) 16h; therapeutic dose: CL 16L/h, CL(R) 6.2L/h, V(ss) 64L, t(1/2) 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound.

A technique for pediatric total skin electron irradiation.

PubMed

Bao, Qinan; Hrycushko, Brian A; Dugas, Joseph P; Hager, Frederick H; Solberg, Timothy D

2012-03-20

Total skin electron irradiation (TSEI) is a special radiotherapy technique which has generally been used for treating adult patients with mycosis fungoides. Recently, two infants presented with leukemia cutis isolated to the skin requiring TSEI. This work discusses the commissioning and quality assurance (QA) methods for implementing a modified Stanford technique using a rotating harness system to position sedated pediatric patients treated with electrons to the total skin. Commissioning of pediatric TSEI consisted of absolute calibration, measurement of dosimetric parameters, and subsequent verification in a pediatric patient sized cylindrical phantom using radiographic film and optically stimulated luminance (OSL) dosimeters. The depth of dose penetration under TSEI treatment condition was evaluated using radiographic film sandwiched in the phantom and demonstrated a 2 cm penetration depth with the maximum dose located at the phantom surface. Dosimetry measurements on the cylindrical phantom and in-vivo measurements from the patients suggested that, the factor relating the skin and calibration point doses (i.e., the B-factor) was larger for the pediatric TSEI treatments as compared to adult TSEI treatments. Custom made equipment, including a rotating plate and harness, was fabricated and added to a standard total body irradiation stand and tested to facilitate patient setup under sedated condition. A pediatric TSEI QA program, consisting of daily output, energy, flatness, and symmetry measurements as well as in-vivo dosimetry verification for the first cycle was developed. With a long interval between pediatric TSEI cases, absolute dosimetry was also repeated as part of the QA program. In-vivo dosimetry for the first two infants showed that a dose of ± 10% of the prescription dose can be achieved over the entire patient body. Though pediatric leukemia cutis and the subsequent need for TSEI are rare, the ability to commission the technique on a modified TBI stand is appealing for clinical implementation and has been successfully used for the treatment of two pediatric patients at our institution.

A technique for pediatric total skin electron irradiation

PubMed Central

2012-01-01

Background Total skin electron irradiation (TSEI) is a special radiotherapy technique which has generally been used for treating adult patients with mycosis fungoides. Recently, two infants presented with leukemia cutis isolated to the skin requiring TSEI. This work discusses the commissioning and quality assurance (QA) methods for implementing a modified Stanford technique using a rotating harness system to position sedated pediatric patients treated with electrons to the total skin. Methods and Results Commissioning of pediatric TSEI consisted of absolute calibration, measurement of dosimetric parameters, and subsequent verification in a pediatric patient sized cylindrical phantom using radiographic film and optically stimulated luminance (OSL) dosimeters. The depth of dose penetration under TSEI treatment condition was evaluated using radiographic film sandwiched in the phantom and demonstrated a 2 cm penetration depth with the maximum dose located at the phantom surface. Dosimetry measurements on the cylindrical phantom and in-vivo measurements from the patients suggested that, the factor relating the skin and calibration point doses (i.e., the B-factor) was larger for the pediatric TSEI treatments as compared to adult TSEI treatments. Custom made equipment, including a rotating plate and harness, was fabricated and added to a standard total body irradiation stand and tested to facilitate patient setup under sedated condition. A pediatric TSEI QA program, consisting of daily output, energy, flatness, and symmetry measurements as well as in-vivo dosimetry verification for the first cycle was developed. With a long interval between pediatric TSEI cases, absolute dosimetry was also repeated as part of the QA program. In-vivo dosimetry for the first two infants showed that a dose of ± 10% of the prescription dose can be achieved over the entire patient body. Conclusion Though pediatric leukemia cutis and the subsequent need for TSEI are rare, the ability to commission the technique on a modified TBI stand is appealing for clinical implementation and has been successfully used for the treatment of two pediatric patients at our institution. PMID:22433063

In vivo dosimetry for external photon treatments of head and neck cancers by diodes and TLDS.

PubMed

Tung, C J; Wang, H C; Lo, S H; Wu, J M; Wang, C J

2004-01-01

In vivo dosimetry was implemented for treatments of head and neck cancers in the large fields. Diode and thermoluminescence dosemeter (TLD) measurements were carried out for the linear accelerators of 6 MV photon beams. ESTRO in vivo dosimetry protocols were followed in the determination of midline doses from measurements of entrance and exit doses. Of the fields monitored by diodes, the maximum absolute deviation of measured midline doses from planned target doses was 8%, with the mean value and the standard deviation of -1.0 and 2.7%. If planned target doses were calculated using radiological water equivalent thicknesses rather than patient geometric thicknesses, the maximum absolute deviation dropped to 4%, with the mean and the standard deviation of 0.7 and 1.8%. For in vivo dosimetry monitored by TLDs, the shift in mean dose remained small but the statistical precision became poor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to testmore » the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.« less

Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer

PubMed Central

Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G.; Royalty, Jane; Ortega, Demetrio; Pack, Brian W.; Begum, Syeda L.; Annes, William F.; Lin, Qun; Small, David S.

2015-01-01

This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. PMID:26639670

Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.

PubMed

Harty, P D; Lye, J E; Ramanathan, G; Butler, D J; Hall, C J; Stevenson, A W; Johnston, P N

2014-05-01

The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line. The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%. The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.

SU-E-T-145: Beam Characteristics of Flattening Filter Free Beams Including Low Dose Rate Setting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uehara, K; Ogata, T; Nakayama, M

2015-06-15

Purpose: In commissioning of volumetric modulated arc therapy (VMAT), it is necessary to evaluate the beam characteristics of various dose rate settings with potential to use. The aim of this study is to evaluate the beam characteristics of flattened and flattening filter free (FFF) including low dose rate setting. Methods: We used a Varian TrueBeam with Millennium 120 MLC. Both 6 and 10 MV beams with or without flattening filter were used for this study. To evaluate low-dose rate FFF beams, specially-designed leaf sequence files control out-of-field MLC leaf pair at constant dose rate ranging from 80 to 400 MU/min.more » For dose rate from 80 MU/min to the maximum usable value of all energies, beam output were measured using ionization chamber (CC04, IBA). The ionization chamber was inserted into water equivalent phantom (RT3000-New, R-tech), and the phantom was set with SAD of 100cm. The beam profiles were performed using the 2D diode array (Profiler2, Sun Nuclear). The SSD was set to 90cm and a combined 30cmx30cmx9cm phantom which consisted of solid water slabs was put on the device. All measurement were made using 100MU irradiation for 10cmx10cm jaw-defined field size with a gantry angle of 0°. Results: In all energies, the dose rate dependences with beam output and variation coefficient were within 0.2% and 0.07%, respectively. The flatness and symmetry exhibited small variations (flatness ≤0.1 point and symmetry≤0.3 point at absolute difference). Conclusion: We had studied the characteristics of flattened and FFF beam over the 80 MU/min. Our results indicated that the beam output and profiles of FFF of TrueBeam linac were highly stable at low dose rate setting.« less

SU-E-T-149: Brachytherapy Patient Specific Quality Assurance for a HDR Vaginal Cylinder Case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbiere, J; Napoli, J; Ndlovu, A

2015-06-15

Purpose: Commonly Ir-192 HDR treatment planning system commissioning is only based on a single absolute measurement of source activity supplemented by tabulated parameters for multiple factors without independent verification that the planned distribution corresponds to the actual delivered dose. The purpose on this work is to present a methodology using Gafchromic film with a statistically valid calibration curve that can be used to validate clinical HDR vaginal cylinder cases by comparing the calculated plan dose distribution in a plane with the corresponding measured planar dose. Methods: A vaginal cylinder plan was created with Oncentra treatment planning system. The 3D dosemore » matrix was exported to a Varian Eclipse work station for convenient extraction of a 2D coronal dose plane corresponding to the film position. The plan was delivered with a sheet of Gafchromic EBT3 film positioned 1mm from the catheter using an Ir-192 Nucletron HDR source. The film was then digitized with an Epson 10000 XL color scanner. Film analysis is performed with MatLab imaging toolbox. A density to dose calibration curve was created using TG43 formalism for a single dwell position exposure at over 100 points for statistical accuracy. The plan and measured film dose planes were registered using a known dwell position relative to four film marks. The plan delivered 500 cGy to points 2 cm from the sources. Results: The distance to agreement of the 500 cGy isodose between the plan and film measurement laterally was 0.5 mm but can be as much as 1.5 mm superior and inferior. The difference between the computed plan dose and film measurement was calculated per pixel. The greatest errors up to 50 cGy are near the apex. Conclusion: The methodology presented will be useful to implement more comprehensive quality assurance to verify patient-specific dose distributions.« less

TH-C-BRD-04: Beam Modeling and Validation with Triple and Double Gaussian Dose Kernel for Spot Scanning Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirayama, S; Takayanagi, T; Fujii, Y

2014-06-15

Purpose: To present the validity of our beam modeling with double and triple Gaussian dose kernels for spot scanning proton beams in Nagoya Proton Therapy Center. This study investigates the conformance between the measurements and calculation results in absolute dose with two types of beam kernel. Methods: A dose kernel is one of the important input data required for the treatment planning software. The dose kernel is the 3D dose distribution of an infinitesimal pencil beam of protons in water and consists of integral depth doses and lateral distributions. We have adopted double and triple Gaussian model as lateral distributionmore » in order to take account of the large angle scattering due to nuclear reaction by fitting simulated inwater lateral dose profile for needle proton beam at various depths. The fitted parameters were interpolated as a function of depth in water and were stored as a separate look-up table for the each beam energy. The process of beam modeling is based on the method of MDACC [X.R.Zhu 2013]. Results: From the comparison results between the absolute doses calculated by double Gaussian model and those measured at the center of SOBP, the difference is increased up to 3.5% in the high-energy region because the large angle scattering due to nuclear reaction is not sufficiently considered at intermediate depths in the double Gaussian model. In case of employing triple Gaussian dose kernels, the measured absolute dose at the center of SOBP agrees with calculation within ±1% regardless of the SOBP width and maximum range. Conclusion: We have demonstrated the beam modeling results of dose distribution employing double and triple Gaussian dose kernel. Treatment planning system with the triple Gaussian dose kernel has been successfully verified and applied to the patient treatment with a spot scanning technique in Nagoya Proton Therapy Center.« less

Incidence of adrenal insufficiency and impact of corticosteroid supplementation in critically ill children with systemic inflammatory syndrome and vasopressor-dependent shock.

PubMed

Hebbar, Kiran B; Stockwell, Jana A; Leong, Traci; Fortenberry, James D

2011-05-01

Adrenal insufficiency may be common in adults and children with vasopressor-resistant shock. We developed a protocolized approach to low-dose adrenocorticotropin testing and empirical low-dose glucocorticoid/mineralocorticoid supplementation in children with systemic inflammatory response syndrome and persistent hypotension following fluid resuscitation and vasopressor infusion. We hypothesized that absolute and relative adrenal insufficiency was common in children with systemic inflammatory response syndrome requiring vasopressor support and that steroid administration would be associated with decreased vasopressor need. Retrospective review of pediatric patients with systemic inflammatory response syndrome and vasopressor-dependent shock receiving protocol-based adrenocorticotropin testing and low-dose steroid supplementation. The incidence of absolute and relative adrenal insufficiency was determined using several definitions. Vasopressor dose requirements were evaluated before, and following, initiation of corticosteroids. Seventy-eight patients met inclusion criteria for systemic inflammatory response syndrome and shock; 40 had septic shock. Median age was 84 months (range, 0.5-295). By adrenocorticotropin testing, 44 (56%) had absolute adrenal insufficiency, 39 (50%) had relative adrenal insufficiency, and 69 (88%) had either form of adrenal insufficiency. Adrenal insufficiency incidence was significantly higher in children >2 yrs (p = .0209). Therapeutic interventions included median 80-mL/kg fluid resuscitation; 65% of patients required dopamine, 58% norepinephrine, and 49% dopamine plus norepinephrine. With steroid supplementation, median dopamine dose decreased from 10 to 4 μg/kg/min at 4 hrs (p = .0001), and median dose of norepinephrine decreased from 0.175 μg/kg/min to 0.05 μg/kg/min at 4 hrs (p = .039). Absolute and relative adrenal insufficiency was prevalent in this cohort of children with systemic inflammatory response syndrome and vasopressor-dependent shock and increased with age. Introduction of steroids produced a significant reduction in vasopressor duration and dosage. Use of low-dose adrenocorticotropin testing may help further delineate populations who require steroid supplementation.

A randomized study of rotigotine dose response on 'off' time in advanced Parkinson's disease.

PubMed

Nicholas, Anthony P; Borgohain, Rupam; Chaná, Pedro; Surmann, Erwin; Thompson, Emily L; Bauer, Lars; Whitesides, John; Elmer, Lawrence W

2014-01-01

Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established. This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h. Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses of levodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'. 409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily 'off' times (h/day) were placebo: 6.4 (±2.5), rotigotine 2-8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (±SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (±0.28) with rotigotine 8 mg/24 h, and -1.5 (±0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.

Automated estimation of abdominal effective diameter for body size normalization of CT dose.

PubMed

Cheng, Phillip M

2013-06-01

Most CT dose data aggregation methods do not currently adjust dose values for patient size. This work proposes a simple heuristic for reliably computing an effective diameter of a patient from an abdominal CT image. Evaluation of this method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore scanners demonstrates close correspondence between computed and manually measured patient effective diameters, with a mean absolute error of 1.0 cm (error range +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60 patients on Siemens, General Electric, and Toshiba scanners. A calculated effective diameter in the middle slice of an abdominal CT study was found to be a close approximation of the mean calculated effective diameter for the study, with a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm). Furthermore, the mean absolute error for an adjusted mean volume computed tomography dose index (CTDIvol) using a mid-study calculated effective diameter, versus a mean per-slice adjusted CTDIvol based on the calculated effective diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These results are used to calculate approximate normalized dose length product values in an abdominal CT dose database of 12,506 studies.

[A Quality Assurance (QA) System with a Web Camera for High-dose-rate Brachytherapy].

PubMed

Hirose, Asako; Ueda, Yoshihiro; Oohira, Shingo; Isono, Masaru; Tsujii, Katsutomo; Inui, Shouki; Masaoka, Akira; Taniguchi, Makoto; Miyazaki, Masayoshi; Teshima, Teruki

2016-03-01

The quality assurance (QA) system that simultaneously quantifies the position and duration of an (192)Ir source (dwell position and time) was developed and the performance of this system was evaluated in high-dose-rate brachytherapy. This QA system has two functions to verify and quantify dwell position and time by using a web camera. The web camera records 30 images per second in a range from 1,425 mm to 1,505 mm. A user verifies the source position from the web camera at real time. The source position and duration were quantified with the movie using in-house software which was applied with a template-matching technique. This QA system allowed verification of the absolute position in real time and quantification of dwell position and time simultaneously. It was evident from the verification of the system that the mean of step size errors was 0.31±0.1 mm and that of dwell time errors 0.1±0.0 s. Absolute position errors can be determined with an accuracy of 1.0 mm at all dwell points in three step sizes and dwell time errors with an accuracy of 0.1% in more than 10.0 s of the planned time. This system is to provide quick verification and quantification of the dwell position and time with high accuracy at various dwell positions without depending on the step size.

Evaluation of the Eclipse eMC algorithm for bolus electron conformal therapy using a standard verification dataset.

PubMed

Carver, Robert L; Sprunger, Conrad P; Hogstrom, Kenneth R; Popple, Richard A; Antolak, John A

2016-05-08

The purpose of this study was to evaluate the accuracy and calculation speed of electron dose distributions calculated by the Eclipse electron Monte Carlo (eMC) algorithm for use with bolus electron conformal therapy (ECT). The recent com-mercial availability of bolus ECT technology requires further validation of the eMC dose calculation algorithm. eMC-calculated electron dose distributions for bolus ECT have been compared to previously measured TLD-dose points throughout patient-based cylindrical phantoms (retromolar trigone and nose), whose axial cross sections were based on the mid-PTV (planning treatment volume) CT anatomy. The phantoms consisted of SR4 muscle substitute, SR4 bone substitute, and air. The treatment plans were imported into the Eclipse treatment planning system, and electron dose distributions calculated using 1% and < 0.2% statistical uncertainties. The accuracy of the dose calculations using moderate smoothing and no smooth-ing were evaluated. Dose differences (eMC-calculated less measured dose) were evaluated in terms of absolute dose difference, where 100% equals the given dose, as well as distance to agreement (DTA). Dose calculations were also evaluated for calculation speed. Results from the eMC for the retromolar trigone phantom using 1% statistical uncertainty without smoothing showed calculated dose at 89% (41/46) of the measured TLD-dose points was within 3% dose difference or 3 mm DTA of the measured value. The average dose difference was -0.21%, and the net standard deviation was 2.32%. Differences as large as 3.7% occurred immediately distal to the mandible bone. Results for the nose phantom, using 1% statistical uncertainty without smoothing, showed calculated dose at 93% (53/57) of the measured TLD-dose points within 3% dose difference or 3 mm DTA. The average dose difference was 1.08%, and the net standard deviation was 3.17%. Differences as large as 10% occurred lateral to the nasal air cavities. Including smoothing had insignificant effects on the accuracy of the retromolar trigone phantom calculations, but reduced the accuracy of the nose phantom calculations in the high-gradient dose areas. Dose calculation times with 1% statistical uncertainty for the retromolar trigone and nose treatment plans were 30 s and 24 s, respectively, using 16 processors (Intel Xeon E5-2690, 2.9 GHz) on a framework agent server (FAS). In comparison, the eMC was significantly more accurate than the pencil beam algorithm (PBA). The eMC has comparable accuracy to the pencil beam redefinition algorithm (PBRA) used for bolus ECT planning and has acceptably low dose calculation times. The eMC accuracy decreased when smoothing was used in high-gradient dose regions. The eMC accuracy was consistent with that previously reported for accuracy of the eMC electron dose algorithm and shows that the algorithm is suitable for clinical implementation of bolus ECT.

SU-F-T-138: Commissioning and Evaluating Dose Computation Models for a Dedicated Proton Line Scanning Beam Nozzle in Eclipse Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, P; Chang Gung University, Taoyuan, Taiwan; Huang, H

Purpose: In this study, we present an effective method to derive low dose envelope of the proton in-air spot fluence at beam positions other than the isocenter to reduce amount of measurements required for planning commission. Also, we demonstrate commissioning and validation results of this method to the Eclipse treatment planning system (version 13.0.29) for a Sumitomo dedicated proton line scanning beam nozzle. Methods: The in-air spot profiles at five beam-axis positions (±200, ±100 and 0 mm) were obtained in trigger mode using a MP3 Water tank (PTW-Freiburg) and a pinpoint ionization chamber (model 31014, PTW-Freiburg). Low dose envelope (belowmore » 1% of the center dose) of the spot profile at isocenter was obtained by repeated point measurements to minimize dosimetry uncertainty. The double Gaussian (DG) model was used to fit and obtain optimal σ1, σ2 and their corresponding weightings through our in-house MATLAB (Mathworks) program. σ1, σ2 were assumed to expand linearly along the beam axis from a virtual source position calculated by back projecting fitted sigmas from the single Gaussian (SG) model. Absolute doses in water were validated using an Advanced Markus chamber at the depth of 2cm with Pristine Peak (BP) R90d ranging from 5–32 cm for 10×10 cm2 scanned fields. The field size factors were verified with square fields from 2 to 20 cm at 2cm and before BP depth. Results: The absolute dose outputs were found to be within ±3%. For field size factor, the agreement between calculated and measurement were within ±2% at 2cm and ±3% before BP, except for the field size below 2×2 cm2. Conclusion: The double Gaussian model was found to be sufficient for characterizing the Sumitomo dedicated proton line scanning nozzle. With our effective double Gaussian fitting method, we are able to save significant proton beam time with acceptable output accuracy.« less

SU-E-T-799: Verification of a Simultaneous Treatment of Multiple Brain Metastases Using VMAT Technique by a Composite Alanine-Gel Dosimeter Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavoni, J; Silveira, M; Filho, O Baffa

Purpose: This work presents an end-to-end test using a Gel-Alanine phantom to validate the three-dimensional (3D) dose distribution (DD) delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. Methods: Three cylindrical phantons containing MAGIC-f gel dosimeter were used to measure the 3D DD of a VMAT treatment, the first two were filled with the gel dosimeter (Gel 1 and 2) and the third one was filled with gel and 12 alanine dosimeters distributed along it (Gel 3). Gels 1 and 3 were irradiated and gel 2 was used to map the magnetic resonance imagemore » (MRI) scanner field inomogeneities. A CT scan of gel 3 was used for the VMAT treatment planning and 5 alanine pellets were chosen as lesions, around them a PTV was grown and different dose prescriptions were assigned for each one, varying from 5 to 9Gy. Before treatment, the plan was approved in a QA based on an ionization chamber absolute dose measurement, a radiochromic film planar dose measurement and a portal dosimetry per field verification; and also the phantons positioning were verified by ExacTrac 6D correction and OBI kV Cone Beam CT. The gels were irradiated, the MRIs were acquired 24 hours after irradiation and finally, the alanine dosimeters were analysed in a X-band Electron Spin Resonance spectrometer. Results: The association of the two detectors enabled the 3D dose evaluation by gel and punctually inside target volumes by alanine. In the gamma analyses (3%/3mm) comparing the 5 PTVs’ central images DD with TPS expected DD more than 95% of the points were approved. The alanine absolute dose measurements were in agreement with TPS by less than 5%. Conclusion: The gel-alanine phantom enabled the dosimetric validation of multiple brain metastases treatment using VMAT, being an almost ideal tool for this application. This work is partially supported by FAPESP.« less

Poster — Thur Eve — 72: Clinical Subtleties of Flattening-Filter-Free Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corns, Robert; Thomas, Steven; Huang, Vicky

2014-08-15

Flattening-filter-free (fff) beams offer superior dose rates, reducing treatment times for important techniques that utilize small field sizes, such as stereotactic ablative radiotherapy (SABR). The impact of ion collection efficiency (P{sub ion}) on the percent depth dose (PDD) has been discussed at length in the literature. Relative corrections of the order of l%–2% are possible. In the process of commissioning 6fff and 10fff beams, we identified a number of other important details that influence commissioning. We looked at the absolute dose difference between corrected and uncorrected PDD. We discovered a curve with a broad maximum between 10 and 20 cm.more » We wondered about the consequences of this PDD correction on the absolute dose calibration of the linac because the TG-51 protocol does not correct the PDD curve. The quality factor k{sub Q} depends on the PDD, so in principle, a correction to the PDD will alter the absolute calibration of the linac. Finally, there are other clinical tables, such as TMR, which are derived from PDD. Attention to details on how this computation is performed is important because different corrections are possible depending the method of calculation.« less

Anatomic motor point localization for partial quadriceps block in spasticity.

PubMed

Albert, T; Yelnik, A; Colle, F; Bonan, I; Lassau, J P

2000-03-01

To identify the location of the vastus intermedius nerve and its motor point (point M) and to precisely identify its coordinates in relation to anatomic surface landmarks. Descriptive study. Anatomy institute of a university school of medicine. Twenty-nine adult cadaver limbs immobilized in anatomic position. Anatomic dissection to identify point M. Anatomic surface landmarks were point F, the issuing point of femoral nerve under the inguinal ligament; point R, the middle of superior edge of the patella; segment FR, which corresponds to thigh length; point M', point M orthogonal projection on segment FR. Absolute vertical coordinate, distance FM, relative vertical coordinate compared to the thigh length, FM'/FR ratio; absolute horizontal coordinate, distance MM'. The absolute vertical coordinate was 11.7+/-2 cm. The relative vertical coordinate was at .29+/-.04 of thigh length. The horizontal coordinate was at 2+/-.5 cm lateral to the FR line. Point M can be defined with relative precision by two coordinates. Application and clinical interest of nerve blocking using these coordinates in quadriceps spasticity should be studied.

SU-F-T-492: The Impact of Water Temperature On Absolute Dose Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Islam, N; Podgorsak, M; Roswell Park Cancer Institute, Buffalo, NY

Purpose: The Task Group 51 (TG 51) protocol prescribes that dose calibration of photon beams be done by irradiating an ionization chamber in a water tank at pre-defined depths. Methodologies are provided to account for variations in measurement conditions by applying correction factors. However, the protocol does not completely account for the impact of water temperature. It is well established that water temperature will influence the density of air in the ion chamber collecting volume. Water temperature, however, will also influence the size of the collecting volume via thermal expansion of the cavity wall and the density of the watermore » in the tank. In this work the overall effect of water temperature on absolute dosimetry has been investigated. Methods: Dose measurements were made using a Farmer-type ion chamber for 6 and 23 MV photon beams with water temperatures ranging from 10 to 40°C. A reference ion chamber was used to account for fluctuations in beam output between successive measurements. Results: For the same beam output, the dose determined using TG 51 was dependent on the temperature of the water in the tank. A linear regression of the data suggests that the dependence is statistically significant with p-values of the slope equal to 0.003 and 0.01 for 6 and 23 MV beams, respectively. For a 10 degree increase in water phantom temperature, the absolute dose determined with TG 51 increased by 0.27% and 0.31% for 6 and 23 MV beams, respectively. Conclusion: There is a measurable effect of water temperature on absolute dose calibration. To account for this effect, a reference temperature can be defined and a correction factor applied to account for deviations from this reference temperature during beam calibration. Such a factor is expected to be of similar magnitude to most of the existing TG 51 correction factors.« less

The Berg Balance Scale has high intra- and inter-rater reliability but absolute reliability varies across the scale: a systematic review.

PubMed

Downs, Stephen; Marquez, Jodie; Chiarelli, Pauline

2013-06-01

What is the intra-rater and inter-rater relative reliability of the Berg Balance Scale? What is the absolute reliability of the Berg Balance Scale? Does the absolute reliability of the Berg Balance Scale vary across the scale? Systematic review with meta-analysis of reliability studies. Any clinical population that has undergone assessment with the Berg Balance Scale. Relative intra-rater reliability, relative inter-rater reliability, and absolute reliability. Eleven studies involving 668 participants were included in the review. The relative intrarater reliability of the Berg Balance Scale was high, with a pooled estimate of 0.98 (95% CI 0.97 to 0.99). Relative inter-rater reliability was also high, with a pooled estimate of 0.97 (95% CI 0.96 to 0.98). A ceiling effect of the Berg Balance Scale was evident for some participants. In the analysis of absolute reliability, all of the relevant studies had an average score of 20 or above on the 0 to 56 point Berg Balance Scale. The absolute reliability across this part of the scale, as measured by the minimal detectable change with 95% confidence, varied between 2.8 points and 6.6 points. The Berg Balance Scale has a higher absolute reliability when close to 56 points due to the ceiling effect. We identified no data that estimated the absolute reliability of the Berg Balance Scale among participants with a mean score below 20 out of 56. The Berg Balance Scale has acceptable reliability, although it might not detect modest, clinically important changes in balance in individual subjects. The review was only able to comment on the absolute reliability of the Berg Balance Scale among people with moderately poor to normal balance. Copyright © 2013 Australian Physiotherapy Association. Published by .. All rights reserved.

Using, Seeing, Feeling, and Doing Absolute Value for Deeper Understanding

ERIC Educational Resources Information Center

Ponce, Gregorio A.

2008-01-01

Using sticky notes and number lines, a hands-on activity is shared that anchors initial student thinking about absolute value. The initial point of reference should help students successfully evaluate numeric problems involving absolute value. They should also be able to solve absolute value equations and inequalities that are typically found in…

A general model for stray dose calculation of static and intensity-modulated photon radiation.

PubMed

Hauri, Pascal; Hälg, Roger A; Besserer, Jürgen; Schneider, Uwe

2016-04-01

There is an increasing number of cancer survivors who are at risk of developing late effects caused by ionizing radiation such as induction of second tumors. Hence, the determination of out-of-field dose for a particular treatment plan in the patient's anatomy is of great importance. The purpose of this study was to analytically model the stray dose according to its three major components. For patient scatter, a mechanistic model was developed. For collimator scatter and head leakage, an empirical approach was used. The models utilize a nominal beam energy of 6 MeV to describe two linear accelerator types of a single vendor. The parameters of the models were adjusted using ionization chamber measurements registering total absorbed dose in simple geometries. Whole-body dose measurements using thermoluminescent dosimeters in an anthropomorphic phantom for static and intensity-modulated treatment plans were compared to the 3D out-of-field dose distributions calculated by a combined model. The absolute mean difference between the whole-body predicted and the measured out-of-field dose of four different plans was 11% with a maximum difference below 44%. Computation time of 36 000 dose points for one field was around 30 s. By combining the model-calculated stray dose with the treatment planning system dose, the whole-body dose distribution can be viewed in the treatment planning system. The results suggest that the model is accurate, fast and can be used for a wide range of treatment modalities to calculate the whole-body dose distribution for clinical analysis. For similar energy spectra, the mechanistic patient scatter model can be used independently of treatment machine or beam orientation.

Randomised controlled trials define shape of dose-response for Pollinex Quattro Birch allergoid immunotherapy.

PubMed

Worm, Margitta; Higenbottam, Tim; Pfaar, Oliver; Mösges, Ralph; Aberer, Werner; Gunawardena, Kulasiri; Wessiepe, Dorothea; Lee, Denise; Kramer, Matthias F; Skinner, Murray; Lees, Bev; Zielen, Stefan

2018-05-19

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed two phase II studies to determine its optimal cumulative dose. The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction of Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modelling analysis was used to test for the dose-response, shape of the curve, and estimation of the median effective dose (ED 50 ), a measure of potency. Statistically significant dose-responses (p<0.01 & 0.001) were seen respectively. The highest cumulative dose in PQBirch204 (27300 standardised units [SU]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED 50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. Increasing the cumulative dose of PQ Birch 5.5-fold from 5100 to 27300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase of efficacy of 50%, without compromising safety. The cumulative dose-response was confirmed to be curvilinear in shape. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparison of IPSM 1990 photon dosimetry code of practice with IAEA TRS‐398 and AAPM TG‐51.

PubMed Central

Henríquez, Francisco Cutanda

2009-01-01

Several codes of practice for photon dosimetry are currently used around the world, supported by different organizations. A comparison of IPSM 1990 with both IAEA TRS‐398 and AAPM TG‐51 has been performed. All three protocols are based on the calibration of ionization chambers in terms of standards of absorbed dose to water, as it is the case with other modern codes of practice. This comparison has been carried out for photon beams of nominal energies: 4 MV, 6 MV, 8 MV, 10 MV and 18 MV. An NE 2571 graphite ionization chamber was used in this study, cross‐calibrated against an NE 2611A Secondary Standard, calibrated in the National Physical Laboratory (NPL). Absolute dose in reference conditions was obtained using each of these three protocols including: beam quality indices, beam quality conversion factors both theoretical and NPL experimental ones, correction factors for influence quantities and absolute dose measurements. Each protocol recommendations have been strictly followed. Uncertainties have been obtained according to the ISO Guide to the Expression of Uncertainty in Measurement. Absorbed dose obtained according to all three protocols agree within experimental uncertainty. The largest difference between absolute dose results for two protocols is obtained for the highest energy: 0.7% between IPSM 1990 and IAEA TRS‐398 using theoretical beam quality conversion factors. PACS number: 87.55.tm

Accuracy of Monte Carlo photon transport simulation in characterizing brachytherapy dosimeter energy-response artefacts.

PubMed

Das, R K; Li, Z; Perera, H; Williamson, J F

1996-06-01

Practical dosimeters in brachytherapy, such as thermoluminescent dosimeters (TLD) and diodes, are usually calibrated against low-energy megavoltage beams. To measure absolute dose rate near a brachytherapy source, it is necessary to establish the energy response of the detector relative to that of the calibration energy. The purpose of this paper is to assess the accuracy of Monte Carlo photon transport (MCPT) simulation in modelling the absolute detector response as a function of detector geometry and photon energy. We have exposed two different sizes of TLD-100 (LiF chips) and p-type silicon diode detectors to calibrated 60Co, HDR source (192Ir) and superficial x-ray beams. For the Scanditronix electron-field diode, the relative detector response, defined as the measured detector readings per measured unit of air kerma, varied from 38.46 V cGy-1 (40 kVp beam) to 6.22 V cGy-1 (60Co beam). Similarly for the large and small chips the same quantity varied from 2.08-3.02 nC cGy-1 and 0.171-0.244 nC cGy-1, respectively. Monte Carlo simulation was used to calculate the absorbed dose to the active volume of the detector per unit air kerma. If the Monte Carlo simulation is accurate, then the absolute detector response, which is defined as the measured detector reading per unit dose absorbed by the active detector volume, and is calculated by Monte Carlo simulation, should be a constant. For the diode, the absolute response is 5.86 +/- 0.15 (V cGy-1). For TLDs of size 3 x 3 x 1 mm3 the absolute response is 2.47 +/- 0.07 (nC cGy-1) and for TLDs of 1 x 1 x 1 mm3 it is 0.201 +/- 0.008 (nC cGy-1). From the above results we can conclude that the absolute response function of detectors (TLDs and diodes) is directly proportional to absorbed dose by the active volume of the detector and is independent of beam quality.

Bioavailability of dexmedetomidine after extravascular doses in healthy subjects

PubMed Central

Anttila, Markku; Penttilä, Jani; Helminen, Antti; Vuorilehto, Lauri; Scheinin, Harry

2003-01-01

Aim To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects. Methods Single 2 µg kg−1 doses of dexmedetomidine were given intravenously, intramuscularly, perorally and buccally (where the solution is not swallowed) to 12 healthy male subjects. The drug concentration-time data were analysed using linear one-compartment (buccal and peroral data), or two-compartment modelling (intravenous data), or noncompartmental methods (intramuscular data). Results Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12–20%), 82% (73–92%) and 104% (96–112%), respectively. Conclusion Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug. PMID:14616431

Absolute dose calculations for Monte Carlo simulations of radiotherapy beams.

PubMed

Popescu, I A; Shaw, C P; Zavgorodni, S F; Beckham, W A

2005-07-21

Monte Carlo (MC) simulations have traditionally been used for single field relative comparisons with experimental data or commercial treatment planning systems (TPS). However, clinical treatment plans commonly involve more than one field. Since the contribution of each field must be accurately quantified, multiple field MC simulations are only possible by employing absolute dosimetry. Therefore, we have developed a rigorous calibration method that allows the incorporation of monitor units (MU) in MC simulations. This absolute dosimetry formalism can be easily implemented by any BEAMnrc/DOSXYZnrc user, and applies to any configuration of open and blocked fields, including intensity-modulated radiation therapy (IMRT) plans. Our approach involves the relationship between the dose scored in the monitor ionization chamber of a radiotherapy linear accelerator (linac), the number of initial particles incident on the target, and the field size. We found that for a 10 x 10 cm2 field of a 6 MV photon beam, 1 MU corresponds, in our model, to 8.129 x 10(13) +/- 1.0% electrons incident on the target and a total dose of 20.87 cGy +/- 1.0% in the monitor chambers of the virtual linac. We present an extensive experimental verification of our MC results for open and intensity-modulated fields, including a dynamic 7-field IMRT plan simulated on the CT data sets of a cylindrical phantom and of a Rando anthropomorphic phantom, which were validated by measurements using ionization chambers and thermoluminescent dosimeters (TLD). Our simulation results are in excellent agreement with experiment, with percentage differences of less than 2%, in general, demonstrating the accuracy of our Monte Carlo absolute dose calculations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellefson, S; Department of Human Oncology, University of Wisconsin, Madison, WI; Culberson, W

Purpose: Discrepancies in absolute dose values have been detected between the ViewRay treatment planning system and ArcCHECK readings when performing delivery quality assurance on the ViewRay system with the ArcCHECK-MR diode array (SunNuclear Corporation). In this work, we investigate whether these discrepancies are due to errors in the ViewRay planning and/or delivery system or due to errors in the ArcCHECK’s readings. Methods: Gamma analysis was performed on 19 ViewRay patient plans using the ArcCHECK. Frequency analysis on the dose differences was performed. To investigate whether discrepancies were due to measurement or delivery error, 10 diodes in low-gradient dose regions weremore » chosen to compare with ion chamber measurements in a PMMA phantom with the same size and shape as the ArcCHECK, provided by SunNuclear. The diodes chosen all had significant discrepancies in absolute dose values compared to the ViewRay TPS. Absolute doses to PMMA were compared between the ViewRay TPS calculations, ArcCHECK measurements, and measurements in the PMMA phantom. Results: Three of the 19 patient plans had 3%/3mm gamma passing rates less than 95%, and ten of the 19 plans had 2%/2mm passing rates less than 95%. Frequency analysis implied a non-random error process. Out of the 10 diode locations measured, ion chamber measurements were all within 2.2% error relative to the TPS and had a mean error of 1.2%. ArcCHECK measurements ranged from 4.5% to over 15% error relative to the TPS and had a mean error of 8.0%. Conclusion: The ArcCHECK performs well for quality assurance on the ViewRay under most circumstances. However, under certain conditions the absolute dose readings are significantly higher compared to the planned doses. As the ion chamber measurements consistently agree with the TPS, it can be concluded that the discrepancies are due to ArcCHECK measurement error and not TPS or delivery system error. This work was funded by the Bhudatt Paliwal Professorship and the University of Wisconsin Medical Radiation Research Center.« less

Dosimetric uncertainty in prostate cancer proton radiotherapy.

PubMed

Lin, Liyong; Vargas, Carlos; Hsi, Wen; Indelicato, Daniel; Slopsema, Roelf; Li, Zuofeng; Yeung, Daniel; Horne, Dave; Palta, Jatinder

2008-11-01

The authors we evaluate the uncertainty in proton therapy dose distribution for prostate cancer due to organ displacement, varying penumbra width of proton beams, and the amount of rectal gas inside the rectum. Proton beam treatment plans were generated for ten prostate patients with a minimum dose of 74.1 cobalt gray equivalent (CGE) to the planning target volume (PTV) while 95% of the PTV received 78 CGE. Two lateral or lateral oblique proton beams were used for each plan. The authors we investigated the uncertainty in dose to the rectal wall (RW) and the bladder wall (BW) due to organ displacement by comparing the dose-volume histograms (DVH) calculated with the original or shifted contours. The variation between DVHs was also evaluated for patients with and without rectal gas in the rectum for five patients who had 16 to 47 cc of visible rectal gas in their planning computed tomography (CT) imaging set. The uncertainty due to the varying penumbra width of the delivered protons for different beam setting options on the proton delivery system was also evaluated. For a 5 mm anterior shift, the relative change in the RW volume receiving 70 CGE dose (V70) was 37.9% (5.0% absolute change in 13.2% of a mean V70). The relative change in the BW volume receiving 70 CGE dose (V70) was 20.9% (4.3% absolute change in 20.6% of a mean V70) with a 5 mm inferior shift. A 2 mm penumbra difference in beam setting options on the proton delivery system resulted in the relative variations of 6.1% (0.8% absolute change) and 4.4% (0.9% absolute change) in V70 of RW and BW, respectively. The data show that the organ displacements produce absolute DVH changes that generally shift the entire isodose line while maintaining the same shape. The overall shape of the DVH curve for each organ is determined by the penumbra and the distance of the target in beam's eye view (BEV) from the block edge. The beam setting option producing a 2 mm sharper penumbra at the isocenter can reduce the magnitude of maximal doses to the RW by 2% compared to the alternate option utilizing the same block margin of 7 mm. The dose to 0.1 cc of the femoral head on the distal side of the lateral-posterior oblique beam is increased by 25 CGE for a patient with 25 cc of rectal gas. Variation in the rectal and bladder wall DVHs due to uncertainty in the position of the organs relative to the location of sharp dose falloff gradients should be accounted for when evaluating treatment plans. The proton beam delivery option producing a sharper penumbra reduces maximal doses to the rectal wall. Lateral-posterior oblique beams should be avoided in patients prone to develop a large amount of rectal gas.

SU-E-T-436: Fluence-Based Trajectory Optimization for Non-Coplanar VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smyth, G; Bamber, JC; Bedford, JL

2015-06-15

Purpose: To investigate a fluence-based trajectory optimization technique for non-coplanar VMAT for brain cancer. Methods: Single-arc non-coplanar VMAT trajectories were determined using a heuristic technique for five patients. Organ at risk (OAR) volume intersected during raytracing was minimized for two cases: absolute volume and the sum of relative volumes weighted by OAR importance. These trajectories and coplanar VMAT formed starting points for the fluence-based optimization method. Iterative least squares optimization was performed on control points 24° apart in gantry rotation. Optimization minimized the root-mean-square (RMS) deviation of PTV dose from the prescription (relative importance 100), maximum dose to the brainstemmore » (10), optic chiasm (5), globes (5) and optic nerves (5), plus mean dose to the lenses (5), hippocampi (3), temporal lobes (2), cochleae (1) and brain excluding other regions of interest (1). Control point couch rotations were varied in steps of up to 10° and accepted if the cost function improved. Final treatment plans were optimized with the same objectives in an in-house planning system and evaluated using a composite metric - the sum of optimization metrics weighted by importance. Results: The composite metric decreased with fluence-based optimization in 14 of the 15 plans. In the remaining case its overall value, and the PTV and OAR components, were unchanged but the balance of OAR sparing differed. PTV RMS deviation was improved in 13 cases and unchanged in two. The OAR component was reduced in 13 plans. In one case the OAR component increased but the composite metric decreased - a 4 Gy increase in OAR metrics was balanced by a reduction in PTV RMS deviation from 2.8% to 2.6%. Conclusion: Fluence-based trajectory optimization improved plan quality as defined by the composite metric. While dose differences were case specific, fluence-based optimization improved both PTV and OAR dosimetry in 80% of cases.« less

Absolute Points for Multiple Assignment Problems

ERIC Educational Resources Information Center

Adlakha, V.; Kowalski, K.

2006-01-01

An algorithm is presented to solve multiple assignment problems in which a cost is incurred only when an assignment is made at a given cell. The proposed method recursively searches for single/group absolute points to identify cells that must be loaded in any optimal solution. Unlike other methods, the first solution is the optimal solution. The…

A Signal-to-Noise Crossover Dose as the Point of Departure for Health Risk Assessment

PubMed Central

Portier, Christopher J.; Krewski, Daniel

2011-01-01

Background: The U.S. National Toxicology Program (NTP) cancer bioassay database provides an opportunity to compare both existing and new approaches to determining points of departure (PoDs) for establishing reference doses (RfDs). Objectives: The aims of this study were a) to investigate the risk associated with the traditional PoD used in human health risk assessment [the no observed adverse effect level (NOAEL)]; b) to present a new approach based on the signal-to-noise crossover dose (SNCD); and c) to compare the SNCD and SNCD-based RfD with PoDs and RfDs based on the NOAEL and benchmark dose (BMD) approaches. Methods: The complete NTP database was used as the basis for these analyses, which were performed using the Hill model. We determined NOAELs and estimated corresponding extra risks. Lower 95% confidence bounds on the BMD (BMDLs) corresponding to extra risks of 1%, 5%, and 10% (BMDL01, BMDL05, and BMDL10, respectively) were also estimated. We introduce the SNCD as a new PoD, defined as the dose where the additional risk is equal to the “background noise” (the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute risk) or a specified fraction thereof. Results: The median risk at the NOAEL was approximately 10%, and the default uncertainty factor (UF = 100) was considered most applicable to the BMDL10. Therefore, we chose a target risk of 1/1,000 (0.1/100) to derive an SNCD-based RfD by linear extrapolation. At the median, this approach provided the same RfD as the BMDL10 divided by the default UF. Conclusions: Under a standard BMD approach, the BMDL10 is considered to be the most appropriate PoD. The SNCD approach, which is based on the lowest dose at which the signal can be reliably detected, warrants further development as a PoD for human health risk assessment. PMID:21813365

[Development of external quality control protocol for CyberKnife beams dosimetry: preliminary tests multicentre].

PubMed

Guinement, L; Marchesi, V; Veres, A; Lacornerie, T; Buchheit, I; Peiffert, D

2013-01-01

To develop an external quality control procedure for CyberKnife(®) beams. This work conducted in Nancy, has included a test protocol initially drawn by the medical physicist of Nancy and Lille in collaboration with Equal-Estro Laboratory. A head and neck anthropomorphic phantom and a water-equivalent homogeneous cubic plastic test-object, so-called "MiniCube", have been used. Powder and solid thermoluminescent dosimeters as well as radiochromic films have been used to perform absolute and relative dose studies, respectively. The comparison between doses calculated by Multiplan treatment planning system and measured doses have been studied in absolute dose. The dose distributions measured with films and treatment planning system calculations have been compared via the gamma function, configured with different tolerance criteria. This work allowed, via solid thermoluminescent dosimeter measurements, verifying the beam reliability with a reproducibility of 1.7 %. The absolute dose measured in the phantom irradiated by the seven participating centres has shown an error inferior to the standard tolerance limits (± 5 %), for most of participating centres. The relative dose measurements performed at Nancy and by the Equal-Estro laboratory allowed defining the most adequate parameters for gamma index (5 %/2mm--with at least 95 % of pixels satisfying acceptability criteria: γ<1). These parameters should be independent of the film analysis software. This work allowed defining a dosimetric external quality control for CyberKnife(®) systems, based on a reproducible irradiation plan through measurements performed with thermoluminescent dosimeters and radiochromic films. This protocol should be validated by a new series of measurement and taking into account the lessons of this work. Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

SU-F-T-383: Robustness for Patient Setup Error in Total Body Irradiation Using Volumetric Modulated Arc Therapy (VMAT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Y; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Total body irradiation (TBI) and total marrow irradiation (TMI) using Tomotherapy have been reported. A gantry-based linear accelerator uses one isocenter during one rotational irradiation. Thus, 3–5 isocenter points should be used for a whole plan of TBI-VMAT during smoothing out the junctional dose distribution. IGRT provides accurate and precise patient setup for the multiple junctions, however it is evident that some setup errors should occur and affect accuracy of dose distribution in the area. In this study, we evaluated the robustness for patient’s setup error in VMAT-TBI. Methods: VMAT-TBI Planning was performed in an adult whole-body human phantommore » using Eclipse. Eight full arcs with four isocenter points using 6MV-X were used to cover the entire whole body. Dose distribution was optimized using two structures of patient’s body as PTV and lung. The two arcs were shared with one isocenter and the two arcs were 5 cm-overlapped with the other two arcs. Point absolute dose using ionization-chamber and planer relative dose distribution using film in the junctional regions were performed using water-equivalent slab phantom. In the measurements, several setup errors of (+5∼−5mm) were added. Results: The result of the chamber measurement shows the deviations were within ±3% when the setup errors were within ±3 mm. In the planer evaluation, the pass ratio of gamma evaluation (3%/2mm) shows more than 90% if the errors within ±3 mm. However, there were hot/cold areas in the edge of the junction even with acceptable gamma pass ratio. 5 mm setup error caused larger hot and cold areas and the dosimetric acceptable areas were decreased in the overlapped areas. Conclusion: It can be clinically acceptable for VMAT-TBI when patient setup error is within ±3mm. Averaging effects from patient random error would be helpful to blur the hot/cold area in the junction.« less

Ninety-day toxicity evaluation of 1,3,5-trinitrobenzene (Tnb) in Peromyscus leucopus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, T.V.; Torsella, J.; Daniel, F.B.

1995-12-31

The subchronic toxicity of TNB in P. leucopus was evaluated by feeding Certified Rodent Diet 5002 supplemented with TNB (0, 150, 375, and 750 mg of TNB/kg diet), for 90 days. The food and water consumption was not significantly different between dose groups (for either sex). The calculated average daily TNB intake for female and male P. leucopus respectively, was 0, 20, 65, 108 and 0, 23, 67, and 113 mg/kg body weight (BW). There were no differences in the absolute body weights between sexes as well as between dose groups. Similarly, the organ weights (absolute and relative) did notmore » differ significantly between the dose groups (in both sexes) with an exception of male P. leucopus group receiving 750 mg TNB diet. In this group the spleen weights, both absolute and relative (g/100 g bw), were increased significantly. A significant increase in white blood cells and reticulocytes were detected. In addition, histopathological examinations in the aforementioned dose group revealed erythroid cell hyperplasia (spleen) and seminiferous tubular degeneration (testes). Although not significant, an increase in methemoglobin levels with an increased dose was evident. When the TNB concentration in the diet was increased to 1,200 and 1,800 mg/kg (used in the range finding study), the above indicated effects were much more prominent and were seen in both sexes. From this study a NOAEL of 20 mg/day/kg for female and 23 mg/day/kg for male is suggested.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiyagarajan, Rajesh; Karrthick, KP; Kataria, Tejinder

Purpose: Performing DQA for Bilateral (B-L) breast tomotherapy is a challenging task due to the limitation of any commercially available detector array or film. Aim of this study is to perform DQA for B-L breast tomotherapy plan using MLC fluence sinogram. Methods: Treatment plan was generated on Tomotherapy system for B-L breast tumour. B-L breast targets were given 50.4 Gy prescribed over 28 fractions. Plan is generated with 6 MV photon beam & pitch was set to 0.3. As the width of the total target is 39 cm (left & right) length is 20 cm. DQA plan delivered without anymore » phantom on the mega voltage computed tomography (MCVT) detector system. The pulses recorded by MVCT system were exported to the delivery analysis software (Tomotherapy Inc.) for reconstruction. The detector signals are reconstructed to a sonogram and converted to MLC fluence sonogram. The MLC fluence sinogram compared with the planned fluence sinogram. Also point dose measured with cheese phantom and ionization chamber to verify the absolute dose component Results: Planned fluence sinogram and reconstructed MLC fluence sinogram were compared using Gamma metric. MLC positional difference and intensity of the beamlet were used as parameters to evaluate gamma. 3 mm positional difference and 3% beamlet intensity difference were used set for gamma calculation. A total of 26784 non-zero beamlets were included in the analysis out of which 161 beamlets had gamma more than 1. The gamma passing rate found to be 99.4%. Point dose measurements were within 1.3% of the calculated dose. Conclusion: MLC fluence sinogram based delivery quality assurance performed for bilateral breast irradiation. This would be a suitable alternate for large volume targets like bilateral breast, Total body irradiation etc. However conventional method of DQA should be used to validate this method periodically.« less

Involved Node, Site, Field and Residual Volume Radiotherapy for Lymphoma: A Comparison of Organ at Risk Dosimetry and Second Malignancy Risks.

PubMed

Murray, L; Sethugavalar, B; Robertshaw, H; Bayman, E; Thomas, E; Gilson, D; Prestwich, R J D

2015-07-01

Recent radiotherapy guidelines for lymphoma have included involved site radiotherapy (ISRT), involved node radiotherapy (INRT) and irradiation of residual volume after full-course chemotherapy. In the absence of late toxicity data, we aim to compare organ at risk (OAR) dose-metrics and calculated second malignancy risks. Fifteen consecutive patients who had received mediastinal radiotherapy were included. Four radiotherapy plans were generated for each patient using a parallel pair photon technique: (i) involved field radiotherapy (IFRT), (ii) ISRT, (iii) INRT, (iv) residual post-chemotherapy volume. The radiotherapy dose was 30 Gy in 15 fractions. The OARs evaluated were: breasts, lungs, thyroid, heart, oesophagus. Relative and absolute second malignancy rates were estimated using the concept of organ equivalent dose. Significance was defined as P < 0.005. Compared with ISRT, IFRT significantly increased doses to lung, thyroid, heart and oesophagus, whereas INRT and residual volume techniques significantly reduced doses to all OARs. The relative risks of second cancers were significantly higher with IFRT compared with ISRT for lung, breast and thyroid; INRT and residual volume resulted in significantly lower relative risks compared with ISRT for lung, breast and thyroid. The median excess absolute risks of second cancers were consistently lowest for the residual technique and highest for IFRT in terms of thyroid, lung and breast cancers. The risk of oesophageal cancer was similar for all four techniques. Overall, the absolute risk of second cancers was very similar for ISRT and INRT. Decreasing treatment volumes from IFRT to ISRT, INRT or residual volume reduces radiation exposure to OARs. Second malignancy modelling suggests that this reduction in treatment volumes will lead to a reduction in absolute excess second malignancy. Little difference was observed in second malignancy risks between ISRT and INRT, supporting the use of ISRT in the absence of a pre-chemotherapy positron emission tomography scan in the radiotherapy treatment position. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Absolute dose calculations for Monte Carlo simulations of radiotherapy beams

NASA Astrophysics Data System (ADS)

Popescu, I. A.; Shaw, C. P.; Zavgorodni, S. F.; Beckham, W. A.

2005-07-01

Monte Carlo (MC) simulations have traditionally been used for single field relative comparisons with experimental data or commercial treatment planning systems (TPS). However, clinical treatment plans commonly involve more than one field. Since the contribution of each field must be accurately quantified, multiple field MC simulations are only possible by employing absolute dosimetry. Therefore, we have developed a rigorous calibration method that allows the incorporation of monitor units (MU) in MC simulations. This absolute dosimetry formalism can be easily implemented by any BEAMnrc/DOSXYZnrc user, and applies to any configuration of open and blocked fields, including intensity-modulated radiation therapy (IMRT) plans. Our approach involves the relationship between the dose scored in the monitor ionization chamber of a radiotherapy linear accelerator (linac), the number of initial particles incident on the target, and the field size. We found that for a 10 × 10 cm2 field of a 6 MV photon beam, 1 MU corresponds, in our model, to 8.129 × 1013 ± 1.0% electrons incident on the target and a total dose of 20.87 cGy ± 1.0% in the monitor chambers of the virtual linac. We present an extensive experimental verification of our MC results for open and intensity-modulated fields, including a dynamic 7-field IMRT plan simulated on the CT data sets of a cylindrical phantom and of a Rando anthropomorphic phantom, which were validated by measurements using ionization chambers and thermoluminescent dosimeters (TLD). Our simulation results are in excellent agreement with experiment, with percentage differences of less than 2%, in general, demonstrating the accuracy of our Monte Carlo absolute dose calculations.

Analysis of the sources of uncertainty for EDR2 film‐based IMRT quality assurance

PubMed Central

Shi, Chengyu; Papanikolaou, Nikos; Yan, Yulong; Weng, Xuejun; Jiang, gyu

2006-01-01

In our institution, patient‐specific quality assurance (QA) for intensity‐modulated radiation therapy (IMRT) is usually performed by measuring the dose to a point using an ion chamber and by measuring the dose to a plane using film. In order to perform absolute dose comparison measurements using film, an accurate calibration curve should be used. In this paper, we investigate the film response curve uncertainty factors, including film batch differences, film processor temperature effect, film digitization, and treatment unit. In addition, we reviewed 50 patient‐specific IMRT QA procedures performed in our institution in order to quantify the sources of error in film‐based dosimetry. Our study showed that the EDR2 film dosimetry can be done with less than 3% uncertainty. The EDR2 film response was not affected by the choice of treatment unit provided the nominal energy was the same. This investigation of the different sources of uncertainties in the film calibration procedure can provide a better understanding of the film‐based dosimetry and can improve quality control for IMRT QA. PACS numbers: 87.86.Cd, 87.53.Xd, 87.57.Nk PMID:17533329

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acar, Hilal; Chiu-Tsao, Sou-Tung; Oezbay, Ismail

Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eyemore » plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.« less

IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases.

PubMed

Wen, Ning; Zhao, Bo; Kim, Jinkoo; Chin-Snyder, Karen; Bellon, Maria; Glide-Hurst, Carri; Barton, Kenneth; Chen, Daiquan; Chetty, Indrin J

2014-09-08

The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

Estimate of the risk of radiation-induced cancers after linear-accelerator-based breast-cancer radiotherapy

NASA Astrophysics Data System (ADS)

Koh, Eui Kwan; Seo, Jungju; Baek, Tae Seong; Chung, Eun Ji; Yoon, Myonggeun; Lee, Hyun-ho

2013-07-01

The aim of this study is to assess and compare the excess absolute risks (EARs) of radiation-induced cancers following conformal (3D-CRT), fixed-field intensity-modulated (IMRT) and volumetric modulated arc (RapidArc) radiation therapy in patients with breast cancer. 3D-CRT, IMRT and RapidArc were planned for 10 breast cancer patients. The organ-specific EAR for cancer induction was estimated using the organ equivalent dose (OED) based on computed dose volume histograms (DVHs) and the secondary doses measured at various points from the field edge. The average secondary dose per Gy treatment dose from 3D-CRT, measured 10 to 50 cm from the field edge, ranged from 8.27 to 1.04 mGy. The secondary doses per Gy from IMRT and RapidArc, however, ranged between 5.86 and 0.54 mGy, indicating that IMRT and RapidArc are associated with smaller doses of secondary radiation than 3D-CRT. The organ specific EARs for out-of-field organs, such as the thyroid, liver and colon, were higher with 3D-CRT than with IMRT or RapidArc. In contrast, EARs for in-field organs were much lower with 3D-CRT than with IMRT or RapidArc. The overall estimate of EAR indicated that the radiation-induced cancer risk was 1.8-2.0 times lower with 3D-CRT than with IMRT or RapidArc. Comparisons of EARs during breast irradiation suggested that the predicted risk of secondary cancers was lower with 3D-CRT than with IMRT or RapidArc.

Altered mental status in older adults with histamine2-receptor antagonists: a population-based study.

PubMed

Tawadrous, Davy; Dixon, Stephanie; Shariff, Salimah Z; Fleet, Jamie; Gandhi, Sonja; Jain, Arsh K; Weir, Matthew A; Gomes, Tara; Garg, Amit X

2014-10-01

Standard doses of histamine2-receptor antagonists (H2RAs) may induce altered mental status in older adults, especially in those with chronic kidney disease (CKD). Population-based cohort study of older adults who started a new H2RA between 2002 and 2011 was conducted. Ninety percent received the current standard H2RA dose in routine care. There was no significant difference in 27 baseline patient characteristics. The primary outcome was hospitalization with an urgent head computed tomography (CT) scan (proxy for altered mental status), and the secondary outcome was all-cause mortality also within 30days of a new H2RA prescription. Standard vs. low H2RA dose was associated with a higher risk of hospitalization with an urgent head CT scan (0.98% vs. 0.74%, absolute risk difference 0.24% [95% CI 0.11% to 0.36%], relative risk 1.33 [95% CI 1.12 to 1.58]). This risk was not modified by the presence of CKD (interaction P value=0.71). Standard vs. low H2RA dose was associated with a higher risk of mortality (1.07% vs.0.74%; absolute risk difference 0.34% [95% CI 0.20% to 0.46%], relative risk 1.46 [95% CI 1.23 to 1.73]). Compared to a lower dose, initiation of the current standard dose of H2RA in older adults is associated with a small absolute increase in the 30-day risk of altered mental status (using neuroimaging as a proxy), even in the absence of CKD. This risk may be avoided by initiating older adults on low doses of H2RAs for gastroesophogeal reflux disease, and increasing dosing as necessary for symptom control. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

75 FR 30370 - Certain Coated Paper Suitable For High-Quality Print Graphics Using Sheet-Fed Presses from the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

...) a change of at least five absolute percentage points in, but not less than 25 percent of, the... between a countervailable subsidy rate of zero (or de minimis) and a countervailable subsidy rate of... absolute points and not less than 25 percent of the originally calculated margin. Thus, the ministerial...

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 03: Energy dependence of a clinical probe-format calorimeter and its pertinence to absolute photon and electron beam dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, James; Seuntjens, Jan; Sarfehnia, Arman

Purpose: To evaluate the intrinsic and absorbed-dose energy dependence of a small-scale graphite calorimeter probe (GPC) developed for use as a routine clinical dosimeter. The influence of charge deposition on the response of the GPC was also assessed by performing absolute dosimetry in clinical linac-based electron beams. Methods: Intrinsic energy dependence was determined by performing constant-temperature calorimetry dose measurements in a water-equivalent solid phantom, under otherwise reference conditions, in five high-energy photon (63.5 < %dd(10){sub X} < 76.3), and five electron (2.3 cm < R{sub 50} < 8.3 cm) beams. Reference dosimetry was performed for all beams in question usingmore » an Exradin A19 ion chamber with a calibration traceable to national standards. The absorbed-dose component of the overall energy dependence was calculated using the EGSnrc egs-chamber user code. Results: A total of 72 measurements were performed with the GPC, resulting in a standard error on the mean absorbed dose of better than 0.3 % for all ten beams. For both the photon and electron beams, no statistically-significant energy dependence was observed experimentally. Peak-to-peak, variations in the relative response of the GPC across all beam qualities of a given radiation type were on the order of 1 %. No effects, either transient or permanent, were attributable to the charge deposited by the electron beams. Conclusions: The GPC’s apparent energy-independence, combined with its well-established linearity and dose rate independence, make it a potentially useful dosimetry system capable measuring photon and electron doses in absolute terms at the clinical level.« less

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

PubMed

He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Reproducibility of Blood Acid Base Responses in Male Collegiate Athletes Following Individualised Doses of Sodium Bicarbonate: A Randomised Controlled Crossover Study.

PubMed

Gough, Lewis A; Deb, Sanjoy K; Sparks, Andy S; McNaughton, Lars R

2017-10-01

Current evidence suggests sodium bicarbonate (NaHCO 3 ) should be ingested based upon the individualised alkalotic peak of either blood pH or bicarbonate (HCO 3 - ) because of large inter-individual variations (10-180 min). If such a strategy is to be practical, the blood analyte response needs to be reproducible. This study aimed to evaluate the degree of reproducibility of both time to peak (TTP) and absolute change in blood pH, HCO 3 - and sodium (Na + ) following acute NaHCO 3 ingestion. Male participants (n = 15) with backgrounds in rugby, football or sprinting completed six randomised treatments entailing ingestion of two doses of 0.2 g·kg -1 body mass (BM) NaHCO 3 (SBC2a and b), two doses of 0.3 g·kg -1 BM NaHCO 3 (SBC3a and b) or two control treatments (CON1a and b) on separate days. Blood analysis included pH, HCO 3 - and Na + prior to and at regular time points following NaHCO 3 ingestion over a 3-h period. HCO 3 - displayed greater reproducibility than pH in intraclass correlation coefficient (ICC) analysis for both TTP (HCO 3 - SBC2 r = 0.77, P = 0.003; SBC3 r = 0.94, P < 0.001; pH SBC2 r = 0.62, P = 0.044; SBC3 r = 0.71, P = 0.016) and absolute change (HCO 3 - SBC2 r = 0.89, P < 0.001; SBC3 r = 0.76, P = 0.008; pH SBC2 r = 0.84, P = 0.001; SBC3 r = 0.62, P = 0.041). Our results indicate that both TTP and absolute change in HCO 3 - is more reliable than pH. As such, these data provide support for an individualised NaHCO 3 ingestion strategy to consistently elicit peak alkalosis before exercise. Future work should utilise an individualised NaHCO 3 ingestion strategy based on HCO 3 - responses and evaluate effects on exercise performance.

Effects of extended-release niacin with laropiprant in high-risk patients.

PubMed

Landray, Martin J; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Aung, Theingi; Tomson, Joseph; Wallendszus, Karl; Craig, Martin; Jiang, Lixin; Collins, Rory; Armitage, Jane

2014-07-17

Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain. After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization). During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001). Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).

Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

PubMed Central

Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

2014-01-01

The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study.

PubMed

Collaku, Agron; Yue, Yong; Reed, Kenneth

2017-01-01

Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0=not present to 10=unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed.

Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

PubMed Central

Collaku, Agron; Yue, Yong; Reed, Kenneth

2017-01-01

Background/objective Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0=not present to 10=unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. Results A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Conclusion Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed. PMID:28356767

In vitro permeation and disposition of niacinamide in silicone and porcine skin of skin barrier-mimetic formulations.

PubMed

Haque, Tasnuva; Lane, Majella E; Sil, Bruno C; Crowther, Jonathan M; Moore, David J

2017-03-30

Niacinamide (NIA) is an amide form of vitamin B3 which is used in cosmetic formulations to improve various skin conditions and it has also been shown to increase stratum corneum thickness following repeated application. In this study, three doses (5, 20 and 50μL per cm 2 ) of two NIA containing oil-in-water skin barrier-mimetic formulations were evaluated in silicone membrane and porcine ear skin and compared with a commercial control formulation. Permeation studies were conducted over 24h in Franz cells and at the end of the experiment membranes were washed and niacinamide was extracted. For the three doses, retention or deposition of NIA was generally higher in porcine skin compared with silicone membrane, consistent with the hydrophilic nature of the active. Despite the control containing a higher amount of active, comparable amounts of NIA were deposited in skin for all formulations for all doses; total skin absorption values (permeation and retention) of NIA were also comparable across all formulations. For infinite (50μL) and finite (5μL) doses the absolute permeation of NIA from the control formulation was significantly higher in porcine skin compared with both test formulations. This likely reflects differences in formulation components and/or presence of skin penetration enhancers in the formulations. Higher permeation for the 50 and 20μL dose was also evident in porcine skin compared with silicone membrane but the opposite is the case for the finite dose. The findings point to the critical importance of dose and occlusion when evaluating topical formulations in vitro and also the likelihood of exaggerated effects of excipients on permeation at infinite and pseudo-finite dose applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Cross-species prediction of human survival probabilities for accelerated anthrax vaccine absorbed (AVA) regimens and the potential for vaccine and antibiotic dose sparing.

PubMed

Stark, G V; Sivko, G S; VanRaden, M; Schiffer, J; Taylor, K L; Hewitt, J A; Quinn, C P; Nuzum, E O

2016-12-12

Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2weeks) aerosol challenged with high levels of B. anthracis spores at week4- the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Absolute Bioavailability of Osimertinib in Healthy Adults.

PubMed

Vishwanathan, Karthick; So, Karen; Thomas, Karen; Bramley, Alex; English, Stephen; Collier, Jo

2018-04-23

Osimertinib is a third-generation, central nervous system-active, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) selective for EGFR-TKI sensitizing and T790M resistance mutations. This phase 1, open-label study (NCT02491944) investigated absolute bioavailability and pharmacokinetics (PK) of oral and intravenous (IV) osimertinib. Ten healthy subjects (21-61 years) received a single oral 80-mg dose concomitantly with a 100 μg (containing 1 μCi) IV microtracer dose of [ 14 C]osimertinib. Oral and IV PK were determined simultaneously for osimertinib and its active metabolites, AZ5104 and AZ7550. High-performance liquid chromatography and accelerator mass spectrometry were used to characterize IV dose PK. Geometric mean absolute oral bioavailability of osimertinib was 69.8% (90% confidence interval, 66.7, 72.9). Oral osimertinib was slowly absorbed (median time to maximum plasma concentration [t max ] 7.0 hours). Following t max , plasma concentrations fell in an apparent monophasic manner. IV clearance and volume of distribution were 16.8 L/h and 1285 L, respectively. Arithmetic mean elimination half-life estimates were 59.7, 52.6, and 72.6 hours for osimertinib, AZ5104, and AZ7550, respectively (oral dosing), and 54.9, 68.4, and 99.7 hours for [ 14 C]osimertinib, [ 14 C]AZ5104, and [ 14 C]AZ7550, respectively (IV dosing). Oral osimertinib was well absorbed. Simultaneous IV and oral PK analysis proved useful for complete understanding of osimertinib PK and showed that the first-pass effect was minimal for osimertinib. © 2018, The American College of Clinical Pharmacology.

Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects.

PubMed

Morcos, Peter N; Yu, Li; Bogman, Katrijn; Sato, Mika; Katsuki, Hisakazu; Kawashima, Kosuke; Moore, David J; Whayman, Matt; Nieforth, Keith; Heinig, Katja; Guerini, Elena; Muri, Dieter; Martin-Facklam, Meret; Phipps, Alex

2017-03-01

1. Alectinib is a highly selective, central nervous system-active small molecule anaplastic lymphoma kinase inhibitor. 2. The absolute bioavailability, metabolism, excretion and pharmacokinetics of alectinib were studied in a two-period single-sequence crossover study. A 50 μg radiolabelled intravenous microdose of alectinib was co-administered with a single 600 mg oral dose of alectinib in the first period, and a single 600 mg/67 μCi oral dose of radiolabelled alectinib was administered in the second period to six healthy male subjects. 3. The absolute bioavailability of alectinib was moderate at 36.9%. Geometric mean clearance was 34.5 L/h, volume of distribution was 475 L and the hepatic extraction ratio was low (0.14). 4. Near-complete recovery of administered radioactivity was achieved within 168 h post-dose (98.2%) with excretion predominantly in faeces (97.8%) and negligible excretion in urine (0.456%). Alectinib and its major active metabolite, M4, were the main components in plasma, accounting for 76% of total plasma radioactivity. In faeces, 84% of dose was excreted as unchanged alectinib with metabolites M4, M1a/b and M6 contributing to 5.8%, 7.2% and 0.2% of dose, respectively. 5. This novel study design characterised the full absorption, distribution, metabolism and excretion properties in each subject, providing insight into alectinib absorption and disposition in humans.

The protoelectric potential map (PPM): an absolute two-dimensional chemical potential scale for a global understanding of chemistry.

PubMed

Radtke, Valentin; Himmel, Daniel; Pütz, Katharina; Goll, Sascha K; Krossing, Ingo

2014-04-07

We introduce the protoelectric potential map (PPM) as a novel, two-dimensional plot of the absolute reduction potential (peabs scale) combined with the absolute protochemical potential (Brønsted acidity: pHabs scale). The validity of this thermodynamically derived PPM is solvent-independent due to the scale zero points, which were chosen as the ideal electron gas and the ideal proton gas at standard conditions. To tie a chemical environment to these reference states, the standard Gibbs energies for the transfer of the gaseous electrons/protons to the medium are needed as anchor points. Thereby, the thermodynamics of any redox, acid-base or combined system in any medium can be related to any other, resulting in a predictability of reactions even over different media or phase boundaries. Instruction is given on how to construct the PPM from the anchor points derived and tabulated with this work. Since efforts to establish "absolute" reduction potential scales and also "absolute" pH scales already exist, a short review in this field is given and brought into relation to the PPM. Some comments on the electrochemical validation and realization conclude this concept article. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SU-E-T-365: Dosimetric Impact of Dental Amalgam CT Image Artifacts On IMRT and VMAT Head and Neck Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, N; Young, L; Parvathaneni, U

Purpose: The presence of high density dental amalgam in patient CT image data sets causes dose calculation errors for head and neck (HN) treatment planning. This study assesses and compares dosimetric variations in IMRT and VMAT treatment plans due to dental artifacts. Methods: Sixteen HN patients with similar treatment sites (oropharynx), tumor volume and extensive dental artifacts were divided into two groups: IMRT (n=8, 6 to 9 beams) and VMAT (n=8, 2 arcs with 352° rotation). All cases were planned with the Pinnacle 9.2 treatment planning software using the collapsed cone convolution superposition algorithm and a range of prescription dosemore » from 60 to 72Gy. Two different treatment plans were produced, each based on one of two image sets: (a)uncorrected; (b)dental artifacts density overridden (set to 1.0g/cm{sup 3}). Differences between the two treatment plans for each of the IMRT and VMAT techniques were quantified by the following dosimetric parameters: maximum point dose, maximum spinal cord and brainstem dose, mean left and right parotid dose, and PTV coverage (V95%Rx). Average differences generated for these dosimetric parameters were compared between IMRT and VMAT plans. Results: The average absolute dose differences (plan a minus plan b) for the VMAT and IMRT techniques, respectively, caused by dental artifacts were: 2.2±3.3cGy vs. 37.6±57.5cGy (maximum point dose, P=0.15); 1.2±0.9cGy vs. 7.9±6.7cGy (maximum spinal cord dose, P=0.026); 2.2±2.4cGy vs. 12.1±13.0cGy (maximum brainstem dose, P=0.077); 0.9±1.1cGy vs. 4.1±3.5cGy (mean left parotid dose, P=0.038); 0.9±0.8cGy vs. 7.8±11.9cGy (mean right parotid dose, P=0.136); 0.021%±0.014% vs. 0.803%±1.44% (PTV coverage, P=0.17). Conclusion: For the HN plans studied, dental artifacts demonstrated a greater dose calculation error for IMRT plans compared to VMAT plans. Rotational arcs appear on the average to compensate dose calculation errors induced by dental artifacts. Thus, compared to VMAT, density overrides for dental artifacts are more important when planning IMRT of HN.« less

Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam photon and proton dosimetry

NASA Astrophysics Data System (ADS)

Kuess, Peter; Böhlen, Till T.; Lechner, Wolfgang; Elia, Alessio; Georg, Dietmar; Palmans, Hugo

2017-12-01

Large area ionization chambers (LAICs) can be used to measure output factors of narrow beams. Dose area product measurements are proposed as an alternative to central-axis point dose measurements. Using such detectors requires detailed information on the uniformity of the response along the sensitive area. Eight LAICs were investigated in this study: four of type PTW-34070 (LAICThick) and four of type PTW-34080 (LAICThin). Measurements were performed in an x-ray unit using peak voltages of 100-200 kVp and a collimated beam of 3.1 mm (FWHM). The LAICs were moved with a step size of 5 mm to measure the chamber response at lateral positions. To account for beam positions where only a fraction of the beam impinged within the sensitive area of the LAICs, a corrected response was calculated which was the basis to calculate the relative response. The impact of a heterogeneous LAIC response, based on the obtained response maps was henceforth investigated for proton pencil beams and small field photon beams. A pronounced heterogeneity of the responses was observed in the investigated LAICs. The response of LAICThick generally decreased with increasing radius, resulting in a response correction of up to 5%. This correction was more pronounced and more diverse (up to 10%) for LAICThin. Considering a proton pencil beam the systematic offset for reference dosimetry was 2.4-4.1% for LAICThick and  -9.5 to 9.4% for LAICThin. For relative dosimetry (e.g. integral depth-dose curves) systematic response variation by 0.8-1.9% were found. For a decreasing photon field size the systematic offset for absolute dose measurements showed a 2.5-4.5% overestimation of the response for 6  ×  6 mm2 field sizes for LAICThick. For LAICThin the response varied even over a range of 20%. This study highlights the need for chamber-dependent response maps when using LAICs for absolute and relative dosimetry with proton pencil beams or small photon beams.

Limited Sampling Strategy for Accurate Prediction of Pharmacokinetics of Saroglitazar: A 3-point Linear Regression Model Development and Successful Prediction of Human Exposure.

PubMed

Joshi, Shuchi N; Srinivas, Nuggehally R; Parmar, Deven V

2018-03-01

Our aim was to develop and validate the extrapolative performance of a regression model using a limited sampling strategy for accurate estimation of the area under the plasma concentration versus time curve for saroglitazar. Healthy subject pharmacokinetic data from a well-powered food-effect study (fasted vs fed treatments; n = 50) was used in this work. The first 25 subjects' serial plasma concentration data up to 72 hours and corresponding AUC 0-t (ie, 72 hours) from the fasting group comprised a training dataset to develop the limited sampling model. The internal datasets for prediction included the remaining 25 subjects from the fasting group and all 50 subjects from the fed condition of the same study. The external datasets included pharmacokinetic data for saroglitazar from previous single-dose clinical studies. Limited sampling models were composed of 1-, 2-, and 3-concentration-time points' correlation with AUC 0-t of saroglitazar. Only models with regression coefficients (R 2 ) >0.90 were screened for further evaluation. The best R 2 model was validated for its utility based on mean prediction error, mean absolute prediction error, and root mean square error. Both correlations between predicted and observed AUC 0-t of saroglitazar and verification of precision and bias using Bland-Altman plot were carried out. None of the evaluated 1- and 2-concentration-time points models achieved R 2 > 0.90. Among the various 3-concentration-time points models, only 4 equations passed the predefined criterion of R 2 > 0.90. Limited sampling models with time points 0.5, 2, and 8 hours (R 2 = 0.9323) and 0.75, 2, and 8 hours (R 2 = 0.9375) were validated. Mean prediction error, mean absolute prediction error, and root mean square error were <30% (predefined criterion) and correlation (r) was at least 0.7950 for the consolidated internal and external datasets of 102 healthy subjects for the AUC 0-t prediction of saroglitazar. The same models, when applied to the AUC 0-t prediction of saroglitazar sulfoxide, showed mean prediction error, mean absolute prediction error, and root mean square error <30% and correlation (r) was at least 0.9339 in the same pool of healthy subjects. A 3-concentration-time points limited sampling model predicts the exposure of saroglitazar (ie, AUC 0-t ) within predefined acceptable bias and imprecision limit. Same model was also used to predict AUC 0-∞ . The same limited sampling model was found to predict the exposure of saroglitazar sulfoxide within predefined criteria. This model can find utility during late-phase clinical development of saroglitazar in the patient population. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

PubMed

Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

1993-01-01

The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

Mind and body therapy for fibromyalgia.

PubMed

Theadom, Alice; Cropley, Mark; Smith, Helen E; Feigin, Valery L; McPherson, Kathryn

2015-04-09

Mind-body interventions are based on the holistic principle that mind, body and behaviour are all interconnected. Mind-body interventions incorporate strategies that are thought to improve psychological and physical well-being, aim to allow patients to take an active role in their treatment, and promote people's ability to cope. Mind-body interventions are widely used by people with fibromyalgia to help manage their symptoms and improve well-being. Examples of mind-body therapies include psychological therapies, biofeedback, mindfulness, movement therapies and relaxation strategies. To review the benefits and harms of mind-body therapies in comparison to standard care and attention placebo control groups for adults with fibromyalgia, post-intervention and at three and six month follow-up. Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), AMED (EBSCO) and CINAHL (Ovid) were conducted up to 30 October 2013. Searches of reference lists were conducted and authors in the field were contacted to identify additional relevant articles. All relevant randomised controlled trials (RCTs) of mind-body interventions for adults with fibromyalgia were included. Two authors independently selected studies, extracted the data and assessed trials for low, unclear or high risk of bias. Any discrepancy was resolved through discussion and consensus. Continuous outcomes were analysed using mean difference (MD) where the same outcome measure and scoring method was used and standardised mean difference (SMD) where different outcome measures were used. For binary data standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was used. Seventy-four papers describing 61 trials were identified, with 4234 predominantly female participants. The nature of fibromyalgia varied from mild to severe across the study populations. Twenty-six studies were classified as having a low risk of bias for all domains assessed. The findings of mind-body therapies compared with usual care were prioritised.There is low quality evidence that in comparison to usual care controls psychological therapies have favourable effects on physical functioning (SMD -0.4, 95% CI -0.6 to -0.3, -7.5% absolute change, 2 point shift on a 0 to 100 scale), pain (SMD -0.3, 95% CI -0.5 to -0.2, -3.5% absolute change, 2 point shift on a 0 to 100 scale) and mood (SMD -0.5, 95% CI -0.6 to -0.3, -4.8% absolute change, 3 point shift on a 20 to 80 scale). There is very low quality evidence of more withdrawals in the psychological therapy group in comparison to usual care controls (RR 1.38, 95% CI 1.12 to 1.69, 6% absolute risk difference). There is lack of evidence of a difference between the number of adverse events in the psychological therapy and control groups (RR 0.38, 95% CI 0.06 to 2.50, 4% absolute risk difference).There was very low quality evidence that biofeedback in comparison to usual care controls had an effect on physical functioning (SMD -0.1, 95% CI -0.4 to 0.3, -1.2% absolute change, 1 point shift on a 0 to 100 scale), pain (SMD -2.6, 95% CI -91.3 to 86.1, -2.6% absolute change) and mood (SMD 0.1, 95% CI -0.3 to 0.5, 1.9% absolute change, less than 1 point shift on a 0 to 90 scale) post-intervention. In view of the quality of evidence we cannot be certain that biofeedback has a little or no effect on these outcomes. There was very low quality evidence that biofeedback led to more withdrawals from the study (RR 4.08, 95% CI 1.43 to 11.62, 20% absolute risk difference). No adverse events were reported.There was no advantage observed for mindfulness in comparison to usual care for physical functioning (SMD -0.3, 95% CI -0.6 to 0.1, -4.8% absolute change, 4 point shift on a scale 0 to 100), pain (SMD -0.1, CI -0.4 to 0.3, -1.3% absolute change, less than 1 point shift on a 0 to 10 scale), mood (SMD -0.2, 95% CI -0.5 to 0.0, -3.7% absolute change, 2 point shift on a 20 to 80 scale) or withdrawals (RR 1.07, 95% CI 0.67 to 1.72, 2% absolute risk difference) between the two groups post-intervention. However, the quality of the evidence was very low for pain and moderate for mood and number of withdrawals. No studies reported any adverse events.Very low quality evidence revealed that movement therapies in comparison to usual care controls improved pain (MD -2.3, CI -4.2 to -0.4, -23% absolute change) and mood (MD -9.8, 95% CI -18.5 to -1.2, -16.4% absolute change) post-intervention. There was no advantage for physical functioning (SMD -0.2, 95% CI -0.5 to 0.2, -3.4% absolute change, 2 point shift on a 0 to 100 scale), participant withdrawals (RR 1.95, 95% CI 1.13 to 3.38, 11% absolute difference) or adverse events (RR 4.62, 95% CI 0.23 to 93.92, 4% absolute risk difference) between the two groups, however rare adverse events may include worsening of pain.Low quality evidence revealed that relaxation based therapies in comparison to usual care controls showed an advantage for physical functioning (MD -8.3, 95% CI -10.1 to -6.5, -10.4% absolute change) and pain (SMD -1.0, 95% CI -1.6 to -0.5, -3.5% absolute change, 2 point shift on a 0 to 78 scale) but not for mood (SMD -4.4, CI -14.5 to 5.6, -7.4% absolute change) post-intervention. There was no difference between the groups for number of withdrawals (RR 4.40, 95% CI 0.59 to 33.07, 31% absolute risk difference) and no adverse events were reported. Psychological interventions therapies may be effective in improving physical functioning, pain and low mood for adults with fibromyalgia in comparison to usual care controls but the quality of the evidence is low. Further research on the outcomes of therapies is needed to determine if positive effects identified post-intervention are sustained. The effectiveness of biofeedback, mindfulness, movement therapies and relaxation based therapies remains unclear as the quality of the evidence was very low or low. The small number of trials and inconsistency in the use of outcome measures across the trials restricted the analysis.

TU-D-201-05: Validation of Treatment Planning Dose Calculations: Experience Working with MPPG 5.a

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, J; Park, J; Kim, L

2016-06-15

Purpose: Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a. Methods: In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommendedmore » by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom. Results: Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results. Conclusion: The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.« less

40 CFR 92.105 - General equipment specifications.

Code of Federal Regulations, 2011 CFR

2011-07-01

... accuracy and precision of 0.1 percent of absolute pressure at point or better. (2) Gauges and transducers used to measure any other pressures shall have an accuracy and precision of 1 percent of absolute...

Estimation of rhG-CSF absorption kinetics after subcutaneous administration using a modified Wagner-Nelson method with a nonlinear elimination model.

PubMed

Hayashi, N; Aso, H; Higashida, M; Kinoshita, H; Ohdo, S; Yukawa, E; Higuchi, S

2001-05-01

The clearance of recombinant human granulocyte-colony stimulating factor (rhG-CSF) is known to decrease with dose increase, and to be saturable. The average clearance after intravenous administration will be lower than that after subcutaneous administration. Therefore, the apparent absolute bioavailability with subcutaneous administration calculated from the AUC ratio is expected to be an underestimate. The absorption pharmacokinetics after subcutaneous administration was examined using the results of the bioequivalency study between two rhG-CSF formulations with a dose of 2 microg/kg. The analysis was performed using a modified Wagner-Nelson method with the nonlinear elimination model. The apparent absolute bioavailability for subcutaneous administration was 56.9 and 67.5% for each formulation, and the ratio between them was approximately 120%. The true absolute bioavailability was, however, estimated to be 89.8 and 96.9%, respectively, and the ratio was approximately 108%. The absorption pattern was applied to other doses, and the predicted clearance values for subcutaneous and intravenous administrations were then similar to the values for several doses reported in the literature. The underestimation of bioavailability was around 30%, and the amplification of difference was 2.5 times, from 8 to 20%, because of the nonlinear pharmacokinetics. The neutrophil increases for each formulation were identical, despite the different bioavailabilities. The reason for this is probably that the amount eliminated through the saturable process, which might indicate the amount consumed by the G-CSF receptor, was identical for each formulation.

A cumulative dose comparison between salbutamol and fenoterol metered dose aerosols in asthmatic patients.

PubMed Central

Bellamy, D.; Penketh, A.

1987-01-01

The potency and side effects of salbutamol and fenoterol inhalers have been compared in 8 asthmatic patients using a dose response curve. There was no significant difference in the absolute or percentage increase in FEV1 with the two treatments, but fenoterol caused a significantly greater (P less than 0.01) increase in heart rate than did salbutamol. A greater degree of bronchodilatation was observed with increased doses and we suggest that regular higher doses may provide better bronchodilatation and control of asthma in selected patients. PMID:3432172

Study of Fricke-gel dosimeter calibration for attaining precise measurements of the absorbed dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liosi, Giulia Maria; Benedini, Sara; Giacobbo, Francesca

2015-07-01

A method has been studied for attaining, with good precision, absolute measurements of the spatial distribution of the absorbed dose by means of the Fricke gelatin Xylenol Orange dosimetric system. With this aim, the dose response to subsequent irradiations was analyzed. In fact, the proposed modality is based on a pre-irradiation of each single dosimeter in a uniform field with a known dose, in order to extrapolate a calibration image for a subsequent non-uniform irradiation with an un-known dose to be measured. (authors)

Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal

PubMed Central

van Gorp, Freek; Duffull, Stephen; Hackett, L Peter; Isbister, Geoffrey K

2012-01-01

AIMS To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). METHODS The data set included 78 escitalopram overdose events (median dose, 140 mg [10–560 mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. RESULTS A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUCi/dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (α = 0.35). The heart rate corrected QT interval (QTc) was linearly dependent on predicted escitalopram concentration [slope = 87 ms/(mg l–1)], using a hypothetical effect-compartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200 mg. CONCLUSIONS There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal. PMID:21883384

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PubMed

Ahamed, Shabbir; Singh, Navin; Gudipudi, Deleep; Mulinti, Suneetha; Talluri, Anil; Soubhagya, Bhudevi; Sresty, Madhusudhana

2017-03-01

To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Using lean to improve medication administration safety: in search of the "perfect dose".

PubMed

Ching, Joan M; Long, Christina; Williams, Barbara L; Blackmore, C Craig

2013-05-01

At Virginia Mason Medical Center (Seattle), the Collaborative Alliance for Nursing Outcomes (CALNOC) Medication Administration Accuracy Quality Study was used in combination with Lean quality improvement efforts to address medication administration safety. Lean interventions were targeted at improving the medication room layout, applying visual controls, and implementing nursing standard work. The interventions were designed to prevent medication administration errors through improving six safe practices: (1) comparing medication with medication administration record, (2) labeling medication, (3) checking two forms of patient identification, (4) explaining medication to patient, (5) charting medication immediately, and (6) protecting the process from distractions/interruptions. Trained nurse auditors observed 9,244 doses for 2,139 patients. Following the intervention, the number of safe-practice violations decreased from 83 violations/100 doses at baseline (January 2010-March 2010) to 42 violations/100 doses at final follow-up (July 2011-September 2011), resulting in an absolute risk reduction of 42 violations/100 doses (95% confidence interval [CI]: 35-48), p < .001). The number of medication administration errors decreased from 10.3 errors/100 doses at baseline to 2.8 errors/100 doses at final follow-up (absolute risk reduction: 7 violations/100 doses [95% CI: 5-10, p < .001]). The "perfect dose" score, reflecting compliance with all six safe practices and absence of any of the eight medication administration errors, improved from 37 in compliance/100 doses at baseline to 68 in compliance/100 doses at the final follow-up. Lean process improvements coupled with direct observation can contribute to substantial decreases in errors in nursing medication administration.

Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.

PubMed

Sandborn, William J; Rutgeerts, Paul; Enns, Robert; Hanauer, Stephen B; Colombel, Jean-Frédéric; Panaccione, Remo; D'Haens, Geert; Li, Ju; Rosenfeld, Marie R; Kent, Jeffrey D; Pollack, Paul F

2007-06-19

Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). 52 sites in the United States, Canada, and Europe. 325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points). Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection. The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or long-term immunogenicity of adalimumab. Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy. For more information on adalimumab in Crohn disease, click here. ClinicalTrials.gov registration number: NCT00105300.

SU-F-T-472: Validation of Absolute Dose Measurements for MR-IGRT With and Without Magnetic Field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, O; Li, H; Goddu, S

Purpose: To validate absolute dose measurements for a MR-IGRT system without presence of the magnetic field. Methods: The standard method (AAPM’s TG-51) of absolute dose measurement with ionization chambers was tested with and without the presence of the magnetic field for a clinical 0.32-T Co-60 MR-IGRT system. Two ionization chambers were used - the Standard Imaging (Madison, WI) A18 (0.123 cc) and the PTW (Freiburg, Germany). A previously reported Monte Carlo simulation suggested a difference on the order of 0.5% for dose measured with and without the presence of the magnetic field, but testing this was not possible until anmore » engineering solution to allow the radiation system to be used without the nominal magnetic field was found. A previously identified effect of orientation in the magnetic field was also tested by placing the chamber either parallel or perpendicular to the field and irradiating from two opposing angles (90 and 270). Finally, the Imaging and Radiation Oncology Core provided OSLD detectors for five irradiations each with and without the field - with two heads at both 0 and 90 degrees, and one head at 90 degrees only as it doesn’t reach 0 (IEC convention). Results: For the TG-51 comparison, expected dose was obtained by decaying values measured at the time of source installation. The average measured difference was 0.4%±0.12% for A18 and 0.06%±0.15% for Farmer chamber. There was minimal (0.3%) orientation dependence without the magnetic field for the A18 chamber, while previous measurements with the magnetic field had a deviation of 3.2% with chamber perpendicular to magnetic field. Results reported by IROC for the OSLDs with and without the field had a maximum difference of 2%. Conclusion: Accurate absolute dosimetry was verified by measurement under the same conditions with and without the magnetic field for both ionization chambers and independently-verifiable OSLDs.« less

Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

PubMed

Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

2012-12-01

Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

WE-F-16A-04: Micro-Irradiator Treatment Verification with High-Resolution 3D-Printed Rodent-Morphic Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bache, S; Belley, M; Benning, R

2014-06-15

Purpose: Pre-clinical micro-radiation therapy studies often utilize very small beams (∼0.5-5mm), and require accurate dose delivery in order to effectively investigate treatment efficacy. Here we present a novel high-resolution absolute 3D dosimetry procedure, capable of ∼100-micron isotopic dosimetry in anatomically accurate rodent-morphic phantoms Methods: Anatomically accurate rat-shaped 3D dosimeters were made using 3D printing techniques from outer body contours and spinal contours outlined on CT. The dosimeters were made from a radiochromic plastic material PRESAGE, and incorporated high-Z PRESASGE inserts mimicking the spine. A simulated 180-degree spinal arc treatment was delivered through a 2 step process: (i) cone-beam-CT image-guided positioningmore » was performed to precisely position the rat-dosimeter for treatment on the XRad225 small animal irradiator, then (ii) treatment was delivered with a simulated spine-treatment with a 180-degree arc with 20mm x 10mm cone at 225 kVp. Dose distribution was determined from the optical density change using a high-resolution in-house optical-CT system. Absolute dosimetry was enabled through calibration against a novel nano-particle scintillation detector positioned in a channel in the center of the distribution. Results: Sufficient contrast between regular PRESAGE (tissue equivalent) and high-Z PRESAGE (spinal insert) was observed to enable highly accurate image-guided alignment and targeting. The PRESAGE was found to have linear optical density (OD) change sensitivity with respect to dose (R{sup 2} = 0.9993). Absolute dose for 360-second irradiation at isocenter was found to be 9.21Gy when measured with OD change, and 9.4Gy with nano-particle detector- an agreement within 2%. The 3D dose distribution was measured at 500-micron resolution Conclusion: This work demonstrates for the first time, the feasibility of accurate absolute 3D dose measurement in anatomically accurate rat phantoms containing variable density PRESAGE material (tissue equivalent and bone equivalent). This method enables precise treatment verification of micro-radiation therapies, and enhances the robustness of tumor radio-response studies. This work was supported by NIH R01CA100835.« less

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy.

PubMed

Trnková, Petra; Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2010-12-01

The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy

PubMed Central

Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2011-01-01

Purpose The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. Material and methods For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. Results HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. Conclusions HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning. PMID:27853479

Comparison of Monte Carlo and analytical dose computations for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Yepes, Pablo; Adair, Antony; Grosshans, David; Mirkovic, Dragan; Poenisch, Falk; Titt, Uwe; Wang, Qianxia; Mohan, Radhe

2018-02-01

To evaluate the effect of approximations in clinical analytical calculations performed by a treatment planning system (TPS) on dosimetric indices in intensity modulated proton therapy. TPS calculated dose distributions were compared with dose distributions as estimated by Monte Carlo (MC) simulations, calculated with the fast dose calculator (FDC) a system previously benchmarked to full MC. This study analyzed a total of 525 patients for four treatment sites (brain, head-and-neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD and Mean Dose) and a gamma-index analysis were utilized to evaluate the differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels with a dose larger than 10% of the maximum dose had a median larger than 98% for all sites. The median difference for all dosimetric indices for target volumes was less than 2% for all cases. However, differences for target volumes as large as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the median absolute dose difference was smaller than 2 Gy for all indices and cohorts. However, absolute dose differences as large as 10 Gy were found for some small volume organs in brain and head-and-neck patients. This analysis concludes that for a fraction of the patients studied, TPS may overestimate the dose in the target by as much as 10%, while for some OARs the dose could be underestimated by as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more accurate dose computations to improve target coverage and sparing of OARs in proton therapy.

TH-AB-201-12: Using Machine Log-Files for Treatment Planning and Delivery QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanhope, C; Liang, J; Drake, D

2016-06-15

Purpose: To determine the segment reduction and dose resolution necessary for machine log-files to effectively replace current phantom-based patient-specific quality assurance, while minimizing computational cost. Methods: Elekta’s Log File Convertor R3.2 records linac delivery parameters (dose rate, gantry angle, leaf position) every 40ms. Five VMAT plans [4 H&N, 1 Pulsed Brain] comprised of 2 arcs each were delivered on the ArcCHECK phantom. Log-files were reconstructed in Pinnacle on the phantom geometry using 1/2/3/4° control point spacing and 2/3/4mm dose grid resolution. Reconstruction effectiveness was quantified by comparing 2%/2mm gamma passing rates of the original and log-file plans. Modulation complexity scoresmore » (MCS) were calculated for each beam to correlate reconstruction accuracy and beam modulation. Percent error in absolute dose for each plan-pair combination (log-file vs. ArcCHECK, original vs. ArcCHECK, log-file vs. original) was calculated for each arc and every diode greater than 10% of the maximum measured dose (per beam). Comparing standard deviations of the three plan-pair distributions, relative noise of the ArcCHECK and log-file systems was elucidated. Results: The original plans exhibit a mean passing rate of 95.1±1.3%. The eight more modulated H&N arcs [MCS=0.088±0.014] and two less modulated brain arcs [MCS=0.291±0.004] yielded log-file pass rates most similar to the original plan when using 1°/2mm [0.05%±1.3% lower] and 2°/3mm [0.35±0.64% higher] log-file reconstructions respectively. Log-file and original plans displayed percent diode dose errors 4.29±6.27% and 3.61±6.57% higher than measurement. Excluding the phantom eliminates diode miscalibration and setup errors; log-file dose errors were 0.72±3.06% higher than the original plans – significantly less noisy. Conclusion: For log-file reconstructed VMAT arcs, 1° control point spacing and 2mm dose resolution is recommended, however, less modulated arcs may allow less stringent reconstructions. Following the aforementioned reconstruction recommendations, the log-file technique is capable of detecting delivery errors with equivalent accuracy and less noise than ArcCHECK QA. I am funded by an Elekta Research Grant.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Bria M.; Brady, Samuel L., E-mail: samuel.brady@stjude.org; Kaufman, Robert A.

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (CF{sub SSDE}{sup organ}) were then multiplied by patient-specific SSDE to estimate patient organ dose. Themore » CF{sub SSDE}{sup organ} were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. IndividualCF{sub SSDE}{sup organ} were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and CF{sub SSDE}{sup organ}, was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (CF{sub SSDE}{sup organ}) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.« less

Impact of the radiotherapy technique on the correlation between dose-volume histograms of the bladder wall defined on MRI imaging and dose-volume/surface histograms in prostate cancer patients

NASA Astrophysics Data System (ADS)

Maggio, Angelo; Carillo, Viviana; Cozzarini, Cesare; Perna, Lucia; Rancati, Tiziana; Valdagni, Riccardo; Gabriele, Pietro; Fiorino, Claudio

2013-04-01

The aim of this study was to evaluate the correlation between the ‘true’ absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80-0.94) compared to relative (R = 0.66-0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001).

Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

PubMed

Huang, Bao-Tian; Lin, Zhu; Lin, Pei-Xian; Lu, Jia-Yang; Chen, Chuang-Zhen

2016-06-28

This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 × 34 Gy (34 Gy in 1 fraction) and 4 × 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 × 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 × 34 Gy dose schedule.

Impact of spot charge inaccuracies in IMPT treatments.

PubMed

Kraan, Aafke C; Depauw, Nicolas; Clasie, Ben; Giunta, Marina; Madden, Tom; Kooy, Hanne M

2017-08-01

Spot charge is one parameter of pencil-beam scanning dose delivery system whose accuracy is typically high but whose required value has not been investigated. In this work we quantify the dose impact of spot charge inaccuracies on the dose distribution in patients. Knowing the effect of charge errors is relevant for conventional proton machines, as well as for new generation proton machines, where ensuring accurate charge may be challenging. Through perturbation of spot charge in treatment plans for seven patients and a phantom, we evaluated the dose impact of absolute (up to 5× 10 6 protons) and relative (up to 30%) charge errors. We investigated the dependence on beam width by studying scenarios with small, medium and large beam sizes. Treatment plan statistics included the Γ passing rate, dose-volume-histograms and dose differences. The allowable absolute charge error for small spot plans was about 2× 10 6 protons. Larger limits would be allowed if larger spots were used. For relative errors, the maximum allowable error size for small, medium and large spots was about 13%, 8% and 6% for small, medium and large spots, respectively. Dose distributions turned out to be surprisingly robust against random spot charge perturbation. Our study suggests that ensuring spot charge errors as small as 1-2% as is commonly aimed at in conventional proton therapy machines, is clinically not strictly needed. © 2017 American Association of Physicists in Medicine.

Absolute dose determination in high-energy electron beams: Comparison of IAEA dosimetry protocols

PubMed Central

Sathiyan, S.; Ravikumar, M.

2008-01-01

In this study, absorbed doses were measured and compared for high-energy electrons (6, 9, 12, 16, and 20 MeV) using International Atomic Energy Agency (IAEA), Technical Reports Series No. 277 (TRS), TRS 381, and TRS 398 dosimetry protocols. Absolute dose measurements were carried out using FC65-G Farmer chamber and Nordic Association of Clinical Physicists (NACP) parallel plate chamber with DOSE1 electrometer in WP1-D water phantom for reference field size of 15 × 15 cm2 at 100 cm source-to-surface distance. The results show that the difference between TRS 398 and TRS 381 was about 0.24% to 1.3% depending upon the energy, and the maximum difference between TRS 398 and TRS 277 was 1.5%. The use of cylindrical chamber in electron beam gives the maximum dose difference between the TRS 398 and TRS 277 in the order of 1.4% for energies above 10 MeV (R50 > 4 g/cm2). It was observed that the accuracy of dose estimation was better with the protocols based on the water calibration procedures, as no conversion quantities are involved for conversion of dose from air to water. The cross-calibration procedure of parallel plate chamber with high-energy electron beams is recommended as it avoids pwall correction factor entering into the determination of kQ,Qo. PMID:19893700

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

PubMed

Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

2017-03-15

Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

In vivo dosimetry and shielding disk alignment verification by EBT3 GAFCHROMIC film in breast IOERT treatment.

PubMed

Severgnini, Mara; de Denaro, Mario; Bortul, Marina; Vidali, Cristiana; Beorchia, Aulo

2014-01-08

Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose-optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off-line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%.

SU-F-T-569: Implementation of a Patient Specific QA Method Using EBT-XD for CyberKnife SRS/SBRT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zerouali, K; Aubry, J; Doucet, R

2016-06-15

Purpose: To implement the new EBT-XD Gafchromic films for accurate dosimetric and geometric validation of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) CyberKnife (CK) patient specific QA. Methods: Film calibration was performed using a triplechannel film analysis on an Epson 10000XL scanner. Calibration films were irradiated using a Varian Clinac 21EX flattened beam (0 to 20 Gy), to ensure sufficient dose homogeneity. Films were scanned to a resolution of 0.3 mm, 24 hours post irradiation following a well-defined protocol. A set of 12 QA was performed for several types of CK plans: trigeminal neuralgia, brain metastasis, prostate andmore » lung tumors. A custom made insert for the CK head phantom has been manufactured to yield an accurate measured to calculated dose registration. When the high dose region was large enough, absolute dose was also measured with an ionization chamber. Dose calculation is performed using MultiPlan Ray-tracing algorithm for all cases since the phantom is mostly made from near water-equivalent plastic. Results: Good agreement (<2%) was found between the dose to the chamber and the film, when a chamber measurement was possible The average dose difference and standard deviations between film measurements and TPS calculations were respectively 1.75% and 3%. The geometric accuracy has been estimated to be <1 mm, combining robot positioning uncertainty and film registration to calculated dose. Conclusion: Patient specific QA measurements using EBT-XD films yielded a full 2D dose plane with high spatial resolution and acceptable dose accuracy. This method is particularly promising for trigeminal neuralgia plan QA, where the positioning of the spatial dose distribution is equally or more important than the absolute delivered dose to achieve clinical goals.« less

Absolute and relative educational inequalities in depression in Europe.

PubMed

Dudal, Pieter; Bracke, Piet

2016-09-01

To investigate (1) the size of absolute and relative educational inequalities in depression, (2) their variation between European countries, and (3) their relationship with underlying prevalence rates. Analyses are based on the European Social Survey, rounds three and six (N = 57,419). Depression is measured using the shortened Centre of Epidemiologic Studies Depression Scale. Education is coded by use of the International Standard Classification of Education. Country-specific logistic regressions are applied. Results point to an elevated risk of depressive symptoms among the lower educated. The cross-national patterns differ between absolute and relative measurements. For men, large relative inequalities are found for countries including Denmark and Sweden, but are accompanied by small absolute inequalities. For women, large relative and absolute inequalities are found in Belgium, Bulgaria, and Hungary. Results point to an empirical association between inequalities and the underlying prevalence rates. However, the strength of the association is only moderate. This research stresses the importance of including both measurements for comparative research and suggests the inclusion of the level of population health in research into inequalities in health.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Shulian; Liao Zhongxing; Vaporciyan, Ara A.

Purpose: To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Method and Materials: Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy)more » was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V{sub dose} and absolute V{sub dose}), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS{sub dose}). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V{sub dose} or VS{sub dose}) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Results: Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving {>=}5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses {>=}5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses {>=}5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Conclusions: Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of {>=}5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.« less

Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.

PubMed

Wang, Shu-lian; Liao, Zhongxing; Vaporciyan, Ara A; Tucker, Susan L; Liu, Helen; Wei, Xiong; Swisher, Stephen; Ajani, Jaffer A; Cox, James D; Komaki, Ritsuko

2006-03-01

To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving > or = 5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses > or = 5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses > or = 5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of > or = 5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.

SU-E-T-68: A Quality Assurance System with a Web Camera for High Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ueda, Y; Hirose, A; Oohira, S

Purpose: The purpose of this work was to develop a quality assurance (QA) system for high dose rate (HDR) brachytherapy to verify the absolute position of an 192Ir source in real time and to measure dwell time and position of the source simultaneously with a movie recorded by a web camera. Methods: A web camera was fixed 15 cm above a source position check ruler to monitor and record 30 samples of the source position per second over a range of 8.0 cm, from 1425 mm to 1505 mm. Each frame had a matrix size of 480×640 in the movie.more » The source position was automatically quantified from the movie using in-house software (built with LabVIEW) that applied a template-matching technique. The source edge detected by the software on each frame was corrected to reduce position errors induced by incident light from an oblique direction. The dwell time was calculated by differential processing to displacement of the source. The performance of this QA system was illustrated by recording simple plans and comparing the measured dwell positions and time with the planned parameters. Results: This QA system allowed verification of the absolute position of the source in real time. The mean difference between automatic and manual detection of the source edge was 0.04 ± 0.04 mm. Absolute position error can be determined within an accuracy of 1.0 mm at dwell points of 1430, 1440, 1450, 1460, 1470, 1480, 1490, and 1500 mm, in three step sizes and dwell time errors, with an accuracy of 0.1% in more than 10.0 sec of planned time. The mean step size error was 0.1 ± 0.1 mm for a step size of 10.0 mm. Conclusion: This QA system provides quick verifications of the dwell position and time, with high accuracy, for HDR brachytherapy. This work was supported by the Japan Society for the Promotion of Science Core-to-Core program (No. 23003)« less

Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.

2009-04-01

Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of thismore » study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome points were higher for the apex model compared with the non-apex model. Mean doses to the optimization points for both the cylinder models and all the cylinder diameters were 6 Gy, matching with the prescription dose of 6 Gy. Iterative optimization routine resulted in the highest dose to apex point and dome points. The mean dose for optimization point was 6.01 Gy for iterative optimization and was much higher than 5.74 Gy for geometric and equal times routines. Step size of 1 cm gave the highest dose to the apex point. This step size was superior in terms of mean dose to optimization points. Selection of dose optimization points for the derivation of optimized dose distributions for vaginal cylinders affects the dose distributions.« less

In vivo dosimetry and shielding disk alignment verification by EBT3 GAFCHROMIC film in breast IOERT treatment

PubMed Central

de Denaro, Mario; Bortul, Marina; Vidali, Cristiana; Beorchia, Aulo

2014-01-01

Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose‐optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off‐line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%. PACS number: 87.55.kh

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections.

PubMed

Zhang, You; Yin, Fang-Fang; Ren, Lei

2015-08-01

Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the "gold-standard" on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔDmin), maximum dose (ΔDmax), and mean dose (ΔDmean), and the absolute deviations of prescription dose coverage (ΔV100%) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔDmin, ΔDmax, ΔDmean, and ΔV100% (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔDmin, ΔDmax, ΔDmean, and ΔV100% of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasui, Keisuke, E-mail: k.yasui.20@west-med.jp; Toshito, Toshiyuki; Omachi, Chihiro

Purpose: In the authors’ proton therapy system, the patient-specific aperture can be attached to the nozzle of spot scanning beams to shape an irradiation field and reduce lateral fall-off. The authors herein verified this system for clinical application. Methods: The authors prepared four types of patient-specific aperture systems equipped with an energy absorber to irradiate shallow regions less than 4 g/cm{sup 2}. The aperture was made of 3-cm-thick brass and the maximum water equivalent penetration to be used with this system was estimated to be 15 g/cm{sup 2}. The authors measured in-air lateral profiles at the isocenter plane and integralmore » depth doses with the energy absorber. All input data were obtained by the Monte Carlo calculation, and its parameters were tuned to reproduce measurements. The fluence of single spots in water was modeled as a triple Gaussian function and the dose distribution was calculated using a fluence dose model. The authors compared in-air and in-water lateral profiles and depth doses between calculations and measurements for various apertures of square, half, and U-shaped fields. The absolute doses and dose distributions with the aperture were then validated by patient-specific quality assurance. Measured data were obtained by various chambers and a 2D ion chamber detector array. Results: The patient-specific aperture reduced the penumbra from 30% to 70%, for example, from 34.0 to 23.6 mm and 18.8 to 5.6 mm. The calculated field width for square-shaped apertures agreed with measurements within 1 mm. Regarding patient-specific aperture plans, calculated and measured doses agreed within −0.06% ± 0.63% (mean ± SD) and 97.1% points passed the 2%-dose/2 mm-distance criteria of the γ-index on average. Conclusions: The patient-specific aperture system improved dose distributions, particularly in shallow-region plans.« less

Implementation of IMRT and VMAT using Delta4 phantom and portal dosimetry as dosimetry verification tools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daci, Lulzime, E-mail: lulzime.daci@nodlandssykehuset.no; Malkaj, Partizan, E-mail: malkaj-p@hotmail.com

2016-03-25

In this study we analyzed and compared the dose distribution of different IMRT and VMAT plans with the intent to provide pre-treatment quality assurance using two different tools. Materials/Methods: We have used the electronic portal imaging device EPID after calibration to dose and correction for the background offset signal and also the Delta4 phantom after en evaluation of angular sensitivity. The Delta4 phantom has a two-dimensional array with ionization chambers. We analyzed three plans for each anatomical site calculated by Eclipse treatment planning system. The measurements were analyzed using γ-evaluation method with passing criteria 3% absolute dose and 3 mm distancemore » to agreement (DTA). For all the plans the range of score has been from 97% to 99% for gantry fixed at 0° while for rotational planes there was a slightly decreased pass rates and above 95%. Point measurement with a ionization chamber were done in additional to see the accuracy of portal dosimetry and to evaluate the Delta4 device to various dose rates. Conclusions: Both Delt4 and Portal dosimetry shows good results between the measured and calculated doses. While Delta4 is more accurate in measurements EPID is more time efficient. We have decided to use both methods in the first steps of IMRT and VMAT implementation and later on to decide which of the tools to use depending on the complexity of plans, how much accurate we want to be and the time we have on the machine.« less

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Response functions for computing absorbed dose to skeletal tissues from photon irradiation—an update

NASA Astrophysics Data System (ADS)

Johnson, Perry B.; Bahadori, Amir A.; Eckerman, Keith F.; Lee, Choonsik; Bolch, Wesley E.

2011-04-01

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues—active and total shallow marrow—within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

γTools: A modular multifunction phantom for quality assurance in GammaKnife treatments.

PubMed

Calusi, Silvia; Noferini, Linhsia; Marrazzo, Livia; Casati, Marta; Arilli, Chiara; Compagnucci, Antonella; Talamonti, Cinzia; Scoccianti, Silvia; Greto, Daniela; Bordi, Lorenzo; Livi, Lorenzo; Pallotta, Stefania

2017-11-01

We present the γTools, a new phantom designed to assess geometric and dosimetric accuracy in Gamma Knife treatments, together with first tests and results of applications. The phantom is composed of two modules: the imaging module, a regular grid of 1660 control points to evaluate image distortions and image registration result and the dosimetry module for delivered dose distribution measurements. The phantom is accompanied by a MatLab routine for image distortions quantification. Dose measurement are performed with Gafchromic films fixed between two inserts and placed in various positions and orientations inside the dosimetry module thus covering a volume comparable to the full volume of a head. Tests performed to assess the accuracy and precision of the imaging module demonstrated sub-millimetric values. As an example of possible applications, the phantom was employed to measure image distortions of two MRI scanners and to perform dosimetric studies of single shots delivered to homogeneous and heterogeneous materials. Due to the phantom material, the measured absolute dose do not correspond to the planned dose; doses comparisons are thus carried out between normalized dose distributions. Finally, an end-to-end test was carried out in the treatment of a neuroma-like target which resulted in a 100% gamma passing rate (2% local, 2 mm) and a distance between the real target perimeter and the prescription isodose centroids of about 1 mm. The tests demonstrate that the proposed phantom is suitable to assess both the geometrical and relative dosimetric accuracy of Gamma Knife radiosurgery treatments. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Response functions for computing absorbed dose to skeletal tissues from photon irradiation--an update.

PubMed

Johnson, Perry B; Bahadori, Amir A; Eckerman, Keith F; Lee, Choonsik; Bolch, Wesley E

2011-04-21

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R(2) = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

RESPONSE FUNCTIONS FOR COMPUTING ABSORBED DOSE TO SKELETAL TISSUES FROM PHOTON IRRADIATION – AN UPDATE

PubMed Central

Johnson, Perry; Bahadori, Amir; Eckerman, Keith; Lee, Choonsik; Bolch, Wesley E.

2014-01-01

A comprehensive set of photon fluence-to-dose response functions (DRFs) are presented for two radiosensitive skeletal tissues – active and total shallow marrow – within 15 and 32 bones sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon microCT images of trabecular spongiosa taken from a 40-year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, as well as a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In the present study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma factors for active marrow, inactive marrow, trabecular bone, and spongiosa at higher energies are calculated using the DRF algorithm setting the electron absorbed fraction for self-irradiation to unity. By comparing kerma factors and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites PMID:21427484

Design and implementation of a head-and-neck phantom for system audit and verification of intensity-modulated radiation therapy.

PubMed

Webster, Gareth J; Hardy, Mark J; Rowbottom, Carl G; Mackay, Ranald I

2008-04-16

The head and neck is a challenging anatomic site for intensity-modulated radiation therapy (IMRT), requiring thorough testing of planning and treatment delivery systems. Ideally, the phantoms used should be anatomically realistic, have radiologic properties identical to those of the tissues concerned, and allow for the use of a variety of devices to verify dose and dose distribution in any target or normaltissue structure. A phantom that approaches the foregoing characteristics has been designed and built; its specific purpose is verification for IMRT treatments in the head-andneck region. This semi-anatomic phantom, HANK, is constructed of Perspex (Imperial Chemical Industries, London, U.K.) and provides for the insertion of heterogeneities simulating air cavities in a range of fixed positions. Chamber inserts are manufactured to incorporate either a standard thimble ionization chamber (0.125 cm3: PTW, Freiburg, Germany) or a smaller PinPoint chamber (0.015 cm3: PTW), and measurements can be made with either chamber in a range of positions throughout the phantom. Coronal films can also be acquired within the phantom, and additional solid blocks of Perspex allow for transverse films to be acquired within the head region. Initial studies using simple conventional head-and-neck plans established the reproducibility of the phantom and the measurement devices to within the setup uncertainty of +/- 0.5 mm. Subsequent verification of 9 clinical head-and-neck IMRT plans demonstrated the efficacy of the phantom in making a range of patient-specific dose measurements in regions of dosimetric and clinical interest. Agreement between measured values and those predicted by the Pinnacle3 treatment planning system (Philips Medical Systems, Andover, MA) was found to be generally good, with a mean error on the calculated dose to each point of +0.2% (range: -4.3% to +2.2%; n = 9) for the primary planning target volume (PTV), -0.1% (range: -1.5% to +2.0%; n = 8) for the nodal PTV, and +0.0% (range: -1.8% to +4.3%, n = 9) for the spinal cord. The suitability of the phantom for measuring combined dose distributions using radiographic film was also evaluated. The phantom has proved to be a valuable tool in the development and implementation of clinical head-and-neck IMRT, allowing for accurate verification of absolute dose and dose distributions in regions of clinical and dosimetric interest.

Microionization chamber for reference dosimetry in IMRT verification: clinical implications on OAR dosimetric errors

NASA Astrophysics Data System (ADS)

Sánchez-Doblado, Francisco; Capote, Roberto; Leal, Antonio; Roselló, Joan V.; Lagares, Juan I.; Arráns, Rafael; Hartmann, Günther H.

2005-03-01

Intensity modulated radiotherapy (IMRT) has become a treatment of choice in many oncological institutions. Small fields or beamlets with sizes of 1 to 5 cm2 are now routinely used in IMRT delivery. Therefore small ionization chambers (IC) with sensitive volumes <=0.1 cm3are generally used for dose verification of an IMRT treatment. The measurement conditions during verification may be quite different from reference conditions normally encountered in clinical beam calibration, so dosimetry of these narrow photon beams pertains to the so-called non-reference conditions for beam calibration. This work aims at estimating the error made when measuring the organ at risk's (OAR) absolute dose by a micro ion chamber (μIC) in a typical IMRT treatment. The dose error comes from the assumption that the dosimetric parameters determining the absolute dose are the same as for the reference conditions. We have selected two clinical cases, treated by IMRT, for our dose error evaluations. Detailed geometrical simulation of the μIC and the dose verification set-up was performed. The Monte Carlo (MC) simulation allows us to calculate the dose measured by the chamber as a dose averaged over the air cavity within the ion-chamber active volume (Dair). The absorbed dose to water (Dwater) is derived as the dose deposited inside the same volume, in the same geometrical position, filled and surrounded by water in the absence of the ion chamber. Therefore, the Dwater/Dair dose ratio is the MC estimator of the total correction factor needed to convert the absorbed dose in air into the absorbed dose in water. The dose ratio was calculated for the μIC located at the isocentre within the OARs for both clinical cases. The clinical impact of the calculated dose error was found to be negligible for the studied IMRT treatments.

Accuracy assessment of the global TanDEM-X Digital Elevation Model with GPS data

NASA Astrophysics Data System (ADS)

Wessel, Birgit; Huber, Martin; Wohlfart, Christian; Marschalk, Ursula; Kosmann, Detlev; Roth, Achim

2018-05-01

The primary goal of the German TanDEM-X mission is the generation of a highly accurate and global Digital Elevation Model (DEM) with global accuracies of at least 10 m absolute height error (linear 90% error). The global TanDEM-X DEM acquired with single-pass SAR interferometry was finished in September 2016. This paper provides a unique accuracy assessment of the final TanDEM-X global DEM using two different GPS point reference data sets, which are distributed across all continents, to fully characterize the absolute height error. Firstly, the absolute vertical accuracy is examined by about three million globally distributed kinematic GPS (KGPS) points derived from 19 KGPS tracks covering a total length of about 66,000 km. Secondly, a comparison is performed with more than 23,000 "GPS on Bench Marks" (GPS-on-BM) points provided by the US National Geodetic Survey (NGS) scattered across 14 different land cover types of the US National Land Cover Data base (NLCD). Both GPS comparisons prove an absolute vertical mean error of TanDEM-X DEM smaller than ±0.20 m, a Root Means Square Error (RMSE) smaller than 1.4 m and an excellent absolute 90% linear height error below 2 m. The RMSE values are sensitive to land cover types. For low vegetation the RMSE is ±1.1 m, whereas it is slightly higher for developed areas (±1.4 m) and for forests (±1.8 m). This validation confirms an outstanding absolute height error at 90% confidence level of the global TanDEM-X DEM outperforming the requirement by a factor of five. Due to its extensive and globally distributed reference data sets, this study is of considerable interests for scientific and commercial applications.

Sharpening peripheral dose gradient via beam number enhancement from patient head tilt for stereotactic brain radiosurgery

NASA Astrophysics Data System (ADS)

Chiu, Joshua; Pierce, Marlon; Braunstein, Steve E.; Theodosopoulos, Philip V.; McDermott, Michael W.; Sneed, Penny K.; Ma, Lijun

2016-10-01

Sharp dose fall-off is the hallmark of brain radiosurgery for the purpose of delivering high dose radiation to the target while minimizing peripheral dose to regional normal brain tissue. In this study, a technique was developed to enhance the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter through pre-programmed patient head tilting. This technique was tested in clinical settings on a dedicated brain radiosurgical system (GKPFX, Gamma Knife Perfexion, Elekta Oncology) by comparing dosimetry as well as delivery efficiency for 20 radiosurgical cases previously treated with the system. The 3-fold beam number enhancement (BNE) treatment plans were found to produce nearly identical target volume coverage (absolute value  <  0.5%, P  >  0.2) and dose conformity (BNE CI  =  1.41  ±  0.22 versus 1.41  ±  0.11, P  >  0.99) as the original treatment plans. The total beam-on time for the 3-fold BNE treatment plans were also found to be comparable (<0.5 min or 2%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI  =  2.94  ±  0.27 versus original GI  =  2.98  ±  0.28 P  <  0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 1.7%-3.9% (P  <  0.03). With further 4-5-fold increase in the total number of beams, the absolute gradient index can decrease by as much as  -0.5 in absolute value or  -20% for a treatment. In conclusion, BNE via patient head tilt has been demonstrated to be a clinically suitable and efficient technique for physically sharpening the peripheral dose gradient for brain radiosurgery. This work was presented in part at the 2015 ISRS Congress in Yokohama Japan.

Determination of quality factors by microdosimetry

NASA Astrophysics Data System (ADS)

Al-Affan, I. A. M.; Watt, D. E.

1987-03-01

The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a mean of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

Absolute Bioavailability and Effect of Food on the Disposition of Safinamide Immediate Release Tablets in Healthy Adult Subjects.

PubMed

Seithel-Keuth, Annick; Johne, Andreas; Freisleben, Achim; Kupas, Katrin; Lissy, Michael; Krösser, Sonja

2013-01-01

The objectives of this study were to establish the basic intravenous (IV) single-dose PK of safinamide and its major human metabolites, the absolute bioavailability (BA) and food effect on safinamide tablets. Fourteen healthy adult male and female subjects received 50 mg safinamide single-dose treatments according to a randomized, 3-period, 2-sequence crossover design: immediate release (IR) tablets, administered after an overnight fast and after a standardized high-fat, high-calorie breakfast, and IV solution, administered over 30 minutes. Treatments were separated by wash-out intervals of at least 17 days. Serial blood samples were collected for 240 hours postdosing to evaluate safinamide parent drug and metabolite concentrations for the determination of PK parameters. The absolute BA of safinamide 50 mg IR tablets was high, with geoMean AUC0-∞ ratios of about 95% (90% CI: 90-99%) indicating that safinamide is virtually completely absorbed after oral administration. Safinamide IR tablets did not display a food effect on exposure parameters; both 90% CIs for the ratios fed/fasted of AUC0-∞ and Cmax were entirely within the bioequivalence acceptance margins of 80-125%. Only tmax was delayed by about 30% in the fed state. Oral and IV safinamide 50 mg single-dose administrations were generally well tolerated. © The Author(s) 2013.

Thyroid neoplasia following low-dose radiation in childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ron, E.; Modan, B.; Preston, D.

1989-12-01

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benignmore » tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tucker, Susan L.; Liu, H. Helen; Wang, Shulian

Purpose: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. Methods and Materials: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. Results: Normal-tissue complicationmore » probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses {>=}5 Gy (VS5), that is, exposed to doses <5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving {>=}5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, {infinity}), m = 0.55 (0.22, 1.02), and D {sub 5} = 17.5 Gy (9.4 Gy, 102 Gy). Conclusions: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving <5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of Radiation dose distribution in the lung.« less

Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers

NASA Astrophysics Data System (ADS)

Lye, J. E.; Harty, P. D.; Butler, D. J.; Crosbie, J. C.; Livingstone, J.; Poole, C. M.; Ramanathan, G.; Wright, T.; Stevenson, A. W.

2016-06-01

The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free-air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

PubMed

Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

2018-02-01

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Poster - Thurs Eve-09: Evaluation of a commercial 2D ion-chamber array for intensity modulated radiation therapy dose measurements.

PubMed

Mei, X; Bracken, G; Kerr, A

2008-07-01

Experimental verification of calculated dose from a treatment planning system is often essential for quality assurance (QA) of intensity modulated radiation therapy (IMRT). Film dosimetry and single ion chamber measurements are commonly used for IMRT QA. Film dosimetry has very good spatial resolution, but is labor intensive and absolute dose is not reliable. Ion chamber measurements are still required for absolute dose after measurements using films. Dosimeters based on 2D detector arrays that can measure 2D dose in real-time are gaining wider use. These devices provide a much easier and reliable tool for IMRT QA. We report the evaluation of a commercial 2D ion chamber array, including its basic performance characteristics, such as linearity, reproducibility and uniformity of relative ion chamber sensitivities, and comparisons between measured 2D dose and calculated dose with a commercial treatment planning system. Our analysis shows this matrix has excellent linearity and reproducibility, but relative sensitivities are tilted such that the +Y region is over sensitive, while the -Y region is under sensitive. Despite this behavior, our results show good agreement between measured 2D dose profiles and Eclipse planned data for IMRT test plans and a few verification plans for clinical breast field-in-field plans. The gamma values (3% or 3 mm distance-to-agreement) are all less than 1 except for one or two pixels at the field edge This device provides a fast and reliable stand-alone dosimeter for IMRT QA. © 2008 American Association of Physicists in Medicine.

Commissioning and validation of fluence-based 3D VMAT dose reconstruction system using new transmission detector.

PubMed

Nakaguchi, Yuji; Oono, Takeshi; Maruyama, Masato; Shimohigashi, Yoshinobu; Kai, Yudai; Nakamura, Yuya

2018-06-01

In this study, we evaluated the basic performance of the three-dimensional dose verification system COMPASS (IBA Dosimetry). This system is capable of reconstructing 3D dose distributions on the patient anatomy based on the fluence measured using a new transmission detector (Dolphin, IBA Dosimetry) during treatment. The stability of the absolute dose and geometric calibrations of the COMPASS system with the Dolphin detector were investigated for fundamental validation. Furthermore, multileaf collimator (MLC) test patterns and a complicated volumetric modulated arc therapy (VMAT) plan were used to evaluate the accuracy of the reconstructed dose distributions determined by the COMPASS. The results from the COMPASS were compared with those of a Monte Carlo simulation (MC), EDR2 film measurement, and a treatment planning system (TPS). The maximum errors for the absolute dose and geometrical position were - 0.28% and 1.0 mm for 3 months, respectively. The Dolphin detector, which consists of ionization chamber detectors, was firmly mounted on the linear accelerator and was very stable. For the MLC test patterns, the TPS showed a > 5% difference at small fields, while the COMPASS showed good agreement with the MC simulation at small fields. However, the COMPASS produced a large error for complex small fields. For a clinical VMAT plan, COMPASS was more accurate than TPS. COMPASS showed real delivered-dose distributions because it uses the measured fluence, a high-resolution detector, and accurate beam modeling. We confirm here that the accuracy and detectability of the delivered dose of the COMPASS system are sufficient for clinical practice.

SU-E-I-16: Scan Length Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakalyar, D; McKenney, S; Feng, W

Purpose: The area-averaged dose in the central plane of a long cylinder following a CT scan depends upon the radial dose distribution and the length of the scan. The ICRU/TG200 phantom, a polyethylene cylinder 30 cm in diameter and 60 cm long, was the subject of this study. The purpose was to develop an analytic function that could determine the dose for a scan length L at any point in the central plane of this phantom. Methods: Monte Carlo calculations were performed on a simulated ICRU/TG200 phantom under conditions of cylindrically symmetric conditions of irradiation. Thus, the radial dose distributionmore » function must be an even function that accounts for two competing effects: The direct beam makes its weakest contribution at the center while the scatter begins abruptly at the outer radius and grows as the center is approached. The scatter contribution also increases with scan length with the increase approaching its limiting value at the periphery faster than along the central axis. An analytic function was developed that fit the data and possessed these features. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the ICRU/TG200 phantom. The relative depth of the minimum decreases as the scan length grows and an absolute maximum can occur between the center and outer edge of the cylinders. As the scan length grows, the relative dip in the center decreases so that for very long scan lengths, the dose profile is relatively flat. Conclusion: An analytic function characterizes the radial and scan length dependency of dose for long cylindrical phantoms. The function can be integrated with the results expressed in closed form. One use for this is to help determine average dose distribution over the central cylinder plane for any scan length.« less

Evaluation of a magnetic resonance guided linear accelerator for stereotactic radiosurgery treatment.

PubMed

Wen, Ning; Kim, Joshua; Doemer, Anthony; Glide-Hurst, Carri; Chetty, Indrin J; Liu, Chang; Laugeman, Eric; Xhaferllari, Ilma; Kumarasiri, Akila; Victoria, James; Bellon, Maria; Kalkanis, Steve; Siddiqui, M Salim; Movsas, Benjamin

2018-06-01

The purpose of this study was to investigate the systematic localization accuracy, treatment planning capability, and delivery accuracy of an integrated magnetic resonance imaging guided Linear Accelerator (MR-Linac) platform for stereotactic radiosurgery. The phantom for the end-to-end test comprises three different compartments: a rectangular MR/CT target phantom, a Winston-Lutz cube, and a rectangular MR/CT isocenter phantom. Hidden target tests were performed at gantry angles of 0, 90, 180, and 270 degrees to quantify the systematic accuracy. Five patient plans with a total of eleven lesions were used to evaluate the dosimetric accuracy. Single-isocenter IMRT treatment plans using 10-15 coplanar beams were generated to treat the multiple metastases. The end-to-end localization accuracy of the system was 1.0 ± 0.1 mm. The conformity index, homogeneity index and gradient index of the plans were 1.26 ± 0.22, 1.22 ± 0.10, and 5.38 ± 1.44, respectively. The average absolute point dose difference between measured and calculated dose was 1.64 ± 1.90%, and the mean percentage of points passing the 3%/1 mm gamma criteria was 96.87%. Our experience demonstrates that excellent plan quality and delivery accuracy was achievable on the MR-Linac for treating multiple brain metastases with a single isocenter. Copyright © 2018 Elsevier B.V. All rights reserved.

Waist circumference values equivalent to body mass index points for predicting absolute cardiovascular disease risks among adults in an Aboriginal community: a prospective cohort study.

PubMed

Adegbija, Odewumi; Hoy, Wendy E; Wang, Zhiqiang

2015-11-13

There have been suggestions that currently recommended waist circumference (WC) cut-off points for Australians of European origin may not be applicable to Aboriginal people who have different body habitus profiles. We aimed to generate equivalent WC values that correspond to body mass index (BMI) points for identifying absolute cardiovascular disease (CVD) risks. Prospective cohort study. An Aboriginal community in Australia's Northern Territory. From 1992 to 1998, 920 adults without CVD, with age, WC and BMI measurements were followed-up for up to 20 years. Incident CVD, coronary artery disease (CAD) and heart failure (HF) events during the follow-up period ascertained from hospitalisation data. We generated WC values with 10-year absolute risks equivalent for the development of CVD as BMI values (20-34 kg/m(2)) using the Weibull accelerated time-failure model. There were 211 incident cases of CVD over 13,669 person-years of follow-up. At the average age of 35 years, WC values with absolute CVD, CAD and HF risks equivalent to BMI of 25 kg/m(2) were 91.5, 91.8 and 91.7 cm, respectively, for males, and corresponding WC values were 92.5, 92.7 and 93 cm for females. WC values with equal absolute CVD, CAD and HF risks to BMI of 30 kg/m(2) were 101.7, 103.1 and 102.6 cm, respectively, for males, and corresponding values were 99.2, 101.6 and 101.5 cm for females. Association between WC and CVD did not depend on gender (p=0.54). WC ranging from 91 to 93 cm was equivalent to BMI 25 kg/m(2) for overweight, and 99 to 103 cm was equivalent to BMI of 30 kg/m(2) for obesity in terms of predicting 10-year absolute CVD risk. Replicating the absolute risk method in other Aboriginal communities will further validate the WC values generated for future development of WC cut-off points for Aboriginal people. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A comparison study on various low energy sources in interstitial prostate brachytherapy

PubMed Central

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Knaup, Courtney; Meigooni, Ali S.

2016-01-01

Purpose Low energy sources are routinely used in prostate brachytherapy. 125I is one of the most commonly used sources. Low energy 131Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of 125I, 103Pd, and 131Cs sources in interstitial brachytherapy of prostate. Material and methods ProstaSeed 125I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of 103Pd and 131Cs were simulated with the same geometry as the ProstaSeed 125I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Results Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, 131Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the 103Pd source. Conclusions The higher initial absolute dose in cGy/(h.U) of 131Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the 103Pd source are advantages of this later brachytherapy source. Based on the total dose the 125I source has advantage over the others due to its longer half-life. PMID:26985200

A comparison study on various low energy sources in interstitial prostate brachytherapy.

PubMed

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Khosroabadi, Mohsen; Knaup, Courtney; Meigooni, Ali S

2016-02-01

Low energy sources are routinely used in prostate brachytherapy. (125)I is one of the most commonly used sources. Low energy (131)Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of (125)I, (103)Pd, and (131)Cs sources in interstitial brachytherapy of prostate. ProstaSeed (125)I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of (103)Pd and (131)Cs were simulated with the same geometry as the ProstaSeed (125)I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, (131)Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the (103)Pd source. The higher initial absolute dose in cGy/(h.U) of (131)Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the (103)Pd source are advantages of this later brachytherapy source. Based on the total dose the (125)I source has advantage over the others due to its longer half-life.

High-resolution absolute position detection using a multiple grating

NASA Astrophysics Data System (ADS)

Schilling, Ulrich; Drabarek, Pawel; Kuehnle, Goetz; Tiziani, Hans J.

1996-08-01

To control electro-mechanical engines, high-resolution linear and rotary encoders are needed. Interferometric methods (grating interferometers) promise a resolution of a few nanometers, but have an ambiguity range of some microns. Incremental encoders increase the absolute measurement range by counting the signal periods starting from a defined initial point. In many applications, however, it is not possible to move to this initial point, so that absolute encoders have to be used. Absolute encoders generally have a scale with two or more tracks placed next to each other. Therefore, they use a two-dimensional grating structure to measure a one-dimensional position. We present a new method, which uses a one-dimensional structure to determine the position in one dimension. It is based on a grating with a large grating period up to some millimeters, having the same diffraction efficiency in several predefined diffraction orders (multiple grating). By combining the phase signals of the different diffraction orders, it is possible to establish the position in an absolute range of the grating period with a resolution like incremental grating interferometers. The principal functionality was demonstrated by applying the multiple grating in a heterodyne grating interferometer. The heterodyne frequency was generated by a frequency modulated laser in an unbalanced interferometer. In experimental measurements an absolute range of 8 mm was obtained while achieving a resolution of 10 nm.

SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeid, L; Esteve, F; Adam, J

2014-06-15

Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0more » and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.« less

Stable isotope-labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults.

PubMed

de Vries, Ronald; Smit, Johan W; Hellemans, Peter; Jiao, James; Murphy, Joseph; Skee, Donna; Snoeys, Jan; Sukbuntherng, Juthamas; Vliegen, Maarten; de Zwart, Loeckie; Mannaert, Erik; de Jong, Jan

2016-02-01

Ibrutinib, an inhibitor of Bruton's tyrosine kinase, is used in the treatment of mantle cell lymphoma or chronic lymphocytic leukaemia. Ibrutinib undergoes extensive rapid oxidative metabolism mediated by cytochrome P450 3A both at the level of first pass and clearance, which might result in low oral bioavailability. The present study was designed to investigate the absolute bioavailability (F) of ibrutinib in the fasting and fed state and assess the effect of grapefruit juice (GFJ) on the systemic exposure of ibrutinib in order to determine the fraction escaping the gut (Fg ) and the fraction escaping hepatic extraction (Fh ) in the fed state. All participants received treatment A [560 mg oral ibrutinib, under fasting conditions], B (560 mg PO ibrutinib, fed, administered after drinking glucose drink) and C (140 mg oral ibrutinib, fed, with intake of GFJ before dosing). A single intravenous (i.v.) dose of 100 μg (13) C6 -ibrutinib was administered 2 h after each oral dose. The estimated 'F' for treatments A, B and C was 3.9%, 8.4% and 15.9%, respectively. Fg and Fh in the fed state were 47.0% and 15.9%, respectively. Adverse events were mild to moderate in severity (Grade 1-2) and resolved without sequelae by the end of the study. The absolute oral bioavailability of ibrutinib was low, ranging from 3.9% in the fasting state to 8.4% when administered 30 min before a standard breakfast without GFJ and 15.9% with GFJ. Ibrutinib was well tolerated following a single oral and i.v. dose, under both fasted and fed conditions and regardless of GFJ intake status. © 2015 The British Pharmacological Society.

Stable isotope‐labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults

PubMed Central

Smit, Johan W.; Hellemans, Peter; Jiao, James; Murphy, Joseph; Skee, Donna; Snoeys, Jan; Sukbuntherng, Juthamas; Vliegen, Maarten; de Zwart, Loeckie; Mannaert, Erik; de Jong, Jan

2016-01-01

Aims Ibrutinib, an inhibitor of Bruton's tyrosine kinase, is used in the treatment of mantle cell lymphoma or chronic lymphocytic leukaemia. Ibrutinib undergoes extensive rapid oxidative metabolism mediated by cytochrome P450 3A both at the level of first pass and clearance, which might result in low oral bioavailability. The present study was designed to investigate the absolute bioavailability (F) of ibrutinib in the fasting and fed state and assess the effect of grapefruit juice (GFJ) on the systemic exposure of ibrutinib in order to determine the fraction escaping the gut (Fg) and the fraction escaping hepatic extraction (Fh) in the fed state. Methods All participants received treatment A [560 mg oral ibrutinib, under fasting conditions], B (560 mg PO ibrutinib, fed, administered after drinking glucose drink) and C (140 mg oral ibrutinib, fed, with intake of GFJ before dosing). A single intravenous (i.v.) dose of 100 μg 13C6‐ibrutinib was administered 2 h after each oral dose. Results The estimated ‘F’ for treatments A, B and C was 3.9%, 8.4% and 15.9%, respectively. Fg and Fh in the fed state were 47.0% and 15.9%, respectively. Adverse events were mild to moderate in severity (Grade 1–2) and resolved without sequelae by the end of the study. Conclusion The absolute oral bioavailability of ibrutinib was low, ranging from 3.9% in the fasting state to 8.4% when administered 30 min before a standard breakfast without GFJ and 15.9% with GFJ. Ibrutinib was well tolerated following a single oral and i.v. dose, under both fasted and fed conditions and regardless of GFJ intake status. PMID:26382728

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

PubMed

Kaiser, Christoph; Galatius, Soeren; Jeger, Raban; Gilgen, Nicole; Skov Jensen, Jan; Naber, Christoph; Alber, Hannes; Wanitschek, Maria; Eberli, Franz; Kurz, David J; Pedrazzini, Giovanni; Moccetti, Tiziano; Rickli, Hans; Weilenmann, Daniel; Vuillomenet, André; Steiner, Martin; Von Felten, Stefanie; Vogt, Deborah R; Wadt Hansen, Kim; Rickenbacher, Peter; Conen, David; Müller, Christian; Buser, Peter; Hoffmann, Andreas; Pfisterer, Matthias

2015-01-06

Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. http://www.clinicaltrials.gov. Unique identifier: NCT01166685. © 2014 American Heart Association, Inc.

[Oral contraception].

PubMed

Montloin, A

1990-11-01

This brief discussion of the different types of oral contraceptives (OCs) makes abundant use of flow charts, tables, and diagrams to present information and stress specific points. The work begins by defining the different hypothalamic, pituitary, and ovarian hormones and diagramming and describing the menstrual cycle. A discussion of combined OCs defines and diagrams monophasic, biphasic, and triphasic pills, distinguishes between different dose levels, and describes the mechanisms of action of OCs. Sequential pills and their mechanism of action are briefly discussed. The discussion of OCs containing progestins distinguishes between low does pills and high dose pills and describes the use of injectable progestins. A table then lists the dose-dependent side effects of estrogens and progestins. Simple instructions are provided for administering pills beginning on the 1st cycle day and for actions to take in the event a pill is forgotten. A flow chart taking into account age and presence or absence of vascular and gynecologic risk factors indicates which type of OC should be selected. Some advantages of OCs are identified, including maximum effectiveness and prevention of benign breast disease and perhaps of some type of rheumatoid arthritis. Another flow chart, on patient monitoring, identifies the contraindications that should be ruled out before OCs are prescribed and the routine follow-up examinations required for safe use. Other charts list absolute and relative contraindications and possible drug interferences.

The existence of negative absolute temperatures in Axelrod’s social influence model

NASA Astrophysics Data System (ADS)

Villegas-Febres, J. C.; Olivares-Rivas, W.

2008-06-01

We introduce the concept of temperature as an order parameter in the standard Axelrod’s social influence model. It is defined as the relation between suitably defined entropy and energy functions, T=(. We show that at the critical point, where the order/disorder transition occurs, this absolute temperature changes in sign. At this point, which corresponds to the transition homogeneous/heterogeneous culture, the entropy of the system shows a maximum. We discuss the relationship between the temperature and other properties of the model in terms of cultural traits.

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

PubMed

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc.

Dosimetry for audit and clinical trials: challenges and requirements

NASA Astrophysics Data System (ADS)

Kron, T.; Haworth, A.; Williams, I.

2013-06-01

Many important dosimetry audit networks for radiotherapy have their roots in clinical trial quality assurance (QA). In both scenarios it is essential to test two issues: does the treatment plan conform with the clinical requirements and is the plan a reasonable representation of what is actually delivered to a patient throughout their course of treatment. Part of a sound quality program would be an external audit of these issues with verification of the equivalence of plan and treatment typically referred to as a dosimetry audit. The increasing complexity of radiotherapy planning and delivery makes audits challenging. While verification of absolute dose delivered at a reference point was the standard of external dosimetry audits two decades ago this is often deemed inadequate for verification of treatment approaches such as Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT). As such, most dosimetry audit networks have successfully introduced more complex tests of dose delivery using anthropomorphic phantoms that can be imaged, planned and treated as a patient would. The new challenge is to adapt this approach to ever more diversified radiotherapy procedures with image guided/adaptive radiotherapy, motion management and brachytherapy being the focus of current research.

Scattered radiation doses absorbed by technicians at different distances from X-ray exposure: Experiments on prosthesis.

PubMed

Chiang, Hsien-Wen; Liu, Ya-Ling; Chen, Tou-Rong; Chen, Chun-Lon; Chiang, Hsien-Jen; Chao, Shin-Yu

2015-01-01

This work aimed to investigate the spatial distribution of scattered radiation doses induced by exposure to the portable X-ray, the C-arm machine, and to simulate the radiologist without a shield of lead clothing, radiation doses absorbed by medical staff at 2 m from the central exposure point. With the adoption of the Rando Phantom, several frequently X-rayed body parts were exposed to X-ray radiation, and the scattered radiation doses were measured by ionization chamber dosimeters at various angles from the patient. Assuming that the central point of the X-ray was located at the belly button, five detection points were distributed in the operation room at 1 m above the ground and 1-2 m from the central point horizontally. The radiation dose measured at point B was the lowest, and the scattered radiation dose absorbed by the prosthesis from the X-ray's vertical projection was 0.07 ±0.03 μGy, which was less than the background radiation levels. The Fluke biomedical model 660-5DE (400 cc) and 660-3DE (4 cc) ion chambers were used to detect air dose at a distance of approximately two meters from the central point. The AP projection radiation doses at point B was the lowest (0.07±0.03 μGy) and the radiation doses at point D was the highest (0.26±0.08 μGy) .Only taking the vertical projection into account, the radiation doses at point B was the lowest (0.52 μGy), and the radiation doses at point E was the highest (4 μGy).The PA projection radiation at point B was the lowest (0.36 μGy) and the radiation doses at point E was the highest(2.77 μGy), occupying 10-32% of the maximum doses. The maximum dose in five directions was nine times to the minimum dose. When the PX and the C-arm machine were used, the radiation doses at a distance of 2 m were attenuated to the background radiation level. The radiologist without a lead shield should stand at point B of patient's feet. Accordingly, teaching materials on radiation safety for radiological interns and clinical technicians were formulated.

Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

PubMed

Stang, Andreas; Schuler, Martin; Kowall, Bernd; Darwiche, Kaid; Kühl, Hilmar; Jöckel, Karl-Heinz

2015-09-18

It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany. The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany. If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening. The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

[Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

PubMed

Raschka, C; Koch, H J

2001-01-01

We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks.

Some Radiation Techniques Used in the GU-3 Gamma Irradiator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dodbiba, Andon; Ylli, Ariana; Stamo, Iliriana

2007-04-23

Different radiation techniques, measurement of dose and its distibution throughout the irradiated materials are the main problems treated in this paper. The oscillometry method combined with the ionization chamber, as an absolute dosimeter, is used for calibration of routine ECB dosimeters. The dose uniformity, for the used radiation techniques in our GU-3 Gamma Irradiator with Cs-137, is from 93% up to 99%.

Risk of Developing Cardiovascular Disease After Involved Node Radiotherapy Versus Mantle Field for Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maraldo, Maja V., E-mail: dra.maraldo@gmail.com; Brodin, Nils Patrik; Vogelius, Ivan R.

2012-07-15

Purpose: Hodgkin lymphoma (HL) survivors are known to have increased cardiac mortality and morbidity. The risk of developing cardiovascular disease after involved node radiotherapy (INRT) is currently unresolved, inasmuch as present clinical data are derived from patients treated with the outdated mantle field (MF) technique. Methods and Materials: We included all adolescents and young adults with supradiaphragmatic, clinical Stage I-II HL treated at our institution from 2006 to 2010 (29 patients). All patients were treated with chemotherapy and INRT to 30 to 36 Gy. We then simulated a MF plan for each patient with a prescribed dose of 36 Gy.more » A logistic dose-response curve for the 25-year absolute excess risk of cardiovascular disease was derived and applied to each patient using the individual dose-volume histograms. Results: The mean doses to the heart, four heart valves, and coronary arteries were significantly lower for INRT than for MF treatment. However, the range in doses with INRT treatment was substantial, and for a subgroup of patients, with lymphoma below the fourth thoracic vertebrae, we estimated a 25-year absolute excess risk of any cardiac event of as much as 5.1%. Conclusions: Our study demonstrates a potential for individualizing treatment by selecting the patients for whom INRT provides sufficient cardiac protection for current technology; and a subgroup of patients, who still receive high cardiac doses, who would benefit from more advanced radiation technique.« less

The impact of water temperature on the measurement of absolute dose

NASA Astrophysics Data System (ADS)

Islam, Naveed Mehdi

To standardize reference dosimetry in radiation therapy, Task Group 51 (TG 51) of American Association of Physicist's in Medicine (AAPM) recommends that dose calibration measurements be made in a water tank at a depth of 10 cm and at a reference geometry. Methodologies are provided for calculating various correction factors to be applied in calculating the absolute dose. However the protocol does not specify the water temperature to be used. In practice, the temperature of water during dosimetry may vary considerably between independent sessions and different centers. In this work the effect of water temperature on absolute dosimetry has been investigated. Density of water varies with temperature, which in turn may impact the beam attenuation and scatter properties. Furthermore, due to thermal expansion or contraction air volume inside the chamber may change. All of these effects can result in a change in the measurement. Dosimetric measurements were made using a Farmer type ion chamber on a Varian Linear Accelerator for 6 MV and 23 MV photon energies for temperatures ranging from 10 to 40 °C. A thermal insulation was designed for the water tank in order to maintain relatively stable temperature over the duration of the experiment. Dose measured at higher temperatures were found to be consistently higher by a very small magnitude. Although the differences in dose were less than the uncertainty in each measurement, a linear regression of the data suggests that the trend is statistically significant with p-values of 0.002 and 0.013 for 6 and 23 MV beams respectively. For a 10 degree difference in water phantom temperatures, which is a realistic deviation across clinics, the final calculated reference dose can differ by 0.24% or more. To address this effect, first a reference temperature (e.g.22 °C) can be set as the standard; subsequently a correction factor can be implemented for deviations from this reference. Such a correction factor is expected to be of similar magnitude as existing TG 51 recommended correction factors.

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination

PubMed Central

Schneider, M; Paulin, A; Dron, F; Woehrlé, F

2014-01-01

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl®). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4–16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. PMID:24666477

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

PubMed

Schneider, M; Paulin, A; Dron, F; Woehrlé, F

2014-12-01

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, H; Menon, G; Sloboda, R

The purpose of this study was to investigate the accuracy of radiochromic film calibration procedures used in external beam radiotherapy when applied to I-125 brachytherapy sources delivering higher doses, and to determine any necessary modifications to achieve similar accuracy in absolute dose measurements. GafChromic EBT3 film was used to measure radiation doses upwards of 35 Gy from 6 MV, 75 kVp and (∼28 keV) I-125 photon sources. A custom phantom was used for the I-125 irradiations to obtain a larger film area with nearly constant dose to reduce the effects of film heterogeneities on the optical density (OD) measurements. RGBmore » transmission images were obtained with an Epson 10000XL flatbed scanner, and calibration curves relating OD and dose using a rational function were determined for each colour channel and at each energy using a non-linear least square minimization method. Differences found between the 6 MV calibration curve and those for the lower energy sources are large enough that 6 MV beams should not be used to calibrate film for low-energy sources. However, differences between the 75 kVp and I-125 calibration curves were quite small; indicating that 75 kVp is a good choice. Compared with I-125 irradiation, this gives the advantages of lower type B uncertainties and markedly reduced irradiation time. To obtain high accuracy calibration for the dose range up to 35 Gy, two-segment piece-wise fitting was required. This yielded absolute dose measurement accuracy above 1 Gy of ∼2% for 75 kVp and ∼5% for I-125 seed exposures.« less

Diagnostic accuracy of 256-row multidetector CT coronary angiography with prospective ECG-gating combined with fourth-generation iterative reconstruction algorithm in the assessment of coronary artery bypass: evaluation of dose reduction and image quality.

PubMed

Ippolito, Davide; Fior, Davide; Franzesi, Cammillo Talei; Riva, Luca; Casiraghi, Alessandra; Sironi, Sandro

2017-12-01

Effective radiation dose in coronary CT angiography (CTCA) for coronary artery bypass graft (CABG) evaluation is remarkably high because of long scan lengths. Prospective electrocardiographic gating with iterative reconstruction can reduce effective radiation dose. To evaluate the diagnostic performance of low-kV CT angiography protocol with prospective ecg-gating technique and iterative reconstruction (IR) algorithm in follow-up of CABG patients compared with standard retrospective protocol. Seventy-four non-obese patients with known coronary disease treated with artery bypass grafting were prospectively enrolled. All the patients underwent 256 MDCT (Brilliance iCT, Philips) CTCA using low-dose protocol (100 kV; 800 mAs; rotation time: 0.275 s) combined with prospective ECG-triggering acquisition and fourth-generation IR technique (iDose 4 ; Philips); all the lengths of the bypass graft were included in the evaluation. A control group of 42 similar patients was evaluated with a standard retrospective ECG-gated CTCA (100 kV; 800 mAs).On both CT examinations, ROIs were placed to calculate standard deviation of pixel values and intra-vessel density. Diagnostic quality was also evaluated using a 4-point quality scale. Despite the statistically significant reduction of radiation dose evaluated with DLP (study group mean DLP: 274 mGy cm; control group mean DLP: 1224 mGy cm; P value < 0.001). No statistical differences were found between PGA group and RGH group regarding intra-vessel density absolute values and SNR. Qualitative analysis, evaluated by two radiologists in "double blind", did not reveal any significant difference in diagnostic quality of the two groups. The development of high-speed MDCT scans combined with modern IR allows an accurate evaluation of CABG with prospective ECG-gating protocols in a single breath hold, obtaining a significant reduction in radiation dose.

Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method.

PubMed

Khosravi, H; Hashemi, B; Mahdavi, S R; Hejazi, P

2015-03-01

Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokharel, S; Rana, S

Purpose: purpose of this study is to evaluate the effect of grid size in Eclipse AcurosXB dose calculation algorithm for SBRT lung. Methods: Five cases of SBRT lung previously treated have been chosen for present study. Four of the plans were 5 fields conventional IMRT and one was Rapid Arc plan. All five cases have been calculated with five grid sizes (1, 1.5, 2, 2.5 and 3mm) available for AXB algorithm with same plan normalization. Dosimetric indices relevant to SBRT along with MUs and time have been recorded for different grid sizes. The maximum difference was calculated as a percentagemore » of mean of all five values. All the plans were IMRT QAed with portal dosimetry. Results: The maximum difference of MUs was within 2%. The time increased was as high as 7 times from highest 3mm to lowest 1mm grid size. The largest difference of PTV minimum, maximum and mean dose were 7.7%, 1.5% and 1.6% respectively. The highest D2-Max difference was 6.1%. The highest difference in ipsilateral lung mean, V5Gy, V10Gy and V20Gy were 2.6%, 2.4%, 1.9% and 3.8% respectively. The maximum difference of heart, cord and esophagus dose were 6.5%, 7.8% and 4.02% respectively. The IMRT Gamma passing rate at 2%/2mm remains within 1.5% with at least 98% points passing with all grid sizes. Conclusion: This work indicates the lowest grid size of 1mm available in AXB is not necessarily required for accurate dose calculation. The IMRT passing rate was insignificant or not observed with the reduction of grid size less than 2mm. Although the maximum percentage difference of some of the dosimetric indices appear large, most of them are clinically insignificant in absolute dose values. So we conclude that 2mm grid size calculation is best compromise in light of dose calculation accuracy and time it takes to calculate dose.« less

Absolute versus relative intensity of physical activity in a dose-response context.

PubMed

Shephard, R J

2001-06-01

To examine the importance of relative versus absolute intensities of physical activity in the context of population health. A standard computer-search of the literature was supplemented by review of extensive personal files. Consensus reports (Category D Evidence) have commonly recommended moderate rather than hard physical activity in the context of population health. Much of the available literature provides Category C Evidence. It has often confounded issues of relative intensity with absolute intensity or total weekly dose of exercise. In terms of cardiovascular health, there is some evidence for a threshold intensity of effort, perhaps as high as 6 METs, in addition to a minimum volume of physical activity. Decreases in blood pressure and prevention of stroke seem best achieved by moderate rather than high relative intensities of physical activity. Many aspects of metabolic health depend on the total volume of activity; moderate relative intensities of effort are more effective in mobilizing body fat, but harder relative intensities may help to increase energy expenditures postexercise. Hard relative intensities seem needed to augment bone density, but this may reflect an associated increase in volume of activity. Hard relative intensities of exercise induce a transient immunosuppression. The optimal intensity of effort, relative or absolute, for protection against various types of cancer remains unresolved. Acute effects of exercise on mood state also require further study; long-term benefits seem associated with a moderate rather than a hard relative intensity of effort. The importance of relative versus absolute intensity of effort depends on the desired health outcome, and many issues remain to be resolved. Progress will depend on more precise epidemiological methods of assessing energy expenditures and studies that equate total energy expenditures between differing relative intensities. There is a need to focus on gains in quality-adjusted life expectancy.

Calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry assays and its application in supporting microdose absolute bioavailability studies.

PubMed

Gu, Huidong; Wang, Jian; Aubry, Anne-Françoise; Jiang, Hao; Zeng, Jianing; Easter, John; Wang, Jun-sheng; Dockens, Randy; Bifano, Marc; Burrell, Richard; Arnold, Mark E

2012-06-05

A methodology for the accurate calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays and its application in supporting microdose absolute bioavailability studies are reported for the first time. For simplicity, this calculation methodology and the strategy to minimize the isotopic interference are demonstrated using a simple molecule entity, then applied to actual development drugs. The exact isotopic interferences calculated with this methodology were often much less than the traditionally used, overestimated isotopic interferences simply based on the molecular isotope abundance. One application of the methodology is the selection of a stable isotopically labeled internal standard (SIL-IS) for an LC-MS/MS bioanalytical assay. The second application is the selection of an SIL analogue for use in intravenous (i.v.) microdosing for the determination of absolute bioavailability. In the case of microdosing, the traditional approach of calculating isotopic interferences can result in selecting a labeling scheme that overlabels the i.v.-dosed drug or leads to incorrect conclusions on the feasibility of using an SIL drug and analysis by LC-MS/MS. The methodology presented here can guide the synthesis by accurately calculating the isotopic interferences when labeling at different positions, using different selective reaction monitoring (SRM) transitions or adding more labeling positions. This methodology has been successfully applied to the selection of the labeled i.v.-dosed drugs for use in two microdose absolute bioavailability studies, before initiating the chemical synthesis. With this methodology, significant time and cost saving can be achieved in supporting microdose absolute bioavailability studies with stable labeled drugs.

The Long-Wave Infrared Earth Image as a Pointing Reference for Deep-Space Optical Communications

NASA Astrophysics Data System (ADS)

Biswas, A.; Piazzolla, S.; Peterson, G.; Ortiz, G. G.; Hemmati, H.

2006-11-01

Optical communications from space require an absolute pointing reference. Whereas at near-Earth and even planetary distances out to Mars and Jupiter a laser beacon transmitted from Earth can serve as such a pointing reference, for farther distances extending to the outer reaches of the solar system, the means for meeting this requirement remains an open issue. We discuss in this article the prospects and consequences of utilizing the Earth image sensed in the long-wave infrared (LWIR) spectral band as a beacon to satisfy the absolute pointing requirements. We have used data from satellite-based thermal measurements of Earth to synthesize images at various ranges and have shown the centroiding accuracies that can be achieved with prospective LWIR image sensing arrays. The nonuniform emissivity of Earth causes a mispointing bias error term that exceeds a provisional pointing budget allocation when using simple centroiding algorithms. Other issues related to implementing thermal imaging of Earth from deep space for the purposes of providing a pointing reference are also reported.

An absolute interval scale of order for point patterns

PubMed Central

Protonotarios, Emmanouil D.; Baum, Buzz; Johnston, Alan; Hunter, Ginger L.; Griffin, Lewis D.

2014-01-01

Human observers readily make judgements about the degree of order in planar arrangements of points (point patterns). Here, based on pairwise ranking of 20 point patterns by degree of order, we have been able to show that judgements of order are highly consistent across individuals and the dimension of order has an interval scale structure spanning roughly 10 just-notable-differences (jnd) between disorder and order. We describe a geometric algorithm that estimates order to an accuracy of half a jnd by quantifying the variability of the size and shape of spaces between points. The algorithm is 70% more accurate than the best available measures. By anchoring the output of the algorithm so that Poisson point processes score on average 0, perfect lattices score 10 and unit steps correspond closely to jnds, we construct an absolute interval scale of order. We demonstrate its utility in biology by using this scale to quantify order during the development of the pattern of bristles on the dorsal thorax of the fruit fly. PMID:25079866

Using lean "automation with a human touch" to improve medication safety: a step closer to the "perfect dose".

PubMed

Ching, Joan M; Williams, Barbara L; Idemoto, Lori M; Blackmore, C Craig

2014-08-01

Virginia Mason Medical Center (Seattle) employed the Lean concept of Jidoka (automation with a human touch) to plan for and deploy bar code medication administration (BCMA) to hospitalized patients. Integrating BCMA technology into the nursing work flow with minimal disruption was accomplished using three steps ofJidoka: (1) assigning work to humans and machines on the basis of their differing abilities, (2) adapting machines to the human work flow, and (3) monitoring the human-machine interaction. Effectiveness of BCMA to both reinforce safe administration practices and reduce medication errors was measured using the Collaborative Alliance for Nursing Outcomes (CALNOC) Medication Administration Accuracy Quality Study methodology. Trained nurses observed a total of 16,149 medication doses for 3,617 patients in a three-year period. Following BCMA implementation, the number of safe practice violations decreased from 54.8 violations/100 doses (January 2010-September 2011) to 29.0 violations/100 doses (October 2011-December 2012), resulting in an absolute risk reduction of 25.8 violations/100 doses (95% confidence interval [CI]: 23.7, 27.9, p < .001). The number of medication errors decreased from 5.9 errors/100 doses at baseline to 3.0 errors/100 doses after BCMA implementation (absolute risk reduction: 2.9 errors/100 doses [95% CI: 2.2, 3.6,p < .001]). The number of unsafe administration practices (estimate, -5.481; standard error 1.133; p < .001; 95% CI: -7.702, -3.260) also decreased. As more hospitals respond to health information technology meaningful use incentives, thoughtful, methodical, and well-managed approaches to technology deployment are crucial. This work illustrates how Jidoka offers opportunities for a smooth transition to new technology.

Evaluation of equivalent and effective dose by KAP for patient and orthopedic surgeon in vertebral compression fracture surgery

NASA Astrophysics Data System (ADS)

Santos, Felipe A.; Galeano, Diego C.; Santos, William S.; Silva, Ademir X.; Souza, Susana O.; Carvalho Júnior, Albérico B.

2017-03-01

Clinical scenarios were virtually modeled to estimate both the equivalent and effective doses normalized by KAP (Kerma Area Product) to vertebra compression fracture surgery in patient and surgeon. This surgery is known as kyphoplasty and involves the use of X-ray equipment, the C-arm, which provides real-time images to assist the surgeon in conducting instruments inserted into the patient and in the delivery of surgical cement into the fractured vertebra. The radiation transport code used was MCNPX (Monte Carlo N-Particle eXtended) and a pair of UFHADM (University of Florida Hybrid ADult Male) virtual phantoms. The developed scenarios allowed us to calculate a set of equivalent dose (HT) and effective dose (E) for patients and surgeons. In additional, the same scenario was calculated KAP in the tube output and was used for calculating conversion coefficients (E/KAP and HT/KAP). From the knowledge of the experimental values of KAP and the results presented in this study, it is possible to estimate absolute values of effective doses for different exposure conditions. In this work, we developed scenarios with and without the surgical table with the purpose of comparison with the existing data in the literature. The absence of the bed in the scenario promoted a percentage absolute difference of 56% in the patient effective doses in relation to scenarios calculated with a bed. Regarding the surgeon, the use of the personal protective equipment (PPE) reduces between 75% and 79% the effective dose and the use of the under table shield (UTS) reduces the effective dose of between 3% and 7%. All these variations emphasize the importance of the elaboration of virtual scenarios that approach the actual clinical conditions generating E/KAP and HT/KAP closer to the actual values.

A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.

PubMed

Cini, Michela; Legnani, Cristina; Cosmi, Benilde; Guazzaloca, Giuliana; Valdrè, Lelia; Frascaro, Mirella; Palareti, Gualtiero

2012-08-01

Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 04: On 3D Fabrication of Phantoms and Experimental Verification of Patient Dose Computation Algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Rao; Zavan, Rodolfo; McGeachy, Philip

2016-08-15

Purpose: Transport based dose calculation algorithm Acuros XB (AXB) has been shown to accurately account for heterogeneities mostly through comparisons with Monte Carlo simulations. This study aims at providing additional experimental verification for AXB for flattened and unflattened clinical energies in low density phantoms of the same material. Materials and Methods: Polystyrene slabs were created using a bench-top 3D printer. Six slabs were printed at varying densities from 0.23 g/cm{sup 3} to 0.68 g/cm{sup 3}, corresponding to different density humanoid tissues. The slabs were used to form different single and multilayer geometries. Dose was calculated with AXB 11.0.31 for 6MV,more » 15MV flattened and 6FFF (flattening filter free) energies for field sizes of 2×2 cm{sup 2} and 5×5 cm{sup 2}. The phantoms containing radiochromic EBT3 films were irradiated. Absolute dose profiles and 2D gamma analyses were performed for 96 dose planes. Results: For all single slab, multislab configurations and energies, absolute dose differences between the AXB calculation and film measurements remained <3% for both fields, with slightly poor disagreement in penumbra. The gamma index at 2% / 2mm averaged 98% in all combinations of fields, phantoms and photon energies. Conclusions: The transport based dose algorithm AXB is in good agreement with the experimental measurements for small field sizes using 6MV, 6FFF and 15MV beams adjacent to low density heterogeneous media. This work provides sufficient experimental ground to support the use of AXB for heterogeneous dose calculation purposes.« less

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Absolute instability of the Gaussian wake profile

NASA Technical Reports Server (NTRS)

Hultgren, Lennart S.; Aggarwal, Arun K.

1987-01-01

Linear parallel-flow stability theory has been used to investigate the effect of viscosity on the local absolute instability of a family of wake profiles with a Gaussian velocity distribution. The type of local instability, i.e., convective or absolute, is determined by the location of a branch-point singularity with zero group velocity of the complex dispersion relation for the instability waves. The effects of viscosity were found to be weak for values of the wake Reynolds number, based on the center-line velocity defect and the wake half-width, larger than about 400. Absolute instability occurs only for sufficiently large values of the center-line wake defect. The critical value of this parameter increases with decreasing wake Reynolds number, thereby indicating a shrinking region of absolute instability with decreasing wake Reynolds number. If backflow is not allowed, absolute instability does not occur for wake Reynolds numbers smaller than about 38.

Free-energy calculations using classical molecular simulation: application to the determination of the melting point and chemical potential of a flexible RDX model.

PubMed

Sellers, Michael S; Lísal, Martin; Brennan, John K

2016-03-21

We present an extension of various free-energy methodologies to determine the chemical potential of the solid and liquid phases of a fully-flexible molecule using classical simulation. The methods are applied to the Smith-Bharadwaj atomistic potential representation of cyclotrimethylene trinitramine (RDX), a well-studied energetic material, to accurately determine the solid and liquid phase Gibbs free energies, and the melting point (Tm). We outline an efficient technique to find the absolute chemical potential and melting point of a fully-flexible molecule using one set of simulations to compute the solid absolute chemical potential and one set of simulations to compute the solid-liquid free energy difference. With this combination, only a handful of simulations are needed, whereby the absolute quantities of the chemical potentials are obtained, for use in other property calculations, such as the characterization of crystal polymorphs or the determination of the entropy. Using the LAMMPS molecular simulator, the Frenkel and Ladd and pseudo-supercritical path techniques are adapted to generate 3rd order fits of the solid and liquid chemical potentials. Results yield the thermodynamic melting point Tm = 488.75 K at 1.0 atm. We also validate these calculations and compare this melting point to one obtained from a typical superheated simulation technique.

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, You; Yin, Fang-Fang; Ren, Lei, E-mail: lei.ren@duke.edu

2015-08-15

Purpose: Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Methods: Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated onmore » the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the “gold-standard” on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔD{sub min}), maximum dose (ΔD{sub max}), and mean dose (ΔD{sub mean}), and the absolute deviations of prescription dose coverage (ΔV{sub 100%}) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Results: Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). Conclusions: MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.« less

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

PubMed

Wang, Kang-Ling; Giugliano, Robert P; Goto, Shinya; Chiu, Chun-Chih; Lin, Chun-Yi; Lai, En-Yu; Chiang, Chern-En

2016-12-01

Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia. The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs. We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method. Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants. In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Comparison of elicitation potential of chloroatranol and atranol--2 allergens in oak moss absolute.

PubMed

Johansen, Jeanne D; Bernard, Guillaume; Giménez-Arnau, Elena; Lepoittevin, Jean-Pierre; Bruze, Magnus; Andersen, Klaus E

2006-04-01

Chloroatranol and atranol are degradation products of chloroatranorin and atranorin, respectively, and have recently been identified as important contact allergens in the natural fragrance extract, oak moss absolute. Oak moss absolute is widely used in perfumery and is the cause of many cases of fragrance allergic contact dermatitis. Chloroatranol elicits reactions at very low levels of exposure. In oak moss absolute, chloroatranol and atranol are present together and both may contribute to the allergenicity and eliciting capacity of the natural extract. In this study, 10 eczema patients with known sensitization to chloroatranol and oak moss absolute were tested simultaneously to a serial dilution of chloroatranol and atranol in ethanol, in equimolar concentrations (0.0034-1072 microM). Dose-response curves were estimated and analysed by logistic regression. The estimated difference in elicitation potency of chloroatranol relative to atranol based on testing with equimolar concentrations was 217% (95% confidence interval 116-409%). Both substances elicited reactions at very low levels of exposure. It is concluded that the differences in elicitation capacity between the 2 substances are counterbalanced by exposure being greater to atranol than to chloroatranol and that both substances contribute to the clinical problems seen in oak moss absolute-sensitized individuals.

Digital evaluation of absolute marginal discrepancy: A comparison of ceramic crowns fabricated with conventional and digital techniques.

PubMed

Liang, Shanshan; Yuan, Fusong; Luo, Xu; Yu, Zhuoren; Tang, Zhihui

2018-04-05

Marginal discrepancy is key to evaluating the accuracy of fixed dental prostheses. An improved method of evaluating marginal discrepancy is needed. The purpose of this in vitro study was to evaluate the absolute marginal discrepancy of ceramic crowns fabricated using conventional and digital methods with a digital method for the quantitative evaluation of absolute marginal discrepancy. The novel method was based on 3-dimensional scanning, iterative closest point registration techniques, and reverse engineering theory. Six standard tooth preparations for the right maxillary central incisor, right maxillary second premolar, right maxillary second molar, left mandibular lateral incisor, left mandibular first premolar, and left mandibular first molar were selected. Ten conventional ceramic crowns and 10 CEREC crowns were fabricated for each tooth preparation. A dental cast scanner was used to obtain 3-dimensional data of the preparations and ceramic crowns, and the data were compared with the "virtual seating" iterative closest point technique. Reverse engineering software used edge sharpening and other functional modules to extract the margins of the preparations and crowns. Finally, quantitative evaluation of the absolute marginal discrepancy of the ceramic crowns was obtained from the 2-dimensional cross-sectional straight-line distance between points on the margin of the ceramic crowns and the standard preparations based on the circumferential function module along the long axis. The absolute marginal discrepancy of the ceramic crowns fabricated using conventional methods was 115 ±15.2 μm, and 110 ±14.3 μm for those fabricated using the digital technique was. ANOVA showed no statistical difference between the 2 methods or among ceramic crowns for different teeth (P>.05). The digital quantitative evaluation method for the absolute marginal discrepancy of ceramic crowns was established. The evaluations determined that the absolute marginal discrepancies were within a clinically acceptable range. This method is acceptable for the digital evaluation of the accuracy of complete crowns. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Potential utilization of the absolute point cumulative semivariogram technique for the evaluation of distribution coefficient.

PubMed

Külahci, Fatih; Sen, Zekâi

2009-09-15

The classical solid/liquid distribution coefficient, K(d), for radionuclides in water-sediment systems is dependent on many parameters such as flow, geology, pH, acidity, alkalinity, total hardness, radioactivity concentration, etc. in a region. Considerations of all these effects require a regional analysis with an effective methodology, which has been based on the concept of the cumulative semivariogram concept in this paper. Although classical K(d) calculations are punctual and cannot represent regional pattern, in this paper a regional calculation methodology is suggested through the use of Absolute Point Cumulative SemiVariogram (APCSV) technique. The application of the methodology is presented for (137)Cs and (90)Sr measurements at a set of points in Keban Dam reservoir, Turkey.

Is Dose Deformation–Invariance Hypothesis Verified in Prostate IGRT?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, Antoine, E-mail: antoine.simon@univ-rennes1.fr; Laboratoire Traitement du Signal et de l'Image, Université de Rennes 1, 35000 Rennes; Le Maitre, Amandine

Purpose: To assess dose uncertainties resulting from the dose deformation–invariance hypothesis in prostate cone beam computed tomography (CT)–based image guided radiation therapy (IGRT), namely to evaluate whether rigidly propagated planned dose distribution enables good estimation of fraction dose distributions. Methods and Materials: Twenty patients underwent a CT scan for planning intensity modulated radiation therapy–IGRT delivering 80 Gy to the prostate, followed by weekly CT scans. Two methods were used to obtain the dose distributions on the weekly CT scans: (1) recalculating the dose using the original treatment plan; and (2) rigidly propagating the planned dose distribution. The cumulative doses were then estimatedmore » in the organs at risk for each dose distribution by deformable image registration. The differences between recalculated and propagated doses were finally calculated for the fraction and the cumulative dose distributions, by use of per-voxel and dose-volume histogram (DVH) metrics. Results: For the fraction dose, the mean per-voxel absolute dose difference was <1 Gy for 98% and 95% of the fractions for the rectum and bladder, respectively. The maximum dose difference within 1 voxel reached, however, 7.4 Gy in the bladder and 8.0 Gy in the rectum. The mean dose differences were correlated with gas volume for the rectum and patient external contour variations for the bladder. The mean absolute differences for the considered volume receiving greater than or equal to dose x (V{sub x}) of the DVH were between 0.37% and 0.70% for the rectum and between 0.53% and 1.22% for the bladder. For the cumulative dose, the mean differences in the DVH were between 0.23% and 1.11% for the rectum and between 0.55% and 1.66% for the bladder. The largest dose difference was 6.86%, for bladder V{sub 80Gy}. The mean dose differences were <1.1 Gy for the rectum and <1 Gy for the bladder. Conclusions: The deformation–invariance hypothesis was corroborated for the organs at risk in prostate IGRT except in cases of a large disappearance or appearance of rectal gas for the rectum and large external contour variations for the bladder.« less

Absolute measurements of the triplet-triplet annihilation rate and the charge-carrier recombination layer thickness in working polymer light-emitting diodes based on polyspirobifluorene

NASA Astrophysics Data System (ADS)

Rothe, C.; Al Attar, H. A.; Monkman, A. P.

2005-10-01

The triplet exciton densities in electroluminescent devices prepared from two polyspirobifluorene derivatives have been investigated by means of time-resolved transient triplet absorption as a function of optical and electrical excitation power at 20 K. Because of the low mobility of the triplet excitons at this temperature, the triplet generation profile within the active polymer layer is preserved throughout the triplet lifetime and as a consequence the absolute triplet-triplet annihilation efficiency is not homogeneously distributed but depends on position within the active layer. This then gives a method to measure the charge-carrier recombination layer after electrical excitation relative to the light penetration depth, which is identical to the triplet generation layer after optical excitation. With the latter being obtained from ellipsometry, an absolute value of 5 nm is found for the exciton formation layer in polyspirobifluorene devices. This layer increases to 11 nm if the balance between the electron and the hole mobility is improved by chemically modifying the polymer backbone. Also, and consistent with previous work, triplet diffusion is dispersive at low temperature. As a consequence of this, the triplet-triplet annihilation rate is not a constant in the classical sense but depends on the triplet excitation dose. At 20 K and for typical excitation doses, absolute values of the latter rate are of the order of 10-14cm3s-1 .

Accuracy of Monte Carlo photon transport simulation in characterizing brachytherapy dosimeter energy-response artefacts

NASA Astrophysics Data System (ADS)

Das, R. K.; Li, Z.; Perera, H.; Williamson, J. F.

1996-06-01

Practical dosimeters in brachytherapy, such as thermoluminescent dosimeters (TLD) and diodes, are usually calibrated against low-energy megavoltage beams. To measure absolute dose rate near a brachytherapy source, it is necessary to establish the energy response of the detector relative to that of the calibration energy. The purpose of this paper is to assess the accuracy of Monte Carlo photon transport (MCPT) simulation in modelling the absolute detector response as a function of detector geometry and photon energy. We have exposed two different sizes of TLD-100 (LiF chips) and p-type silicon diode detectors to calibrated , HDR source and superficial x-ray beams. For the Scanditronix electron-field diode, the relative detector response, defined as the measured detector readings per measured unit of air kerma, varied from (40 kVp beam) to ( beam). Similarly for the large and small chips the same quantity varied from and , respectively. Monte Carlo simulation was used to calculate the absorbed dose to the active volume of the detector per unit air kerma. If the Monte Carlo simulation is accurate, then the absolute detector response, which is defined as the measured detector reading per unit dose absorbed by the active detector volume, and is calculated by Monte Carlo simulation, should be a constant. For the diode, the absolute response is . For TLDs of size the absolute response is and for TLDs of it is . From the above results we can conclude that the absolute response function of detectors (TLDs and diodes) is directly proportional to absorbed dose by the active volume of the detector and is independent of beam quality.

Calibrating page sized Gafchromic EBT3 films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crijns, W.; Maes, F.; Heide, U. A. van der

2013-01-15

Purpose: The purpose is the development of a novel calibration method for dosimetry with Gafchromic EBT3 films. The method should be applicable for pretreatment verification of volumetric modulated arc, and intensity modulated radiotherapy. Because the exposed area on film can be large for such treatments, lateral scan errors must be taken into account. The correction for the lateral scan effect is obtained from the calibration data itself. Methods: In this work, the film measurements were modeled using their relative scan values (Transmittance, T). Inside the transmittance domain a linear combination and a parabolic lateral scan correction described the observed transmittancemore » values. The linear combination model, combined a monomer transmittance state (T{sub 0}) and a polymer transmittance state (T{sub {infinity}}) of the film. The dose domain was associated with the observed effects in the transmittance domain through a rational calibration function. On the calibration film only simple static fields were applied and page sized films were used for calibration and measurements (treatment verification). Four different calibration setups were considered and compared with respect to dose estimation accuracy. The first (I) used a calibration table from 32 regions of interest (ROIs) spread on 4 calibration films, the second (II) used 16 ROIs spread on 2 calibration films, the third (III), and fourth (IV) used 8 ROIs spread on a single calibration film. The calibration tables of the setups I, II, and IV contained eight dose levels delivered to different positions on the films, while for setup III only four dose levels were applied. Validation was performed by irradiating film strips with known doses at two different time points over the course of a week. Accuracy of the dose response and the lateral effect correction was estimated using the dose difference and the root mean squared error (RMSE), respectively. Results: A calibration based on two films was the optimal balance between cost effectiveness and dosimetric accuracy. The validation resulted in dose errors of 1%-2% for the two different time points, with a maximal absolute dose error around 0.05 Gy. The lateral correction reduced the RMSE values on the sides of the film to the RMSE values at the center of the film. Conclusions: EBT3 Gafchromic films were calibrated for large field dosimetry with a limited number of page sized films and simple static calibration fields. The transmittance was modeled as a linear combination of two transmittance states, and associated with dose using a rational calibration function. Additionally, the lateral scan effect was resolved in the calibration function itself. This allows the use of page sized films. Only two calibration films were required to estimate both the dose and the lateral response. The calibration films were used over the course of a week, with residual dose errors Less-Than-Or-Slanted-Equal-To 2% or Less-Than-Or-Slanted-Equal-To 0.05 Gy.« less

A single dose comparison of a combination of fenoterol and ipratropium aerosols in bronchial asthma.

PubMed Central

Lawford, P.; Palmer, K. N.

1983-01-01

Nine patients with reversible obstructive airways disease were studied to compare the bronchodilator response to a combination of fenoterol and ipratropium aerosols with two dose levels of fenoterol alone. Using a double-blind, cross-over, single dose regime, 200 micrograms fenoterol hydrobromide and 80 micrograms ipratropium bromide was compared to 400 micrograms fenoterol + placebo, and to 200 micrograms fenoterol + placebo. There was no significant difference between the combination and either dose of fenoterol in terms of peak or duration of response as determined by absolute or percent change in forced expiratory volume in one second, or forced vital capacity, over baseline. PMID:6223289

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Rachel; Ng, Angela; Constine, Louis S.

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohortmore » and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.« less

Absolute calibration of optical flats

DOEpatents

Sommargren, Gary E.

2005-04-05

The invention uses the phase shifting diffraction interferometer (PSDI) to provide a true point-by-point measurement of absolute flatness over the surface of optical flats. Beams exiting the fiber optics in a PSDI have perfect spherical wavefronts. The measurement beam is reflected from the optical flat and passed through an auxiliary optic to then be combined with the reference beam on a CCD. The combined beams include phase errors due to both the optic under test and the auxiliary optic. Standard phase extraction algorithms are used to calculate this combined phase error. The optical flat is then removed from the system and the measurement fiber is moved to recombine the two beams. The newly combined beams include only the phase errors due to the auxiliary optic. When the second phase measurement is subtracted from the first phase measurement, the absolute phase error of the optical flat is obtained.

Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting.

PubMed

van Adrichem, Raymond A; Nemeth, Banne; Algra, Ale; le Cessie, Saskia; Rosendaal, Frits R; Schipper, Inger B; Nelissen, Rob G H H; Cannegieter, Suzanne C

2017-02-09

The use of thromboprophylaxis to prevent clinically apparent venous thromboembolism after knee arthroscopy or casting of the lower leg is disputed. We compared the incidence of symptomatic venous thromboembolism after these procedures between patients who received anticoagulant therapy and those who received no anticoagulant therapy. We conducted two parallel, pragmatic, multicenter, randomized, controlled, open-label trials with blinded outcome evaluation: the POT-KAST trial, which included patients undergoing knee arthroscopy, and the POT-CAST trial, which included patients treated with casting of the lower leg. Patients were assigned to receive either a prophylactic dose of low-molecular-weight heparin (for the 8 days after arthroscopy in the POT-KAST trial or during the full period of immobilization due to casting in the POT-CAST trial) or no anticoagulant therapy. The primary outcomes were the cumulative incidences of symptomatic venous thromboembolism and major bleeding within 3 months after the procedure. In the POT-KAST trial, 1543 patients underwent randomization, of whom 1451 were included in the intention-to-treat population. Venous thromboembolism occurred in 5 of the 731 patients (0.7%) in the treatment group and in 3 of the 720 patients (0.4%) in the control group (relative risk, 1.6; 95% confidence interval [CI], 0.4 to 6.8; absolute difference in risk, 0.3 percentage points; 95% CI, -0.6 to 1.2). Major bleeding occurred in 1 patient (0.1%) in the treatment group and in 1 (0.1%) in the control group (absolute difference in risk, 0 percentage points; 95% CI, -0.6 to 0.7). In the POT-CAST trial, 1519 patients underwent randomization, of whom 1435 were included in the intention-to-treat population. Venous thromboembolism occurred in 10 of the 719 patients (1.4%) in the treatment group and in 13 of the 716 patients (1.8%) in the control group (relative risk, 0.8; 95% CI, 0.3 to 1.7; absolute difference in risk, -0.4 percentage points; 95% CI, -1.8 to 1.0). No major bleeding events occurred. In both trials, the most common adverse event was infection. The results of our trials showed that prophylaxis with low-molecular-weight heparin for the 8 days after knee arthroscopy or during the full period of immobilization due to casting was not effective for the prevention of symptomatic venous thromboembolism. (Funded by the Netherlands Organization for Health Research and Development; POT-KAST and POT-CAST ClinicalTrials.gov numbers, NCT01542723 and NCT01542762 , respectively.).

Topical herbal therapies for treating osteoarthritis

PubMed Central

Cameron, Melainie; Chrubasik, Sigrun

2014-01-01

Background Before extraction and synthetic chemistry were invented, musculoskeletal complaints were treated with preparations from medicinal plants. They were either administered orally or topically. In contrast to the oral medicinal plant products, topicals act in part as counterirritants or are toxic when given orally. Objectives To update the previous Cochrane review of herbal therapy for osteoarthritis from 2000 by evaluating the evidence on effectiveness for topical medicinal plant products. Search methods Databases for mainstream and complementary medicine were searched using terms to include all forms of arthritis combined with medicinal plant products. We searched electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to February 2013, unrestricted by language. We also searched the reference lists from retrieved trials. Selection criteria Randomised controlled trials of herbal interventions used topically, compared with inert (placebo) or active controls, in people with osteoarthritis were included. Data collection and analysis Two review authors independently selected trials for inclusion, assessed the risk of bias of included studies and extracted data. Main results Seven studies (seven different medicinal plant interventions; 785 participants) were included. Single studies (five studies, six interventions) and non-comparable studies (two studies, one intervention) precluded pooling of results. Moderate evidence from a single study of 174 people with hand osteoarthritis indicated that treatment with Arnica extract gel probably results in similar benefits as treatment with ibuprofen (non-steroidal anti-inflammatory drug) with a similar number of adverse events. Mean pain in the ibuprofen group was 44.2 points on a 100 point scale; treatment with Arnica gel reduced the pain by 4 points after three weeks: mean difference (MD) −3.8 points (95% confidence intervals (CI) −10.1 to 2.5), absolute reduction 4% (10% reduction to 3% increase). Hand function was 7.5 points on a 30 point scale in the ibuprofen-treated group; treatment with Arnica gel reduced function by 0.4 points (MD −0.4, 95% CI −1.75 to 0.95), absolute improvement 1% (6% improvement to 3% decline)). Total adverse events were higher in the Arnica gel group (13% compared to 8% in the ibuprofen group): relative risk (RR) 1.65 (95% CI 0.72 to 3.76). Moderate quality evidence from a single trial of 99 people with knee osteoarthritis indicated that compared with placebo, Capsicum extract gel probably does not improve pain or knee function, and is commonly associated with treatment-related adverse events including skin irritation and a burning sensation. At four weeks follow-up, mean pain in the placebo group was 46 points on a 100 point scale; treatment with Capsicum extract reduced pain by 1 point (MD −1, 95%CI −6.8 to 4.8), absolute reduction of 1%(7%reduction to 5% increase). Mean knee function in the placebo group was 34.8 points on a 96 point scale at four weeks; treatment with Capsicum extract improved function by a mean of 2.6 points (MD −2.6, 95% CI −9.5 to 4.2), an absolute improvement of 3% (10% improvement to 4% decline). Adverse event rates were greater in the Capsicum extract group (80% compared with 20% in the placebo group, rate ratio 4.12, 95% CI 3.30 to 5.17). The number needed to treat to result in adverse events was 2 (95% CI 1 to 2). Moderate evidence from a single trial of 220 people with knee osteoarthritis suggested that comfrey extract gel probably improves pain without increasing adverse events. At three weeks, the mean pain in the placebo group was 83.5 points on a 100 point scale. Treatment with comfrey reduced pain by a mean of 41.5 points (MD −41.5, 95% CI −48 to −34), an absolute reduction of 42% (34% to 48% reduction). Function was not reported. Adverse events were similar: 6%(7/110) reported adverse events in the comfrey group compared with 14% (15/110) in the placebo group (RR 0.47, 95% CI 0.20 to 1.10). Although evidence from a single trial indicated that adhesive patches containing Chinese herbal mixtures FNZG and SJG may improve pain and function, the clinical applicability of these findings are uncertain because participants were only treated and followed up for seven days. We are also uncertain if other topical herbal products (Marhame-Mafasel compress, stinging nettle leaf) improve osteoarthritis symptoms due to the very low quality evidence from single trials. No serious side effects were reported. Authors’ conclusions Although the mechanism of action of the topical medicinal plant products provides a rationale basis for their use in the treatment of osteoarthritis, the quality and quantity of current research studies of effectiveness are insufficient. Arnica gel probably improves symptoms as effectively as a gel containing non-steroidal anti-inflammatory drug, but with no better (and possibly worse) adverse event profile. Comfrey extract gel probably improves pain, and Capsicum extract gel probably will not improve pain or function at the doses examined in this review. Further high quality, fully powered studies are required to confirm the trends of effectiveness identifed in studies so far. PMID:23728701

Experimental Estimating Deflection of a Simple Beam Bridge Model Using Grating Eddy Current Sensors

PubMed Central

Lü, Chunfeng; Liu, Weiwen; Zhang, Yongjie; Zhao, Hui

2012-01-01

A novel three-point method using a grating eddy current absolute position sensor (GECS) for bridge deflection estimation is proposed in this paper. Real spatial positions of the measuring points along the span axis are directly used as relative reference points of each other rather than using any other auxiliary static reference points for measuring devices in a conventional method. Every three adjacent measuring points are defined as a measuring unit and a straight connecting bar with a GECS fixed on the center section of it links the two endpoints. In each measuring unit, the displacement of the mid-measuring point relative to the connecting bar measured by the GECS is defined as the relative deflection. Absolute deflections of each measuring point can be calculated from the relative deflections of all the measuring units directly without any correcting approaches. Principles of the three-point method and displacement measurement of the GECS are introduced in detail. Both static and dynamic experiments have been carried out on a simple beam bridge model, which demonstrate that the three-point deflection estimation method using the GECS is effective and offers a reliable way for bridge deflection estimation, especially for long-term monitoring. PMID:23112583

Experimental estimating deflection of a simple beam bridge model using grating eddy current sensors.

PubMed

Lü, Chunfeng; Liu, Weiwen; Zhang, Yongjie; Zhao, Hui

2012-01-01

A novel three-point method using a grating eddy current absolute position sensor (GECS) for bridge deflection estimation is proposed in this paper. Real spatial positions of the measuring points along the span axis are directly used as relative reference points of each other rather than using any other auxiliary static reference points for measuring devices in a conventional method. Every three adjacent measuring points are defined as a measuring unit and a straight connecting bar with a GECS fixed on the center section of it links the two endpoints. In each measuring unit, the displacement of the mid-measuring point relative to the connecting bar measured by the GECS is defined as the relative deflection. Absolute deflections of each measuring point can be calculated from the relative deflections of all the measuring units directly without any correcting approaches. Principles of the three-point method and displacement measurement of the GECS are introduced in detail. Both static and dynamic experiments have been carried out on a simple beam bridge model, which demonstrate that the three-point deflection estimation method using the GECS is effective and offers a reliable way for bridge deflection estimation, especially for long-term monitoring.

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Relative and Absolute Error Control in a Finite-Difference Method Solution of Poisson's Equation

ERIC Educational Resources Information Center

Prentice, J. S. C.

2012-01-01

An algorithm for error control (absolute and relative) in the five-point finite-difference method applied to Poisson's equation is described. The algorithm is based on discretization of the domain of the problem by means of three rectilinear grids, each of different resolution. We discuss some hardware limitations associated with the algorithm,…

Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

PubMed

Davidsson, Pia; Söderling, Ann-Sofi; Svensson, Lena; Ahnmark, Andrea; Flodin, Christine; Wanag, Ewa; Screpanti-Sundqvist, Valentina; Gennemark, Peter

2015-05-01

Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

A change in paradigm: lowering blood pressure in everyone over a certain age.

PubMed

Law, Malcolm

2012-06-01

Dividing people into 'hypertensives' and 'normotensives' is commonplace but problematic. The relationship between blood pressure and cardiovascular disease is continuous. The Prospective Studies Collaboration analysis shows a continuous straight line dose-response relationship across the entire population down to blood pressure levels of 115 mmHg systolic and 75 mmHg diastolic, the confidence limits on the individual data points being sufficiently narrow to exclude even a minor deviation from a linear relationship. Meta-analysis of randomized controlled trials shows that blood pressure-lowering drugs produce similar proportional reductions in risk of coronary heart disease (CHD) and stroke irrespective of pre-treatment blood pressure, down to levels of 110 mmHg systolic and 70 mmHg diastolic. There are also now sufficient trial data to show a statistically significant risk reduction in 'normotensive' people without known vascular disease on entry. The straight line (log-linear) relationship means that the benefit derived from lowering blood pressure is proportional to existing risk, so the decision on whom to treat with blood pressure-lowering drugs should depend on a person's overall absolute risk irrespective of blood pressure. In primary prevention, basing treatment on age alone rather than overall absolute risk entails little loss of efficacy and may be preferred on the basis of simplicity and avoidance of anxiety in telling people they are at elevated risk.

A mathematical model for evaluating the impact of vaccination schedules: application to Neisseria meningitidis.

PubMed

Tuckwell, H C; Hanslik, T; Valleron, A J; Flahault, A

2003-06-01

A mathematical model is described which determines the impact of a schedule of vaccination on the time course of a certain class of diseases. The data are the demographic variables and parameters and age-dependent non-fatal and fatal case rates. Given the age- and time-dependent rates of vaccination including coverage and corresponding efficacies, various schedules may be distinguished by either the absolute numbers of cases and deaths avoided or the numbers of cases and deaths avoided per dose of vaccine. The model was applied to meningo-coccal serogroup C disease in France. The outcomes of six different vaccination schedules were examined. In absolute terms, a schedule in which all individuals aged between 2 and 20 years were vaccinated performed best, but this schedule and that in which only 1-year olds were vaccinated performed equally and best in terms of cases prevented, but not lives saved, per dose.

Neutron skyshine from intense 14-MeV neutron source facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, T.; Hayashi, K.; Takahashi, A.

1985-07-01

The dose distribution and the spectrum variation of neutrons due to the skyshine effect have been measured with the high-efficiency rem counter, the multisphere spectrometer, and the NE-213 scintillator in the environment surrounding an intense 14-MeV neutron source facility. The dose distribution and the energy spectra of neutrons around the facility used as a skyshine source have also been measured to enable the absolute evaluation of the skyshine effect. The skyshine effect was analyzed by two multigroup Monte Carlo codes, NIMSAC and MMCR-2, by two discrete ordinates S /sub n/ codes, ANISN and DOT3.5, and by the shield structure designmore » code for skyshine, SKYSHINE-II. The calculated results show good agreement with the measured results in absolute values. These experimental results should be useful as benchmark data for shyshine analysis and for shielding design of fusion facilities.« less

Localization of an Underwater Control Network Based on Quasi-Stable Adjustment.

PubMed

Zhao, Jianhu; Chen, Xinhua; Zhang, Hongmei; Feng, Jie

2018-03-23

There exists a common problem in the localization of underwater control networks that the precision of the absolute coordinates of known points obtained by marine absolute measurement is poor, and it seriously affects the precision of the whole network in traditional constraint adjustment. Therefore, considering that the precision of underwater baselines is good, we use it to carry out quasi-stable adjustment to amend known points before constraint adjustment so that the points fit the network shape better. In addition, we add unconstrained adjustment for quality control of underwater baselines, the observations of quasi-stable adjustment and constrained adjustment, to eliminate the unqualified baselines and improve the results' accuracy of the two adjustments. Finally, the modified method is applied to a practical LBL (Long Baseline) experiment and obtains a mean point location precision of 0.08 m, which improves by 38% compared with the traditional method.

Localization of an Underwater Control Network Based on Quasi-Stable Adjustment

PubMed Central

Chen, Xinhua; Zhang, Hongmei; Feng, Jie

2018-01-01

There exists a common problem in the localization of underwater control networks that the precision of the absolute coordinates of known points obtained by marine absolute measurement is poor, and it seriously affects the precision of the whole network in traditional constraint adjustment. Therefore, considering that the precision of underwater baselines is good, we use it to carry out quasi-stable adjustment to amend known points before constraint adjustment so that the points fit the network shape better. In addition, we add unconstrained adjustment for quality control of underwater baselines, the observations of quasi-stable adjustment and constrained adjustment, to eliminate the unqualified baselines and improve the results’ accuracy of the two adjustments. Finally, the modified method is applied to a practical LBL (Long Baseline) experiment and obtains a mean point location precision of 0.08 m, which improves by 38% compared with the traditional method. PMID:29570627

Gabapentin dose and the 30-day risk of altered mental status in older adults: A retrospective population-based study

PubMed Central

Dixon, Stephanie N.; Kuwornu, Paul John; Dev, Varun K.; Montero-Odasso, Manuel; Burneo, Jorge; Garg, Amit X.

2018-01-01

Gabapentin is an effective treatment for chronic neuropathic pain but may cause dizziness, drowsiness, and confusion in some older adults. The goal of this study was to assess the association between gabapentin dosing and adverse outcomes by obtaining estimates of the 30-day risk of hospitalization with altered mental status and mortality in older adults (mean age 76 years) in Ontario, Canada initiated on high dose (>600 mg/day; n = 34,159) compared to low dose (≤600 mg/day; n = 76,025) oral gabapentin in routine outpatient care. A population-based, retrospective cohort study assessing new gabapentin use between 2002 to 2014 was conducted. The primary outcome was 30-day hospitalization with an urgent head computed tomography (CT) scan in the absence of evidence of stroke (a proxy for altered mental status). The secondary outcome was 30-day all-cause mortality. The baseline characteristics measured in the two dose groups were similar. Initiation of a high versus low dose of gabapentin was associated with a higher risk of hospitalization with head CT scan (1.27% vs. 1.06%, absolute risk difference 0.21%, adjusted relative risk 1.29 [95% CI 1.14 to 1.46], number needed to treat 477) but not a statistically significant higher risk of mortality (1.25% vs. 1.16%, absolute risk difference of 0.09%, adjusted relative risk of 1.01 [95% CI 0.89 to 1.14]). Overall, the risk of being hospitalized with altered mental status after initiating gabapentin remains low, but may be reduced through the judicious use of gabapentin, use of the lowest dose to control pain, and vigilance for early signs of altered mental status. PMID:29538407

Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two iodine seeds in LDR brachytherapy.

PubMed

Furstoss, C; Bertrand, M J; Poon, E; Reniers, B; Pignol, J P; Carrier, J F; Beaulieu, L; Verhaegen, F

2008-07-01

This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model seed. Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post-implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG-43 approximation effects were studied for a prostate and breast post-implant. The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post-implant studies, a 10% difference between MC calculations and the TG-43 is found for both models of seeds. This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post-implant treatments. © 2008 American Association of Physicists in Medicine.

Problems in evaluating radiation dose via terrestrial and aquatic pathways.

PubMed Central

Vaughan, B E; Soldat, J K; Schreckhise, R G; Watson, E C; McKenzie, D H

1981-01-01

This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being. PMID:7037381

SU-E-T-539: Fixed Versus Variable Optimization Points in Combined-Mode Modulated Arc Therapy Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kainz, K; Prah, D; Ahunbay, E

2014-06-01

Purpose: A novel modulated arc therapy technique, mARC, enables superposition of step-and-shoot IMRT segments upon a subset of the optimization points (OPs) of a continuous-arc delivery. We compare two approaches to mARC planning: one with the number of OPs fixed throughout optimization, and another where the planning system determines the number of OPs in the final plan, subject to an upper limit defined at the outset. Methods: Fixed-OP mARC planning was performed for representative cases using Panther v. 5.01 (Prowess, Inc.), while variable-OP mARC planning used Monaco v. 5.00 (Elekta, Inc.). All Monaco planning used an upper limit of 91more » OPs; those OPs with minimal MU were removed during optimization. Plans were delivered, and delivery times recorded, on a Siemens Artiste accelerator using a flat 6MV beam with 300 MU/min rate. Dose distributions measured using ArcCheck (Sun Nuclear Corporation, Inc.) were compared with the plan calculation; the two were deemed consistent if they agreed to within 3.5% in absolute dose and 3.5 mm in distance-to-agreement among > 95% of the diodes within the direct beam. Results: Example cases included a prostate and a head-and-neck planned with a single arc and fraction doses of 1.8 and 2.0 Gy, respectively. Aside from slightly more uniform target dose for the variable-OP plans, the DVHs for the two techniques were similar. For the fixed-OP technique, the number of OPs was 38 and 39, and the delivery time was 228 and 259 seconds, respectively, for the prostate and head-and-neck cases. For the final variable-OP plans, there were 91 and 85 OPs, and the delivery time was 296 and 440 seconds, correspondingly longer than for fixed-OP. Conclusion: For mARC, both the fixed-OP and variable-OP approaches produced comparable-quality plans whose delivery was successfully verified. To keep delivery time per fraction short, a fixed-OP planning approach is preferred.« less

SU-G-TeP4-04: An Automated Monte Carlo Based QA Framework for Pencil Beam Scanning Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, J; Jee, K; Clasie, B

2016-06-15

Purpose: Prior to treating new PBS field, multiple (three) patient-field-specific QA measurements are performed: two 2D dose distributions at shallow depth (M1) and at the tumor depth (M2) with treatment hardware at zero gantry angle; one 2D dose distribution at iso-center (M3) without patient specific devices at the planned gantry angle. This patient-specific QA could be simplified by the use of MC model. The results of MC model commissioning for a spot-scanning system and the fully automated TOPAS/MC-based QA framework will be presented. Methods: We have developed in-house MC interface to access a TPS (Astroid) database from a computer clustermore » remotely. Once a plan is identified, the interface downloads information for the MC simulations, such as patient images, apertures points, and fluence maps and initiates calculations in both the patient and QA geometries. The resulting calculations are further analyzed to evaluate the TPS dose accuracy and the PBS delivery. Results: The Monte Carlo model of our system was validated within 2.0 % accuracy over the whole range of the dose distribution (proximal/shallow part, as well as target dose part) due to the location of the measurements. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. Conclusion: As M1 depths range typically from 1 cm to 4 cm from the phantom surface, The Monte Carlo model of our system was validated within +− 2.0 % in absolute dose level over a whole treatment range. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. This work was supported by NIH/NCI under CA U19 21239.« less

On the calculation of the absolute grand potential of confined smectic-A phases

NASA Astrophysics Data System (ADS)

Huang, Chien-Cheng; Baus, Marc; Ryckaert, Jean-Paul

2015-09-01

We determine the absolute grand potential Λ along a confined smectic-A branch of a calamitic liquid crystal system enclosed in a slit pore of transverse area A and width L, using the rod-rod Gay-Berne potential and a rod-wall potential favouring perpendicular orientation at the walls. For a confined phase with an integer number of smectic layers sandwiched between the opposite walls, we obtain the excess properties (excess grand potential Λexc, solvation force fs and adsorption Γ) with respect to the bulk phase at the same μ (chemical potential) and T (temperature) state point. While usual thermodynamic integration methods are used along the confined smectic branch to estimate the grand potential difference as μ is varied at fixed L, T, the absolute grand potential at one reference state point is obtained via the evaluation of the absolute Helmholtz free energy in the (N, L, A, T) canonical ensemble. It proceeds via a sequence of free energy difference estimations involving successively the cost of localising rods on layers and the switching on of a one-dimensional harmonic field to keep layers integrity coupled to the elimination of inter-layers and wall interactions. The absolute free energy of the resulting set of fully independent layers of interacting rods is finally estimated via the existing procedures. This work opens the way to the computer simulation study of phase transitions implying confined layered phases.

Poster - 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGeachy, Philip; Villarreal-Barajas, Jose Eduardo

Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization. Methods: Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetricmore » prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution. Results: Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non-SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant. Conclusions: For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.« less

Evaluation of the influence of double and triple Gaussian proton kernel models on accuracy of dose calculations for spot scanning technique.

PubMed

Hirayama, Shusuke; Takayanagi, Taisuke; Fujii, Yusuke; Fujimoto, Rintaro; Fujitaka, Shinichiro; Umezawa, Masumi; Nagamine, Yoshihiko; Hosaka, Masahiro; Yasui, Keisuke; Omachi, Chihiro; Toshito, Toshiyuki

2016-03-01

The main purpose in this study was to present the results of beam modeling and how the authors systematically investigated the influence of double and triple Gaussian proton kernel models on the accuracy of dose calculations for spot scanning technique. The accuracy of calculations was important for treatment planning software (TPS) because the energy, spot position, and absolute dose had to be determined by TPS for the spot scanning technique. The dose distribution was calculated by convolving in-air fluence with the dose kernel. The dose kernel was the in-water 3D dose distribution of an infinitesimal pencil beam and consisted of an integral depth dose (IDD) and a lateral distribution. Accurate modeling of the low-dose region was important for spot scanning technique because the dose distribution was formed by cumulating hundreds or thousands of delivered beams. The authors employed a double Gaussian function as the in-air fluence model of an individual beam. Double and triple Gaussian kernel models were also prepared for comparison. The parameters of the kernel lateral model were derived by fitting a simulated in-water lateral dose profile induced by an infinitesimal proton beam, whose emittance was zero, at various depths using Monte Carlo (MC) simulation. The fitted parameters were interpolated as a function of depth in water and stored as a separate look-up table. These stored parameters for each energy and depth in water were acquired from the look-up table when incorporating them into the TPS. The modeling process for the in-air fluence and IDD was based on the method proposed in the literature. These were derived using MC simulation and measured data. The authors compared the measured and calculated absolute doses at the center of the spread-out Bragg peak (SOBP) under various volumetric irradiation conditions to systematically investigate the influence of the two types of kernel models on the dose calculations. The authors investigated the difference between double and triple Gaussian kernel models. The authors found that the difference between the two studied kernel models appeared at mid-depths and the accuracy of predicting the double Gaussian model deteriorated at the low-dose bump that appeared at mid-depths. When the authors employed the double Gaussian kernel model, the accuracy of calculations for the absolute dose at the center of the SOBP varied with irradiation conditions and the maximum difference was 3.4%. In contrast, the results obtained from calculations with the triple Gaussian kernel model indicated good agreement with the measurements within ±1.1%, regardless of the irradiation conditions. The difference between the results obtained with the two types of studied kernel models was distinct in the high energy region. The accuracy of calculations with the double Gaussian kernel model varied with the field size and SOBP width because the accuracy of prediction with the double Gaussian model was insufficient at the low-dose bump. The evaluation was only qualitative under limited volumetric irradiation conditions. Further accumulation of measured data would be needed to quantitatively comprehend what influence the double and triple Gaussian kernel models had on the accuracy of dose calculations.

SU-F-T-70: A High Dose Rate Total Skin Electron Irradiation Technique with A Specific Inter-Film Variation Correction Method for Very Large Electron Beam Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, X; Rosenfield, J; Dong, X

2016-06-15

Purpose: Rotational total skin electron irradiation (RTSEI) is used in the treatment of cutaneous T-cell lymphoma. Due to inter-film uniformity variations the dosimetry measurement of a large electron beam of a very low energy is challenging. This work provides a method to improve the accuracy of flatness and symmetry for a very large treatment field of low electron energy used in dual beam RTSEI. Methods: RTSEI is delivered by dual angles field a gantry of ±20 degrees of 270 to cover the upper and the lower halves of the patient body with acceptable beam uniformity. The field size is inmore » the order of 230cm in vertical height and 120 cm in horizontal width and beam energy is a degraded 6 MeV (6 mm of PMMA spoiler). We utilized parallel plate chambers, Gafchromic films and OSLDs as a measuring devices for absolute dose, B-Factor, stationary and rotational percent depth dose and beam uniformity. To reduce inter-film dosimetric variation we introduced a new specific correction method to analyze beam uniformity. This correction method uses some image processing techniques combining film value before and after radiation dose to compensate the inter-variation dose response differences among films. Results: Stationary and rotational depth of dose demonstrated that the Rp is 2 cm for rotational and the maximum dose is shifted toward the surface (3mm). The dosimetry for the phantom showed that dose uniformity reduced to 3.01% for the vertical flatness and 2.35% for horizontal flatness after correction thus achieving better flatness and uniformity. The absolute dose readings of calibrated films after our correction matched with the readings from OSLD. Conclusion: The proposed correction method for Gafchromic films will be a useful tool to correct inter-film dosimetric variation for the future clinical film dosimetry verification in very large fields, allowing the optimizations of other parameters.« less

Simple Method to Estimate Mean Heart Dose From Hodgkin Lymphoma Radiation Therapy According to Simulation X-Rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nimwegen, Frederika A. van; Cutter, David J.; Oxford Cancer Centre, Oxford University Hospitals NHS Trust, Oxford

Purpose: To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Methods and Materials: Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case–controlmore » study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. Results: According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Conclusion: Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor-intensive representative CT-based method. This simpler method may produce a meaningful measure of mean heart dose for use in studies of late cardiac complications.« less

Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

Simple method to estimate mean heart dose from Hodgkin lymphoma radiation therapy according to simulation X-rays.

PubMed

van Nimwegen, Frederika A; Cutter, David J; Schaapveld, Michael; Rutten, Annemarieke; Kooijman, Karen; Krol, Augustinus D G; Janus, Cécile P M; Darby, Sarah C; van Leeuwen, Flora E; Aleman, Berthe M P

2015-05-01

To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case-control study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor-intensive representative CT-based method. This simpler method may produce a meaningful measure of mean heart dose for use in studies of late cardiac complications. Copyright © 2015 Elsevier Inc. All rights reserved.

An Analytical Approach for Relating Boiling Points of Monofunctional Organic Compounds to Intermolecular Forces

ERIC Educational Resources Information Center

Struyf, Jef

2011-01-01

The boiling point of a monofunctional organic compound is expressed as the sum of two parts: a contribution to the boiling point due to the R group and a contribution due to the functional group. The boiling point in absolute temperature of the corresponding RH hydrocarbon is chosen for the contribution to the boiling point of the R group and is a…

Test-retest reliability of the Middlesex Assessment of Mental State (MEAMS): a preliminary investigation in people with probable dementia.

PubMed

Powell, T; Brooker, D J; Papadopolous, A

1993-05-01

Relative and absolute test-retest reliability of the MEAMS was examined in 12 subjects with probable dementia and 12 matched controls. Relative reliability was good. Measures of absolute reliability showed scores changing by up to 3 points over an interval of a week. A version effect was found to be in evidence.

Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis.

PubMed

Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

2015-11-01

The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5-30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5-30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose-volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P < 0.05). Multivariate analysis indicated AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102-0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm(3); sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm(3) than with AVS5 < 564.9 cm(3) (P = 0.008). Low-dose irradiation relative volumes and MLD of the bilateral or ipsilateral lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Accuracy of a dose-area product compared to an absorbed dose to water at a point in a 2 cm diameter field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dufreneix, S.; Ostrowsky, A.; Rapp, B.

Purpose: Graphite calorimeters with a core diameter larger than the beam can be used to establish dosimetric references in small fields. The dose-area product (DAP) measured can theoretically be linked to an absorbed dose at a point by the determination of a profile correction. This study aims at comparing the DAP-based protocol to the usual absorbed dose at a point protocol in a 2 cm diameter field for which both references exist. Methods: Two calorimeters were used, respectively, with a sensitive volume of 0.6 cm (for the absorbed dose at a point measurement) and 3 cm diameter (for the DAPmore » measurement). Profile correction was calculated from a 2D dose mapping using three detectors: a PinPoint chamber, a synthetic diamond, and EBT3 films. A specific protocol to read EBT3 films was implemented and the dose-rate and energy dependences were studied to assure a precise measurement, especially in the penumbra and out-of-field regions. Results: EBT3 films were found independent on dose rates over the range studied but showed a strong under-response (18%) at low energies. Depending on the dosimeter used for calculating the profile correction, a deviation of 0.8% (PinPoint chamber), 0.9% (diamond), or 1.9% (EBT3 films) was observed between the calibration coefficient derived from DAP measurements and the one directly established in terms of absorbed dose to water at a point. Conclusions: The DAP method can currently be linked to the classical dosimetric reference system based in an absorbed dose at a point only with a confidence interval of 95% (k = 2). None of the detectors studied can be used to determine an absorbed dose to water at a point from a DAP measurement with an uncertainty smaller than 1.2%.« less

Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

PubMed

Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

2017-02-01

This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA ® Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

SU-F-T-590: Modeling PTV Dose Fall-Off for Cervical Cancer SBRT Treatment Planning Using VMAT and Step-And-Shoot IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delgado, A Brito; Cohen, D; Eng, T

Purpose: Due to the high dose per fraction in SBRT, dose conformity and dose fall-off are critical. In patients with cervical cancer, rapid dose fall-off is particularly important to limit dose to the nearby rectum, small bowel, and bladder. This study compares the target volume dose fall-off for two radiation delivery techniques, fixed-field IMRT & VMAT, using non-coplanar beam geometries. Further comparisons are made between 6 and 10MV photon beam energies. Methods: Eleven (n=11) patients were planned in Pinnacle3 v9.10 with a NovalisTx (HD120 MLC) machine model using 6 and 10 MV photons. The following three techniques were used: (1)more » IMRT (10 non-coplanar beams) (2) Dual, coplanar 360° VMAT arcs (4° spacing), and (3) Triple, non-coplanar VMAT arcs (1 full arc and dual partial arcs). All plans were normalized such that 98% of the PTV received at least 28Gy/4Fx. Dose was calculated using a 2.0mm isotropic dose grid. To assess dose fall-off, twenty concentric 2mm thick rings were created around the PTV. The maximum dose in each ring was recorded and the data was fitted to model dose fall-off. A separate analysis was performed by separating target volumes into small (0–50cc), medium (51–80cc), and large (81–110cc). Results: Triple, non-coplanar VMAT arcs showed the best dose fall-off for all patients evaluated. All fitted regressions had an R{sup 2}≥0.99. At 10mm from the PTV edge, 10 MV VMAT3-arc had an absolute improvement in dose fall-off of 3.8% and 6.9% over IMRT and VMAT2-arc, respectively. At 30mm, 10 MV VMAT3-arc had an absolute improvement of 12.0% and 7.0% over IMRT and VMAT2-arc, respectively. Faster dose fall-off was observed for small volumes as opposed to medium and large ones—9.6% at 20mm. Conclusion: Triple, non-coplanar VMAT arcs offer the sharpest dose fall-off for cervical SBRT plans. This improvement is most pronounced when treating smaller target volumes.« less

Effect of various methods for rectum delineation on relative and absolute dose-volume histograms for prostate IMRT treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusumoto, Chiaki; Ohira, Shingo; Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita

2016-07-01

Several reports have dealt with correlations of late rectal toxicity with rectal dose-volume histograms (DVHs) for high dose levels. There are 2 techniques to assess rectal volume for reception of a specific dose: relative-DVH (R-DVH, %) that indicates relative volume for a vertical axis, and absolute-DVH (A-DVH, cc) with its vertical axis showing absolute volume of the rectum. The parameters of DVH vary depending on the rectum delineation method, but the literature does not present any standardization of such methods. The aim of the present study was to evaluate the effects of different delineation methods on rectal DVHs. The enrollmentmore » for this study comprised 28 patients with high-risk localized prostate cancer, who had undergone intensity-modulated radiation therapy (IMRT) with the prescription dose of 78 Gy. The rectum was contoured with 4 different methods using 2 lengths, short (Sh) and long (Lg), and 2 cross sections, rectum (Rec) and rectal wall (Rw). Sh means the length from 1 cm above the seminal vesicles to 1 cm below the prostate and Lg the length from the rectosigmoid junction to the anus. Rec represents the entire rectal volume including the rectal contents and Rw the rectal volume of the area with a wall thickness of 4 mm. We compared dose-volume parameters by using 4 rectal contour methods for the same plan with the R-DVHs as well as the A-DVHs. For the high dose levels, the R-DVH parameters varied widely. The mean of V{sub 70} for Sh-Rw was the highest (19.4%) and nearly twice as high as that for Lg-Rec (10.4%). On the contrary, only small variations were observed in the A-DVH parameters (4.3, 4.3, 5.5, and 5.5 cc for Sh-Rw, Lg-Rw, Sh-Rec, and Lg-Rec, respectively). As for R-DVHs, the parameters of V{sub 70} varied depending on the rectal lengths (Sh-Rec vs Lg-Rec: R = 0.76; Sh-Rw vs Lg-Rw: R = 0.85) and cross sections (Sh-Rec vs Sh-Rw: R = 0.49; Lg-Rec vs Lg-Rw: R = 0.65). For A-DVHs, however, the parameters of Sh rectal A-DVHs hardly changed regardless of differences in rectal length at all dose levels. Moreover, at high dose levels (V{sub 70}), the parameters of A-DVHs showed less dependence on rectal cross sections (Sh-Rec vs Sh-Rw: R = 0.66; Lg-Rec vs Lg-Rw: R = 0.59). This study showed that A-DVHs were less dependent on the delineation methods than R-DVHs, especially for evaluating the rectal dose at higher dose levels. It can therefore be assumed that, in addition to R-DVHs, A-DVHs can be used for evaluating rectal toxicity.« less

Decision-making in an era of cancer prevention via aspirin: New Zealand needs updated guidelines and risk calculators.

PubMed

Wilson, Nick; Selak, Vanessa; Blakely, Tony; Leung, William; Clarke, Philip; Jackson, Rod; Knight, Josh; Nghiem, Nhung

2016-03-11

Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk ≥5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non-smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes.

Calculating tumor trajectory and dose-of-the-day using cone-beam CT projections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Bernard L., E-mail: bernard.jones@ucdenver.edu; Westerly, David; Miften, Moyed

2015-02-15

Purpose: Cone-beam CT (CBCT) projection images provide anatomical data in real-time over several respiratory cycles, forming a comprehensive picture of tumor movement. The authors developed and validated a method which uses these projections to determine the trajectory of and dose to highly mobile tumors during each fraction of treatment. Methods: CBCT images of a respiration phantom were acquired, the trajectory of which mimicked a lung tumor with high amplitude (up to 2.5 cm) and hysteresis. A template-matching algorithm was used to identify the location of a steel BB in each CBCT projection, and a Gaussian probability density function for themore » absolute BB position was calculated which best fit the observed trajectory of the BB in the imager geometry. Two modifications of the trajectory reconstruction were investigated: first, using respiratory phase information to refine the trajectory estimation (Phase), and second, using the Monte Carlo (MC) method to sample the estimated Gaussian tumor position distribution. The accuracies of the proposed methods were evaluated by comparing the known and calculated BB trajectories in phantom-simulated clinical scenarios using abdominal tumor volumes. Results: With all methods, the mean position of the BB was determined with accuracy better than 0.1 mm, and root-mean-square trajectory errors averaged 3.8% ± 1.1% of the marker amplitude. Dosimetric calculations using Phase methods were more accurate, with mean absolute error less than 0.5%, and with error less than 1% in the highest-noise trajectory. MC-based trajectories prevent the overestimation of dose, but when viewed in an absolute sense, add a small amount of dosimetric error (<0.1%). Conclusions: Marker trajectory and target dose-of-the-day were accurately calculated using CBCT projections. This technique provides a method to evaluate highly mobile tumors using ordinary CBCT data, and could facilitate better strategies to mitigate or compensate for motion during stereotactic body radiotherapy.« less

SU-G-206-15: Effects of Dose Reduction On Emphysema Score

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, P; Wahi-Anwar, M; Kim, H

Purpose: The purpose of this study was to investigate the effects of reducing radiation dose levels on emphysema scores from lung cancer screening CT exams. Methods: 52 cases were selected from the National Lung Screening Trial (NLST) patients for which we had both the image series and the raw CT data. All scans were acquired with fixed effective mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare) using 120kV, 64×0.6mm collimation and pitch 1.0. All images were reconstructed with 1mm slice thickness, B50 kernel. Based on a previously-published technique, we added noisemore » to the raw data to simulate reduced-dose versions at 50% and 25% of the original dose (approximately 1.0- and 0.5-mGy CTDIvol). Lung segmentations were obtained via region growing from manual seed point at a threshold of 600HU followed by manual removal of trachea and major airways. Lung segmentations were only performed on original dose scans, and mapped to simulated reduced-dose scans. Emphysema scores based on relative area of lung with attenuation values lower than −950HU (RA950) were computed for all cases. Results: Average RA950 of all 50 cases were 31.6 (±5.5), 32.5 (±4.9) and 32.8 (±4.6) for 100%, 50% and 25% dose level respectively. The average absolute difference in RA950 between simulated and original dose scans were 1.0 (±0.7) and 1.4 (±1.1) for 50% and 25% dose level respectively. Conclusion: RA950 is relatively robust to dose level, with a difference of no more than 5 from the original dose scans. The average RA950 of this population was high for a two reasons: This was a high risk population of patients with substantial smoking history; The use of B50 kernel, which may be biased towards high emphysema scores. Further exploration with smoother kernels will be conducted in the future. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics; NIH grant support from U01 CA181156.« less

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis.

PubMed

Elborn, J Stuart; Ramsey, Bonnie W; Boyle, Michael P; Konstan, Michael W; Huang, Xiaohong; Marigowda, Gautham; Waltz, David; Wainwright, Claire E

2016-08-01

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function. Both trials (TRAFFIC and TRANSPORT) included in this pooled analysis were multinational, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Eligible patients from 187 participating centres in North America, Australia, and the European Union (both trials) were aged 12 years or older with a confirmed diagnosis of cystic fibrosis, homozygous for the Phe508del CFTR mutation, and with a percent predicted FEV1 (ppFEV1) of 40-90 at the time of screening. Patients were randomly assigned with an interactive web response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg every 12 h) for 24 weeks. Prespecified subgroup analyses of pooled efficacy and safety data by lung function, as measured by ppFEV1, were done for patients with baseline ppFEV1 (<40 and ≥40) and screening ppFEV1 (<70 and ≥70). The primary endpoint was the absolute change from baseline in ppFEV1 at week 24 analysed in all randomised patients who received at least one dose of study drug. Both trials are registered with ClinicalTrials.gov (TRAFFIC: NCT01807923; TRANSPORT: NCT01807949). Both trials were done between April, 2013, and April, 2014. Of the 1108 patients included in the efficacy analysis, 81 patients had a ppFEV1 that decreased to lower than 40 between screening and baseline and 1016 had a ppFEV1 of 40 or higher at baseline. At screening, 730 had a ppFEV1 of less than 70, and 342 had a ppFEV1 of 70 or higher. Improvements in the absolute change from baseline at week 24 in ppFEV1 were observed with both lumacaftor/ivacaftor doses in the subgroup with baseline ppFEV1 levels lower than 40 (least-squares mean difference vs placebo was 3·7 percentage points [95% CI 0·5-6·9; p=0·024] in the lumacaftor [600 mg/day]-ivacaftor group and 3·3 percentage points [0·2-6·4; p=0·036] in the lumacaftor [400 mg/12 h]-ivacaftor group). Improvements in ppFEV1 compared with placebo were also reported in the subgroup with baseline ppFEV1 levels of 40 or higher (3·3 percentage points [2·3-4·4; p<0·0001] in the lumacaftor [600 mg per day]-ivacaftor group and 2·8 percentage points [1·7-3·8; p<0·0001] in the lumacaftor [400 mg/12 h]-ivacaftor group). Similar absolute improvements in ppFEV1 compared with placebo were observed in subgroups with screening ppFEV1 levels lower than 70 and ppFEV1 levels of 70 or higher. Increases in body-mass index and reduction in number of pulmonary exacerbation events were observed in both lumacaftor/ivacaftor dose groups compared with placebo across all lung function subgroups. Treatment was generally well tolerated, although the incidence of some respiratory adverse events was higher with lumacaftor/ivacaftor than with placebo in all subgroups. In patients with baseline ppFEV1 levels lower than 40, these adverse events included cough, dyspnoea, and abnormal respiration. These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patients with cystic fibrosis homozygous for Phe508del CFTR who have varying degrees of lung function impairment. Vertex Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo antiulcer activity of the aqueous extract of Bauhinia purpurea leaf.

PubMed

Zakaria, Z A; Abdul Hisam, E E; Rofiee, M S; Norhafizah, M; Somchit, M N; Teh, L K; Salleh, M Z

2011-09-02

Bauhinia purpurea (Fabaceae) is a medicinal plant traditionally used to treat various ailments, including ulcers. In order to establish pharmacological properties of the leaf of Bauhinia purpurea, studies were performed on antiulcer activity of the plant's aqueous extract. The Bauhinia purpurea aqueous extract (BPAE) was prepared in the doses of 100, 500 and 1,000 mg/kg. Antiulcer activity of BPAE was evaluated by absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation models. Acute toxicity was also carried out. BPAE, at the dose of 5,000 mg/kg, did not cause any signs of toxicity to rats when given orally. Oral administration of BPAE exhibited antiulcer activity (p<0.05) in all models used. However, the dose-dependent activity was observed only in the absolute ethanol-induced gastric ulcer model. Histological studies supported the observed antiulcer activity of BPAE. In pyloric ligation assay, BPAE increased the gastric wall mucus secretion. The BPAE exhibits antiulcer activity, which could be due to the presence of saponins or sugar-free polyphenols, and, thus, confirmed the traditional uses of Bauhinia purpurea in the treatment of ulcers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty

PubMed Central

Bass, Anne R.; Lin, Hannah; Woller, Scott C.; Stevens, Scott M.; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J. Philip; McMillin, Gwendolyn A.; Pendleton, Robert C.; Jaffer, Amir K.; King, Cristi R.; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M.; Hyun, Gina; Anderson, Jeffrey L.; Hollomon, Wesley; Barrack, Robert L.; Nunley, Ryan M.; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S.

2017-01-01

Importance Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. Main Outcomes and Measures The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Results Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Conclusions and Relevance Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. Trial Registration clinicaltrials.gov Identifier: NCT01006733 PMID:28973620

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

PubMed

Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

2017-09-26

Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. clinicaltrials.gov Identifier: NCT01006733.

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koivula, Lauri

Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity valuesmore » of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm gamma index criteria were over 91%, 85%, and 38% with heterogeneous, dual bulk, and homogeneous sCTs, respectively. There were no significant changes to gamma index pass rates for IMPT plans first optimized in CT and then calculated in heterogeneous sCT versus IMPT plans first optimized in heterogeneous sCT and then calculated on standard CT. Conclusions: This study demonstrates that proton therapy dose calculations on heterogeneous sCTs are in good agreement with plans generated with standard planning CT. An MRI-only based RTP workflow is feasible in IMPT for brain tumors and prostate cancers.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Y; Giebeler, A; Mascia, A

Purpose: To quantitatively evaluate dosimetric consequence of spot size variations and validate beam-matching criteria for commissioning a pencil beam model for multiple treatment rooms. Methods: A planning study was first conducted by simulating spot size variations to systematically evaluate dosimetric impact of spot size variations in selected cases, which was used to establish the in-air spot size tolerance for beam matching specifications. A beam model in treatment planning system was created using in-air spot profiles acquired in one treatment room. These spot profiles were also acquired from another treatment room for assessing the actual spot size variations between the twomore » treatment rooms. We created twenty five test plans with targets of different sizes at different depths, and performed dose measurement along the entrance, proximal and distal target regions. The absolute doses at those locations were measured using ionization chambers at both treatment rooms, and were compared against the calculated doses by the beam model. Fifteen additional patient plans were also measured and included in our validation. Results: The beam model is relatively insensitive to spot size variations. With an average of less than 15% measured in-air spot size variations between two treatment rooms, the average dose difference was −0.15% with a standard deviation of 0.40% for 55 measurement points within target region; but the differences increased to 1.4%±1.1% in the entrance regions, which are more affected by in-air spot size variations. Overall, our single-room based beam model in the treatment planning system agreed with measurements in both rooms < 0.5% within the target region. For fifteen patient cases, the agreement was within 1%. Conclusion: We have demonstrated that dosimetrically equivalent machines can be established when in-air spot size variations are within 15% between the two treatment rooms.« less

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

PubMed Central

Boeckh, Michael; Harrison, Ryan W.; McCullough, Jeffrey; Ness, Paul M.; Strauss, Ronald G.; Nichols, W. Garrett; Hamza, Taye H.; Cushing, Melissa M.; King, Karen E.; Young, Jo-Anne H.; Williams, Eliot; McFarland, Janice; Holter Chakrabarty, Jennifer; Sloan, Steven R.; Friedman, David; Parekh, Samir; Sachais, Bruce S.; Kiss, Joseph E.; Assmann, Susan F.

2015-01-01

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393. PMID:26333778

Dose measurement in heterogeneous phantoms with an extrapolation chamber

NASA Astrophysics Data System (ADS)

Deblois, Francois

A hybrid phantom-embedded extrapolation chamber (PEEC) made of Solid Water(TM) and bone-equivalent material was used for determining absolute dose in a bone-equivalent phantom irradiated with clinical radiation beams (cobalt-60 gamma rays; 6 and 18 MV x-rays; and 9 and 15 MeV electrons). The dose was determined with the Spencer-Attix cavity theory, using ionization gradient measurements and an indirect determination of the chamber air-mass through measurements of chamber capacitance. The air gaps used were between 2 and 3 mm and the sensitive air volume of the extrapolation chamber was remotely controlled through the motion of the motorized piston with a precision of +/-0.0025 mm. The collected charge was corrected for ionic recombination and diffusion in the chamber air volume following the standard two-voltage technique. Due to the hybrid chamber design, correction factors accounting for scatter deficit and electrode composition were determined and applied in the dose equation to obtain dose data for the equivalent homogeneous bone phantom. Correction factors for graphite electrodes were calculated with Monte Carlo techniques and the calculated results were verified through relative air cavity dose measurements for three different polarizing electrode materials: graphite, steel, and brass in conjunction with a graphite collecting electrode. Scatter deficit, due mainly to loss of lateral scatter in the hybrid chamber, reduces the dose to the air cavity in the hybrid PEEC in comparison with full bone PEEC from 0.7 to ˜2% depending on beam quality and energy. In megavoltage photon and electron beams, graphite electrodes do not affect the dose measurement in the Solid Water(TM) PEEC but decrease the cavity dose by up to 5% in the bone-equivalent PEEC even for very thin graphite electrodes (<0.0025 cm). The collecting electrode material in comparison with the polarizing electrode material has a larger effect on the electrode correction factor; the thickness of thin electrodes, on the other hand, has a negligible effect on dose determination. The uncalibrated hybrid PEEC is an accurate and absolute device for measuring the dose directly in bone material in conjunction with appropriate correction factors determined with Monte Carlo techniques.

Organ Doses Associated with Partial-Body Irradiation with 2.5% Bone Marrow Sparing of the Non-Human Primate: A Retrospective Study.

PubMed

Prado, C; MacVittie, T J; Bennett, A W; Kazi, A; Farese, A M; Prado, K

2017-12-01

A partial-body irradiation model with approximately 2.5% bone marrow sparing (PBI/BM2.5) was established to determine the radiation dose-response relationships for the prolonged and delayed multi-organ effects of acute radiation exposure. Historically, doses reported to the entire body were assumed to be equal to the prescribed dose at some defined calculation point, and the dose-response relationship for multi-organ injury has been defined relative to the prescribed dose being delivered at this point, e.g., to a point at mid-depth at the level of the xiphoid of the non-human primate (NHP). In this retrospective-dose study, the true distribution of dose within the major organs of the NHP was evaluated, and these doses were related to that at the traditional dose-prescription point. Male rhesus macaques were exposed using the PBI/BM2.5 protocol to a prescribed dose of 10 Gy using 6-MV linear accelerator photons at a rate of 0.80 Gy/min. Point and organ doses were calculated for each NHP from computed tomography (CT) scans using heterogeneous density data. The prescribed dose of 10.0 Gy to a point at midline tissue assuming homogeneous media resulted in 10.28 Gy delivered to the prescription point when calculated using the heterogeneous CT volume of the NHP. Respective mean organ doses to the volumes of nine organs, including the heart, lung, bowel and kidney, were computed. With modern treatment planning systems, utilizing a three-dimensional reconstruction of the NHP's CT images to account for the variations in body shape and size, and using density corrections for each of the tissue types, bone, water, muscle and air, accurate determination of the differences in dose to the NHP can be achieved. Dose and volume statistics can be ascertained for any body structure or organ that has been defined using contouring tools in the planning system. Analysis of the dose delivered to critical organs relative to the total-body target dose will permit a more definitive analysis of organ-specific effects and their respective influence in multiple organ injury.

SU-E-T-157: Evaluation and Comparison of Doses to Pelvic Lymph Nodes and to Point B with 3D Image Guided Treatment Planning for High Dose Brachytherapy for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, N.

2014-06-01

Purpose: To estimate and compare the doses received by the obturator, external and internal iliac lymph nodes and point Methods: CT-MR fused image sets of 15 patients obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicator, were used to generate treatment plans optimized to deliver a prescription dose to HRCTV-D90 and to minimize the doses to organs at risk (OARs). For each set of image, target volume (GTV, HRCTV) OARs (Bladder, Rectum, Sigmoid), and both left and right pelvic lymph nodes (obturator, external and internal iliac lymph nodes) were delineated. Dose-volume histograms (DVH) were generatedmore » for pelvic nodal groups (left and right obturator group, internal and external iliac chains) Per fraction DVH parameters used for dose comparison included dose to 100% volume (D100), and dose received by 2cc (D2cc), 1cc (D1cc) and 0.1 cc (D0.1cc) of nodal volume. Dose to point B was compared with each DVH parameter using 2 sided t-test. Pearson correlation were determined to examine relationship of point B dose with nodal DVH parameters. Results: FIGO clinical stage varied from 1B1 to IIIB. The median pretreatment tumor diameter measured on MRI was 4.5 cm (2.7– 6.4cm).The median dose to bilateral point B was 1.20 Gy ± 0.12 or 20% of the prescription dose. The correlation coefficients were all <0.60 for all nodal DVH parameters indicating low degree of correlation. Only 2 cc of obturator nodes was not significantly different from point B dose on t-test. Conclusion: Dose to point B does not adequately represent the dose to any specific pelvic nodal group. When using image guided 3D dose-volume optimized treatment nodal groups should be individually identified and delineated to obtain the doses received by pelvic nodes.« less

Point Organ Radiation Dose in Abdominal CT: Effect of Patient Off-Centering in an Experimental Human Cadaver Study.

PubMed

Ali Khawaja, Ranish Deedar; Singh, Sarabjeet; Padole, Atul; Otrakji, Alexi; Lira, Diego; Zhang, Da; Liu, Bob; Primak, Andrew; Xu, George; Kalra, Mannudeep K

2017-08-01

To determine the effect of patient off-centering on point organ radiation dose measurements in a human cadaver scanned with routine abdominal CT protocol. A human cadaver (88 years, body-mass-index 20 kg/m2) was scanned with routine abdominal CT protocol on 128-slice dual source MDCT (Definition Flash, Siemens). A total of 18 scans were performed using two scan protocols (a) 120 kV-200 mAs fixed-mA (CTDIvol 14 mGy) (b) 120 kV-125 ref mAs (7 mGy) with automatic exposure control (AEC, CareDose 4D) at three different positions (a) gantry isocenter, (b) upward off-centering and (c) downward off-centering. Scanning was repeated three times at each position. Six thimble (in liver, stomach, kidney, pancreas, colon and urinary bladder) and four MOSFET dosimeters (on cornea, thyroid, testicle and breast) were placed for calculation of measured point organ doses. Organ dose estimations were retrieved from dose-tracking software (eXposure, Radimetrics). Statistical analysis was performed using analysis of variance. There was a significant difference between the trends of point organ doses with AEC and fixed-mA at all three positions (p < 0.01). Variation in point doses between fixed-mA and AEC protocols were statistically significant across all organs at all Table positions (p < 0.001). There was up to 5-6% decrease in point doses with upward off-centering and in downward off-centering. There were statistical significant differences in point doses from dosimeters and dose-tracking software (mean difference for internal organs, 5-36% for fixed-mA & 7-48% for AEC protocols; p < 0.001; mean difference for surface organs, >92% for both protocols; p < 0.0001). For both protocols, the highest mean difference in point doses was found for stomach and lowest for colon. Measured absorbed point doses in abdominal CT vary with patient-centering in the gantry isocenter. Due to lack of consideration of patient positioning in the dose estimation on automatic software-over estimation of the doses up to 92% was reported. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Effect of a three-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women

PubMed Central

Alekel, D. Lee; Genschel, Ulrike; Koehler, Kenneth J; Hofmann, Heike; Van Loan, Marta D; Beer, Bonnie S.; Hanson, Laura N; Peterson, Charles T; Kurzer, Mindy S

2014-01-01

Objectives To assess the overall safety and potential endometrial stimulation of soy isoflavone tablets consumed (3-year) by postmenopausal women. To determine the endometrial thickness response-to-treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. Methods We randomized healthy postmenopausal women (45.8–65.0 years) to placebo control or two doses (80 or 120 mg/day) of soy isoflavones at two sites. We used intent-to-treat (N=224) and compliant (>95%; N=208) analyses to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). Results Median values for endometrial thickness (mm) declined from baseline through 36 mo. Nonparametric ANOVA for treatment differences among groups showed no differences in absolute (or percentage change) endometrial thickness at any time point (Chi-Square p-values ranged from 0.12–0.69), nor in circulating hormones at any time point. A greater number of adverse events for the genitourinary system (p=0.005) was noted in the 80 compared to 120 mg/day group, whereas other systems showed no treatment effects. The model predicting the endometrial thickness response-(using natural logarithm)-to-treatment with compliant women across time points was significant (p<0.0001), indicating that estrogen exposure (p=0.0013), plasma 17 β-estradiol (p=0.0086), and alcohol intake (p=0.023) contributed significantly to the response. Neither the 80 (p=0.57) nor 120 (p=0.43) mg/day dose exerted an effect on endometrial thickness across time. Conclusions Our RCT verified the long-term overall safety of consuming soy isoflavone tablets by postmenopausal women who displayed excellent compliance. We found no evidence of a treatment effect on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, during a three year period. PMID:25003624

Evaluation of a single-scan protocol for radiochromic film dosimetry.

PubMed

Shimohigashi, Yoshinobu; Araki, Fujio; Maruyama, Masato; Nakaguchi, Yuji; Kuwahara, Satoshi; Nagasue, Nozomu; Kai, Yudai

2015-03-08

The purpose of this study was to evaluate a single-scan protocol using Gafchromic EBT3 film (EBT3) by comparing it with the commonly used 24-hr measurement protocol for radiochromic film dosimetry. Radiochromic film is generally scanned 24 hr after film exposure (24-hr protocol). The single-scan protocol enables measurement results within a short time using only the verification film, one calibration film, and unirradiated film. The single-scan protocol was scanned 30 min after film irradiation. The EBT3 calibration curves were obtained with the multichannel film dosimetry method. The dose verifications for each protocol were performed with the step pattern, pyramid pattern, and clinical treatment plans for intensity-modulated radiation therapy (IMRT). The absolute dose distributions for each protocol were compared with those calculated by the treatment planning system (TPS) using gamma evaluation at 3% and 3 mm. The dose distribution for the single-scan protocol was within 2% of the 24-hr protocol dose distribution. For the step pattern, the absolute dose discrepancies between the TPS for the single-scan and 24-hr protocols were 2.0 ± 1.8 cGy and 1.4 ± 1.2 cGy at the dose plateau, respectively. The pass rates were 96.0% for the single-scan protocol and 95.9% for the 24-hr protocol. Similarly, the dose discrepancies for the pyramid pattern were 3.6 ± 3.5cGy and 2.9 ± 3.3 cGy, respectively, while the pass rates for the pyramid pattern were 95.3% and 96.4%, respectively. The average pass rates for the four IMRT plans were 96.7% ± 1.8% for the single-scan protocol and 97.3% ± 1.4% for the 24-hr protocol. Thus, the single-scan protocol measurement is useful for dose verification of IMRT, based on its accuracy and efficiency.

Evaluation of a single‐scan protocol for radiochromic film dosimetry

PubMed Central

Araki, Fujio; Maruyama, Masato; Nakaguchi, Yuji; Kuwahara, Satoshi; Nagasue, Nozomu; Kai, Yudai

2015-01-01

The purpose of this study was to evaluate a single‐scan protocol using Gafchromic EBT3 film (EBT3) by comparing it with the commonly used 24‐hr measurement protocol for radiochromic film dosimetry. Radiochromic film is generally scanned 24 hr after film exposure (24‐hr protocol). The single‐scan protocol enables measurement results within a short time using only the verification film, one calibration film, and unirradiated film. The single‐scan protocol was scanned 30 min after film irradiation. The EBT3 calibration curves were obtained with the multichannel film dosimetry method. The dose verifications for each protocol were performed with the step pattern, pyramid pattern, and clinical treatment plans for intensity‐modulated radiation therapy (IMRT). The absolute dose distributions for each protocol were compared with those calculated by the treatment planning system (TPS) using gamma evaluation at 3% and 3 mm. The dose distribution for the single‐scan protocol was within 2% of the 24‐hr protocol dose distribution. For the step pattern, the absolute dose discrepancies between the TPS for the single‐scan and 24‐hr protocols were 2.0±1.8 cGy and 1.4±1.2 cGy at the dose plateau, respectively. The pass rates were 96.0% for the single‐scan protocol and 95.9% for the 24‐hr protocol. Similarly, the dose discrepancies for the pyramid pattern were 3.6±3.5 cGy and 2.9±3.3 cGy, respectively, while the pass rates for the pyramid pattern were 95.3% and 96.4%, respectively. The average pass rates for the four IMRT plans were 96.7%±1.8% for the single‐scan protocol and 97.3%±1.4% for the 24‐hr protocol. Thus, the single‐scan protocol measurement is useful for dose verification of IMRT, based on its accuracy and efficiency. PACS number: 87.55.Qr PMID:26103194

Effective and absolute cross sections for low-energy (1-30 eV) electron interactions with condensed biomolecules

NASA Astrophysics Data System (ADS)

Zheng, Yi; Sanche, Léon

2018-06-01

Ionizing radiation is intensively used for therapeutic [e.g., radiotherapy, brachytherapy, and targeted radionuclide therapy (TRT)], as well as for diagnostic medical imaging purposes. In these applications, the radiation dose given to the patient should be known and controlled. In conventional cancer treatments, absorbed dose calculations rely essentially on scattering cross sections (CSs) of the primary high-energy radiation. In more sophisticated treatments, such as combined radio- and chemo-therapy, a description of the details of energy deposits at the micro- and nano-scopic level is preferred to relate dose to radiobiological effectiveness or to evaluate doses at the biomolecular level, when radiopharmaceuticals emitting short-range radiation are delivered to critical molecular components of cancer cells (e.g., TRT). These highly radiotoxic compounds emit large densities of low-energy electrons (LEEs). More generally, LEE (0-30 eV) are emitted in large numbers by any type of high-energy radiation; i.e., about 30 000 per MeV of deposited primary energy. Thus, to optimize the effectiveness of several types of radiation treatments, the energy deposited by LEEs must be known at the level of the cell, nucleus, chromosome, or DNA. Such local doses can be evaluated by Monte Carlo (MC) calculations, which account event-by-event, for the slowing down of all generations of particles. In particular, these codes require as input parameters absolute LEE CSs for elastic scattering, energy losses, and direct damage to vital cellular molecules, particularly DNA, the main target of radiation therapy. In the last decade, such CSs have emerged in the literature. Furthermore, a method was developed to transform relative yields of damages into absolute CSs by measuring specific parameters in the experiments. In this review article, we first present a general description of dose calculations in biological media via MC simulation and give an overview of the CSs available from theoretical calculations and gas-phase experiments. The properties of LEE scattering in the gas-phase are then compared to those in the condensed phase. The remaining portion of the article is devoted to condensed-phase CSs. We provide absolute LEE scattering CSs for electronic, vibrational, and phonon excitation of biomolecules as well as for dissociative electron attachment, electron intra- and inter-molecular stabilization, and bond dissociation, including strand breaks and degradation product formation. The biomolecules are O2, CO2, H2O, DNA bases, sugar and phosphate unit analogs, oligonucleotides, plasmid DNA, and the amino acid tryptophan. CSs for strand breaks in radiosensitizing and chemotherapeutic molecules bond or not to a short DNA strand are also listed. The principle of each experimental technique and mathematical methods utilized to generate all condensed-phase CSs are briefly explained. The mechanisms responsible for the magnitudes of the CSs are discussed.

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow.

PubMed

Lewis, Candace R; Preller, Katrin H; Kraehenmann, Rainer; Michels, Lars; Staempfli, Philipp; Vollenweider, Franz X

2017-10-01

Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations. Copyright © 2017 Elsevier Inc. All rights reserved.

Acetaminophen structure-toxicity studies: In vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, S.A.; Price, V.F.; Jollow, D.J.

1990-09-01

High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled (3H or 14C)3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of (G-3H)acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAAmore » was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of (ring-3H)3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential.« less

Three-dimensional dosimetric considerations from different point A definitions in cervical cancer low-dose-rate brachytherapy

PubMed Central

Chen, Ting; Kim, Leonard H.; Nelson, Carl; Gabel, Molly; Narra, Venkat; Haffty, Bruce; Yue, Ning J.

2013-01-01

Purpose To investigate the dosimetric difference due to the different point A definitions in cervical cancer low-dose-rate (LDR) intracavitary brachytherapy. Material and methods Twenty CT-based LDR brachytherapy plans of 11 cervical patients were retrospectively reviewed. Two plans with point As following the modified Manchester system which defines point A being 2 cm superior to the cervical os along the tandem and 2 cm lateral (Aos), and the American Brachytherapy Society (ABS) guideline definition in which the point A is 2 cm superior to the vaginal fornices instead of os (Aovoid) were generated. Using the same source strength, two plans prescribed the same dose to Aos and Aovoid. Dosimetric differences between plans including point A dose rate, treatment volume encompassed by the prescription isodose line (TV), and dose rate of 2 cc of the rectum and bladder to the prescription dose were measured. Results On average Aovoid was 8.9 mm superior to Aos along the tandem direction with a standard deviation of 5.4 mm. With the same source strength and arrangement, Aos dose rate was 19% higher than Aovoid dose rate. The average TV(Aovoid) was 118.0 cc, which was 30% more than the average TV(Aos) of 93.0 cc. D2cc/D(Aprescribe) increased from 51% to 60% for rectum, and increased from 89% and 106% for bladder, if the prescription point changed from Aos to Aovoid. Conclusions Different point A definitions lead to significant dose differences. Careful consideration should be given when changing practice from one point A definition to another, to ensure dosimetric and clinical equivalency from the previous clinical experiences. PMID:24474971

Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shwetha, Bondel; Ravikumar, Manickam, E-mail: drravikumarm@gmail.com; Supe, Sanjay S.

2012-04-01

Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder,more » and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.« less

Thermodynamic Temperature Measurement to the Indium Point Based on Radiance Comparison

NASA Astrophysics Data System (ADS)

Yamaguchi, Y.; Yamada, Y.

2017-04-01

A multi-national project (the EMRP InK project) was completed recently, which successfully determined the thermodynamic temperatures of several of the high-temperature fixed points above the copper point. The National Metrology Institute of Japan contributed to this project with its newly established absolute spectral radiance calibration capability. In the current study, we have extended the range of thermodynamic temperature measurement to below the copper point and measured the thermodynamic temperatures of the indium point (T_{90} = 429.748 5 K), tin point (505.078 K), zinc point (692.677 K), aluminum point (933.473 K) and the silver point (1 234.93 K) by radiance comparison against the copper point, with a set of radiation thermometers having center wavelengths ranging from 0.65 μm to 1.6 μm. The copper-point temperature was measured by the absolute radiation thermometer which was calibrated by radiance method traceable to the electrical substitution cryogenic radiometer. The radiance of the fixed-point blackbodies was measured by standard radiation thermometers whose spectral responsivity and nonlinearity are precisely evaluated, and then the thermodynamic temperatures were determined from radiance ratios to the copper point. The values of T-T_{90} for the silver-, aluminum-, zinc-, tin- and indium-point cells were determined as -4 mK (U = 104 mK, k=2), -99 mK (88 mK), -76 mK (76 mK), -68 mK (163 mK) and -42 mK (279 mK), respectively.

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.

PubMed

Hart, Robert G; Pearce, Lesly A; Aguilar, Maria I

2007-06-19

Atrial fibrillation is a strong independent risk factor for stroke. To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis. Methodological features and quality varied substantially and often were incompletely reported. Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Graphs to estimate an individualized risk of breast cancer.

PubMed

Benichou, J; Gail, M H; Mulvihill, J J

1996-01-01

Clinicians who counsel women about their risk for developing breast cancer need a rapid method to estimate individualized risk (absolute risk), as well as the confidence limits around that point. The Breast Cancer Detection Demonstration Project (BCDDP) model (sometimes called the Gail model) assumes no genetic model and simultaneously incorporates five risk factors, but involves cumbersome calculations and interpolations. This report provides graphs to estimate the absolute risk of breast cancer from the BCDDP model. The BCDDP recruited 280,000 women from 1973 to 1980 who were monitored for 5 years. From this cohort, 2,852 white women developed breast cancer and 3,146 controls were selected, all with complete risk-factor information. The BCDDP model, previously developed from these data, was used to prepare graphs that relate a specific summary relative-risk estimate to the absolute risk of developing breast cancer over intervals of 10, 20, and 30 years. Once a summary relative risk is calculated, the appropriate graph is chosen that shows the 10-, 20-, or 30-year absolute risk of developing breast cancer. A separate graph gives the 95% confidence limits around the point estimate of absolute risk. Once a clinician rules out a single gene trait that predisposes to breast cancer and elicits information on age and four risk factors, the tables and figures permit an estimation of a women's absolute risk of developing breast cancer in the next three decades. These results are intended to be applied to women who undergo regular screening. They should be used only in a formal counseling program to maximize a woman's understanding of the estimates and the proper use of them.

Acupuncture for peripheral joint osteoarthritis

PubMed Central

Manheimer, Eric; Cheng, Ke; Linde, Klaus; Lao, Lixing; Yoo, Junghee; Wieland, Susan; van der Windt, Daniëlle AWM; Berman, Brian M; Bouter, Lex M

2011-01-01

Background Peripheral joint osteoarthritis is a major cause of pain and functional limitation. Few treatments are safe and effective. Objectives To assess the effects of acupuncture for treating peripheral joint osteoarthritis. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE, and EMBASE (both through December 2007), and scanned reference lists of articles. Selection criteria Randomized controlled trials (RCTs) comparing needle acupuncture with a sham, another active treatment, or a waiting list control group in people with osteoarthritis of the knee, hip, or hand. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We calculated standardized mean differences using the differences in improvements between groups. Main results Sixteen trials involving 3498 people were included. Twelve of the RCTs included only people with OA of the knee, 3 only OA of the hip, and 1 a mix of people with OA of the hip and/or knee. In comparison with a sham control, acupuncture showed statistically significant, short-term improvements in osteoarthritis pain (standardized mean difference -0.28, 95% confidence interval -0.45 to -0.11; 0.9 point greater improvement than sham on 20 point scale; absolute percent change 4.59%; relative percent change 10.32%; 9 trials; 1835 participants) and function (-0.28, -0.46 to -0.09; 2.7 point greater improvement on 68 point scale; absolute percent change 3.97%; relative percent change 8.63%); however, these pooled short-term benefits did not meet our predefined thresholds for clinical relevance (i.e. 1.3 points for pain; 3.57 points for function) and there was substantial statistical heterogeneity. Additionally, restriction to sham-controlled trials using shams judged most likely to adequately blind participants to treatment assignment (which were also the same shams judged most likely to have physiological activity), reduced heterogeneity and resulted in pooled short-term benefits of acupuncture that were smaller and non-significant. In comparison with sham acupuncture at the six-month follow-up, acupuncture showed borderline statistically significant, clinically irrelevant improvements in osteoarthritis pain (-0.10, -0.21 to 0.01; 0.4 point greater improvement than sham on 20 point scale; absolute percent change 1.81%; relative percent change 4.06%; 4 trials;1399 participants) and function (-0.11, -0.22 to 0.00; 1.2 point greater improvement than sham on 68 point scale; absolute percent change 1.79%; relative percent change 3.89%). In a secondary analysis versus a waiting list control, acupuncture was associated with statistically significant, clinically relevant short-term improvements in osteoarthritis pain (-0.96, -1.19 to -0.72; 14.5 point greater improvement than sham on 100 point scale; absolute percent change 14.5%; relative percent change 29.14%; 4 trials; 884 participants) and function (-0.89, -1.18 to -0.60; 13.0 point greater improvement than sham on 100 point scale; absolute percent change 13.0%; relative percent change 25.21%). In the head-on comparisons of acupuncture with the ‘supervised osteoarthritis education’ and the ‘physician consultation’ control groups, acupuncture was associated with clinically relevant short- and long-term improvements in pain and function. In the head on comparisons of acupuncture with ‘home exercises/advice leaflet’ and ‘supervised exercise’, acupuncture was associated with similar treatment effects as the controls. Acupuncture as an adjuvant to an exercise based physiotherapy program did not result in any greater improvements than the exercise program alone. Information on safety was reported in only 8 trials and even in these trials there was limited reporting and heterogeneous methods. Authors' conclusions Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our pre-defined thresholds for clinical relevance, and are probably due at least partially to placebo effects from incomplete blinding. Waiting list-controlled trials of acupuncture for peripheral joint osteoarthritis suggest statistically significant and clinically relevant benefits, much of which may be due to expectation or placebo effects. PMID:20091527

Comparison of film measurements and Monte Carlo simulations of dose delivered with very high-energy electron beams in a polystyrene phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bazalova-Carter, Magdalena; Liu, Michael; Palma, Bianey

2015-04-15

Purpose: To measure radiation dose in a water-equivalent medium from very high-energy electron (VHEE) beams and make comparisons to Monte Carlo (MC) simulation results. Methods: Dose in a polystyrene phantom delivered by an experimental VHEE beam line was measured with Gafchromic films for three 50 MeV and two 70 MeV Gaussian beams of 4.0–6.9 mm FWHM and compared to corresponding MC-simulated dose distributions. MC dose in the polystyrene phantom was calculated with the EGSnrc/BEAMnrc and DOSXYZnrc codes based on the experimental setup. Additionally, the effect of 2% beam energy measurement uncertainty and possible non-zero beam angular spread on MC dosemore » distributions was evaluated. Results: MC simulated percentage depth dose (PDD) curves agreed with measurements within 4% for all beam sizes at both 50 and 70 MeV VHEE beams. Central axis PDD at 8 cm depth ranged from 14% to 19% for the 5.4–6.9 mm 50 MeV beams and it ranged from 14% to 18% for the 4.0–4.5 mm 70 MeV beams. MC simulated relative beam profiles of regularly shaped Gaussian beams evaluated at depths of 0.64 to 7.46 cm agreed with measurements to within 5%. A 2% beam energy uncertainty and 0.286° beam angular spread corresponded to a maximum 3.0% and 3.8% difference in depth dose curves of the 50 and 70 MeV electron beams, respectively. Absolute dose differences between MC simulations and film measurements of regularly shaped Gaussian beams were between 10% and 42%. Conclusions: The authors demonstrate that relative dose distributions for VHEE beams of 50–70 MeV can be measured with Gafchromic films and modeled with Monte Carlo simulations to an accuracy of 5%. The reported absolute dose differences likely caused by imperfect beam steering and subsequent charge loss revealed the importance of accurate VHEE beam control and diagnostics.« less

Simultaneous integrated protection : A new concept for high-precision radiation therapy.

PubMed

Brunner, Thomas B; Nestle, Ursula; Adebahr, Sonja; Gkika, Eleni; Wiehle, Rolf; Baltas, Dimos; Grosu, Anca-Ligia

2016-12-01

Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described. An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTV SIP ). The remainder of the PTV represented the dominant PTV (PTV dom ). Planning was performed using IMRT. Dose was prescribed to PTV dom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTV SIP was required to be as high as possible within the constraints to avoid local relapse. SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTV SIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low. SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

Absolute calibration of ultraviolet filter photometry

NASA Technical Reports Server (NTRS)

Bless, R. C.; Fairchild, T.; Code, A. D.

1972-01-01

The essential features of the calibration procedure can be divided into three parts. First, the shape of the bandpass of each photometer was determined by measuring the transmissions of the individual optical components and also by measuring the response of the photometer as a whole. Secondly, each photometer was placed in the essentially-collimated synchrotron radiation bundle maintained at a constant intensity level, and the output signal was determined from about 100 points on the objective. Finally, two or three points on the objective were illuminated by synchrotron radiation at several different intensity levels covering the dynamic range of the photometers. The output signals were placed on an absolute basis by the electron counting technique described earlier.

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

PubMed

Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

2017-02-01

1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

A comparison between anisotropic analytical and multigrid superposition dose calculation algorithms in radiotherapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Vincent W.C., E-mail: htvinwu@polyu.edu.hk; Tse, Teddy K.H.; Ho, Cola L.M.

2013-07-01

Monte Carlo (MC) simulation is currently the most accurate dose calculation algorithm in radiotherapy planning but requires relatively long processing time. Faster model-based algorithms such as the anisotropic analytical algorithm (AAA) by the Eclipse treatment planning system and multigrid superposition (MGS) by the XiO treatment planning system are 2 commonly used algorithms. This study compared AAA and MGS against MC, as the gold standard, on brain, nasopharynx, lung, and prostate cancer patients. Computed tomography of 6 patients of each cancer type was used. The same hypothetical treatment plan using the same machine and treatment prescription was computed for each casemore » by each planning system using their respective dose calculation algorithm. The doses at reference points including (1) soft tissues only, (2) bones only, (3) air cavities only, (4) soft tissue-bone boundary (Soft/Bone), (5) soft tissue-air boundary (Soft/Air), and (6) bone-air boundary (Bone/Air), were measured and compared using the mean absolute percentage error (MAPE), which was a function of the percentage dose deviations from MC. Besides, the computation time of each treatment plan was recorded and compared. The MAPEs of MGS were significantly lower than AAA in all types of cancers (p<0.001). With regards to body density combinations, the MAPE of AAA ranged from 1.8% (soft tissue) to 4.9% (Bone/Air), whereas that of MGS from 1.6% (air cavities) to 2.9% (Soft/Bone). The MAPEs of MGS (2.6%±2.1) were significantly lower than that of AAA (3.7%±2.5) in all tissue density combinations (p<0.001). The mean computation time of AAA for all treatment plans was significantly lower than that of the MGS (p<0.001). Both AAA and MGS algorithms demonstrated dose deviations of less than 4.0% in most clinical cases and their performance was better in homogeneous tissues than at tissue boundaries. In general, MGS demonstrated relatively smaller dose deviations than AAA but required longer computation time.« less

Observation of dose-rate dependence in a Fricke dosimeter irradiated at low dose rates with monoenergetic X-rays.

PubMed

O'Leary, Mel; Boscolo, Daria; Breslin, Nicole; Brown, Jeremy M C; Dolbnya, Igor P; Emerson, Chris; Figueira, Catarina; Fox, Oliver J L; Grimes, David Robert; Ivosev, Vladimir; Kleppe, Annette K; McCulloch, Aaron; Pape, Ian; Polin, Chris; Wardlow, Nathan; Currell, Fred J

2018-03-16

Absolute measurements of the radiolytic yield of Fe3+ in a ferrous sulphate dosimeter formulation (6 mM Fe2+), with a 20 keV x-ray monoenergetic beam, are reported. Dose-rate suppression of the radiolytic yield was observed at dose rates lower than and different in nature to those previously reported with x-rays. We present evidence that this effect is most likely to be due to recombination of free radicals radiolytically produced from water. The method used to make these measurements is also new and it provides radiolytic yields which are directly traceable to the SI standards system. The data presented provides new and exacting tests of radiation chemistry codes.

The influence of maturation, body size and physical self-perceptions on longitudinal changes in physical activity in adolescent girls.

PubMed

Fawkner, Samantha; Henretty, Joan; Knowles, Ann-Marie; Nevill, Alan; Niven, Ailsa

2014-01-01

The aim of this study was to adopt a longitudinal design to explore the direct effects of both absolute and relative maturation and changes in body size on physical activity, and explore if, and how, physical self-perceptions might mediate this effect. We recruited 208 girls (11.8 ± 0.4 years) at baseline. Data were collected at three subsequent time points, each 6 months apart. At 18 months, 119 girls remained in the study. At each time point, girls completed the Physical Activity Questionnaire for Children, the Pubertal Development Scale (from which, both a measure of relative and absolute maturation were defined) and the Physical Self-Perception Profile, and had physical size characteristics assessed. Multilevel modelling for physical activity indicated a significant negative effect of age, positive effect for physical condition and sport competence and positive association for relatively early maturers. Absolute maturation, body mass, waist circumference and sum of skinfolds did not significantly contribute to the model. Contrary to common hypotheses, relatively more mature girls may, in fact, be more active than their less mature peers. However, neither changes in absolute maturation nor physical size appear to directly influence changes in physical activity in adolescent girls.

COMBINATION THERAPY EFFECTIVENESS OF EZETIMIBE AND ATORVASTATIN IN PATIENTS WITH ACUTE CORONARY SYNDROME.

PubMed

Japaridze, L; Sadunishvili, M; Megreladze, I

2016-03-01

Atorvastatin reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe (EZE) , a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a 16-week one-center, prospective, randomized, and open-label clinical trial, involving 323 patients who had been hospitalized for an acute coronary syndrome within the preceding 14 days. They were received atorvastatin 20 mg during 28 days and after that 292 patients, who had LDL cholesterol levels≥1.81 mmol/L, were randomized to ezetimibe 10 mg/day co-administered with atorvastatin therapy (EZE+Statin) or doubling their current atorvastatin dose. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. At 16 weeks, the mean LDL cholesterol level during the study was 1.60 mmol per liter in the atorvastatine-ezetimibe group, as compared with 1.91 mmol per liter in the atorvastatin-monotherapy group (p<0.001). The Kaplan-Meier survival rate at 16 weeks were 88 .1 % in the atorvastatin-ezetimibe group and 77.0 % in the atorvastatin monotherapy group (absolute risk reduction, 11.1 percentage points; hazard ratio, 2.099 ; 95% confidence interval, 1.165 to 3.781; p=0.014). Patients receiving ezetimibe and statin were more likely to achieve target LDL-C after 16 weeks compared to patients doubling their statin dose. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Ezetimibe/statin combination therapy was well tolerated among this patients, without safety concerns.

Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.

PubMed

Gupta, Neeraj; Hanley, Michael J; Diderichsen, Paul M; Yang, Huyuan; Ke, Alice; Teng, Zhaoyang; Labotka, Richard; Berg, Deborah; Patel, Chirag; Liu, Guohui; van de Velde, Helgi; Venkatakrishnan, Karthik

2018-02-15

Model-informed drug development (MIDD) was central to the development of the oral proteasome inhibitor ixazomib, facilitating internal decisions (switch from body surface area (BSA)-based to fixed dosing, inclusive phase III trials, portfolio prioritization of ixazomib-based combinations, phase III dose for maintenance treatment), regulatory review (model-informed QT analysis, benefit-risk of 4 mg dose), and product labeling (absolute bioavailability and intrinsic/extrinsic factors). This review discusses the impact of MIDD in enabling patient-centric therapeutic optimization during the development of ixazomib. © 2017 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Improved dewpoint-probe calibration

NASA Technical Reports Server (NTRS)

Stephenson, J. G.; Theodore, E. A.

1978-01-01

Relatively-simple pressure-control apparatus calibrates dewpoint probes considerably faster than conventional methods, with no loss of accuracy. Technique requires only pressure measurement at each calibration point and single absolute-humidity measurement at beginning of run. Several probes can be calibrated simultaneously and points can be checked above room temperature.

Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields

NASA Astrophysics Data System (ADS)

Diego Azcona, Juan; Barbés, Benigno; Wang, Lilie; Burguete, Javier

2016-01-01

This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac’s head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.

COMMENT: Comment on 'Evaluation of the local value of the Earth gravity field in the context of the new definition of the kilogram'

NASA Astrophysics Data System (ADS)

Svitlov, S. M.

2010-06-01

A recent paper (Baumann et al 2009 Metrologia 46 178-86) presents a method to evaluate the free-fall acceleration at a desired point in space, as required for the watt balance experiment. The claimed uncertainty of their absolute gravity measurements is supported by two bilateral comparisons using two absolute gravimeters of the same type. This comment discusses the case where absolute gravity measurements are traceable to a key comparison reference value. Such an approach produces a more complete uncertainty budget and reduces the risk of the results of different watt balance experiments not being compatible.

Mapping with MAV: Experimental Study on the Contribution of Absolute and Relative Aerial Position Control

NASA Astrophysics Data System (ADS)

Skaloud, J.; Rehak, M.; Lichti, D.

2014-03-01

This study highlights the benefit of precise aerial position control in the context of mapping using frame-based imagery taken by small UAVs. We execute several flights with a custom Micro Aerial Vehicle (MAV) octocopter over a small calibration field equipped with 90 signalized targets and 25 ground control points. The octocopter carries a consumer grade RGB camera, modified to insure precise GPS time stamping of each exposure, as well as a multi-frequency/constellation GNSS receiver. The GNSS antenna and camera are rigidly mounted together on a one-axis gimbal that allows control of the obliquity of the captured imagery. The presented experiments focus on including absolute and relative aerial control. We confirm practically that both approaches are very effective: the absolute control allows omission of ground control points while the relative requires only a minimum number of control points. Indeed, the latter method represents an attractive alternative in the context of MAVs for two reasons. First, the procedure is somewhat simplified (e.g. the lever-arm between the camera perspective and antenna phase centers does not need to be determined) and, second, its principle allows employing a single-frequency antenna and carrier-phase GNSS receiver. This reduces the cost of the system as well as the payload, which in turn increases the flying time.

Nanoparticle exposure at nanotechnology workplaces: A review

PubMed Central

2011-01-01

Risk, associated with nanomaterial use, is determined by exposure and hazard potential of these materials. Both topics cannot be evaluated absolutely independently. Realistic dose concentrations should be tested based on stringent exposure assessments for the corresponding nanomaterial taking into account also the environmental and product matrix. This review focuses on current available information from peer reviewed publications related to airborne nanomaterial exposure. Two approaches to derive realistic exposure values are differentiated and independently presented; those based on workplace measurements and the others based on simulations in laboratories. An assessment of the current available workplace measurement data using a matrix, which is related to nanomaterials and work processes, shows, that data are available on the likelihood of release and possible exposure. Laboratory studies are seen as an important complementary source of information on particle release processes and hence for possible exposure. In both cases, whether workplace measurements or laboratories studies, the issue of background particles is a major problem. From this review, major areas for future activities and focal points are identified. PMID:21794132

Vitamin D analogues to target residual proteinuria: potential impact on cardiorenal outcomes

PubMed Central

Humalda, Jelmer K.; Goldsmith, David J. A.; Thadhani, Ravi; de Borst, Martin H.

2015-01-01

Residual proteinuria, the amount of proteinuria that remains during optimally dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent risk factor for progressive renal function loss and cardiovascular complications in chronic kidney disease (CKD) patients. Dual RAAS blockade may reduce residual proteinuria but without translating into improved cardiorenal outcomes at least in diabetic nephropathy; rather, dual RAAS blockade may increase the risk of adverse events. These findings have challenged the concept of residual proteinuria as an absolute treatment target. Therefore, new strategies must be explored to address whether by further reduction of residual proteinuria using interventions not primarily targeting the RAAS benefit in terms of cardiorenal risk reduction would accrue. Both clinical and experimental intervention studies have demonstrated that vitamin D can reduce residual proteinuria through both RAAS-dependent and RAAS-independent pathways. Future research should prospectively explore vitamin D treatment as an adjunct to RAAS blockade in an interventional trial exploring clinically relevant cardiorenal end points. PMID:25609737

Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations

PubMed Central

Moore, Bria M.; Brady, Samuel L.; Mirro, Amy E.; Kaufman, Robert A.

2014-01-01

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) were then multiplied by patient-specific SSDE to estimate patient organ dose. The \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. Individual\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ , was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE. PMID:24989395

SU-F-T-08: Brachytherapy Film Dosimetry in a Water Phantom for a Ring and Tandem HDR Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, B; Grelewicz, Z; Kang, Z

2016-06-15

Purpose: The feasibility of dose measurement using new generation EBT3 film was explored in a water phantom for a ring and tandem HDR applicator for measurements tracking mucosal dose during cervical brachytherapy. Methods: An experimental fixture was assembled to position the applicator in a water phantom. Prior to measurement, calibration curves for EBT3 film in water and in solidwater were verified. EBT3 film was placed at different known locations around the applicator in the water tank. A CT scan of the phantom with applicator was performed using clinical protocol. A typical cervical cancer treatment plan was then generated by Oncentramore » brachytherapy planning system. A dose of 500 cGy was prescribed to point A (2 cm, 2 cm). Locations measured by film included the outer surface of the ring, measurement point A-m (2.2 cm, 2.2 cm), and profiles extending from point A-m parallel to the tandem. Three independent measurements were conducted. The doses recorded by film were carefully analyzed and compared with values calculated by the treatment planning system. Results: Assessment of the EBT3 films indicate that the dose at point A matches the values predicted by the planning system. Dose to the point A-m was 411.5 cGy, and the outer circumferential surface dose of the ring was between 500 and 1150 cGy. It was found that from the point A-m, the dose drops 60% within 4.5 cm on the line parallel to the tandem. The measurement doses agree with the treatment planning system. Conclusion: Use of EBT3 film is feasible for in-water measurements for brachytherapy. A carefully machined apparatus will likely improve measurement accuracy. In a typical plan, our study found that the ring surface dose can be 2.5 times larger than the point A prescription dose. EBT3 film can be used to monitor mucosal dose in brachytherapy treatments.« less

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

PubMed

Mangold, C A; Rijnders, A; Georg, D; Van Limbergen, E; Pötter, R; Huyskens, D

2001-01-01

In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Laser guide star pointing camera for ESO LGS Facilities

NASA Astrophysics Data System (ADS)

Bonaccini Calia, D.; Centrone, M.; Pedichini, F.; Ricciardi, A.; Cerruto, A.; Ambrosino, F.

2014-08-01

Every observatory using LGS-AO routinely has the experience of the long time needed to bring and acquire the laser guide star in the wavefront sensor field of view. This is mostly due to the difficulty of creating LGS pointing models, because of the opto-mechanical flexures and hysteresis in the launch and receiver telescope structures. The launch telescopes are normally sitting on the mechanical structure of the larger receiver telescope. The LGS acquisition time is even longer in case of multiple LGS systems. In this framework the optimization of the LGS systems absolute pointing accuracy is relevant to boost the time efficiency of both science and technical observations. In this paper we show the rationale, the design and the feasibility tests of a LGS Pointing Camera (LPC), which has been conceived for the VLT Adaptive Optics Facility 4LGSF project. The LPC would assist in pointing the four LGS, while the VLT is doing the initial active optics cycles to adjust its own optics on a natural star target, after a preset. The LPC allows minimizing the needed accuracy for LGS pointing model calibrations, while allowing to reach sub-arcsec LGS absolute pointing accuracy. This considerably reduces the LGS acquisition time and observations operation overheads. The LPC is a smart CCD camera, fed by a 150mm diameter aperture of a Maksutov telescope, mounted on the top ring of the VLT UT4, running Linux and acting as server for the client 4LGSF. The smart camera is able to recognize within few seconds the sky field using astrometric software, determining the stars and the LGS absolute positions. Upon request it returns the offsets to give to the LGS, to position them at the required sky coordinates. As byproduct goal, once calibrated the LPC can calculate upon request for each LGS, its return flux, its fwhm and the uplink beam scattering levels.

Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Din, Shaun U.; Williams, Eric L.; Jackson, Andrew

Purpose: To determine the role of patient/tumor characteristics, radiation dose, and fractionation using the linear-quadratic (LQ) model to predict stereotactic body radiation therapy–induced grade ≥2 chest wall pain (CWP2) in a larger series and develop clinically useful constraints for patients treated with different fraction numbers. Methods and Materials: A total of 316 lung tumors in 295 patients were treated with stereotactic body radiation therapy in 3 to 5 fractions to 39 to 60 Gy. Absolute dose–absolute volume chest wall (CW) histograms were acquired. The raw dose-volume histograms (α/β = ∞ Gy) were converted via the LQ model to equivalent doses in 2-Gy fractions (normalizedmore » total dose, NTD) with α/β from 0 to 25 Gy in 0.1-Gy steps. The Cox proportional hazards (CPH) model was used in univariate and multivariate models to identify and assess CWP2 exposed to a given physical and NTD. Results: The median follow-up was 15.4 months, and the median time to development of CWP2 was 7.4 months. On a univariate CPH model, prescription dose, prescription dose per fraction, number of fractions, D83cc, distance of tumor to CW, and body mass index were all statistically significant for the development of CWP2. Linear-quadratic correction improved the CPH model significance over the physical dose. The best-fit α/β was 2.1 Gy, and the physical dose (α/β = ∞ Gy) was outside the upper 95% confidence limit. With α/β = 2.1 Gy, V{sub NTD99Gy} was most significant, with median V{sub NTD99Gy} = 31.5 cm{sup 3} (hazard ratio 3.87, P<.001). Conclusion: There were several predictive factors for the development of CWP2. The LQ-adjusted doses using the best-fit α/β = 2.1 Gy is a better predictor of CWP2 than the physical dose. To aid dosimetrists, we have calculated the physical dose equivalent corresponding to V{sub NTD99Gy} = 31.5 cm{sup 3} for the 3- to 5-fraction groups.« less

SU-F-T-345: Quasi-Dead Beams: Clinical Relevance and Implications for Automatic Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, R; Veltchev, I; Lin, T

Purpose: Beam direction selection for fixed-beam IMRT planning is typically a manual process. Severe dose-volume limits on critical structures in the thorax often result in atypical selection of beam directions as compared to other body sites. This work demonstrates the potential consequences as well as clinical relevance. Methods: 21 thoracic cases treated with 5–7 beam directions, 6 cases including non-coplanar arrangements, with fractional doses of 150–411cGy were analyzed. Endpoints included per-beam modulation scaling factor (MSF), variation from equal weighting, and delivery QA passing rate. Results: During analysis of patient-specific delivery QA a sub-standard passing rate was found for a singlemore » 5-field plan (90.48% of pixels evaluated passing 3% dose, 3mm DTA). During investigation it was found that a single beam demonstrated a MSF of 34.7 and contributed only 2.7% to the mean dose of the target. In addition, the variation from equal weighting for this beam was 17.3% absolute resulting in another beam with a MSF of 4.6 contributing 41.9% to the mean dose to the target; a variation of 21.9% from equal weighting. The average MSF for the remaining 20 cases was 4.0 (SD 1.8) with an average absolute deviation of 2.8% from equal weighting (SD 3.1%). Conclusion: Optimization in commercial treatment planning systems typically results in relatively equally weighted beams. Extreme variation from this can result in excessively high MSFs (very small segments) and potential decreases in agreement between planned and delivered dose distributions. In addition, the resultant beam may contribute minimal dose to the target (quasi-dead beam); a byproduct being increased treatment time and associated localization uncertainties. Potential ramifications exist for automatic planning algorithms should they allow for user-defined beam directions. Additionally, these quasi-dead beams may be embedded in the libraries for model-based systems potentially resulting in inefficient and less accurate deliveries.« less

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, J; Braunstein, S; McDermott, M

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). Tomore » study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.« less

Pharmacokinetics, dose proportionality and permeability of S002-333 and its enantiomers, a potent antithrombotic agent, in rabbits.

PubMed

Saxena, Amrita; Valicherla, Guru R; Joshi, Pankaj; Saxena, Rohit; Cheruvu, Srikanth H; Bhunia, Shome S; Jain, Girish K; Siddiqui, Hefazat H; Saxena, Anil K; Gayen, Jiaur R

2015-01-01

1. S002-333 [(2-(4'-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-pyrido (3,4-b) indole-3-carboxylic acid amide)] is a novel and potent antithrombotic active agent. The present work investigates the pharmacokinetics, bioavailability, dose proportionality and permeability of the racemate, S002-333 in male New Zealand White (NZW) rabbits. 2. Rabbits were administered single intravenous (i.v.) (2 mg/kg) and three oral doses of 10, 20 and 40 mg/kg of S002-333, respectively, at different occasions to evaluate dose proportionality. Serial blood samples were collected and analyzed by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Since S002-333 is a racemate consisting of S004-1032 (R) and S007-1558 (S), same samples were analyzed using a chiralcel column so as to evaluate the respective enantiomers. 3. The peak plasma concentration, after oral administration, occurred at ∼10 h post-dose. The clearance (CL) and volume of distribution (Vd) after i.v. dose were found to be 3.05 ± 0.09 l/h/kg and 6.73 ± 1.16 l/kg, respectively. The absolute oral bioavailability of S002-333 was 16.32%, whereas it was 6.62 and 5.90% for R- and S-enantiomers, respectively. The absolute bioavailability of 10, 20 and 40 mg/kg doses were found to be 27.91, 14.39 and 16.91%, respectively. The PAMPA (parallel artificial membrane permeability assay) assay shows that S002-333 has a low-passive permeability at gastric and intestinal environment. 4. In conclusion, S002-333 has low-passive permeability, low CL and large Vd. The R-enantiomer has a "slightly" greater bioavailability than the S-enantiomer.

Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Budoff, Matthew J; Nasir, Khurram; McClelland, Robyn L; Detrano, Robert; Wong, Nathan; Blumenthal, Roger S; Kondos, George; Kronmal, Richard A

2009-01-27

In this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score. The presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units). There were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank. Using absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.

Fully distributed absolute blood flow velocity measurement for middle cerebral arteries using Doppler optical coherence tomography

PubMed Central

Qi, Li; Zhu, Jiang; Hancock, Aneeka M.; Dai, Cuixia; Zhang, Xuping; Frostig, Ron D.; Chen, Zhongping

2016-01-01

Doppler optical coherence tomography (DOCT) is considered one of the most promising functional imaging modalities for neuro biology research and has demonstrated the ability to quantify cerebral blood flow velocity at a high accuracy. However, the measurement of total absolute blood flow velocity (BFV) of major cerebral arteries is still a difficult problem since it is related to vessel geometry. In this paper, we present a volumetric vessel reconstruction approach that is capable of measuring the absolute BFV distributed along the entire middle cerebral artery (MCA) within a large field-of-view. The Doppler angle at each point of the MCA, representing the vessel geometry, is derived analytically by localizing the artery from pure DOCT images through vessel segmentation and skeletonization. Our approach could achieve automatic quantification of the fully distributed absolute BFV across different vessel branches. Experiments on rodents using swept-source optical coherence tomography showed that our approach was able to reveal the consequences of permanent MCA occlusion with absolute BFV measurement. PMID:26977365

Fully distributed absolute blood flow velocity measurement for middle cerebral arteries using Doppler optical coherence tomography.

PubMed

Qi, Li; Zhu, Jiang; Hancock, Aneeka M; Dai, Cuixia; Zhang, Xuping; Frostig, Ron D; Chen, Zhongping

2016-02-01

Doppler optical coherence tomography (DOCT) is considered one of the most promising functional imaging modalities for neuro biology research and has demonstrated the ability to quantify cerebral blood flow velocity at a high accuracy. However, the measurement of total absolute blood flow velocity (BFV) of major cerebral arteries is still a difficult problem since it is related to vessel geometry. In this paper, we present a volumetric vessel reconstruction approach that is capable of measuring the absolute BFV distributed along the entire middle cerebral artery (MCA) within a large field-of-view. The Doppler angle at each point of the MCA, representing the vessel geometry, is derived analytically by localizing the artery from pure DOCT images through vessel segmentation and skeletonization. Our approach could achieve automatic quantification of the fully distributed absolute BFV across different vessel branches. Experiments on rodents using swept-source optical coherence tomography showed that our approach was able to reveal the consequences of permanent MCA occlusion with absolute BFV measurement.

Betaine synthesis from radioactive precursors in attached, water-stressed barley leaves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, A.D.; Scott, N.A.

1980-08-01

In wilted barley leaves, betaine accumulates at about 200 nanomoles per 10 centimeters leaf per day. Results with /sup 14/C-labeled precursors were qualitatively and quantitatively consistent with de novo synthesis of this betaine from serine via ethanolamine, choline, and betaine aldehyde and indicated that water stress may increase the activities of all steps in this pathway except the last. Doses (I micromole) of each /sup 14/C-labeled precursor were supplied as droplets to the tips of attached, 10-centimeter, second-leaf blades of turgid and wilted plants, and the incorporation of /sup 14/C into betaine was followed. From the rates of betaine labeling,more » estimates were made of the potential capacities (nanomoles per 10 centimeters leaf per day) for the methylation and oxidation steps. Labeling of betaine from absolute value /sup 14/C choline, absolute value /sup 14/C ethanolamine, and absolute value /sup 14/C serine was about 7- to 10-fold greater in leaves wilted for 2 days than in turgid leaves, whereas label from absolute value /sup 14/C betaine aldehyde appeared in betaine at about the same rate in both turgid and wilted leaves. In leaves wilted for 2 days, the potential capacities for converting absolute value /sup 14/C ethanolamine, absolute value /sup 14/C choline, and absolute value /sup 14/C betaine aldehyde to betaine all approached or exceeded the rate of betain accumulation (about 200 nanomoles per 10 centimeters leaf per day); in turgid leaves, only the potential for converting betaine aldehyde to betaine exceeded this rate. The rate of conversion of absolute value /sup 14/C ethanolamine to betaine increased 4-fold after 6 to 10 hours of wilting, which was soon enough to account for the onset of betaine accumulation.« less

40 CFR 1065.659 - Removed water correction.

Code of Federal Regulations, 2011 CFR

2011-07-01

... know that saturated water vapor conditions exist. Use good engineering judgment to measure the... absolute pressure based on an alarm set point, a pressure regulator set point, or good engineering judgment... from raw exhaust, you may determine the amount of water based on intake-air humidity, plus a chemical...

40 CFR 1065.659 - Removed water correction.

Code of Federal Regulations, 2010 CFR

2010-07-01

... know that saturated water vapor conditions exist. Use good engineering judgment to measure the... absolute pressure based on an alarm set point, a pressure regulator set point, or good engineering judgment... from raw exhaust, you may determine the amount of water based on intake-air humidity, plus a chemical...

Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network.

PubMed

Byrd, Darrin; Christopfel, Rebecca; Arabasz, Grae; Catana, Ciprian; Karp, Joel; Lodge, Martin A; Laymon, Charles; Moros, Eduardo G; Budzevich, Mikalai; Nehmeh, Sadek; Scheuermann, Joshua; Sunderland, John; Zhang, Jun; Kinahan, Paul

2018-01-01

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a range of 11%. Dose calibrator bias was not correlated with scanner bias. Calibration factors from the image metadata were nearly as variable as scanner signal, and were correlated with signal for many scanners. SUVs often showed low intrascanner variability between successive measurements but were also prone to shifts in apparent bias, possibly in part due to scanner recalibrations that are part of regular scanner quality control. Biases of key factors in the computation of SUVs were not correlated and their temporal variations did not cancel out of the computation. Long-lived sources and image metadata may provide a check on the recalibration process.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Elsayed

Purpose: To characterize and correct for radiation-induced background (RIB) observed in the signals from a class of scanning water tanks. Methods: A method was developed to isolate the RIB through detector measurements in the background-free linac console area. Variation of the RIB against a large number of parameters was characterized, and its impact on basic clinical data for photon and electron beams was quantified. Different methods to minimize and/or correct for the RIB were proposed and evaluated. Results: The RIB is due to the presence of the electrometer and connection box in a low background radiation field (by design). Themore » absolute RIB current with a biased detector is up to 2 pA, independent of the detector size, which is 0.6% and 1.5% of the central axis reference signal for a standard and a mini scanning chamber, respectively. The RIB monotonically increases with field size, is three times smaller for detectors that do not require a bias (e.g., diodes), is up to 80% larger for positive (versus negative) polarity, decreases with increasing photon energy, exhibits a single curve versus dose rate at the electrometer location, and is negligible for electron beams. Data after the proposed field-size correction method agree with point measurements from an independent system to within a few tenth of a percent for output factor, head scatter, depth dose at depth, and out-of-field profile dose. Manufacturer recommendations for electrometer placement are insufficient and sometimes incorrect. Conclusions: RIB in scanning water tanks can have a non-negligible effect on dosimetric data.« less

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liebl, Jakob, E-mail: jakob.liebl@medaustron.at; Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Therapeutic Radiology and Oncology, Medical University of Graz, 8036 Graz

2014-09-15

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patientmore » positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain as well as target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple fields with smeared compensators while avoiding distal OAR sparing is considered to be safe.« less

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

PubMed Central

Liebl, Jakob; Paganetti, Harald; Zhu, Mingyao; Winey, Brian A.

2014-01-01

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R2 < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain as well as target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple fields with smeared compensators while avoiding distal OAR sparing is considered to be safe. PMID:25186386

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherpak, Amanda

Purpose: The Octavius 1000{sup SRS} detector was commissioned in December 2014 and is used routinely for verification of all SRS and SBRT plans. Results of verifications were analyzed to assess trends and limitations of the device and planning methods. Methods: Plans were delivered using a True Beam STx and results were evaluated using gamma analysis (95%, 3%/3mm) and absolute dose difference (5%). Verification results were analyzed based on several plan parameters including tumour volume, degree of modulation and prescribed dose. Results: During a 12 month period, a total of 124 patient plans were verified using the Octavius detector. Thirteen plansmore » failed the gamma criteria, while 7 plans failed based on the absolute dose difference. When binned according to degree of modulation, a significant correlation was found between MU/cGy and both mean dose difference (r=0.78, p<0.05) and gamma (r=−0.60, p<0.05). When data was binned according to tumour volume, the standard deviation of average gamma dropped from 2.2% – 3.7% for the volumes less than 30 cm{sup 3} to below 1% for volumes greater than 30 cm{sup 3}. Conclusions: The majority of plans and verification failures involved tumour volumes smaller than 30 cm{sup 3}. This was expected due to the nature of disease treated with SBRT and SRS techniques and did not increase rate of failure. Correlations found with MU/cGy indicate that as modulation increased, results deteriorated but not beyond the previously set thresholds.« less

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

Starting Processes of High Contraction Ratio Scramjet Inlets

DTIC Science & Technology

2012-01-01

shortly before injection, at which point the boxes were switched to relative mode via the “ Taka Taka ” box, shown on Fig. 22. This absolute mode...camera used for the Schlieren visualisation, as well as the trigger for the 32 channel data acquisition system used. Figure 22: Taka ... taka box, used to manipulate the resistance mode during testing Figure 23: Typical raw thin film array signal, showing both absolute and relative

Determination of dose distributions and parameter sensitivity. Hanford Environmental Dose Reconstruction Project; dose code recovery activities; Calculation 005

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.; Farris, W.T.; Simpson, J.C.

1992-12-01

A series of scoping calculations has been undertaken to evaluate the absolute and relative contribution of different radionuclides and exposure pathways to doses that may have been received by individuals living in the vicinity of the Hanford site. This scoping calculation (Calculation 005) examined the contributions of numerous parameters to the uncertainty distribution of doses calculated for environmental exposures and accumulation in foods. This study builds on the work initiated in the first scoping study of iodine in cow`s milk and the third scoping study, which added additional pathways. Addressed in this calculation were the contributions to thyroid dose ofmore » infants from (1) air submersion and groundshine external dose, (2) inhalation, (3) ingestion of soil by humans, (4) ingestion of leafy vegetables, (5) ingestion of other vegetables and fruits, (6) ingestion of meat, (7) ingestion of eggs, and (8) ingestion of cows` milk from Feeding Regime 1 as described in Calculation 001.« less

Independent calculation of monitor units for VMAT and SPORT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xin; Bush, Karl; Ding, Aiping

Purpose: Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulatedmore » arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). Methods: The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. Results: For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours, dose profiles, gamma index, and dose volume histogram (DVH) for these cases. For the lung cases, the MC-calculated MUs differ significantly from that of the treatment plan computed using AAA. However, the discrepancies are reduced to within 3% when the TPS dose calculation algorithm is switched to a transport equation-based technique (Acuros™). Comparison in the dose domain between the MC and Eclipse AAA/Acuros calculation yields conclusion consistent with the MU calculation. Conclusions: A computational framework relating the MU and dose domains has been established. The framework does not only enable them to verify the MU values of the involved station points of a VMAT plan directly in the MU domain but also provide a much needed mechanism to adaptively modify the MU values of the station points in accordance to a specific change in the dose domain.« less

Teaching Point-of-Care Lung Ultrasound to Novice Pediatric Learners: Web-Based E-Learning Versus Traditional Classroom Didactic.

PubMed

Soon, Aun Woon; Toney, Amanda Greene; Stidham, Timothy; Kendall, John; Roosevelt, Genie

2018-04-24

To assess whether Web-based teaching is at least as effective as traditional classroom didactic in improving the proficiency of pediatric novice learners in the image acquisition and interpretation of pneumothorax and pleural effusion using point-of-care ultrasound (POCUS). We conducted a randomized controlled noninferiority study comparing the effectiveness of Web-based teaching to traditional classroom didactic. The participants were randomized to either group A (live classroom lecture) or group B (Web-based lecture) and completed a survey and knowledge test. They also received hands-on training and completed an objective structured clinical examination. The participants were invited to return 2 months later to test for retention of knowledge and skills. There were no significant differences in the mean written test scores between the classroom group and Web group for the precourse test (absolute difference, -2.5; 95% confidence interval [CI], -12 to 6.9), postcourse test (absolute difference, 2.0; 95% CI, -1.4, 5.3), and postcourse 2-month retention test (absolute difference, -0.8; 95% CI, -9.6 to 8.1). Similarly, no significant differences were noted in the mean objective structured clinical examination scores for both intervention groups in postcourse (absolute difference, 1.9; 95% CI, -4.7 to 8.5) and 2-month retention (absolute difference, -0.6; 95% CI, -10.7 to 9.5). Web-based teaching is at least as effective as traditional classroom didactic in improving the proficiency of novice learners in POCUS. The usage of Web-based tutorials allows a more efficient use of time and a wider dissemination of knowledge.

Carbohydrate dose influences liver and muscle glycogen oxidation and performance during prolonged exercise.

PubMed

King, Andy J; O'Hara, John P; Morrison, Douglas J; Preston, Tom; King, Roderick F G J

2018-01-01

This study investigated the effect of carbohydrate (CHO) dose and composition on fuel selection during exercise, specifically exogenous and endogenous (liver and muscle) CHO oxidation. Ten trained males cycled in a double-blind randomized order on 5 occasions at 77% V˙O2max for 2 h, followed by a 30-min time-trial (TT) while ingesting either 60 g·h -1 (LG) or 75 g·h -1 13 C-glucose (HG), 90 g·h -1 (LGF) or 112.5 g·h -1 13 C-glucose- 13 C-fructose ([2:1] HGF) or placebo. CHO doses met or exceed reported intestinal transporter saturation for glucose and fructose. Indirect calorimetry and stable mass isotope [ 13 C] tracer techniques were utilized to determine fuel use. TT performance was 93% "likely/probable" to be improved with LGF compared with the other CHO doses. Exogenous CHO oxidation was higher for LGF and HGF compared with LG and HG (ES > 1.34, P < 0.01), with the relative contribution of LGF (24.5 ± 5.3%) moderately higher than HGF (20.6 ± 6.2%, ES = 0.68). Increasing CHO dose beyond intestinal saturation increased absolute (29.2 ± 28.6 g·h -1 , ES = 1.28, P = 0.06) and relative muscle glycogen utilization (9.2 ± 6.9%, ES = 1.68, P = 0.014) for glucose-fructose ingestion. Absolute muscle glycogen oxidation between LG and HG was not significantly different, but was moderately higher for HG (ES = 0.60). Liver glycogen oxidation was not significantly different between conditions, but absolute and relative contributions were moderately attenuated for LGF (19.3 ± 9.4 g·h -1 , 6.8 ± 3.1%) compared with HGF (30.5 ± 17.7 g·h -1 , 10.1 ± 4.0%, ES = 0.79 & 0.98). Total fat oxidation was suppressed in HGF compared with all other CHO conditions (ES > 0.90, P = 0.024-0.17). In conclusion, there was no linear dose response for CHO ingestion, with 90 g·h -1 of glucose-fructose being optimal in terms of TT performance and fuel selection. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

SU-F-P-61: Does It Matter Not to Use Optimization Points at the Apex for Vaginal Cylinder HDR Brachytherapy Planning?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Y

2016-06-15

Purpose: To test the impact of the use of apex optimization points for new vaginal cylinder (VC) applicators. Methods: New “ClickFit” single channel VC applicators (Varian) that have a different top thicknesses but the same diameters as the old VC applicators (2.3 cm diameter, 2.6 cm, 3.0 cm, and 3.5 cm) were compared using phantom studies. Old VC applicator plans without apex optimization points were also compared to the plans with the optimization points. The apex doses were monitored at 5 mm depth doses (8 points) where a prescription dose (Rx) of 6Gy was prescribed. VC surface doses (8 points)more » were also analyzed. Results: The new VC applicator plans without apex optimization points presented significantly lower 5mm depth doses than Rx (on average −31 ± 7%, p <0.00001) due to their thicker VC tops (3.4 ± 1.1 mm thicker with the range of 1.2 to 4.4 mm) than the old VC applicators. Old VC applicator plans also showed a statistically significant reduction (p <0.00001) due to Ir-192 source anisotropic effect at the apex region but the % reduction over Rx was only −7 ± 9%. However, by adding apex optimization points to the new VC applicator plans, the plans improved 5 mm depth doses (−7 ± 9% over Rx) that were not statistically different from old VC plans (p = 0.923), along with apex VC surface doses (−22 ± 10% over old VC versus −46 ± 7% without using apex optimization points). Conclusion: The use of apex optimization points are important in order to avoid significant additional cold doses (−24 ± 2%) at the prescription depth (5 mm) of apex, especially for the new VC applicators that have thicker tops.« less

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

2000-05-01

We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

Performance of Different Light Sources for the Absolute Calibration of Radiation Thermometers

NASA Astrophysics Data System (ADS)

Martín, M. J.; Mantilla, J. M.; del Campo, D.; Hernanz, M. L.; Pons, A.; Campos, J.

2017-09-01

The evolving mise en pratique for the definition of the kelvin (MeP-K) [1, 2] will, in its forthcoming edition, encourage the realization and dissemination of the thermodynamic temperature either directly (primary thermometry) or indirectly (relative primary thermometry) via fixed points with assigned reference thermodynamic temperatures. In the last years, the Centro Español de Metrología (CEM), in collaboration with the Instituto de Óptica of Consejo Superior de Investigaciones Científicas (IO-CSIC), has developed several setups for absolute calibration of standard radiation thermometers using the radiance method to allow CEM the direct dissemination of the thermodynamic temperature and the assignment of the thermodynamic temperatures to several fixed points. Different calibration facilities based on a monochromator and/or a laser and an integrating sphere have been developed to calibrate CEM's standard radiation thermometers (KE-LP2 and KE-LP4) and filter radiometer (FIRA2). This system is based on the one described in [3] placed in IO-CSIC. Different light sources have been tried and tested for measuring absolute spectral radiance responsivity: a Xe-Hg 500 W lamp, a supercontinuum laser NKT SuperK-EXR20 and a diode laser emitting at 6473 nm with a typical maximum power of 120 mW. Their advantages and disadvantages have been studied such as sensitivity to interferences generated by the laser inside the filter, flux stability generated by the radiant sources and so forth. This paper describes the setups used, the uncertainty budgets and the results obtained for the absolute temperatures of Cu, Co-C, Pt-C and Re-C fixed points, measured with the three thermometers with central wavelengths around 650 nm.

Monte Carlo study of LDR seed dosimetry with an application in a clinical brachytherapy breast implant.

PubMed

Furstoss, C; Reniers, B; Bertrand, M J; Poon, E; Carrier, J-F; Keller, B M; Pignol, J P; Beaulieu, L; Verhaegen, F

2009-05-01

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

Testing of the analytical anisotropic algorithm for photon dose calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esch, Ann van; Tillikainen, Laura; Pyykkonen, Jukka

2006-11-15

The analytical anisotropic algorithm (AAA) was implemented in the Eclipse (Varian Medical Systems) treatment planning system to replace the single pencil beam (SPB) algorithm for the calculation of dose distributions for photon beams. AAA was developed to improve the dose calculation accuracy, especially in heterogeneous media. The total dose deposition is calculated as the superposition of the dose deposited by two photon sources (primary and secondary) and by an electron contamination source. The photon dose is calculated as a three-dimensional convolution of Monte-Carlo precalculated scatter kernels, scaled according to the electron density matrix. For the configuration of AAA, an optimizationmore » algorithm determines the parameters characterizing the multiple source model by optimizing the agreement between the calculated and measured depth dose curves and profiles for the basic beam data. We have combined the acceptance tests obtained in three different departments for 6, 15, and 18 MV photon beams. The accuracy of AAA was tested for different field sizes (symmetric and asymmetric) for open fields, wedged fields, and static and dynamic multileaf collimation fields. Depth dose behavior at different source-to-phantom distances was investigated. Measurements were performed on homogeneous, water equivalent phantoms, on simple phantoms containing cork inhomogeneities, and on the thorax of an anthropomorphic phantom. Comparisons were made among measurements, AAA, and SPB calculations. The optimization procedure for the configuration of the algorithm was successful in reproducing the basic beam data with an overall accuracy of 3%, 1 mm in the build-up region, and 1%, 1 mm elsewhere. Testing of the algorithm in more clinical setups showed comparable results for depth dose curves, profiles, and monitor units of symmetric open and wedged beams below d{sub max}. The electron contamination model was found to be suboptimal to model the dose around d{sub max}, especially for physical wedges at smaller source to phantom distances. For the asymmetric field verification, absolute dose difference of up to 4% were observed for the most extreme asymmetries. Compared to the SPB, the penumbra modeling is considerably improved (1%, 1 mm). At the interface between solid water and cork, profiles show a better agreement with AAA. Depth dose curves in the cork are substantially better with AAA than with SPB. Improvements are more pronounced for 18 MV than for 6 MV. Point dose measurements in the thoracic phantom are mostly within 5%. In general, we can conclude that, compared to SPB, AAA improves the accuracy of dose calculations. Particular progress was made with respect to the penumbra and low dose regions. In heterogeneous materials, improvements are substantial and more pronounced for high (18 MV) than for low (6 MV) energies.« less

Development and validation of automated 2D-3D bronchial airway matching to track changes in regional bronchial morphology using serial low-dose chest CT scans in children with chronic lung disease.

PubMed

Raman, Pavithra; Raman, Raghav; Newman, Beverley; Venkatraman, Raman; Raman, Bhargav; Robinson, Terry E

2010-12-01

To address potential concern for cumulative radiation exposure with serial spiral chest computed tomography (CT) scans in children with chronic lung disease, we developed an approach to match bronchial airways on low-dose spiral and low-dose high-resolution CT (HRCT) chest images to allow serial comparisons. An automated algorithm matches the position and orientation of bronchial airways obtained from HRCT slices with those in the spiral CT scan. To validate this algorithm, we compared manual matching vs automatic matching of bronchial airways in three pediatric patients. The mean absolute percentage difference between the manually matched spiral CT airway and the index HRCT airways were 9.4 ± 8.5% for the internal diameter measurements, 6.0 ± 4.1% for the outer diameter measurements, and 10.1 ± 9.3% for the wall thickness measurements. The mean absolute percentage difference between the automatically matched spiral CT airway measurements and index HRCT airway measurements were 9.2 ± 8.6% for the inner diameter, 5.8 ± 4.5% for the outer diameter, and 9.9 ± 9.5% for the wall thickness. The overall difference between manual and automated methods was 2.1 ± 1.2%, which was significantly less than the interuser variability of 5.1 ± 4.6% (p<0.05). Tests of equivalence had p<0.05, demonstrating no significant difference between the two methods. The time required for matching was significantly reduced in the automated method (p<0.01) and was as accurate as manual matching, allowing efficient comparison of airways obtained on low-dose spiral CT imaging with low-dose HRCT scans.

Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy

NASA Astrophysics Data System (ADS)

Murray, Louise J.; Thompson, Christopher M.; Lilley, John; Cosgrove, Vivian; Franks, Kevin; Sebag-Montefiore, David; Henry, Ann M.

2015-02-01

Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute risks are very low, large relative risks become less meaningful. A calculated relative radiation-induced second cancer risk benefit from SABR and FFF techniques was theoretically predicted, although absolute radiation-induced second cancer risks were low for all techniques, and absolute differences between techniques were small.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, R; Zhu, X; Li, S

Purpose: High Dose Rate (HDR) brachytherapy forward planning is principally an iterative process; hence, plan quality is affected by planners’ experiences and limited planning time. Thus, this may lead to sporadic errors and inconsistencies in planning. A statistical tool based on previous approved clinical treatment plans would help to maintain the consistency of planning quality and improve the efficiency of second checking. Methods: An independent dose calculation tool was developed from commercial software. Thirty-three previously approved cervical HDR plans with the same prescription dose (550cGy), applicator type, and treatment protocol were examined, and ICRU defined reference point doses (bladder, vaginalmore » mucosa, rectum, and points A/B) along with dwell times were collected. Dose calculation tool then calculated appropriate range with a 95% confidence interval for each parameter obtained, which would be used as the benchmark for evaluation of those parameters in future HDR treatment plans. Model quality was verified using five randomly selected approved plans from the same dataset. Results: Dose variations appears to be larger at the reference point of bladder and mucosa as compared with rectum. Most reference point doses from verification plans fell between the predicted range, except the doses of two points of rectum and two points of reference position A (owing to rectal anatomical variations & clinical adjustment in prescription points, respectively). Similar results were obtained for tandem and ring dwell times despite relatively larger uncertainties. Conclusion: This statistical tool provides an insight into clinically acceptable range of cervical HDR plans, which could be useful in plan checking and identifying potential planning errors, thus improving the consistency of plan quality.« less

Determination of dose distributions and parameter sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.; Farris, W.T.; Simpson, J.C.

1992-12-01

A series of scoping calculations has been undertaken to evaluate the absolute and relative contribution of different radionuclides and exposure pathways to doses that may have been received by individuals living in the vicinity of the Hanford site. This scoping calculation (Calculation 005) examined the contributions of numerous parameters to the uncertainty distribution of doses calculated for environmental exposures and accumulation in foods. This study builds on the work initiated in the first scoping study of iodine in cow's milk and the third scoping study, which added additional pathways. Addressed in this calculation were the contributions to thyroid dose ofmore » infants from (1) air submersion and groundshine external dose, (2) inhalation, (3) ingestion of soil by humans, (4) ingestion of leafy vegetables, (5) ingestion of other vegetables and fruits, (6) ingestion of meat, (7) ingestion of eggs, and (8) ingestion of cows' milk from Feeding Regime 1 as described in Calculation 001.« less

SU-F-T-586: Pre-Treatment QA of InCise2 MLC Plans On a Cyberknife-M6 Using the Delta4 System in SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidhalter, D; Henzen, D; Malthaner, M

Purpose: Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). Methods: In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed usingmore » a 10×10 cm{sup 2} field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. Results: All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. Conclusion: Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.« less

Pharmacokinetics of low-dose nedaplatin and validation of AUC prediction in patients with non-small-cell lung carcinoma.

PubMed

Niioka, Takenori; Uno, Tsukasa; Yasui-Furukori, Norio; Takahata, Takenori; Shimizu, Mikiko; Sugawara, Kazunobu; Tateishi, Tomonori

2007-04-01

The aim of this study was to determine the pharmacokinetics of low-dose nedaplatin combined with paclitaxel and radiation therapy in patients having non-small-cell lung carcinoma and establish the optimal dosage regimen for low-dose nedaplatin. We also evaluated predictive accuracy of reported formulas to estimate the area under the plasma concentration-time curve (AUC) of low-dose nedaplatin. A total of 19 patients were administered a constant intravenous infusion of 20 mg/m(2) body surface area (BSA) nedaplatin for an hour, and blood samples were collected at 1, 2, 3, 4, 6, 8, and 19 h after the administration. Plasma concentrations of unbound platinum were measured, and the actual value of platinum AUC (actual AUC) was calculated based on these data. The predicted value of platinum AUC (predicted AUC) was determined by three predictive methods reported in previous studies, consisting of Bayesian method, limited sampling strategies with plasma concentration at a single time point, and simple formula method (SFM) without measured plasma concentration. Three error indices, mean prediction error (ME, measure of bias), mean absolute error (MAE, measure of accuracy), and root mean squared prediction error (RMSE, measure of precision), were obtained from the difference between the actual and the predicted AUC, to compare the accuracy between the three predictive methods. The AUC showed more than threefold inter-patient variation, and there was a favorable correlation between nedaplatin clearance and creatinine clearance (Ccr) (r = 0.832, P < 0.01). In three error indices, MAE and RMSE showed significant difference between the three AUC predictive methods, and the method of SFM had the most favorable results, in which %ME, %MAE, and %RMSE were 5.5, 10.7, and 15.4, respectively. The dosage regimen of low-dose nedaplatin should be established based on Ccr rather than on BSA. Since prediction accuracy of SFM, which did not require measured plasma concentration, was most favorable among the three methods evaluated in this study, SFM could be the most practical method to predict AUC of low-dose nedaplatin in a clinical situation judging from its high accuracy in predicting AUC without measured plasma concentration.

The Absolute Magnitude of the Sun in Several Filters

NASA Astrophysics Data System (ADS)

Willmer, Christopher N. A.

2018-06-01

This paper presents a table with estimates of the absolute magnitude of the Sun and the conversions from vegamag to the AB and ST systems for several wide-band filters used in ground-based and space-based observatories. These estimates use the dustless spectral energy distribution (SED) of Vega, calibrated absolutely using the SED of Sirius, to set the vegamag zero-points and a composite spectrum of the Sun that coadds space-based observations from the ultraviolet to the near-infrared with models of the Solar atmosphere. The uncertainty of the absolute magnitudes is estimated by comparing the synthetic colors with photometric measurements of solar analogs and is found to be ∼0.02 mag. Combined with the uncertainty of ∼2% in the calibration of the Vega SED, the errors of these absolute magnitudes are ∼3%–4%. Using these SEDs, for three of the most utilized filters in extragalactic work the estimated absolute magnitudes of the Sun are M B = 5.44, M V = 4.81, and M K = 3.27 mag in the vegamag system and M B = 5.31, M V = 4.80, and M K = 5.08 mag in AB.

Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network.

PubMed

Ralston, Shawn; Garber, Matthew; Narang, Steve; Shen, Mark; Pate, Brian; Pope, John; Lossius, Michele; Croland, Trina; Bennett, Jeff; Jewell, Jennifer; Krugman, Scott; Robbins, Elizabeth; Nazif, Joanne; Liewehr, Sheila; Miller, Ansley; Marks, Michelle; Pappas, Rita; Pardue, Jeanann; Quinonez, Ricardo; Fine, Bryan R; Ryan, Michael

2013-01-01

Acute viral bronchiolitis is the most common diagnosis resulting in hospital admission in pediatrics. Utilization of non-evidence-based therapies and testing remains common despite a large volume of evidence to guide quality improvement efforts. Our objective was to reduce utilization of unnecessary therapies in the inpatient care of bronchiolitis across a diverse network of clinical sites. We formed a voluntary quality improvement collaborative of pediatric hospitalists for the purpose of benchmarking the use of bronchodilators, steroids, chest radiography, chest physiotherapy, and viral testing in bronchiolitis using hospital administrative data. We shared resources within the network, including protocols, scores, order sets, and key bibliographies, and established group norms for decreasing utilization. Aggregate data on 11,568 hospitalizations for bronchiolitis from 17 centers was analyzed for this report. The network was organized in 2008. By 2010, we saw a 46% reduction in overall volume of bronchodilators used, a 3.4 dose per patient absolute decrease in utilization (95% confidence interval [CI] 1.4-5.8). Overall exposure to any dose of bronchodilator decreased by 12 percentage points as well (95% CI 5%-25%). There was also a statistically significant decline in chest physiotherapy usage, but not for steroids, chest radiography, or viral testing. Benchmarking within a voluntary pediatric hospitalist collaborative facilitated decreased utilization of bronchodilators and chest physiotherapy in bronchiolitis. Copyright © 2012 Society of Hospital Medicine.

X-ray-induced debromination of nucleic acids at the Br K absorption edge and implications for MAD phasing.

PubMed

Ennifar, E; Carpentier, P; Ferrer, J L; Walter, P; Dumas, P

2002-08-01

Multi-wavelength anomalous dispersion (MAD) using brominated derivatives is considered a common and convenient technique for solving chemically synthesized nucleic acid structures. Here, it is shown that a relatively moderate X-ray dose (of the order of 5 x 10(15) photons mm(-2)) can induce sufficient debromination to prevent structure determination. The decrease in bromine occupancy with radiation dose can be accounted for by a simple exponential, with an estimated rate constant at the absorption-peak wavelength, 7.4 (0.8) MGy, that is not significantly different from its value at the absorption-edge wavelength, 9.2 (2.6) MGy (the given e.s.d.s assess the relative closeness of the two values, not their absolute accuracy, which is probably worse). Chemically, these results (and others) are consistent with bromine cleavage resulting from direct photodissociation and/or from the action of free electrons, rather than from the action of hydroxyl radicals originating from water dissociation. The free bromine species (Br(-)) diffuse too quickly, even in amorphous ice around 100 K, to allow the determination of a diffusion coefficient. From a practical point of view, it is suggested that a single data collection with a crystal consisting of iodinated instead of brominated derivatives could provide both anomalous scattering and SIR phase information by the progressive cleavage of iodine.

Has the National Cancer Screening Program reduced income inequalities in screening attendance in South Korea?

PubMed

Kim, Sujin; Kwon, Soonman; Subramanian, S V

2015-11-01

In 1999, the Korean government introduced the National Cancer Screening Program (NCSP) to increase the cancer-screening rate, particularly among the low-income population. This study investigates how the NCSP has decreased both relative and absolute income inequalities in the uptake of cancer screening in South Korea. A nationally representative cross-sectional repeated data from the Korea National Health and Nutrition Examination Survey 1998-2012, managed by the Ministry of Health and Welfare, was used to assess changes over time and the extent of discontinuity at the NCSP-recommended initiation age in the uptake of screening for breast, colorectal, and gastric cancers across income quartiles. Relative inequalities in the uptake of screening for all cancers decreased significantly over the policy period. Absolute inequalities did not change for most cancers, but marginally increased from 9 to 14% points in the uptake of screening for colorectal cancer among men. At the recommended initiation age, absolute inequalities did not change for breast and colorectal cancers but increased from 5 to 16% points for gastric cancer, for which relative inequality significantly decreased. The NCSP, which reduced out-of-pocket payment, may not decrease absolute gap although it leads to overall increases in the uptake of cancer screening and decreases in relative inequalities. Further investigations are needed to understand barriers that prevent the low-income population from attending cancer screening.

System and method for calibrating a rotary absolute position sensor

NASA Technical Reports Server (NTRS)

Davis, Donald R. (Inventor); Permenter, Frank Noble (Inventor); Radford, Nicolaus A (Inventor)

2012-01-01

A system includes a rotary device, a rotary absolute position (RAP) sensor generating encoded pairs of voltage signals describing positional data of the rotary device, a host machine, and an algorithm. The algorithm calculates calibration parameters usable to determine an absolute position of the rotary device using the encoded pairs, and is adapted for linearly-mapping an ellipse defined by the encoded pairs to thereby calculate the calibration parameters. A method of calibrating the RAP sensor includes measuring the rotary position as encoded pairs of voltage signals, linearly-mapping an ellipse defined by the encoded pairs to thereby calculate the calibration parameters, and calculating an absolute position of the rotary device using the calibration parameters. The calibration parameters include a positive definite matrix (A) and a center point (q) of the ellipse. The voltage signals may include an encoded sine and cosine of a rotary angle of the rotary device.

Sci—Thur AM: YIS - 11: Estimation of Bladder-Wall Cumulative Dose in Multi-Fraction Image-Based Gynaecological Brachytherapy Using Deformable Point Set Registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakariaee, R; Brown, C J; Hamarneh, G

2014-08-15

Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions ofmore » 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.« less

SU-E-T-614: Derivation of Equations to Define Inflection Points and Its Analysis in Flattening Filter Free Photon Beams Based On the Principle of Polynomial function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidhar, K Raja; Komanduri, K

2014-06-01

Purpose: The objective of this work is to present a mechanism for calculating inflection points on profiles at various depths and field sizes and also a significant study on the percentage of doses at the inflection points for various field sizes and depths for 6XFFF and 10XFFF energy profiles. Methods: Graphical representation was done on Percentage of dose versus Inflection points. Also using the polynomial function, the authors formulated equations for calculating spot-on inflection point on the profiles for 6X FFF and 10X FFF energies for all field sizes and at various depths. Results: In a flattening filter free radiationmore » beam which is not like in Flattened beams, the dose at inflection point of the profile decreases as field size increases for 10XFFF. Whereas in 6XFFF, the dose at the inflection point initially increases up to 10x10cm2 and then decreases. The polynomial function was fitted for both FFF beams for all field sizes and depths. For small fields less than 5x5 cm2 the inflection point and FWHM are almost same and hence analysis can be done just like in FF beams. A change in 10% of dose can change the field width by 1mm. Conclusion: The present study, Derivative of equations based on the polynomial equation to define inflection point concept is precise and accurate way to derive the inflection point dose on any FFF beam profile at any depth with less than 1% accuracy. Corrections can be done in future studies based on the multiple number of machine data. Also a brief study was done to evaluate the inflection point positions with respect to dose in FFF energies for various field sizes and depths for 6XFFF and 10XFFF energy profiles.« less

Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies.

PubMed

Mueller, Silke C; Drewelow, Bernd

2013-05-01

The area under the concentration-time curve (AUC) after oral midazolam administration is commonly used for cytochrome P450 (CYP) 3A phenotyping studies. The aim of this investigation was to evaluate a limited sampling strategy for the prediction of AUC with oral midazolam. A total of 288 concentration-time profiles from 123 healthy volunteers who participated in four previously performed drug interaction studies with intense sampling after a single oral dose of 7.5 mg midazolam were available for evaluation. Of these, 45 profiles served for model building, which was performed by stepwise multiple linear regression, and the remaining 243 datasets served for validation. Mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were calculated to determine bias and precision The one- to four-sampling point models with the best coefficient of correlation were the one-sampling point model (8 h; r (2) = 0.84), the two-sampling point model (0.5 and 8 h; r (2) = 0.93), the three-sampling point model (0.5, 2, and 8 h; r (2) = 0.96), and the four-sampling point model (0.5,1, 2, and 8 h; r (2) = 0.97). However, the one- and two-sampling point models were unable to predict the midazolam AUC due to unacceptable bias and precision. Only the four-sampling point model predicted the very low and very high midazolam AUC of the validation dataset with acceptable precision and bias. The four-sampling point model was also able to predict the geometric mean ratio of the treatment phase over the baseline (with 90 % confidence interval) results of three drug interaction studies in the categories of strong, moderate, and mild induction, as well as no interaction. A four-sampling point limited sampling strategy to predict the oral midazolam AUC for CYP3A phenotyping is proposed. The one-, two- and three-sampling point models were not able to predict midazolam AUC accurately.

SU-F-T-227: A Comprehensive Patient Specific, Structure Specific, Pre-Treatment 3D QA Protocol for IMRT, SBRT and VMAT - Clinical Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gueorguiev, G; Cotter, C; Young, M

2016-06-15

Purpose: To present a 3D QA method and clinical results for 550 patients. Methods: Five hundred and fifty patient treatment deliveries (400 IMRT, 75 SBRT and 75 VMAT) from various treatment sites, planned on Raystation treatment planning system (TPS), were measured on three beam-matched Elekta linear accelerators using IBA’s COMPASS system. The difference between TPS computed and delivered dose was evaluated in 3D by applying three statistical parameters to each structure of interest: absolute average dose difference (AADD, 6% allowed difference), absolute dose difference greater than 6% (ADD6, 4% structure volume allowed to fail) and 3D gamma test (3%/3mm DTA,more » 4% structure volume allowed to fail). If the allowed value was not met for a given structure, manual review was performed. The review consisted of overlaying dose difference or gamma results with the patient CT, scrolling through the slices. For QA to pass, areas of high dose difference or gamma must be small and not on consecutive slices. For AADD to manually pass QA, the average dose difference in cGy must be less than 50cGy. The QA protocol also includes DVH analysis based on QUANTEC and TG-101 recommended dose constraints. Results: Figures 1–3 show the results for the three parameters per treatment modality. Manual review was performed on 67 deliveries (27 IMRT, 22 SBRT and 18 VMAT), for which all passed QA. Results show that statistical parameter AADD may be overly sensitive for structures receiving low dose, especially for the SBRT deliveries (Fig.1). The TPS computed and measured DVH values were in excellent agreement and with minimum difference. Conclusion: Applying DVH analysis and different statistical parameters to any structure of interest, as part of the 3D QA protocol, provides a comprehensive treatment plan evaluation. Author G. Gueorguiev discloses receiving travel and research funding from IBA for unrelated to this project work. Author B. Crawford discloses receiving travel funding from IBA for unrelated to this project work.« less

Multidimensional dosimetry of {sup 106}Ru eye plaques using EBT3 films and its impact on treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heilemann, G., E-mail: gerd.heilemann@meduniwien.ac.at; Kostiukhina, N.; Nesvacil, N.

2015-10-15

Purpose: The purpose of this study was to establish a method to perform multidimensional radiochromic film measurements of {sup 106}Ru plaques and to benchmark the resulting dose distributions against Monte Carlo simulations (MC), microdiamond, and diode measurements. Methods: Absolute dose rates and relative dose distributions in multiple planes were determined for three different plaque models (CCB, CCA, and COB), and three different plaques per model, using EBT3 films in an in-house developed polystyrene phantom and the MCNP6 MC code. Dose difference maps were generated to analyze interplaque variations for a specific type, and for comparing measurements against MC simulations. Furthermore,more » dose distributions were validated against values specified by the manufacturer (BEBIG) and microdiamond and diode measurements in a water scanning phantom. Radial profiles were assessed and used to estimate dosimetric margins for a given combination of representative tumor geometry and plaque size. Results: Absolute dose rates at a reference depth of 2 mm on the central axis of the plaque show an agreement better than 5% (10%) when comparing film measurements (MCNP6) to the manufacturer’s data. The reproducibility of depth-dose profile measurements was <7% (2 SD) for all investigated detectors and plaque types. Dose difference maps revealed minor interplaque deviations for a specific plaque type due to inhomogeneities of the active layer. The evaluation of dosimetric margins showed that for a majority of the investigated cases, the tumor was not completely covered by the 100% isodose prescribed to the tumor apex if the difference between geometrical plaque size and tumor base ≤4 mm. Conclusions: EBT3 film dosimetry in an in-house developed phantom was successfully used to characterize the dosimetric properties of different {sup 106}Ru plaque models. The film measurements were validated against MC calculations and other experimental methods and showed a good agreement with data from BEBIG well within published tolerances. The dosimetric information as well as interplaque comparison can be used for comprehensive quality assurance and for considerations in the treatment planning of ophthalmic brachytherapy.« less

SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation for SmartArc with MOSAIQ R&V System.

PubMed

Kong, X; Clausen, C; Wang, S

2012-06-01

Clinical experience for configuration, commission and implementation of SmartArc with MOSAIQ R&V system. SmartArc is Pinnacle's solution for VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A standalone Eclipse workstation has been used 3 years for VMAT planning. Our clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex driven by sequencer. Some key physics parameters have been studied: machine dose rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by user to improve the dose accuracy for planning. In-house sandwich phantom was used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was included for absolute dose comparison. A copy of current machine data with default highest dose rate is recommended. It is due to after 10th iteration of optimization, the default dose rate will kick in. 2.5cm/s is the constraint for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the MLC error on treatment. 2.25cm/s is used in our configuration. This results in MLC interlock if not configured correct. Maximum leaf motion per gantry rotation of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise, undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the matched tabletop.QA using in-house phantom for different sites were tested. Results for both planner dose and absolute chamber measurement are satisfactory. Special attentions need to be paid for dose rate, MLC leaf speed, leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is supported but is slow for clinical delivery. Users need to create your own tabletop to improve planning accuracy. Conventional commission procedures for RapidArc also apply for SmartArc. © 2012 American Association of Physicists in Medicine.

Episcleral eye plaque dosimetry comparison for the Eye Physics EP917 using Plaque Simulator and Monte Carlo simulation

PubMed Central

Amoush, Ahmad; Wilkinson, Douglas A.

2015-01-01

This work is a comparative study of the dosimetry calculated by Plaque Simulator, a treatment planning system for eye plaque brachytherapy, to the dosimetry calculated using Monte Carlo simulation for an Eye Physics model EP917 eye plaque. Monte Carlo (MC) simulation using MCNPX 2.7 was used to calculate the central axis dose in water for an EP917 eye plaque fully loaded with 17 IsoAid Advantage  125I seeds. In addition, the dosimetry parameters Λ, gL(r), and F(r,θ) were calculated for the IsoAid Advantage model IAI‐125  125I seed and benchmarked against published data. Bebig Plaque Simulator (PS) v5.74 was used to calculate the central axis dose based on the AAPM Updated Task Group 43 (TG‐43U1) dose formalism. The calculated central axis dose from MC and PS was then compared. When the MC dosimetry parameters for the IsoAid Advantage  125I seed were compared with the consensus values, Λ agreed with the consensus value to within 2.3%. However, much larger differences were found between MC calculated gL(r) and F(r,θ) and the consensus values. The differences between MC‐calculated dosimetry parameters are much smaller when compared with recently published data. The differences between the calculated central axis absolute dose from MC and PS ranged from 5% to 10% for distances between 1 and 12 mm from the outer scleral surface. When the dosimetry parameters for the  125I seed from this study were used in PS, the calculated absolute central axis dose differences were reduced by 2.3% from depths of 4 to 12 mm from the outer scleral surface. We conclude that PS adequately models the central dose profile of this plaque using its defaults for the IsoAid model IAI‐125 at distances of 1 to 7 mm from the outer scleral surface. However, improved dose accuracy can be obtained by using updated dosimetry parameters for the IsoAid model IAI‐125  125I seed. PACS number: 87.55.K‐ PMID:26699577

Performance assessment of the BEBIG MultiSource® high dose rate brachytherapy treatment unit

NASA Astrophysics Data System (ADS)

Palmer, Antony; Mzenda, Bongile

2009-12-01

A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource® High Dose Rate (HDR) brachytherapy treatment unit with an 192Ir source. The unit is relatively new to the UK market, with the first installation in the country having been made in the summer of 2009. A detailed commissioning programme was devised and is reported including checks of the fundamental parameters of source positioning, dwell timing, transit doses and absolute dosimetry of the source. Well chamber measurements, autoradiography and video camera analysis techniques were all employed. The absolute dosimetry was verified by the National Physical Laboratory, UK, and compared to a measurement based on a calibration from PTB, Germany, and the supplied source certificate, as well as an independent assessment by a visiting UK centre. The use of the 'Krieger' dosimetry phantom has also been evaluated. Users of the BEBIG HDR system should take care to avoid any significant bend in the transfer tube, as this will lead to positioning errors of the source, of up to 1.0 mm for slight bends, 2.0 mm for moderate bends and 5.0 mm for extreme curvature (depending on applicators and transfer tube used) for the situations reported in this study. The reason for these errors and the potential clinical impact are discussed. Users should also note the methodology employed by the system for correction of transit doses, and that no correction is made for the initial and final transit doses. The results of this investigation found that the uncorrected transit doses lead to small errors in the delivered dose at the first dwell position, of up to 2.5 cGy at 2 cm (5.6 cGy at 1 cm) from a 10 Ci source, but the transit dose correction for other dwells was accurate within 0.2 cGy. The unit has been mechanically reliable, and source positioning accuracy and dwell timing have been reproducible, with overall performance similar to other existing HDR equipment. The unit is capable of high quality brachytherapy treatment delivery, taking the above factors into account.

SU-E-T-133: Dosimetric Impact of Scan Orientation Relative to Target Motion During Spot Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoker, J; Summers, P; Li, X

2014-06-01

Purpose: This study seeks to evaluate the dosimetric effects of intra-fraction motion during spot scanning proton beam therapy as a function of beam-scan orientation and target motion amplitude. Method: Multiple 4DCT scans were collected of a dynamic anthropomorphic phantom mimicking respiration amplitudes of 0 (static), 0.5, 1.0, and 1.5 cm. A spot-scanning treatment plan was developed on the maximum intensity projection image set, using an inverse-planning approach. Dynamic phantom motion was continuous throughout treatment plan delivery.The target nodule was designed to accommodate film and thermoluminescent dosimeters (TLD). Film and TLDs were uniquely labeled by location within the target. The phantommore » was localized on the treatment table using the clinically available orthogonal kV on-board imaging device. Film inserts provided data for dose uniformity; TLDs provided a 3% precision estimate of absolute dose. An inhouse script was developed to modify the delivery order of the beam spots, to orient the scanning direction parallel or perpendicular to target motion.TLD detector characterization and analysis was performed by the Imaging and Radiation Oncology Core group (IROC)-Houston. Film inserts, exhibiting a spatial resolution of 1mm, were analyzed to determine dose homogeneity within the radiation target. Results: Parallel scanning and target motions exhibited reduced target dose heterogeneity, relative to perpendicular scanning orientation. The average percent deviation in absolute dose for the motion deliveries relative to the static delivery was 4.9±1.1% for parallel scanning, and 11.7±3.5% (p<<0.05) for perpendicularly oriented scanning. Individual delivery dose deviations were not necessarily correlated to amplitude of motion for either scan orientation. Conclusions: Results demonstrate a quantifiable difference in dose heterogeneity as a function of scan orientation, more so than target amplitude. Comparison to the analyzed planar dose of a single field hint that multiple-field delivery alters intra-fraction beam-target motion synchronization and may mitigate heterogeneity, though further study is warranted.« less

Dosimetric validation and clinical implementation of two 3D dose verification systems for quality assurance in volumetric‐modulated arc therapy techniques

PubMed Central

Pérez‐Vara, Consuelo

2015-01-01

A pretreatment quality assurance program for volumetric techniques should include redundant calculations and measurement‐based verifications. The patient‐specific quality assurance process must be based in clinically relevant metrics. The aim of this study was to show the commission, clinical implementation, and comparison of two systems that allow performing a 3D redundant dose calculation. In addition, one of them is capable of reconstructing the dose on patient anatomy from measurements taken with a 2D ion chamber array. Both systems were compared in terms of reference calibration data (absolute dose, output factors, percentage depth‐dose curves, and profiles). Results were in good agreement for absolute dose values (discrepancies were below 0.5%) and output factors (mean differences were below 1%). Maximum mean discrepancies were located between 10 and 20 cm of depth for PDDs (‐2.7%) and in the penumbra region for profiles (mean DTA of 1.5 mm). Validation of the systems was performed by comparing point‐dose measurements with values obtained by the two systems for static, dynamic fields from AAPM TG‐119 report, and 12 real VMAT plans for different anatomical sites (differences better than 1.2%). Comparisons between measurements taken with a 2D ion chamber array and results obtained by both systems for real VMAT plans were also performed (mean global gamma passing rates better than 87.0% and 97.9% for the 2%/2 mm and 3%/3 mm criteria). Clinical implementation of the systems was evaluated by comparing dose‐volume parameters for all TG‐119 tests and real VMAT plans with TPS values (mean differences were below 1%). In addition, comparisons between dose distributions calculated by TPS and those extracted by the two systems for real VMAT plans were also performed (mean global gamma passing rates better than 86.0% and 93.0% for the 2%/2 mm and 3%/3 mm criteria). The clinical use of both systems was successfully evaluated. PACS numbers: 87.56.Fc, 87.56.‐v, 87.55.dk, 87.55.Qr, 87.55.‐x, 07.57.Kp, 85.25.Pb PMID:26103189

Residual Stress Analysis Based on Acoustic and Optical Methods.

PubMed

Yoshida, Sanichiro; Sasaki, Tomohiro; Usui, Masaru; Sakamoto, Shuichi; Gurney, David; Park, Ik-Keun

2016-02-16

Co-application of acoustoelasticity and optical interferometry to residual stress analysis is discussed. The underlying idea is to combine the advantages of both methods. Acoustoelasticity is capable of evaluating a residual stress absolutely but it is a single point measurement. Optical interferometry is able to measure deformation yielding two-dimensional, full-field data, but it is not suitable for absolute evaluation of residual stresses. By theoretically relating the deformation data to residual stresses, and calibrating it with absolute residual stress evaluated at a reference point, it is possible to measure residual stresses quantitatively, nondestructively and two-dimensionally. The feasibility of the idea has been tested with a butt-jointed dissimilar plate specimen. A steel plate 18.5 mm wide, 50 mm long and 3.37 mm thick is braze-jointed to a cemented carbide plate of the same dimension along the 18.5 mm-side. Acoustoelasticity evaluates the elastic modulus at reference points via acoustic velocity measurement. A tensile load is applied to the specimen at a constant pulling rate in a stress range substantially lower than the yield stress. Optical interferometry measures the resulting acceleration field. Based on the theory of harmonic oscillation, the acceleration field is correlated to compressive and tensile residual stresses qualitatively. The acoustic and optical results show reasonable agreement in the compressive and tensile residual stresses, indicating the feasibility of the idea.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Kapanen, Mika; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

A dual model HU conversion from MRI intensity values within and outside of bone segment for MRI-based radiotherapy treatment planning of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS; Kapanen, Mika

2014-01-15

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

Final report on EURAMET.M.P-K4.2010: Key and supplementary comparison of national pressure standards in the range 1 Pa to 15 kPa of absolute and gauge pressure

NASA Astrophysics Data System (ADS)

Krajíček, Zdeněk; Bergoglio, Mercede; Jousten, Karl; Otal, Pierre; Sabuga, Wladimir; Saxholm, Sari; Pražák, Dominik; Vičar, Martin

2014-01-01

This report describes a EURAMET comparison of five European National Metrology Institutes in low gauge and absolute pressure in gas (nitrogen), denoted as EURAMET.M.P-K4.2010. Its main intention is to state equivalence of the pressure standards, in particular those based on the technology of force-balanced piston gauges such as e.g. FRS by Furness Controls, UK and FPG8601 by DHI-Fluke, USA. It covers the range from 1 Pa to 15 kPa, both gauge and absolute. The comparison in absolute mode serves as a EURAMET Key Comparison which can be linked to CCM.P-K4 and CCM.P-K2 via PTB. The comparison in gauge mode is a supplementary comparison. The comparison was carried out from September 2008 till October 2012. The participating laboratories were the following: CMI, INRIM, LNE, MIKES, PTB-Berlin (absolute pressure 1 kPa and below) and PTB-Braunschweig (absolute pressure 1 kPa and above and gauge pressure). CMI was the pilot laboratory and provided a transfer standard for the comparison. This transfer standard was also the laboratory standard of CMI at the same time, which resulted in a unique and logistically difficult star comparison. Both in gauge and absolute pressures all the participating institutes successfully proved their equivalence with respect to the reference value and all also proved mutual bilateral equivalences in all the points. All the participating laboratories are also equivalent with the reference values of CCM.P-K4 and CCM.P-K2 in the relevant points. The comparison also proved the ability of FPG8601 to serve as a transfer standard. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

PubMed

Castro, Mario; Corren, Jonathan; Pavord, Ian D; Maspero, Jorge; Wenzel, Sally; Rabe, Klaus F; Busse, William W; Ford, Linda; Sher, Lawrence; FitzGerald, J Mark; Katelaris, Constance; Tohda, Yuji; Zhang, Bingzhi; Staudinger, Heribert; Pirozzi, Gianluca; Amin, Nikhil; Ruddy, Marcella; Akinlade, Bolanle; Khan, Asif; Chao, Jingdong; Martincova, Renata; Graham, Neil M H; Hamilton, Jennifer D; Swanson, Brian N; Stahl, Neil; Yancopoulos, George D; Teper, Ariel

2018-05-21

Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV 1 ) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV 1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV 1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).

Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review.

PubMed

Strojan, Primož; Vermorken, Jan B; Beitler, Jonathan J; Saba, Nabil F; Haigentz, Missak; Bossi, Paolo; Worden, Francis P; Langendijk, Johannes A; Eisbruch, Avraham; Mendenhall, William M; Lee, Anne W M; Harrison, Louis B; Bradford, Carol R; Smee, Robert; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2016-04-01

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016. © 2015 Wiley Periodicals, Inc.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Electron beam collimation with a photon MLC for standard electron treatments

NASA Astrophysics Data System (ADS)

Mueller, S.; Fix, M. K.; Henzen, D.; Frei, D.; Frauchiger, D.; Loessl, K.; Stampanoni, M. F. M.; Manser, P.

2018-01-01

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

PubMed

Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

2016-08-01

Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

Immunogenicity of a three dose and five dose oral human rotavirus vaccine (RIX4414) schedule in south Indian infants.

PubMed

Kompithra, Rajeev Zachariah; Paul, Anu; Manoharan, Divya; Babji, Sudhir; Sarkar, Rajiv; Mathew, Leni G; Kang, Gagandeep

2014-08-11

This study was undertaken to compare the immunogenicity of a three dose and five dose schedule of an oral live-attenuated human rotavirus vaccine, Rotarix in south Indian infants. Healthy infants (N=90), six to seven weeks of age were enrolled to receive three doses (n=45) or five doses of Rotarix vaccine (n=45) along with other scheduled vaccines, each dose separated by a four week interval. Blood samples were taken before vaccination and one month post-dose three in the Rotarix three dose group and one month post-dose five in the Rotarix five dose group; all were tested for anti-rotavirus IgA by an antibody sandwich enzyme immunoassay. At baseline, >50% of infants had >20 units of anti-rotavirus IgA. The seroconversion rates after three and five doses were low and not significantly different in the two groups. However, among vaccine responders, children seropositive at baseline showed a much greater absolute increase in IgA antibody levels than children seronegative at baseline. Rotarix vaccine showed low immunogenicity in south Indian children and increasing the number of doses did not increase the proportion of infants seroconverting after vaccination. Copyright © 2014. Published by Elsevier Ltd.

Campaign-Style Measurements of Vertical Seafloor Deformation in the Cascadia Subduction Zone Using an Absolute Self-Calibrating Pressure Recorder

NASA Astrophysics Data System (ADS)

Cook, M. J.; Sasagawa, G. S.; Roland, E. C.; Schmidt, D. A.; Wilcock, W. S. D.; Zumberge, M. A.

2017-12-01

Seawater pressure can be used to measure vertical seafloor deformation since small seafloor height changes produce measurable pressure changes. However, resolving secular vertical deformation near subduction zones can be difficult due to pressure gauge drift. A typical gauge drift rate of about 10 cm/year exceeds the expected secular rate of 1 cm/year or less in Cascadia. The absolute self-calibrating pressure recorder (ASCPR) was developed to solve the issue of gauge drift by using a deadweight calibrator to make campaign-style measurements of the absolute seawater pressure. Pressure gauges alternate between observing the ambient seawater pressure and the deadweight calibrator pressure, which is an accurately known reference value, every 10-20 minutes for several hours. The difference between the known reference pressure and the observed seafloor pressure allows offsets and transients to be corrected to determine the true, absolute seafloor pressure. Absolute seafloor pressure measurements provide a great utility for geodetic deformation studies. The measurements provide instrument-independent, benchmark values that can be used far into the future as epoch points in long-term time series or as important calibration points for other continuous pressure records. The ASCPR was first deployed in Cascadia in 2014 and 2015, when seven concrete seafloor benchmarks were placed along a trench-perpendicular profile extending from 20 km to 105 km off the central Oregon coast. Two benchmarks have ASCPR measurements that span three years, one benchmark spans two years, and four benchmarks span one year. Measurement repeatability is currently 3 to 4 cm, but we anticipate accuracy on the order of 1 cm with improvements to the instrument metrology and processing tidal and non-tidal oceanographic signals.

On the Use of the Main-sequence Knee (Saddle) to Measure Globular Cluster Ages

NASA Astrophysics Data System (ADS)

Saracino, S.; Dalessandro, E.; Ferraro, F. R.; Lanzoni, B.; Origlia, L.; Salaris, M.; Pietrinferni, A.; Geisler, D.; Kalirai, J. S.; Correnti, M.; Cohen, R. E.; Mauro, F.; Villanova, S.; Moni Bidin, C.

2018-06-01

In this paper, we review the operational definition of the so-called main-sequence knee (MS-knee), a feature in the color-magnitude diagram (CMD) occurring at the low-mass end of the MS. The magnitude of this feature is predicted to be independent of age at fixed chemical composition. For this reason, its difference in magnitude with respect to the MS turn-off (MS-TO) point has been suggested as a possible diagnostic to estimate absolute globular cluster (GC) ages. We first demonstrate that the operational definition of the MS-knee currently adopted in the literature refers to the inflection point of the MS (which we here more appropriately named MS-saddle), a feature that is well distinct from the knee and which cannot be used as its proxy. The MS-knee is only visible in near-infrared CMDs, while the MS-saddle can be also detected in optical–NIR CMDs. By using different sets of isochrones, we then demonstrate that the absolute magnitude of the MS-knee varies by a few tenths of a dex from one model to another, thus showing that at the moment stellar models may not capture the full systematic error in the method. We also demonstrate that while the absolute magnitude of the MS-saddle is almost coincident in different models, it has a systematic dependence on the adopted color combinations which is not predicted by stellar models. Hence, it cannot be used as a reliable reference for absolute age determination. Moreover, when statistical and systematic uncertainties are properly taken into account, the difference in magnitude between the MS-TO and the MS-saddle does not provide absolute ages with better accuracy than other methods like the MS-fitting.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with I-131 radiation dose and other characteristics

PubMed Central

Leeman-Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.

2012-01-01

Background Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Methods We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were <18 y.o. in 1986 and received 0.008-8.6 Gy of I-131 to the thyroid and explored associations between mutation types and I-131 dose and other characteristics. Results RET/PTC rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ rearrangement were identified. We found a significant negative association with I-131 dose for BRAF and RAS point mutations and a significant concave association with I-131 dose, with an inflection point at 1.6 Gy and odds ratio 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared to point mutations, rearrangements were associated with residence in the relatively iodine deficient Zhytomyr region, younger age at exposure or surgery, and male gender. Conclusions Our results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. PMID:23436219

Potential energy hypersurface and molecular flexibility

NASA Astrophysics Data System (ADS)

Koča, Jaroslav

1993-02-01

The molecular flexibility phenomenon is discussed from the conformational potential energy(hyper) surface (PES) point of view. Flexibility is considered as a product of three terms: thermodynamic, kinetic and geometrical. Several expressions characterizing absolute and relative molecular flexibility are introduced, depending on a subspace studied of the entire conformational space, energy level E of PES as well as absolute temperature. Results obtained by programs DAISY, CICADA and PANIC in conjunction with molecular mechanics program MMX for flexibility analysis of isopentane, 2,2-dimethylpentane and isohexane molecules are introduced.

Variation of Wall Shear Stress and Reynolds Stress over a Flat Plate Downstream of a Boundary Layer Manipulator

DTIC Science & Technology

1990-06-01

Layer Manipulator is placed AP differential pressure across the surface fence e, IC, mean and turbulent viscous dissipation Rt absolute viscosity of...feet long. The zero point for the traversing system is situated 3.3 feet from the inlet end of the blockhouse and ranges over 90% of the semi-open...tenth the absolute air pressure in millimeters of water. A voltage divider further reduces CD23 output voltage by one-half to accommodate the MASSCOMP

Two-year experience with the commercial Gamma Knife Check software.

PubMed

Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L Dade; Huq, M Saiful

2016-07-08

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement-based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. © 2016 The Authors.

Two‐year experience with the commercial Gamma Knife Check software

PubMed Central

Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L. Dade; Huq, M. Saiful

2016-01-01

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement‐based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. PACS number(s): 87.55.Qr, 87.56.Fc PMID:27455470

Absolute dose calibration of an X-ray system and dead time investigations of photon-counting techniques

NASA Astrophysics Data System (ADS)

Carpentieri, C.; Schwarz, C.; Ludwig, J.; Ashfaq, A.; Fiederle, M.

2002-07-01

High precision concerning the dose calibration of X-ray sources is required when counting and integrating methods are compared. The dose calibration for a dental X-ray tube was executed with special dose calibration equipment (dosimeter) as function of exposure time and rate. Results were compared with a benchmark spectrum and agree within ±1.5%. Dead time investigations with the Medipix1 photon-counting chip (PCC) have been performed by rate variations. Two different types of dead time, paralysable and non-paralysable will be discussed. The dead time depends on settings of the front-end electronics and is a function of signal height, which might lead to systematic defects of systems. Dead time losses in excess of 30% have been found for the PCC at 200 kHz absorbed photons per pixel.

Hepatic effects of orally administered styrene in rats.

PubMed

Srivastava, S P; Das, M; Mushtaq, M; Chandra, S V; Seth, P K

1982-08-01

Adult male rats receiving styrene by gavage (200 or 400 mg kg-1, 6 days a week) for 100 days exhibited a significant dose-dependent increase in hepatic benzo[a]pyrene hydroxylase and aminopyrine-N-demethylase, a decrease in glutathione-S-transferase and no change in glucose-6-phosphatase. A decrease in the activity of mitochondrial succinic dehydrogenase and beta-glucuronidase was also observed. Activity of acid phosphatase was decreased only at the higher dose level. Levels of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated only at the higher dose level. The absolute and relative weights of the liver of control and treated animals showed no significant difference. Histopathological studies of the liver tissue revealed tiny areas of focal necrosis, consisting of few degenerated hepatocytes and inflammatory cells at the higher dose level only.

Clinical-grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation.

PubMed

Meyer-Monard, Sandrine; Passweg, Jakob; Siegler, Uwe; Kalberer, Christian; Koehl, Ulrike; Rovó, Alicia; Halter, Jörg; Stern, Martin; Heim, Dominik; Alois Gratwohl, Johannes Rischewski; Tichelli, André

2009-02-01

Because of a high risk of graft-versus-host disease (GVHD), donor lymphocyte infusions with unmodified lymphapheresis products are not used after haploidentical hematopoietic stem cell transplantation. Natural killer (NK) cells have antitumor activity and may consolidate engraftment without inducing GVHD. Production of NK cells under good manufacturing practice (GMP) conditions in a sufficient number is difficult. Twenty-four apheresis procedures and subsequent NK-cell enrichment from 14 haploidentical donors were performed. NK-cell enrichment was performed using a GMP suitable immunomagnetic procedure. Factors influencing the NK-cell recovery, purity, and NK-cell dose were analyzed. A median number of 4.9 x 10(8) NK cells were obtained and median NK-cell recovery was 58 percent. Median T-cell depletion was 4.32 log. The absolute NK-cell number in the final product after processing significantly correlated with the preharvest NK-cell content of the peripheral blood (p = 0.002, r = 0.867). The NK-cell recovery was inversely correlated to the absolute NK-cell number in the apheresis product (p = 0.01, r = -0.51). The NK-cell dose per kg of body weight of the patient was inversely correlated to the weight of the patient (p = 0.007, r = -0.533). Donors with a high NK-cell count in peripheral blood are likely to provide NK-cell products with the highest cell number. However, maximal NK-cell dose is limited and high NK-cell doses may only be obtained for patients with a low body weight, making children and young adults the best candidates for NK-cell therapy.

Clopidogrel in infants with systemic-to-pulmonary-artery shunts.

PubMed

Wessel, David L; Berger, Felix; Li, Jennifer S; Dähnert, Ingo; Rakhit, Amit; Fontecave, Sylvie; Newburger, Jane W

2013-06-20

Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).

Development of acute tolerance to the EEG effect of propofol in rats.

PubMed

Ihmsen, H; Schywalsky, M; Tzabazis, A; Schwilden, H

2005-09-01

A previous study in rats with propofol suggested the development of acute tolerance to the EEG effect. The aim of this study was to evaluate acute tolerance by means of EEG-controlled closed-loop anaesthesia as this approach allows precise determination of drug requirement to maintain a defined drug effect. Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were included in the study. The EEG was recorded with occipito-occipital needle electrodes and a modified median frequency (mMEF) of the EEG power spectrum was used as a pharmacodynamic control parameter. The propofol infusion rate was controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3 (0.5) Hz for 90 min. The performance of the closed-loop system was characterized by the prediction error PE=(mMEF-set point)/set point. Plasma propofol concentrations were determined from arterial samples by HPLC. The chosen set point was successfully maintained in all rats. The median (SE) and absolute median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol concentration increased significantly from 2.9 (2.2) microg ml(-1) at the beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg kg(-1) min(-1). The minimum value of the mean arterial pressure during closed-loop administration of propofol was 130 (24) mm Hg, compared with a baseline value of 141 (12) mm Hg. The increase in propofol concentration at constant EEG effect indicates development of acute tolerance to the hypnotic effect of propofol.

Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection.

PubMed

Geisler, William M; Uniyal, Apurva; Lee, Jeannette Y; Lensing, Shelly Y; Johnson, Shacondra; Perry, Raymond C W; Kadrnka, Carmel M; Kerndt, Peter R

2015-12-24

Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection. We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains. Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin. In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.).

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies.

PubMed

Flanagan, Talia; Martin, Paul; Gillen, Michael; Mathews, David; Lisbon, Eleanor; Kruusmägi, Martin

2017-02-01

Fostamatinib is an orally dosed phosphate prodrug that is cleaved by intestinal alkaline phosphatase to the active metabolite R406. Clinical studies were performed to assess the effect of food and ranitidine on exposure, to support in vitro-in vivo relationships (IVIVR) understanding and formulation transitions and to investigate absolute oral bioavailability. A series of in vitro dissolution and clinical pharmacokinetic studies were performed to support the design and introduction of a new formulation, understand the impact of changes in in vitro dissolution on in vivo performance for two fostamatinib formulations, to characterize the effects of food and ranitidine on exposure, and determine the absolute oral bioavailability. The in vivo performance of fostamatinib was generally insensitive to changes in in vitro dissolution performance, although marked slowing of the dissolution rate did impact exposures. Food and ranitidine had minor effects on R406 exposure that were not considered clinically relevant. The absolute oral bioavailability of fostamatinib was 54.6 %. The absolute oral bioavailability of fostamatinib was ~55 %. Food and ranitidine had minor effects on R406 exposure. An in vitro dissolution versus clinical performance relationship was determined that supported formulation transitions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S; Ellis, R; Traughber, B

Purpose: Treating gynecological cancers with interstitial high-dose-rate (HDR) brachytherapy requires precise reconstruction of catheter positions to obtain accurate dosimetric plans. In this study, we investigated the degree of reproducibility of dosimetric plans for Syed HDR brachytherapy. Methods: We randomly selected five patients having cervix-vaginal cancer who were recently treated in our clinic with interstitial HDR brachytherapy with a prescription dose of 25–30 Gy in five fractions. Interstitial needles/catheters were placed under fluoroscopic guidance and intra-operative 3T MRI scan was performed to confirm the desired catheter placement for adequate target volume coverage. A CT scan was performed and fused with themore » MRI for delineating high-risk CTV (HR-CTV), intermediate-risk CTV (IR-CTV) and OARs. HDR treatment plans were generated using Oncentra planning software. A single plan was used for all five fractions of treatment for each patient. For this study, we took the original clinical plan and removed all the reconstructed catheters from the plan keeping the original contours unchanged. Then, we manually reconstructed all the catheters and entered the same dwell time from the first original clinical plan. The dosimetric parameters studied were: D90 for HR-CTV and IR-CV, and D2cc for bladder, rectum, sigmoid and bowel. Results: The mean of absolute differences in dosimetric coverage (D90) were (range): 1.3% (1.0–2.0%) and 2.0% (0.9–3.6%) for HR-CTV and IR-CTV, respectively. In case of OARs, the mean of absolute variations in D2cc were (range): 4.7% (0.7–8.9%) for bladder, 1.60% (0.3–3.2%) for rectum, 1.6% (0–3.9%) for sigmoid, and 1.8% (0–5.1%) for bowel. Conclusion: Overall, the reproducibility of interstitial HDR plans was within clinically acceptable limit. Observed maximum variation in D2cc for bladder. If number of catchers and dwell points were relatively low or any one catheter was heavily loaded, then reproducibility of the plan was more sensitive to the accuracy of catheter reconstruction.« less

Association of Apgar scores with death and neurologic disability

PubMed Central

Ehrenstein, Vera

2009-01-01

Apgar score was devised with the aim to standardize the assessment of newborns. It has been used worldwide to evaluate infants’ condition immediately after birth, to determine their need for resuscitation, and to evaluate the effectiveness of resuscitation. Apgar score was never intended for prediction of outcome beyond the immediate postnatal period; however, since low scores correlate with prenatal and perinatal adversities, multiple studies have examined the relation between the value of Apgar score and duration of low (<7) Apgar score and subsequent death or neurologic disability. This article reviews such studies. The author concludes that the overall evidence shows consistent association of low Apgar scores with increased risks of neonatal and infant death and with neurologic disability, including cerebral palsy, epilepsy, and cognitive impairment. Dose-response patterns have been shown for the value of Apgar score and duration of low score and the outcomes of mortality and neurologic disability. The association of Apgar score <7 at five minutes with increased risks of neurologic disability seems to persist many years postnatally. Some corresponding relative risk estimates are large (eg, four to seven for epilepsy or more than 20 for cerebral palsy), while others are modest (eg, 1.33 for impaired cognitive function). The absolute risks, however, are low (<5% in for most neurologic conditions), and majority of surviving babies with low Apgar scores grow up without disability. The low magnitude of absolute risks makes Apgar score a poor clinical predictor of long-term outcome. Nevertheless, the observed associations point to the importance of fetal and perinatal periods for neurodevelopment. PMID:20865086

The effect of tandem-ovoid titanium applicator on points A, B, bladder, and rectum doses in gynecological brachytherapy using 192Ir.

PubMed

Sadeghi, Mohammad Hosein; Sina, Sedigheh; Mehdizadeh, Amir; Faghihi, Reza; Moharramzadeh, Vahed; Meigooni, Ali Soleimani

2018-02-01

The dosimetry procedure by simple superposition accounts only for the self-shielding of the source and does not take into account the attenuation of photons by the applicators. The purpose of this investigation is an estimation of the effects of the tandem and ovoid applicator on dose distribution inside the phantom by MCNP5 Monte Carlo simulations. In this study, the superposition method is used for obtaining the dose distribution in the phantom without using the applicator for a typical gynecological brachytherapy (superposition-1). Then, the sources are simulated inside the tandem and ovoid applicator to identify the effect of applicator attenuation (superposition-2), and the dose at points A, B, bladder, and rectum were compared with the results of superposition. The exact dwell positions, times of the source, and positions of the dosimetry points were determined in images of a patient and treatment data of an adult woman patient from a cancer center. The MCNP5 Monte Carlo (MC) code was used for simulation of the phantoms, applicators, and the sources. The results of this study showed no significant differences between the results of superposition method and the MC simulations for different dosimetry points. The difference in all important dosimetry points was found to be less than 5%. According to the results, applicator attenuation has no significant effect on the calculated points dose, the superposition method, adding the dose of each source obtained by the MC simulation, can estimate the dose to points A, B, bladder, and rectum with good accuracy.

Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report was to determine the pharmacokinetic properties, safety, and tolerability of single and multiple doses of intravenous delafloxacin. In addition, the absolute bioavailability (BA) of the 450-mg tablet formulation of delafloxacin was determined. Three clinical trials are summarized. The first study was a randomized, double-blind, placebo-controlled, single- (300, 450, 600, 750, 900, and 1200 mg) ascending-dose study of IV delafloxacin in 62 (52 active, 10 placebo) healthy volunteers. The second study was a randomized, double-blind, placebo-controlled study of IV delafloxacin (300 mg) given as a single dose on day 1, followed by twice-daily dosing on days 2 through 14; 12 (8 active, 4 placebo) healthy volunteers were enrolled. The third study was an open-label, randomized, 2-period, 2-sequence crossover study in which 56 healthy volunteers were randomly assigned to 1 of 2 sequences of a single oral dose of delafloxacin (450-mg tablet) or IV delafloxacin (300 mg). Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were calculated. Delafloxacin Cmax values increased proportionally with increasing single IV dose for the dose range of 300 to 1200 mg, whereas the AUC values increased more than proportionally to dose for the same dose range. The mean terminal half-life of delafloxacin was approximately 12 hours (ranging from 8 to 17 hours). The volume of distribution (Vd) at steady state was approximately 35 L, which is similar to the volume of total body water. There was minimal accumulation of delafloxacin after twice-daily IV administration of 300 mg with an accumulation ratio of 1.09. The delafloxacin total exposure after a single 1-hour IV infusion of 300 mg and a single oral dose of a 450-mg tablet were equivalent with geometric least square mean ratio (90% CI) of 0.8768 (0.8356-0.9200) for AUC0-∞ and 0.8445 (0.8090-0.8815) for AUC0-t, respectively. The Cmax values of delafloxacin were not equivalent for the 2 formulations with a ratio (90% CI) of 0.5516 (0.5150-0.5908), respectively. The mean absolute bioavailability of delafloxacin was 58.8%. Delafloxacin was well tolerated in healthy volunteers after single and multiple IV doses. The total systemic exposure to IV (300 mg) and oral (450 mg) delafloxacin is comparable, supporting that a switch between the 2 formulations is appropriate. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Benefits of Reiki therapy for a severely neutropenic patient with associated influences on a true random number generator.

PubMed

Morse, Melvin L; Beem, Lance W

2011-12-01

Reiki therapy is documented for relief of pain and stress. Energetic healing has been documented to alter biologic markers of illness such as hematocrit. True random number generators are reported to be affected by energy healers and spiritually oriented conscious awareness. The patient was a then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did not improve with conventional therapy. He also suffered from obesity, the metabolic syndrome, asthma, and hypertension. He was treated with experimental high-dose interferon/riboviron therapy with resultant profound anemia and neutropenia. Energetic healing and Reiki therapy was administered initially to enhance the patient's sense of well-being and to relieve anxiety. Possible effects on the patient's absolute neutrophil count and hematocrit were incidentally noted. Reiki therapy was then initiated at times of profound neutropenia to assess its possible effect on the patient's absolute neutrophil count (ANC). Reiki and other energetic healing sessions were monitored with a true random number generator (RNG). Statistically significant relationships were documented between Reiki therapy, a quieting of the electronically created white noise of the RNG during healing sessions, and improvement in the patient's ANC. The immediate clinical result was that the patient could tolerate the high-dose interferon regimen without missing doses because of absolute neutropenia. The patient was initially a late responder to interferon and had been given a 5% chance of clearing the virus. He remains clear of the virus 1 year after treatment. The association between changes in the RNG, Reiki therapy, and a patient's ANC is the first to the authors' knowledge in the medical literature. Future studies assessing the effects of energetic healing on specific biologic markers of disease are anticipated. Concurrent use of a true RNG may prove to correlate with the effectiveness of energetic therapy.

Benefits of Reiki Therapy for a Severely Neutropenic Patient with Associated Influences on a True Random Number Generator

PubMed Central

Beem, Lance W.

2011-01-01

Abstract Background Reiki therapy is documented for relief of pain and stress. Energetic healing has been documented to alter biologic markers of illness such as hematocrit. True random number generators are reported to be affected by energy healers and spiritually oriented conscious awareness. Methods The patient was a then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did not improve with conventional therapy. He also suffered from obesity, the metabolic syndrome, asthma, and hypertension. He was treated with experimental high-dose interferon/riboviron therapy with resultant profound anemia and neutropenia. Energetic healing and Reiki therapy was administered initially to enhance the patient's sense of well-being and to relieve anxiety. Possible effects on the patient's absolute neutrophil count and hematocrit were incidentally noted. Reiki therapy was then initiated at times of profound neutropenia to assess its possible effect on the patient's absolute neutrophil count (ANC). Reiki and other energetic healing sessions were monitored with a true random number generator (RNG). Results Statistically significant relationships were documented between Reiki therapy, a quieting of the electronically created white noise of the RNG during healing sessions, and improvement in the patient's ANC. The immediate clinical result was that the patient could tolerate the high-dose interferon regimen without missing doses because of absolute neutropenia. The patient was initially a late responder to interferon and had been given a 5% chance of clearing the virus. He remains clear of the virus 1 year after treatment. Conclusions The association between changes in the RNG, Reiki therapy, and a patient's ANC is the first to the authors' knowledge in the medical literature. Future studies assessing the effects of energetic healing on specific biologic markers of disease are anticipated. Concurrent use of a true RNG may prove to correlate with the effectiveness of energetic therapy. PMID:22132706

Use of Fentanyl in Adolescents with Clinically Severe Obesity Undergoing Bariatric Surgery - a Pilot Study

PubMed Central

Vaughns, Janelle D.; Ziesenitz, Victoria C.; Williams, Elaine F.; Mushtaq, Alvina; Bachmann, Ricarda; Skopp, Gisela; Weiss, Johanna; Mikus, Gerd; van den Anker, Johannes N.

2018-01-01

Background The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there is no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. Materials and Methods An IRB-approved exploratory pilot study was conducted in 6 adolescents aged 14 to 19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg, and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was dosed intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24 hour post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. Results Mean fentanyl AUC0–∞ was 1.5 ± 0.5 h*ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min*kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. Conclusions These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. PMID:28238111

Pneumococcal Conjugate Vaccine and Pneumonia Prevention in Children with Congenital Heart Disease.

PubMed

Solórzano-Santos, Fortino; Espinoza-García, Lilia; Aguilar-Martínez, Glorinella; Beirana-Palencia, Luisa; Echániz-Avilés, Gabriela; Miranda-Novales, Guadalupe

2017-01-01

A successful strategy to prevent Streptococcus pneumoniae infections is the administration of pneumococcal conjugate vaccines (PCVs). To analyze the effectiveness of the 7- and 13-valent PCV for the prevention of all-cause pneumonia. A retrospective cohort of children younger than 5 years of age, with congenital heart disease (CHD) and different vaccination schedules, was analyzed. History of vaccination was confirmed with verifiable records. The outcome measure was all-cause pneumonia or bronchopneumonia. Protocol was approved by the Institutional Review Board. For comparisons, we used inferential statistics with Chi-square and Fisher's exact test; a p ≤ 0.5 was considered statistically significant. Relative and absolute risks reduction and number needed to treat were also calculated. A total of 348 patients were included: 196 with two or more doses of PCV (considered the vaccinated group), and 152 in the unvaccinated group. There was a statistically significant difference for pneumonia events (p < 0.001) between the vaccinated (26/196) and unvaccinated (51/152) groups. The relative risk reduction was 60.5%, and the absolute risk reduction, 20.3%. There were no differences between patients who received two, three or four doses. The number needed to vaccinate to prevent one event of pneumonia was 5 children. At least two doses of PCV in children with CHD reduced the risk of all-cause pneumonia.

Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR.

PubMed

Wainwright, Claire E; Elborn, J Stuart; Ramsey, Bonnie W; Marigowda, Gautham; Huang, Xiaohong; Cipolli, Marco; Colombo, Carla; Davies, Jane C; De Boeck, Kris; Flume, Patrick A; Konstan, Michael W; McColley, Susanna A; McCoy, Karen; McKone, Edward F; Munck, Anne; Ratjen, Felix; Rowe, Steven M; Waltz, David; Boyle, Michael P

2015-07-16

Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation. We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24. A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo. These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.).

The sensitivity of patient specific IMRT QC to systematic MLC leaf bank offset errors.

PubMed

Rangel, Alejandra; Palte, Gesa; Dunscombe, Peter

2010-07-01

Patient specific IMRT QC is performed routinely in many clinics as a safeguard against errors and inaccuracies which may be introduced during the complex planning, data transfer, and delivery phases of this type of treatment. The purpose of this work is to evaluate the feasibility of detecting systematic errors in MLC leaf bank position with patient specific checks. 9 head and neck (H&N) and 14 prostate IMRT beams were delivered using MLC files containing systematic offsets (+/- 1 mm in two banks, +/- 0.5 mm in two banks, and 1 mm in one bank of leaves). The beams were measured using both MAPCHECK (Sun Nuclear Corp., Melbourne, FL) and the aS1000 electronic portal imaging device (Varian Medical Systems, Palo Alto, CA). Comparisons with calculated fields, without offsets, were made using commonly adopted criteria including absolute dose (AD) difference, relative dose difference, distance to agreement (DTA), and the gamma index. The criteria most sensitive to systematic leaf bank offsets were the 3% AD, 3 mm DTA for MAPCHECK and the gamma index with 2% AD and 2 mm DTA for the EPID. The criterion based on the relative dose measurements was the least sensitive to MLC offsets. More highly modulated fields, i.e., H&N, showed greater changes in the percentage of passing points due to systematic MLC inaccuracy than prostate fields. None of the techniques or criteria tested is sufficiently sensitive, with the population of IMRT fields, to detect a systematic MLC offset at a clinically significant level on an individual field. Patient specific QC cannot, therefore, substitute for routine QC of the MLC itself.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 05: A novel respiratory motion simulation program for VMAT treatment plans: a phantom validation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hubley, Emily; Pierce, Greg; Ploquin, Nicolas

Purpose: To develop and validate a computational method to simulate craniocaudal respiratory motion in a VMAT treatment plan. Methods: Three 4DCTs of the QUASAR respiratory motion phantom were acquired with a 2cm water-density spherical tumour embedded in cedar to simulate lung. The phantom was oscillating sinusoidally with an amplitude of 2cm and periods of 3, 4, and 5 seconds. An ITV was contoured and 5mm PTV margin was added. High and a low modulation factor VMAT plans were created for each scan. An in-house program was developed to simulate respiratory motion in the treatment plans by shifting the MLC leafmore » positions relative to the phantom. Each plan was delivered to the phantom and the dose was measured using Gafchromic film. The measured and calculated plans were compared using an absolute dose gamma analysis (3%/3mm). Results: The average gamma pass rate for the low modulation plan and high modulation plans were 91.1% and 51.4% respectively. The difference between the high and low modulation plans gamma pass rates is likely related to the different sampling frequency of the respiratory curve and the higher MLC leaf speeds in the high modulation plan. A high modulation plan has a slower gantry speed and therefore samples the breathing cycle at a coarser frequency leading to inaccuracies between the measured and planned doses. Conclusion: A simple program, including a novel method for increasing sampling frequency beyond the control point frequency, has been developed to simulate respiratory motion in VMAT plans by shifting the MLC leaf positions.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, N

Purpose: Ocular proton therapy has the following advantages: i) sparing optic nerve, ii) the minimal dose is delivered to surrounding normal tissues. Since the proton therapy center was opened in 2007, 30 patients with ocular tumor have been treated at National Cancer Center using single scattering technique. To develop a solid eye phantom which can verify the output and the beam range with EBT3 film for independent patient QA in ocular proton therapy. Methods: The proton therapy is very effective to treat ocular tumor, because of the Bragg peak feature. In general, the beam shape of eye treatment is aboutmore » 3 cm in diameter and the beam range is under 5 cm. However, proton therapy has uncertainty of beam range problem due to various stopping power of normal tissue, bone, air and so on, so that we should verify the beam range before treatment. For this purpose, a new PMMA phantom with wedge has been developed to use the film dosimetry and the ionization chamber. It is able to place a film on the slope of the phantom, which the spread out Bragg Peak by the water equivalent thickness value of PMMA can be made on the film. We considered to relation with quenching effect of proton energy and range for simple second check. In addition, the ionization chamber (Pin-point chamber, PTW 31014) can be inserted into a hole in the phantom to measure the absolute dose. Results: The output difference and beam range difference were less than 2% and 1.0 mm, respectively, between the measurement and the plan. Conclusion: An eye phantom was developed and its performance was evaluated successfully and it was useful to verify the output. Also with EBT3 film with the quenching effect for measurement depth-dose profile, range to patient QA.« less

A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

PubMed

Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

2015-01-01

Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures. © The Author(s) 2014.

SU-F-T-522: Dosimetric Study of Junction Dose in Double Isocenter Flatten and Flatten Filter Free IMRT and VMAT Plan Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samuvel, K; Yadav, G; Bhushan, M

2016-06-15

Purpose: To quantify the dosimetric accuracy of junction dose in double isocenter flattened and flatten filter free(FFF) intensity modulated radiation therapy(IMRT) and volumetric modulated arc therapy(VMAT) plan delivery using pelvis phantom. Methods: Five large field pelvis patients were selected for this study. Double isocenter IMRT and VMAT treatment plans were generated in Eclipse Treatment planning System (V.11.0) using 6MV FB and FFF beams. For all the plans same distance 17.0cm was kept between one isocenter to another isocenter. IMRT Plans were made with 7 coplanar fields and VMAT plans were made with full double arcs. Dose calculation was performed usingmore » AAA algorithms with dose grid size of 0.25 cm. Verification plans were calculated on Scanditronix Wellhofer pelvis slab phantom. Measurement point was selected and calculated, where two isocenter plan fields are overlapping, this measurement point was kept at distance 8.5cm from both isocenter. The plans were delivered using Varian TrueBeamTM machine on pelvis slab phantom. Point dose measurements was carried out using CC13 ion chamber volume of 0.13cm3. Results: The measured junction point dose are compared with TPS calculated dose. The mean difference observed was 4.5%, 6.0%, 4.0% and 7.0% for IMRT-FB,IMRT-FFF, VMAT-FB and VMAT-FFF respectively. The measured dose results shows closer agreement with calculated dose in Flatten beam planning in both IMRT and VMAT, whereas in FFF beam plan dose difference are more compared with flatten beam plan. Conclusion: Dosimetry accuracy of Large Field junction dose difference was found less in Flatten beam compared with FFF beam plan delivery. Even though more dosimetric studies are required to analyse junction dose for FFF beam planning using multiple point dose measurements and fluence map verification in field junction area.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, J; Gu, X; Lu, W

Purpose: A novel distance-dose weighting method for label fusion was developed to increase segmentation accuracy in dosimetrically important regions for prostate radiation therapy. Methods: Label fusion as implemented in the original SIMPLE (OS) for multi-atlas segmentation relies iteratively on the majority vote to generate an estimated ground truth and DICE similarity measure to screen candidates. The proposed distance-dose weighting puts more values on dosimetrically important regions when calculating similarity measure. Specifically, we introduced distance-to-dose error (DDE), which converts distance to dosimetric importance, in performance evaluation. The DDE calculates an estimated DE error derived from surface distance differences between the candidatemore » and estimated ground truth label by multiplying a regression coefficient. To determine the coefficient at each simulation point on the rectum, we fitted DE error with respect to simulated voxel shift. The DEs were calculated by the multi-OAR geometry-dosimetry training model previously developed in our research group. Results: For both the OS and the distance-dose weighted SIMPLE (WS) results, the evaluation metrics for twenty patients were calculated using the ground truth segmentation. The mean difference of DICE, Hausdorff distance, and mean absolute distance (MAD) between OS and WS have shown 0, 0.10, and 0.11, respectively. In partial MAD of WS which calculates MAD within a certain PTV expansion voxel distance, the lower MADs were observed at the closer distances from 1 to 8 than those of OS. The DE results showed that the segmentation from WS produced more accurate results than OS. The mean DE error of V75, V70, V65, and V60 were decreased by 1.16%, 1.17%, 1.14%, and 1.12%, respectively. Conclusion: We have demonstrated that the method can increase the segmentation accuracy in rectum regions adjacent to PTV. As a result, segmentation using WS have shown improved dosimetric accuracy than OS. The WS will provide dosimetrically important label selection strategy in multi-atlas segmentation. CPRIT grant RP150485.« less

MRI-Related Geometric Distortions in Stereotactic Radiotherapy Treatment Planning: Evaluation and Dosimetric Impact.

PubMed

Pappas, Eleftherios P; Alshanqity, Mukhtar; Moutsatsos, Argyris; Lababidi, Hani; Alsafi, Khalid; Georgiou, Konstantinos; Karaiskos, Pantelis; Georgiou, Evangelos

2017-12-01

In view of their superior soft tissue contrast compared to computed tomography, magnetic resonance images are commonly involved in stereotactic radiosurgery/radiotherapy applications for target delineation purposes. It is known, however, that magnetic resonance images are geometrically distorted, thus deteriorating dose delivery accuracy. The present work focuses on the assessment of geometric distortion inherent in magnetic resonance images used in stereotactic radiosurgery/radiotherapy treatment planning and attempts to quantitively evaluate the consequent impact on dose delivery. The geometric distortions for 3 clinical magnetic resonance protocols (at both 1.5 and 3.0 T) used for stereotactic radiosurgery/radiotherapy treatment planning were evaluated using a recently proposed phantom and methodology. Areas of increased distortion were identified at the edges of the imaged volume which was comparable to a brain scan. Although mean absolute distortion did not exceed 0.5 mm on any spatial axis, maximum detected control point disposition reached 2 mm. In an effort to establish what could be considered as acceptable geometric uncertainty, highly conformal plans were utilized to irradiate targets of different diameters (5-50 mm). The targets were mispositioned by 0.5 up to 3 mm, and dose-volume histograms and plan quality indices clinically used for plan evaluation and acceptance were derived and used to investigate the effect of geometrical uncertainty (distortion) on dose delivery accuracy and plan quality. The latter was found to be strongly dependent on target size. For targets less than 20 mm in diameter, a spatial disposition of the order of 1 mm could significantly affect (>5%) plan acceptance/quality indices. For targets with diameter greater than 2 cm, the corresponding disposition was found greater than 1.5 mm. Overall results of this work suggest that efficacy of stereotactic radiosurgery/radiotherapy applications could be compromised in case of very small targets lying distant from the scanner's isocenter (eg, the periphery of the brain).

Evaluation of dosimetric effect caused by slowing with multi-leaf collimator (MLC) leaves for volumetric modulated arc therapy (VMAT)

PubMed Central

Wang, Iris Z.; Kumaraswamy, Lalith K.; Podgorsak, Matthew B.

2016-01-01

Background This study is to report 1) the sensitivity of intensity modulated radiation therapy (IMRT) QA method for clinical volumetric modulated arc therapy (VMAT) plans with multi-leaf collimator (MLC) leaf errors that will not trigger MLC interlock during beam delivery; 2) the effect of non-beam-hold MLC leaf errors on the quality of VMAT plan dose delivery. Materials and methods. Eleven VMAT plans were selected and modified using an in-house developed software. For each control point of a VMAT arc, MLC leaves with the highest speed (1.87-1.95 cm/s) were set to move at the maximal allowable speed (2.3 cm/s), which resulted in a leaf position difference of less than 2 mm. The modified plans were considered as ‘standard’ plans, and the original plans were treated as the ‘slowing MLC’ plans for simulating ‘standard’ plans with leaves moving at relatively lower speed. The measurement of each ‘slowing MLC’ plan using MapCHECK®2 was compared with calculated planar dose of the ‘standard’ plan with respect to absolute dose Van Dyk distance-to-agreement (DTA) comparisons using 3%/3 mm and 2%/2 mm criteria. Results All ‘slowing MLC’ plans passed the 90% pass rate threshold using 3%/3 mm criteria while one brain and three anal VMAT cases were below 90% with 2%/2 mm criteria. For ten out of eleven cases, DVH comparisons between ‘standard’ and ‘slowing MLC’ plans demonstrated minimal dosimetric changes in targets and organs-at-risk. Conclusions For highly modulated VMAT plans, pass rate threshold (90%) using 3%/3mm criteria is not sensitive in detecting MLC leaf errors that will not trigger the MLC leaf interlock. However, the consequential effects of non-beam hold MLC errors on target and OAR doses are negligible, which supports the reliability of current patient-specific IMRT quality assurance (QA) method for VMAT plans. PMID:27069458

Monte Carlo dose calculations in homogeneous media and at interfaces: a comparison between GEPTS, EGSnrc, MCNP, and measurements.

PubMed

Chibani, Omar; Li, X Allen

2002-05-01

Three Monte Carlo photon/electron transport codes (GEPTS, EGSnrc, and MCNP) are bench-marked against dose measurements in homogeneous (both low- and high-Z) media as well as at interfaces. A brief overview on physical models used by each code for photon and electron (positron) transport is given. Absolute calorimetric dose measurements for 0.5 and 1 MeV electron beams incident on homogeneous and multilayer media are compared with the predictions of the three codes. Comparison with dose measurements in two-layer media exposed to a 60Co gamma source is also performed. In addition, comparisons between the codes (including the EGS4 code) are done for (a) 0.05 to 10 MeV electron beams and positron point sources in lead, (b) high-energy photons (10 and 20 MeV) irradiating a multilayer phantom (water/steel/air), and (c) simulation of a 90Sr/90Y brachytherapy source. A good agreement is observed between the calorimetric electron dose measurements and predictions of GEPTS and EGSnrc in both homogeneous and multilayer media. MCNP outputs are found to be dependent on the energy-indexing method (Default/ITS style). This dependence is significant in homogeneous media as well as at interfaces. MCNP(ITS) fits more closely the experimental data than MCNP(DEF), except for the case of Be. At low energy (0.05 and 0.1 MeV), MCNP(ITS) dose distributions in lead show higher maximums in comparison with GEPTS and EGSnrc. EGS4 produces too penetrating electron-dose distributions in high-Z media, especially at low energy (<0.1 MeV). For positrons, differences between GEPTS and EGSnrc are observed in lead because GEPTS distinguishes positrons from electrons for both elastic multiple scattering and bremsstrahlung emission models. For the 60Co source, a quite good agreement between calculations and measurements is observed with regards to the experimental uncertainty. For the other cases (10 and 20 MeV photon sources and the 90Sr/90Y beta source), a good agreement is found between the three codes. In conclusion, differences between GEPTS and EGSnrc results are found to be very small for almost all media and energies studied. MCNP results depend significantly on the electron energy-indexing method.

SU-F-T-565: Assessment of Dosimetric Accuracy for a 3D Gel-Based Dosimetry Service

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosen, B; Lam, K; Moran, J

Purpose: To assess the 3D dosimetric accuracy when using a mail-in service for square and stereotactic fields in a clinical environment. Methods: The 3D dosimetry mail-in service (3DDaaS), offered by Modus QA (London, ON), was used to measure dose distributions from a 6 MV beam of a Varian Clinac. Plastic jars filled with radiosensitive ClearView™ gel were received, CT scanned (for registration and density information), irradiated, and then mailed back to the manufacturer for optical CT readout. Three square field irradiations (2×2, 4×4, and 10×10 cm{sup 2}) were performed with jars immobilized in a water tank, and a composite small-fieldmore » stereotactic delivery was performed using an in-air holder. Dosimetric properties of the gel were quantified within the 25–50 Gy dose range using 3D optical attenuation (OA) distributions provided by the manufacturer. OA was normalized to 100% at the position of isocenter, which received 40Gy. Percentage depth dose, profiles, and 3D gamma distributions (3%/1mm criteria) were calculated to quantify feasibility for relative dosimetry. Results: Mean CT-measured density in the central (3×3×3) cm{sup 3} gel region was 40 ± 3 HU, indicating good homogeneity and near-water-equivalence. Measured and calculated central axis doses agreed to within ±3% in the 25–50 Gy dose range. For the square field irradiations, dose profiles agreed to within 1mm. Gamma analysis of the composite irradiation yielded 99.8%, 91.4%, and 79.1% passing rates for regions receiving at least 10, 5, and 2 Gy, respectively, indicating feasibility for use in high-dose regions. Absolute response varied by up to 16% between jars, indicating limitations for absolute dosimetry under the mail-in conditions. Conclusion: 3DDaaS is a novel near-water-equivalent dosimetry system accurate to within 3% dose and 1mm 3D spatial resolution, and is straightforward to use in a clinical setting. Future investigations are warranted to improve dosimeter response in low-dose regions. The authors would like to thank ModusQA (London, ON) for providing the gels and optical readouts used this work. This work was partially funded by NIH P01CA059827.« less

Dosimetric study of uniform scanning proton therapy planning for prostate cancer patients with a metal hip prosthesis, and comparison with volumetric‐modulated arc therapy

PubMed Central

Cheng, ChihYao; Zheng, Yuanshui; Hsi, Wen; Zeidan, Omar; Schreuder, Niek; Vargas, Carlos; Larson, Gary

2014-01-01

The main purposes of this study were to 1) investigate the dosimetric quality of uniform scanning proton therapy planning (USPT) for prostate cancer patients with a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that of volumetric‐modulated arc therapy (VMAT). Proton plans for prostate cancer (four cases) were generated in XiO treatment planning system (TPS). The beam arrangement in each proton plan consisted of three fields (two oblique fields and one lateral or slightly angled field), and the proton beams passing through a metal hip prosthesis was avoided. Dose calculations in proton plans were performed using the pencil beam algorithm. From each proton plan, planning target volume (PTV) coverage value (i.e., relative volume of the PTV receiving the prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done using two arcs in the Eclipse TPS utilizing 6 MV X‐rays, and beam entrance through metallic hip prosthesis was avoided. Dose computation in the VMAT plans was done using anisotropic analytical algorithm, and calculated VMAT plans were then normalized such that the PTV coverage in the VMAT plan was the same as in the proton plan of the corresponding case. The dose‐volume histograms of calculated treatment plans were used to evaluate the dosimetric quality of USPT and VMAT. In comparison to the proton plans, on average, the maximum and mean doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively, whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton plans had lower (or better) average homogeneity index (HI) of 0.03 compared to the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was lower in the proton plan, with an average absolute difference ranging from 0.1% to 32.6%. In contrast, using proton planning, the relative bladder volume exposed to radiation was higher at high‐dose region with an average absolute difference ranging from 0.4% to 0.8%, and lower at low‐ and medium‐dose regions with an average absolute difference ranging from 2.7% to 10.1%. The average mean dose to the rectum and bladder was lower in the proton plans by 45.1% and 22.0%, respectively, whereas the mean dose to femoral head was lower in VMAT plans by an average difference of 79.6%. In comparison to the VMAT, the proton planning produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4 Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2 CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in this study show that the combination of lateral and oblique fields in USPT planning could potentially provide dosimetric advantage over the VMAT for prostate cancer involving a metallic hip prosthesis. PACS number: 87.55.D‐, 87.55.ne, 87.55.dk PMID:24892333

Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths.

PubMed

Burcu, Mehmet; Zito, Julie M; Safer, Daniel J; Magder, Laurence S; dosReis, Susan; Shaya, Fadia T; Rosenthal, Geoffrey L

2017-12-01

Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment-emergent risk of type 2 diabetes among youths. To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose. A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009. Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose. Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates. In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1.15 per 10 000 person-months vs 1.12 per 10 000 person-months; RR, 0.99; 95% CI, 0.66-1.50). Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use. In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs-the most commonly used antidepressant subclass-was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose.

A segmentation and point-matching enhanced efficient deformable image registration method for dose accumulation between HDR CT images

NASA Astrophysics Data System (ADS)

Zhen, Xin; Chen, Haibin; Yan, Hao; Zhou, Linghong; Mell, Loren K.; Yashar, Catheryn M.; Jiang, Steve; Jia, Xun; Gu, Xuejun; Cervino, Laura

2015-04-01

Deformable image registration (DIR) of fractional high-dose-rate (HDR) CT images is challenging due to the presence of applicators in the brachytherapy image. Point-to-point correspondence fails because of the undesired deformation vector fields (DVF) propagated from the applicator region (AR) to the surrounding tissues, which can potentially introduce significant DIR errors in dose mapping. This paper proposes a novel segmentation and point-matching enhanced efficient DIR (named SPEED) scheme to facilitate dose accumulation among HDR treatment fractions. In SPEED, a semi-automatic seed point generation approach is developed to obtain the incremented fore/background point sets to feed the random walks algorithm, which is used to segment and remove the AR, leaving empty AR cavities in the HDR CT images. A feature-based ‘thin-plate-spline robust point matching’ algorithm is then employed for AR cavity surface points matching. With the resulting mapping, a DVF defining on each voxel is estimated by B-spline approximation, which serves as the initial DVF for the subsequent Demons-based DIR between the AR-free HDR CT images. The calculated DVF via Demons combined with the initial one serve as the final DVF to map doses between HDR fractions. The segmentation and registration accuracy are quantitatively assessed by nine clinical HDR cases from three gynecological cancer patients. The quantitative analysis and visual inspection of the DIR results indicate that SPEED can suppress the impact of applicator on DIR, and accurately register HDR CT images as well as deform and add interfractional HDR doses.

A segmentation and point-matching enhanced efficient deformable image registration method for dose accumulation between HDR CT images.

PubMed

Zhen, Xin; Chen, Haibin; Yan, Hao; Zhou, Linghong; Mell, Loren K; Yashar, Catheryn M; Jiang, Steve; Jia, Xun; Gu, Xuejun; Cervino, Laura

2015-04-07

Deformable image registration (DIR) of fractional high-dose-rate (HDR) CT images is challenging due to the presence of applicators in the brachytherapy image. Point-to-point correspondence fails because of the undesired deformation vector fields (DVF) propagated from the applicator region (AR) to the surrounding tissues, which can potentially introduce significant DIR errors in dose mapping. This paper proposes a novel segmentation and point-matching enhanced efficient DIR (named SPEED) scheme to facilitate dose accumulation among HDR treatment fractions. In SPEED, a semi-automatic seed point generation approach is developed to obtain the incremented fore/background point sets to feed the random walks algorithm, which is used to segment and remove the AR, leaving empty AR cavities in the HDR CT images. A feature-based 'thin-plate-spline robust point matching' algorithm is then employed for AR cavity surface points matching. With the resulting mapping, a DVF defining on each voxel is estimated by B-spline approximation, which serves as the initial DVF for the subsequent Demons-based DIR between the AR-free HDR CT images. The calculated DVF via Demons combined with the initial one serve as the final DVF to map doses between HDR fractions. The segmentation and registration accuracy are quantitatively assessed by nine clinical HDR cases from three gynecological cancer patients. The quantitative analysis and visual inspection of the DIR results indicate that SPEED can suppress the impact of applicator on DIR, and accurately register HDR CT images as well as deform and add interfractional HDR doses.

Experimental evaluation of x-ray acoustic computed tomography for radiotherapy dosimetry applications.

PubMed

Hickling, Susannah; Lei, Hao; Hobson, Maritza; Léger, Pierre; Wang, Xueding; El Naqa, Issam

2017-02-01

The aim of this work was to experimentally demonstrate the feasibility of x-ray acoustic computed tomography (XACT) as a dosimetry tool in a clinical radiotherapy environment. The acoustic waves induced following a single pulse of linear accelerator irradiation in a water tank were detected with an immersion ultrasound transducer. By rotating the collimator and keeping the transducer stationary, acoustic signals at varying angles surrounding the field were detected and reconstructed to form an XACT image. Simulated XACT images were obtained using a previously developed simulation workflow. Profiles extracted from experimental and simulated XACT images were compared to profiles measured with an ion chamber. A variety of radiation field sizes and shapes were investigated. XACT images resembling the geometry of the delivered radiation field were obtained for fields ranging from simple squares to more complex shapes. When comparing profiles extracted from simulated and experimental XACT images of a 4 cm × 4 cm field, 97% of points were found to pass a 3%/3 mm gamma test. Agreement between simulated and experimental XACT images worsened when comparing fields with fine details. Profiles extracted from experimental XACT images were compared to profiles obtained through clinical ion chamber measurements, confirming that the intensity of XACT images is related to deposited radiation dose. Seventy-seven percent of the points in a profile extracted from an experimental XACT image of a 4 cm × 4 cm field passed a 7%/4 mm gamma test when compared to an ion chamber measured profile. In a complicated puzzle-piece shaped field, 86% of the points in an XACT extracted profile passed a 7%/4 mm gamma test. XACT images with intensity related to the spatial distribution of deposited dose in a water tank were formed for a variety of field sizes and shapes. XACT has the potential to be a useful tool for absolute, relative and in vivo dosimetry. © 2016 American Association of Physicists in Medicine.

INTERCOMPARISON ON THE MEASUREMENT OF THE QUANTITY PERSONAL DOSE EQUIVALENT HP(10) IN PHOTON FIELDS. LINEARITY DEPENDENCE, LOWER LIMIT OF DETECTION AND UNCERTAINTY IN MEASUREMENT OF DOSIMETRY SYSTEMS OF INDIVIDUAL MONITORING SERVICES IN GABON AND GHANA.

PubMed

Ondo Meye, P; Schandorf, C; Amoako, J K; Manteaw, P O; Amoatey, E A; Adjei, D N

2017-12-01

An inter-comparison study was conducted to assess the capability of dosimetry systems of individual monitoring services (IMSs) in Gabon and Ghana to measure personal dose equivalent Hp(10) in photon fields. The performance indicators assessed were the lower limit of detection, linearity and uncertainty in measurement. Monthly and quarterly recording levels were proposed with corresponding values of 0.08 and 0.025 mSv, and 0.05 and 0.15 mSv for the TLD and OSL systems, respectively. The linearity dependence of the dosimetry systems was performed following the requirement given in the Standard IEC 62387 of the International Electrotechnical Commission (IEC). The results obtained for the two systems were satisfactory. The procedure followed for the uncertainty assessment is the one given in the IEC technical report TR62461. The maximum relative overall uncertainties, in absolute value, expressed in terms of Hp(10), for the TL dosimetry system Harshaw 6600, are 44. 35% for true doses below 0.40 mSv and 36.33% for true doses ≥0.40 mSv. For the OSL dosimetry system microStar, the maximum relative overall uncertainties, in absolute value, are 52.17% for true doses below 0.40 mSv and 37.43% for true doses ≥0.40 mSv. These results are in good agreement with the requirements for accuracy of the International Commission on Radiological protection. When expressing the uncertainties in terms of response, comparison with the IAEA requirements for overall accuracy showed that the uncertainty results were also acceptable. The values of Hp(10) directly measured by the two dosimetry systems showed a significant underestimation for the Harshaw 6600 system, and a slight overestimation for the microStar system. After correction for linearity of the measured doses, the two dosimetry systems gave better and comparable results. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ultra-low-frequency vertical vibration isolator based on a two-stage beam structure for absolute gravimetry.

PubMed

Wang, G; Wu, K; Hu, H; Li, G; Wang, L J

2016-10-01

To reduce seismic and environmental vibration noise, ultra-low-frequency vertical vibration isolation systems play an important role in absolute gravimetry. For this purpose, an isolator based on a two-stage beam structure is proposed and demonstrated. The isolator has a simpler and more robust structure than the present ultra-low-frequency vertical active vibration isolators. In the system, two beams are connected to a frame using flexural pivots. The upper beam is suspended from the frame with a normal hex spring and the lower beam is suspended from the upper one using a zero-length spring. The pivot of the upper beam is not vertically above the pivot of the lower beam. With this special design, the attachment points of the zero-length spring to the beams can be moved to adjust the effective stiffness. A photoelectric detector is used to detect the angle between the two beams, and a voice coil actuator attached to the upper beam is controlled by a feedback circuit to keep the angle at a fixed value. The system can achieve a natural period of 100 s by carefully moving the attachment points of the zero-length spring to the beams and tuning the feedback parameters. The system has been used as an inertial reference in the T-1 absolute gravimeter. The experiment results demonstrate that the system has significant vibration isolation performance that holds promise in applications such as absolute gravimeters.

Ultra-low-frequency vertical vibration isolator based on a two-stage beam structure for absolute gravimetry

NASA Astrophysics Data System (ADS)

Wang, G.; Wu, K.; Hu, H.; Li, G.; Wang, L. J.

2016-10-01

To reduce seismic and environmental vibration noise, ultra-low-frequency vertical vibration isolation systems play an important role in absolute gravimetry. For this purpose, an isolator based on a two-stage beam structure is proposed and demonstrated. The isolator has a simpler and more robust structure than the present ultra-low-frequency vertical active vibration isolators. In the system, two beams are connected to a frame using flexural pivots. The upper beam is suspended from the frame with a normal hex spring and the lower beam is suspended from the upper one using a zero-length spring. The pivot of the upper beam is not vertically above the pivot of the lower beam. With this special design, the attachment points of the zero-length spring to the beams can be moved to adjust the effective stiffness. A photoelectric detector is used to detect the angle between the two beams, and a voice coil actuator attached to the upper beam is controlled by a feedback circuit to keep the angle at a fixed value. The system can achieve a natural period of 100 s by carefully moving the attachment points of the zero-length spring to the beams and tuning the feedback parameters. The system has been used as an inertial reference in the T-1 absolute gravimeter. The experiment results demonstrate that the system has significant vibration isolation performance that holds promise in applications such as absolute gravimeters.

Laser Truss Sensor for Segmented Telescope Phasing

NASA Technical Reports Server (NTRS)

Liu, Duncan T.; Lay, Oliver P.; Azizi, Alireza; Erlig, Herman; Dorsky, Leonard I.; Asbury, Cheryl G.; Zhao, Feng

2011-01-01

A paper describes the laser truss sensor (LTS) for detecting piston motion between two adjacent telescope segment edges. LTS is formed by two point-to-point laser metrology gauges in a crossed geometry. A high-resolution (<30 nm) LTS can be implemented with existing laser metrology gauges. The distance change between the reference plane and the target plane is measured as a function of the phase change between the reference and target beams. To ease the bandwidth requirements for phase detection electronics (or phase meter), homodyne or heterodyne detection techniques have been used. The phase of the target beam also changes with the refractive index of air, which changes with the air pressure, temperature, and humidity. This error can be minimized by enclosing the metrology beams in baffles. For longer-term (weeks) tracking at the micron level accuracy, the same gauge can be operated in the absolute metrology mode with an accuracy of microns; to implement absolute metrology, two laser frequencies will be used on the same gauge. Absolute metrology using heterodyne laser gauges is a demonstrated technology. Complexity of laser source fiber distribution can be optimized using the range-gated metrology (RGM) approach.

Clinical implementation of total skin electron irradiation treatment with a 6 MeV electron beam in high-dose total skin electron mode

NASA Astrophysics Data System (ADS)

Lucero, J. F.; Rojas, J. I.

2016-07-01

Total skin electron irradiation (TSEI) is a special treatment technique offered by modern radiation oncology facilities, given for the treatment of mycosis fungoides, a rare skin disease, which is type of cutaneous T-cell lymphoma [1]. During treatment the patient's entire skin is irradiated with a uniform dose. The aim of this work is to present implementation of total skin electron irradiation treatment using IAEA TRS-398 code of practice for absolute dosimetry and taking advantage of the use of radiochromic films.

Determination of uranium and thorium using gamma spectrometry: a pilot study

NASA Astrophysics Data System (ADS)

Olivares, D. M. M.; Koch, E. S.; Guevara, M. V. M.; Velasco, F. G.

2018-03-01

This paper presents the results of a pilot experiment aimed at standardizing procedures for the CPqCTR/UESC Gamma Spectrometry Laboratory (LEG) for the quantification of natural radioactive elements in solid environmental samples. The concentrations of 238U, 232Th and 40K in two sediment matrix belonging to the Caetité region were determined, by using the absolute method with uncertainties about 5%. The results were obtained using gamma spectrometry with a high-resolution p-type HPGe detector. As a closure, the absorbed dose, radium equivalent activity and the annual effective dose were calculated.

Nature of gamma rays background radiation in new and old buildings of Qatar University

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Houty, L.; Abou-Leila, H.; El-Kameesy, S.

Measurements and analysis of gamma-background radiation spectrum in four different places of Qatar University campus were performed at the energy range 10 keV-3 MeV using hyper pure Ge-detector. The dependence of the detector absolute photopeak efficiency on gamma-ray energies was determined and correction of the data for that was also done. The absorbed dose for each gamma line was calculated and an estimation of the total absorbed dose for the detected gamma lines in the four different places was obtained. Comparison with other results was also performed.

Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

DTIC Science & Technology

1989-03-01

and absolute efficacy of three doses of Ty2la vaccine given in enteric-coated capsule or liquid formulation. Intensive clinical and bacteriologic...TABLES Table 1. Evaluation of the efficacy of three doses of the enteric-coated capsule formulation of Ty2la live oral vaccine given within one week in...November, 1986 thzough February, 1989 of a field trial in Area Sur Oriente and Area Norte assessing the efficacy of Ty21a vaccine in liquid or enteric

Clinical implementation of total skin electron irradiation treatment with a 6 MeV electron beam in high-dose total skin electron mode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucero, J. F., E-mail: fernando.lucero@hoperadiotherapy.com.gt; Hope International, Guatemala; Rojas, J. I., E-mail: isaac.rojas@siglo21.cr

Total skin electron irradiation (TSEI) is a special treatment technique offered by modern radiation oncology facilities, given for the treatment of mycosis fungoides, a rare skin disease, which is type of cutaneous T-cell lymphoma [1]. During treatment the patient’s entire skin is irradiated with a uniform dose. The aim of this work is to present implementation of total skin electron irradiation treatment using IAEA TRS-398 code of practice for absolute dosimetry and taking advantage of the use of radiochromic films.

Chloroatranol, an extremely potent allergen hidden in perfumes: a dose-response elicitation study.

PubMed

Johansen, Jeanne Duus; Andersen, Klaus Ejner; Svedman, Cecilia; Bruze, Magnus; Bernard, Guillaume; Giménez-Arnau, Elena; Rastogi, Suresh Chandra; Lepoittevin, Jean-Pierre; Menné, Torkil

2003-10-01

Oak moss absolute is a long-known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently, chloroatranol, a hitherto unknown fragrance allergen, was identified in oak moss absolute. The objective was to assess the clinical importance of chloroatranol as a fragrance allergen by characterizing its elicitation profile. 13 patients previously showing a positive patch test to oak moss absolute and chloroatranol were included, together with a control group of 10 patients without sensitization to either of the 2 materials. A serial dilution patch test was performed on the upper back with concentrations ranging from 200 to 0.0063 p.p.m. of chloroatranol in ethanol. Simultaneously, the participant performed an open test simulating the use of perfumes on the volar aspect of the forearms in a randomized and double-blinded design. A solution with 5 p.p.m. chloroatranol was used for 14 days, and, in case of no reaction, the applications were continued for another 14 days with a solution containing 25 p.p.m. All test subjects (13/13) developed an allergic reaction at the site of application of the solution containing chloroatranol. Among them, 12/13 (92%) gave a positive reaction to the 5 p.p.m. solution and 1 to 25 p.p.m. None of the controls reacted (P < 0.001). The use test was terminated at median day 4. The dose eliciting a reaction in 50% of the test subjects at patch testing was 0.2 p.p.m. In conclusion, the hidden exposure to a potent allergen widely used in perfumes has caused a highly sensitized cohort of individuals. Judged from the elicitation profile, chloroatranol is the most potent allergen present in consumer products today.

An Automatic Procedure for Combining Digital Images and Laser Scanner Data

NASA Astrophysics Data System (ADS)

Moussa, W.; Abdel-Wahab, M.; Fritsch, D.

2012-07-01

Besides improving both the geometry and the visual quality of the model, the integration of close-range photogrammetry and terrestrial laser scanning techniques directs at filling gaps in laser scanner point clouds to avoid modeling errors, reconstructing more details in higher resolution and recovering simple structures with less geometric details. Thus, within this paper a flexible approach for the automatic combination of digital images and laser scanner data is presented. Our approach comprises two methods for data fusion. The first method starts by a marker-free registration of digital images based on a point-based environment model (PEM) of a scene which stores the 3D laser scanner point clouds associated with intensity and RGB values. The PEM allows the extraction of accurate control information for the direct computation of absolute camera orientations with redundant information by means of accurate space resection methods. In order to use the computed relations between the digital images and the laser scanner data, an extended Helmert (seven-parameter) transformation is introduced and its parameters are estimated. Precedent to that, in the second method, the local relative orientation parameters of the camera images are calculated by means of an optimized Structure and Motion (SaM) reconstruction method. Then, using the determined transformation parameters results in having absolute oriented images in relation to the laser scanner data. With the resulting absolute orientations we have employed robust dense image reconstruction algorithms to create oriented dense image point clouds, which are automatically combined with the laser scanner data to form a complete detailed representation of a scene. Examples of different data sets are shown and experimental results demonstrate the effectiveness of the presented procedures.

The major influence of the atmosphere on intracranial pressure: an observational study.

PubMed

Herbowski, Leszek

2017-01-01

The impact of the atmosphere on human physiology has been studied widely within the last years. In practice, intracranial pressure is a pressure difference between intracranial compartments and the surrounding atmosphere. This means that gauge intracranial pressure uses atmospheric pressure as its zero point, and therefore, this method of pressure measurement excludes the effects of barometric pressure's fluctuation. The comparison of these two physical quantities can only take place through their absolute value relationship. The aim of this study is to investigate the direct effect of barometric pressure on the absolute intracranial pressure homeostasis. A prospective observational cross-sectional open study was conducted in Szczecin, Poland. In 28 neurosurgical patients with suspected normal-pressure hydrocephalus, intracranial intraventricular pressure was monitored in a sitting position. A total of 168 intracranial pressure and atmospheric pressure measurements were performed. Absolute atmospheric pressure was recorded directly. All values of intracranial gauge pressure were converted to absolute pressure (the sum of gauge intracranial pressure and local absolute atmospheric pressure). The average absolute mean intracranial pressure in the patients is 1006.6 hPa (95 % CI 1004.5 to 1008.8 hPa, SEM 1.1), and the mean absolute atmospheric pressure is 1007.9 hPa (95 % CI 1006.3 to 1009.6 hPa, SEM 0.8). The observed association between atmospheric and intracranial pressure is strongly significant (Spearman correlation r = 0.87, p < 0.05) and all the measurements are perfectly reliable (Bland-Altman coefficient is 4.8 %). It appears from this study that changes in absolute intracranial pressure are related to seasonal variation. Absolute intracranial pressure is shown to be impacted positively by atmospheric pressure.

New experimental methodology, setup and LabView program for accurate absolute thermoelectric power and electrical resistivity measurements between 25 and 1600 K: application to pure copper, platinum, tungsten, and nickel at very high temperatures.

PubMed

Abadlia, L; Gasser, F; Khalouk, K; Mayoufi, M; Gasser, J G

2014-09-01

In this paper we describe an experimental setup designed to measure simultaneously and very accurately the resistivity and the absolute thermoelectric power, also called absolute thermopower or absolute Seebeck coefficient, of solid and liquid conductors/semiconductors over a wide range of temperatures (room temperature to 1600 K in present work). A careful analysis of the existing experimental data allowed us to extend the absolute thermoelectric power scale of platinum to the range 0-1800 K with two new polynomial expressions. The experimental device is controlled by a LabView program. A detailed description of the accurate dynamic measurement methodology is given in this paper. We measure the absolute thermoelectric power and the electrical resistivity and deduce with a good accuracy the thermal conductivity using the relations between the three electronic transport coefficients, going beyond the classical Wiedemann-Franz law. We use this experimental setup and methodology to give new very accurate results for pure copper, platinum, and nickel especially at very high temperatures. But resistivity and absolute thermopower measurement can be more than an objective in itself. Resistivity characterizes the bulk of a material while absolute thermoelectric power characterizes the material at the point where the electrical contact is established with a couple of metallic elements (forming a thermocouple). In a forthcoming paper we will show that the measurement of resistivity and absolute thermoelectric power characterizes advantageously the (change of) phase, probably as well as DSC (if not better), since the change of phases can be easily followed during several hours/days at constant temperature.

New experimental methodology, setup and LabView program for accurate absolute thermoelectric power and electrical resistivity measurements between 25 and 1600 K: Application to pure copper, platinum, tungsten, and nickel at very high temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abadlia, L.; Mayoufi, M.; Gasser, F.

2014-09-15

In this paper we describe an experimental setup designed to measure simultaneously and very accurately the resistivity and the absolute thermoelectric power, also called absolute thermopower or absolute Seebeck coefficient, of solid and liquid conductors/semiconductors over a wide range of temperatures (room temperature to 1600 K in present work). A careful analysis of the existing experimental data allowed us to extend the absolute thermoelectric power scale of platinum to the range 0-1800 K with two new polynomial expressions. The experimental device is controlled by a LabView program. A detailed description of the accurate dynamic measurement methodology is given in thismore » paper. We measure the absolute thermoelectric power and the electrical resistivity and deduce with a good accuracy the thermal conductivity using the relations between the three electronic transport coefficients, going beyond the classical Wiedemann-Franz law. We use this experimental setup and methodology to give new very accurate results for pure copper, platinum, and nickel especially at very high temperatures. But resistivity and absolute thermopower measurement can be more than an objective in itself. Resistivity characterizes the bulk of a material while absolute thermoelectric power characterizes the material at the point where the electrical contact is established with a couple of metallic elements (forming a thermocouple). In a forthcoming paper we will show that the measurement of resistivity and absolute thermoelectric power characterizes advantageously the (change of) phase, probably as well as DSC (if not better), since the change of phases can be easily followed during several hours/days at constant temperature.« less

The major influence of the atmosphere on intracranial pressure: an observational study

NASA Astrophysics Data System (ADS)

Herbowski, Leszek

2017-01-01

The impact of the atmosphere on human physiology has been studied widely within the last years. In practice, intracranial pressure is a pressure difference between intracranial compartments and the surrounding atmosphere. This means that gauge intracranial pressure uses atmospheric pressure as its zero point, and therefore, this method of pressure measurement excludes the effects of barometric pressure's fluctuation. The comparison of these two physical quantities can only take place through their absolute value relationship. The aim of this study is to investigate the direct effect of barometric pressure on the absolute intracranial pressure homeostasis. A prospective observational cross-sectional open study was conducted in Szczecin, Poland. In 28 neurosurgical patients with suspected normal-pressure hydrocephalus, intracranial intraventricular pressure was monitored in a sitting position. A total of 168 intracranial pressure and atmospheric pressure measurements were performed. Absolute atmospheric pressure was recorded directly. All values of intracranial gauge pressure were converted to absolute pressure (the sum of gauge intracranial pressure and local absolute atmospheric pressure). The average absolute mean intracranial pressure in the patients is 1006.6 hPa (95 % CI 1004.5 to 1008.8 hPa, SEM 1.1), and the mean absolute atmospheric pressure is 1007.9 hPa (95 % CI 1006.3 to 1009.6 hPa, SEM 0.8). The observed association between atmospheric and intracranial pressure is strongly significant (Spearman correlation r = 0.87, p < 0.05) and all the measurements are perfectly reliable (Bland-Altman coefficient is 4.8 %). It appears from this study that changes in absolute intracranial pressure are related to seasonal variation. Absolute intracranial pressure is shown to be impacted positively by atmospheric pressure.

Wavefront Intensity Statistics for 284-Hz Broadband Transmissions to 107-km Range in the Philippine Sea: Observations and Modeling

DTIC Science & Technology

2013-10-01

structure reveals four distinct purely refracted acoustic paths: One with a single upper turning point near 80 m depth, two with a pair of upper turning... points at a depth of roughly 300 m, and one with three upper turning points at 420 m. Individual path intensity, defined as the absolute square of...contribu- tion to acoustic scattering is thought to occur at upper turning points (UTP) (Flatte et al., 1979). Here, the acoustic path is horizontal

The effect of tandem-ovoid titanium applicator on points A, B, bladder, and rectum doses in gynecological brachytherapy using 192Ir

PubMed Central

Sadeghi, Mohammad Hosein; Mehdizadeh, Amir; Faghihi, Reza; Moharramzadeh, Vahed; Meigooni, Ali Soleimani

2018-01-01

Purpose The dosimetry procedure by simple superposition accounts only for the self-shielding of the source and does not take into account the attenuation of photons by the applicators. The purpose of this investigation is an estimation of the effects of the tandem and ovoid applicator on dose distribution inside the phantom by MCNP5 Monte Carlo simulations. Material and methods In this study, the superposition method is used for obtaining the dose distribution in the phantom without using the applicator for a typical gynecological brachytherapy (superposition-1). Then, the sources are simulated inside the tandem and ovoid applicator to identify the effect of applicator attenuation (superposition-2), and the dose at points A, B, bladder, and rectum were compared with the results of superposition. The exact dwell positions, times of the source, and positions of the dosimetry points were determined in images of a patient and treatment data of an adult woman patient from a cancer center. The MCNP5 Monte Carlo (MC) code was used for simulation of the phantoms, applicators, and the sources. Results The results of this study showed no significant differences between the results of superposition method and the MC simulations for different dosimetry points. The difference in all important dosimetry points was found to be less than 5%. Conclusions According to the results, applicator attenuation has no significant effect on the calculated points dose, the superposition method, adding the dose of each source obtained by the MC simulation, can estimate the dose to points A, B, bladder, and rectum with good accuracy. PMID:29619061

Comparative evaluation of two-dimensional radiography and three dimensional computed tomography based dose-volume parameters for high-dose-rate intracavitary brachytherapy of cervical cancer: a prospective study.

PubMed

Madan, Renu; Pathy, Sushmita; Subramani, Vellaiyan; Sharma, Seema; Mohanti, Bidhu Kalyan; Chander, Subhash; Thulkar, Sanjay; Kumar, Lalit; Dadhwal, Vatsla

2014-01-01

Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

Audio steganography by amplitude or phase modification

NASA Astrophysics Data System (ADS)

Gopalan, Kaliappan; Wenndt, Stanley J.; Adams, Scott F.; Haddad, Darren M.

2003-06-01

This paper presents the results of embedding short covert message utterances on a host, or cover, utterance by modifying the phase or amplitude of perceptually masked or significant regions of the host. In the first method, the absolute phase at selected, perceptually masked frequency indices was changed to fixed, covert data-dependent values. Embedded bits were retrieved at the receiver from the phase at the selected frequency indices. Tests on embedding a GSM-coded covert utterance on clean and noisy host utterances showed no noticeable difference in the stego compared to the hosts in speech quality or spectrogram. A bit error rate of 2 out of 2800 was observed for a clean host utterance while no error occurred for a noisy host. In the second method, the absolute phase of 10 or fewer perceptually significant points in the host was set in accordance with covert data. This resulted in a stego with successful data retrieval and a slightly noticeable degradation in speech quality. Modifying the amplitude of perceptually significant points caused perceptible differences in the stego even with small changes of amplitude made at five points per frame. Finally, the stego obtained by altering the amplitude at perceptually masked points showed barely noticeable differences and excellent data recovery.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

PubMed

Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

2018-05-08

Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P <0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

A new approach of the Star Excursion Balance Test to assess dynamic postural control in people complaining from chronic ankle instability.

PubMed

Pionnier, Raphaël; Découfour, Nicolas; Barbier, Franck; Popineau, Christophe; Simoneau-Buessinger, Emilie

2016-03-01

The purpose of this study was to quantitatively and qualitatively assess dynamic balance with accuracy in individuals with chronic ankle instability (CAI). To this aim, a motion capture system was used while participants performed the Star Excursion Balance Test (SEBT). Reached distances for the 8 points of the star were automatically computed, thereby excluding any dependence to the experimenter. In addition, new relevant variables were also computed, such as absolute time needed to reach each distance, lower limb ranges of motion during unipodal stance, as well as absolute error of pointing. Velocity of the center of pressure and range of variation of ground reaction forces have also been assessed during the unipodal phase of the SEBT thanks to force plates. CAI group exhibited smaller reached distances and greater absolute error of pointing than the control group (p<0.05). Moreover, the ranges of motion of lower limbs joints, the velocity of the center of pressure and the range of variation of the ground reaction forces were all significantly smaller in the CAI group (p<0.05). These reduced quantitative and qualitative performances highlighted a lower dynamic postural control. The limited body movements and accelerations during the unipodal stance in the CAI group could highlight a protective strategy. The present findings could help clinicians to better understand the motor strategies used by CAI patients during dynamic balance and may guide the rehabilitation process. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-F-T-68: Characterizes of Microdetectors in Electron Beam Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, I; Andersen, A; Akino, Y

Purpose: Electron beam dosimetry requires high resolution data due to finite range that can be accomplished with small volume detectors. The small-field used in advance technologies in photon beam has created a market for microdetectors, however characteristics are significantly variable in photon beams and relatively unknown in electron beam that is investigated in this study. Methods: Among nearly 2 dozen microdetectors that have been investigated in small fields of photon beam, two popular detectors (microDiamond 60019 (PTW)) and W1 plastic scintillator detector (Standard Imaging)) that are tissue equivalent and have very small sensitive volume are selected. Electron beams from Varianmore » linear accelerators were used to investigate dose linearity dose rate dependence, energy dependence, depth dose and profiles in a reference condition in a water phantom. For W1 that has its own Supermax electrometer point by point measurements were performed. For microDiamond, a PTW-scanning tank was used for both scanning and point dose measurements. Results: W1 detector showed excellent dose linearity (r{sup 2} =1.0) from 5–500 MU either with variation of dose rate or beam energy. Similar findings were also observed for microdiamond with r{sup 2}=1.0. Percent variations in dose/MU for W1 and microDiamond were 0.2–1.1% and 0.4–1.2%, respectively among dose rate and beam energy. This variation was random for microDiamond, whereas it decreased with beam energy and dose rate for W1. The depth dose and profiles were within ±1 mm for both detectors. Both detectors did not show any energy dependence in electron beams. Conclusion: Both microDiamond and W1 detectors provided superior characteristics of beam parameters in electron beam including dose, dose rate linearity and energy independence. Both can be used in electron beam except W1 require point by point measurements and microdiamond requires 1500 MU for initial quenching.« less

SU-E-T-184: Clinical VMAT QA Practice Using LINAC Delivery Log Files

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, H; Jacobson, T; Gu, X

2015-06-15

Purpose: To evaluate the accuracy of volumetric modulated arc therapy (VMAT) treatment delivery dose clouds by comparing linac log data to doses measured using an ionization chamber and film. Methods: A commercial IMRT quality assurance (QA) process utilizing a DICOM-RT framework was tested for clinical practice using 30 prostate and 30 head and neck VMAT plans. Delivered 3D VMAT dose distributions were independently checked using a PinPoint ionization chamber and radiographic film in a solid water phantom. DICOM RT coordinates were used to extract the corresponding point and planar doses from 3D log file dose distributions. Point doses were evaluatedmore » by computing the percent error between log file and chamber measured values. A planar dose evaluation was performed for each plan using a 2D gamma analysis with 3% global dose difference and 3 mm isodose point distance criteria. The same analysis was performed to compare treatment planning system (TPS) doses to measured values to establish a baseline assessment of agreement. Results: The mean percent error between log file and ionization chamber dose was 1.0%±2.1% for prostate VMAT plans and −0.2%±1.4% for head and neck plans. The corresponding TPS calculated and measured ionization chamber values agree within 1.7%±1.6%. The average 2D gamma passing rates for the log file comparison to film are 98.8%±1.0% and 96.2%±4.2% for the prostate and head and neck plans, respectively. The corresponding passing rates for the TPS comparison to film are 99.4%±0.5% and 93.9%±5.1%. Overall, the point dose and film data indicate that log file determined doses are in excellent agreement with measured values. Conclusion: Clinical VMAT QA practice using LINAC treatment log files is a fast and reliable method for patient-specific plan evaluation.« less

Acupuncture for treating fibromyalgia

PubMed Central

Deare, John C; Zheng, Zhen; Xue, Charlie CL; Liu, Jian Ping; Shang, Jingsheng; Scott, Sean W; Littlejohn, Geoff

2014-01-01

Background One in five fibromyalgia sufferers use acupuncture treatment within two years of diagnosis. Objectives To examine the benefits and safety of acupuncture treatment for fibromyalgia. Search methods We searched CENTRAL, PubMed, EMBASE, CINAHL, National Research Register, HSR Project and Current Contents, as well as the Chinese databases VIP and Wangfang to January 2012 with no language restrictions. Selection criteria Randomised and quasi-randomised studies evaluating any type of invasive acupuncture for fibromyalgia diagnosed according to the American College of Rheumatology (ACR) criteria, and reporting any main outcome: pain, physical function, fatigue, sleep, total well-being, stiffness and adverse events. Data collection and analysis Two author pairs selected trials, extracted data and assessed risk of bias. Treatment effects were reported as standardised mean differences (SMD) and 95%confidence intervals (CI) for continuous outcomes using different measurement tools (pain, physical function, fatigue, sleep, total well-being and stiffness) and risk ratio (RR) and 95% CI for dichotomous outcomes (adverse events).We pooled data using the random-effects model. Main results Nine trials (395 participants) were included. All studies except one were at low risk of selection bias; five were at risk of selective reporting bias (favouring either treatment group); two were subject to attrition bias (favouring acupuncture); three were subject to performance bias (favouring acupuncture) and one to detection bias (favouring acupuncture). Three studies utilised electro-acupuncture (EA) with the remainder using manual acupuncture (MA) without electrical stimulation. All studies used ’formula acupuncture’ except for one, which used trigger points. Low quality evidence from one study (13 participants) showed EA improved symptoms with no adverse events at one month following treatment. Mean pain in the non-treatment control group was 70 points on a 100 point scale; EA reduced pain by a mean of 22 points (95% confidence interval (CI) 4 to 41), or 22% absolute improvement. Control group global well-being was 66.5 points on a 100 point scale; EA improved well-being by a mean of 15 points (95% CI 5 to 26 points). Control group stiffness was 4.8 points on a 0 to 10 point; EA reduced stiffness by a mean of 0.9 points (95% CI 0.1 to 2 points; absolute reduction 9%, 95% CI 4% to 16%). Fatigue was 4.5 points (10 point scale) without treatment; EA reduced fatigue by a mean of 1 point (95% CI 0.22 to 2 points), absolute reduction 11% (2% to 20%). There was no difference in sleep quality (MD 0.4 points, 95% CI −1 to 0.21 points, 10 point scale), and physical function was not reported. Moderate quality evidence from six studies (286 participants) indicated that acupuncture (EA or MA) was no better than sham acupuncture, except for less stiffness at one month. Subgroup analysis of two studies (104 participants) indicated benefits of EA. Mean pain was 70 points on 0 to 100 point scale with sham treatment; EA reduced pain by 13% (5% to 22%); (SMD −0.63, 95% CI −1.02 to −0.23). Global well-being was 5.2 points on a 10 point scale with sham treatment; EA improved well-being: SMD 0.65, 95% CI 0.26 to 1.05; absolute improvement 11% (4% to 17%). EA improved sleep, from 3 points on a 0 to 10 point scale in the sham group: SMD 0.40 (95% CI 0.01 to 0.79); absolute improvement 8% (0.2% to 16%). Low-quality evidence from one study suggested that MA group resulted in poorer physical function: mean function in the sham group was 28 points (100 point scale); treatment worsened function by a mean of 6 points (95% CI −10.9 to −0.7). Low-quality evidence from three trials (289 participants) suggested no difference in adverse events between real (9%) and sham acupuncture (35%); RR 0.44 (95% CI 0.12 to 1.63). Moderate quality evidence from one study (58 participants) found that compared with standard therapy alone (antidepressants and exercise), adjunct acupuncture therapy reduced pain at one month after treatment: mean pain was 8 points on a 0 to 10 point scale in the standard therapy group; treatment reduced pain by 3 points (95% CI −3.9 to −2.1), an absolute reduction of 30% (21% to 39%). Two people treated with acupuncture reported adverse events; there were none in the control group (RR 3.57; 95% CI 0.18 to 71.21). Global well-being, sleep, fatigue and stiffness were not reported. Physical function data were not usable. Low quality evidence from one study (38 participants) showed a short-term benefit of acupuncture over antidepressants in pain relief: mean pain was 29 points (0 to 100 point scale) in the antidepressant group; acupuncture reduced pain by 17 points (95% CI −24.1 to −10.5). Other outcomes or adverse events were not reported. Moderate-quality evidence from one study (41 participants) indicated that deep needling with or without deqi did not differ in pain, fatigue, function or adverse events. Other outcomes were not reported. Four studies reported no differences between acupuncture and control or other treatments described at six to seven months follow-up. No serious adverse events were reported, but there were insufficient adverse events to be certain of the risks. Authors’ conclusions There is low tomoderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted. PMID:23728665

Validation of sparse sampling strategies to estimate cyclosporine A area under the concentration-time curve using either a specific radioimmunoassay or high-performance liquid chromatography method.

PubMed

Koristkova, Blanka; Grundmann, Milan; Brozmanova, Hana; Perinova, Ilona; Safarcik, Kristian

2010-10-01

Area under the concentration-time curve (AUC) has been advocated as a better parameter to monitor cyclosporine A than trough concentrations. Up to now, more than 100 equations to estimate AUC using a limited sampling strategy have been published, but not all have been validated. Eight equations for AUC0-12h and two for AUC0-8h were validated. Concentrations of cyclosporine A were analyzed by high-performance liquid chromatography (HPLC) and a specific radioimmunoassay (RIA) method. Forty male renal transplant patients were included in the study. Blood samples were taken predose and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose when the patient was in steady state. The percentage prediction error (%pe) was used for an assessment of the performance of the equations. Mean %pe less than ± 15% and absolute %pe less than 30% in 95% of predictions were considered to be acceptable. Other possibilities such as %pe less than 25%, 20%, and 15% were also tested. Eight equations for AUC0-12h met the requirements using both assays, six in the HPLC set only and four in the RIA set only. The highest precision was obtained with AUC0-12h = 123.792 + 1.165*C1h + 3.021*C3h + 7.33*C8h proposed by de Mattos et al. The mean %pe was 1% ± 8% (-16 to 19) for HPLC (values given as mean ± standard deviation [range]) and -1 ± 5 (-17 to 10) for RIA. Mean absolute %pe was 7 ± 5 (0.0 to 19) for HPLC and 4 ± 4 (0.0 to 17) for RIA. For clinical use, the most suitable equation was AUC0-12h = 363.078 + 8.77*C1h + 3.07*C3h proposed by Wacke et al, which produced the second lowest %pe and used two sampling points in the period of 1 to 3 hours after dose. The mean %pe was -7 ± 10 (-25 to 25) for HPLC and 2.3 ± 6 (-10 to 17) for RIA. Mean absolute %pe was 10 ± 7 (0.4 to 25) for HPLC and 5 ± 4 (0.0 to 17) for RIA. The equation: AUC0-8h = 55.37 + 2.89*C0h + 1.08*C1h0.9*C2h + 2.23*C3h proposed by Foradori et al met the criteria with 95% of prediction with absolute %pe less than 15% in the HPLC set and 10% in the RIA set. The validation of equations is of major importance for prediction precision, whereas the analytical method for limited sampling strategy proposals had no influence. Because of the wide interassay variability, it is also important to know which analytical method was used for AUC calculation when interpreting the results.

Cilazapril stability in the presence of hydrochlorothiazide in model mixtures and fixed dose combination.

PubMed

Paszun, Sylwia K; Stanisz, Beata J; Gradowska, Agnieszka

2013-01-01

The presented study aimed at the evaluation of hydrochlorothiazide influence on cilazapril stability in model mixture and fixed dose tablet formulation. The degradation of cilazapril in the presence of hydrochlorothiazide took place according to autocatalytic reaction kinetic mechanism, described mathematically by Prout-Tompkins equation. Hydrochlorothiazide coexistence with cilazapril in model mixture and fixed dose tablet without blister package accelerated cilazapril degradation in comparison with degradation of cilazapril substance. Values of reaction induction time shortened, while those of observed reaction rate constant increased. Increasing values of relative humidity and temperature have negative impact on cilazapril stability. Determined semi-logarithmic relationships: In k = f(RH) and Arrhenius ln k = f(1/T) are linear and are cilazapril stability predictive. The blister (OPA/Alu/PVC//Alu) package of fixed dose tablets, constitutes absolute moisture protection and prevent cilazapril--hydrochlorothiazide interaction occurrence.

Note: An absolute X-Y-Θ position sensor using a two-dimensional phase-encoded binary scale

NASA Astrophysics Data System (ADS)

Kim, Jong-Ahn; Kim, Jae Wan; Kang, Chu-Shik; Jin, Jonghan

2018-04-01

This Note presents a new absolute X-Y-Θ position sensor for measuring planar motion of a precision multi-axis stage system. By analyzing the rotated image of a two-dimensional phase-encoded binary scale (2D), the absolute 2D position values at two separated points were obtained and the absolute X-Y-Θ position could be calculated combining these values. The sensor head was constructed using a board-level camera, a light-emitting diode light source, an imaging lens, and a cube beam-splitter. To obtain the uniform intensity profiles from the vignette scale image, we selected the averaging directions deliberately, and higher resolution in the angle measurement could be achieved by increasing the allowable offset size. The performance of a prototype sensor was evaluated in respect of resolution, nonlinearity, and repeatability. The sensor could resolve 25 nm linear and 0.001° angular displacements clearly, and the standard deviations were less than 18 nm when 2D grid positions were measured repeatedly.

An absolute photometric system at 10 and 20 microns

NASA Technical Reports Server (NTRS)

Rieke, G. H.; Lebofsky, M. J.; Low, F. J.

1985-01-01

Two new direct calibrations at 10 and 20 microns are presented in which terrestrial flux standards are referred to infrared standard stars. These measurements give both good agreement and higher accuracy when compared with previous direct calibrations. As a result, the absolute calibrations at 10 and 20 microns have now been determined with accuracies of 3 and 8 percent, respectively. A variety of absolute calibrations based on extrapolation of stellar spectra from the visible to 10 microns are reviewed. Current atmospheric models of A-type stars underestimate their fluxes by about 10 percent at 10 microns, whereas models of solar-type stars agree well with the direct calibrations. The calibration at 20 microns can probably be determined to about 5 percent by extrapolation from the more accurate result at 10 microns. The photometric system at 10 and 20 microns is updated to reflect the new absolute calibration, to base its zero point directly on the colors of A0 stars, and to improve the accuracy in the comparison of the standard stars.

Comparison of Gafchromic EBT2 and EBT3 for patient-specific quality assurance: Cranial stereotactic radiosurgery using volumetric modulated arc therapy with multiple noncoplanar arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiandra, Christian; Fusella, Marco; Filippi, Andrea Riccardo

2013-08-15

Purpose: Patient-specific quality assurance in volumetric modulated arc therapy (VMAT) brain stereotactic radiosurgery raises specific issues on dosimetric procedures, mainly represented by the small radiation fields associated with the lack of lateral electronic equilibrium, the need of small detectors and the high dose delivered (up to 30 Gy). Gafchromic{sup TM} EBT2 and EBT3 films may be considered the dosimeter of choice, and the authors here provide some additional data about uniformity correction for this new generation of radiochromic films.Methods: A new analysis method using blue channel for marker dye correction was proposed for uniformity correction both for EBT2 and EBT3more » films. Symmetry, flatness, and field-width of a reference field were analyzed to provide an evaluation in a high-spatial resolution of the film uniformity for EBT3. Absolute doses were compared with thermoluminescent dosimeters (TLD) as baseline. VMAT plans with multiple noncoplanar arcs were generated with a treatment planning system on a selected pool of eleven patients with cranial lesions and then recalculated on a water-equivalent plastic phantom by Monte Carlo algorithm for patient-specific QA. 2D quantitative dose comparison parameters were calculated, for the computed and measured dose distributions, and tested for statistically significant differences.Results: Sensitometric curves showed a different behavior above dose of 5 Gy for EBT2 and EBT3 films; with the use of inhouse marker-dye correction method, the authors obtained values of 2.5% for flatness, 1.5% of symmetry, and a field width of 4.8 cm for a 5 × 5 cm{sup 2} reference field. Compared with TLD and selecting a 5% dose tolerance, the percentage of points with ICRU index below 1 was 100% for EBT2 and 83% for EBT3. Patients analysis revealed statistically significant differences (p < 0.05) between EBT2 and EBT3 in the percentage of points with gamma values <1 (p= 0.009 and p= 0.016); the percent difference as well as the mean difference between calculated and measured isodoses (20% and 80%) were found not to be significant (p= 0.074, p= 0.185, and p= 0.57).Conclusions: Excellent performances in terms of dose homogeneity were obtained using a new blue channel method for marker-dye correction on both EBT2 and EBT3 Gafchromic{sup TM} films. In comparison with TLD, the passing rates for the EBT2 film were higher than for EBT3; a good agreement with estimated data by Monte Carlo algorithm was found for both films, with some statistically significant differences again in favor of EBT2. These results suggest that the use of Gafchromic{sup TM} EBT2 and EBT3 films is appropriate for dose verification measurements in VMAT stereotactic radiosurgery; taking into account the uncertainty associated with Gafchromic film dosimetry, the use of adequate action levels is strongly advised, in particular, for EBT3.« less

Practical strategies when using a stable isotope labeled microtracer for absolute bioavailability assessment: A case study of a high oral dose clinical candidate GDC-0810.

PubMed

Chen, Buyun; Lu, Pingping; Freeman, Dugan; Gao, Yang; Choo, Edna; DeMent, Kevin; Savage, Scott; Zhang, Kelly; Milanwoski, Dennis; Liu, Lichuan; Dean, Brian; Deng, Yuzhong

2018-05-30

The pH labile metabolite, hydrophobicity, high oral dose and systematic exposure of GDC-0810 posed tremendous challenges to develop a LC-MS method for a stable isotope labeled aBA study. In this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high C p.o. to C i.v. ratio on the labeling selection and assay dynamic range. A [ 13 C 9 ] GDC-0810 was synthesized to minimize the isotopic interference between PO dose, internal standard and I.V. microtracer. A highly sensitive LC-MS assay was validated for quantitation of [ 13 C 9 ] GDC-0810 from 5 to 1250 pg/mL. The optimized method was applied to a proof of concept cynomolgus monkey aBA study and the bioavailability calculated using microtracer dosing and regular dosing were similar to each other. Copyright © 2018 Elsevier B.V. All rights reserved.

Space Radiation Cancer Risks

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.

2007-01-01

Space radiation presents major challenges to astronauts on the International Space Station and for future missions to the Earth s moon or Mars. Methods used to project risks on Earth need to be modified because of the large uncertainties in projecting cancer risks from space radiation, and thus impact safety factors. We describe NASA s unique approach to radiation safety that applies uncertainty based criteria within the occupational health program for astronauts: The two terrestrial criteria of a point estimate of maximum acceptable level of risk and application of the principle of As Low As Reasonably Achievable (ALARA) are supplemented by a third requirement that protects against risk projection uncertainties using the upper 95% confidence level (CL) in the radiation cancer projection model. NASA s acceptable level of risk for ISS and their new lunar program have been set at the point-estimate of a 3-percent risk of exposure induced death (REID). Tissue-averaged organ dose-equivalents are combined with age at exposure and gender-dependent risk coefficients to project the cumulative occupational radiation risks incurred by astronauts. The 95% CL criteria in practice is a stronger criterion than ALARA, but not an absolute cut-off as is applied to a point projection of a 3% REID. We describe the most recent astronaut dose limits, and present a historical review of astronaut organ doses estimates from the Mercury through the current ISS program, and future projections for lunar and Mars missions. NASA s 95% CL criteria is linked to a vibrant ground based radiobiology program investigating the radiobiology of high-energy protons and heavy ions. The near-term goal of research is new knowledge leading to the reduction of uncertainties in projection models. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. The current model for projecting space radiation cancer risk relies on the three assumptions of linearity, additivity, and scaling along with the use of population averages. We describe uncertainty estimates for this model, and new experimental data that sheds light on the accuracy of the underlying assumptions. These methods make it possible to express risk management objectives in terms of quantitative metrics, i.e., the number of days in space without exceeding a given risk level within well defined confidence limits. The resulting methodology is applied to several human space exploration mission scenarios including lunar station, deep space outpost, and a Mars mission. Factors that dominate risk projection uncertainties and application of this approach to assess candidate mitigation approaches are described.

Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, R. Lee; Thomas, Christopher G., E-mail: Chris.Thomas@cdha.nshealth.ca; Department of Medical Physics, Nova Scotia Cancer Centre, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V7

2015-05-15

Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space,more » indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry motion during radiation therapy to minimize the geometrical overlap in the beams-eye-view of target volumes and the organs-at-risk can have an appreciable dose reduction to organs-at-risk.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Li, Z; Zheng, D

Purpose: In the context of evaluating dosimetric impacts of a variety of uncertainties involved in HDR Tandem-and-Ovoid treatment, to study the correlations between conventional point doses and 3D volumetric doses. Methods: For 5 cervical cancer patients treated with HDR T&O, 150 plans were retrospectively created to study dosimetric impacts of the following uncertainties: (1) inter-fractional applicator displacement between two treatment fractions within a single insertion by applying Fraction#1 plan to Fraction#2 CT; (2) positional dwell error simulated from −5mm to 5mm in 1mm steps; (3) simulated temporal dwell error of 0.05s, 0.1s, 0.5s, and 1s. The original plans were basedmore » on point dose prescription, from which the volume covered by the prescription dose was generated as the pseudo target volume to study the 3D target dose effect. OARs were contoured. The point and volumetric dose errors were calculated by taking the differences between original and simulated plans. The correlations between the point and volumetric dose errors were analyzed. Results: For the most clinically relevant positional dwell uncertainty of 1mm, temporal uncertainty of 0.05s, and inter-fractional applicator displacement within the same insertion, the mean target D90 and V100 deviation were within 1%. Among these uncertainties, the applicator displacement showed the largest potential target coverage impact (2.6% on D90) as well as the OAR dose impact (2.5% and 3.4% on bladder D2cc and rectum D2cc). The Spearman correlation analysis shows a correlation coefficient of 0.43 with a p-value of 0.11 between target D90 coverage and H point dose. Conclusion: With the most clinically relevant positional and temporal dwell uncertainties and patient interfractional applicator displacement within the same insertion, the dose error is within clinical acceptable range. The lack of correlation between H point and 3D volumetric dose errors is a motivator for the use of 3D treatment planning in cervical HDR brachytherapy.« less

Accuracy of patient-specific organ dose estimates obtained using an automated image segmentation algorithm.

PubMed

Schmidt, Taly Gilat; Wang, Adam S; Coradi, Thomas; Haas, Benjamin; Star-Lack, Josh

2016-10-01

The overall goal of this work is to develop a rapid, accurate, and automated software tool to estimate patient-specific organ doses from computed tomography (CT) scans using simulations to generate dose maps combined with automated segmentation algorithms. This work quantified the accuracy of organ dose estimates obtained by an automated segmentation algorithm. We hypothesized that the autosegmentation algorithm is sufficiently accurate to provide organ dose estimates, since small errors delineating organ boundaries will have minimal effect when computing mean organ dose. A leave-one-out validation study of the automated algorithm was performed with 20 head-neck CT scans expertly segmented into nine regions. Mean organ doses of the automatically and expertly segmented regions were computed from Monte Carlo-generated dose maps and compared. The automated segmentation algorithm estimated the mean organ dose to be within 10% of the expert segmentation for regions other than the spinal canal, with the median error for each organ region below 2%. In the spinal canal region, the median error was [Formula: see text], with a maximum absolute error of 28% for the single-atlas approach and 11% for the multiatlas approach. The results demonstrate that the automated segmentation algorithm can provide accurate organ dose estimates despite some segmentation errors.

Accuracy of patient-specific organ dose estimates obtained using an automated image segmentation algorithm

PubMed Central

Schmidt, Taly Gilat; Wang, Adam S.; Coradi, Thomas; Haas, Benjamin; Star-Lack, Josh

2016-01-01

Abstract. The overall goal of this work is to develop a rapid, accurate, and automated software tool to estimate patient-specific organ doses from computed tomography (CT) scans using simulations to generate dose maps combined with automated segmentation algorithms. This work quantified the accuracy of organ dose estimates obtained by an automated segmentation algorithm. We hypothesized that the autosegmentation algorithm is sufficiently accurate to provide organ dose estimates, since small errors delineating organ boundaries will have minimal effect when computing mean organ dose. A leave-one-out validation study of the automated algorithm was performed with 20 head-neck CT scans expertly segmented into nine regions. Mean organ doses of the automatically and expertly segmented regions were computed from Monte Carlo-generated dose maps and compared. The automated segmentation algorithm estimated the mean organ dose to be within 10% of the expert segmentation for regions other than the spinal canal, with the median error for each organ region below 2%. In the spinal canal region, the median error was −7%, with a maximum absolute error of 28% for the single-atlas approach and 11% for the multiatlas approach. The results demonstrate that the automated segmentation algorithm can provide accurate organ dose estimates despite some segmentation errors. PMID:27921070

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Singh, Anurag K; Lockett, Mary Ann; Bradley, Jeffrey D

2003-02-01

To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

PubMed

Kapp, K S; Stuecklschweiger, G F; Kapp, D S; Hackl, A G

1992-07-01

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.

PubMed

Leeman-Neill, Rebecca J; Brenner, Alina V; Little, Mark P; Bogdanova, Tetiana I; Hatch, Maureen; Zurnadzy, Liudmyla Y; Mabuchi, Kiyohiko; Tronko, Mykola D; Nikiforov, Yuri E

2013-05-15

Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored. RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Copyright © 2013 American Cancer Society.

Absolute quantitation of NAPQI-modified rat serum albumin by LC-MS/MS: monitoring acetaminophen covalent binding in vivo.

PubMed

LeBlanc, André; Shiao, Tze Chieh; Roy, René; Sleno, Lekha

2014-09-15

Acetaminophen is known to cause hepatoxicity via the formation of a reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), as a result of covalent binding to liver proteins. Serum albumin (SA) is known to be covalently modified by NAPQI and is present at high concentrations in the bloodstream and is therefore a potential biomarker to assess the levels of protein modification by NAPQI. A newly developed method for the absolute quantitation of serum albumin containing NAPQI covalently bound to its active site cysteine (Cys34) is described. This optimized assay represents the first absolute quantitation of a modified protein, with very low stoichiometric abundance, using a protein-level standard combined with isotope dilution. The LC-MS/MS assay is based on a protein standard modified with a custom-designed reagent, yielding a surrogate peptide (following digestion) that is a positional isomer to the target peptide modified by NAPQI. To illustrate the potential of this approach, the method was applied to quantify NAPQI-modified SA in plasma from rats dosed with acetaminophen. The resulting method is highly sensitive (capable of quantifying down to 0.0006% of total RSA in its NAPQI-modified form) and yields excellent precision and accuracy statistics. A time-course pharmacokinetic study was performed to test the usefulness of this method for following acetaminophen-induced covalent binding at four dosing levels (75-600 mg/kg IP), showing the viability of this approach to directly monitor in vivo samples. This approach can reliably quantify NAPQI-modified albumin, allowing direct monitoring of acetaminophen-related covalent binding.

I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

PubMed Central

Tronko, Mykola D.; Hatch, Maureen; Bogdanova, Tetyana I.; Oliynik, Valery A.; Lubin, Jay H.; Zablotska, Lydia B.; Tereschenko, Valery P.; McConnell, Robert J.; Zamotaeva, Galina A.; O’Kane, Patrick; Bouville, Andre C.; Chaykovskaya, Ludmila V.; Greenebaum, Ellen; Paster, Ihor P.; Shpak, Victor M.; Ron, Elaine

2011-01-01

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose–response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose–response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43–6.34], and the EAR per 104 PY/Gy was 2.21 (95% CI, 0.04–5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131–related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies. PMID:21406336

[Benchmark experiment to verify radiation transport calculations for dosimetry in radiation therapy].

PubMed

Renner, Franziska

2016-09-01

Monte Carlo simulations are regarded as the most accurate method of solving complex problems in the field of dosimetry and radiation transport. In (external) radiation therapy they are increasingly used for the calculation of dose distributions during treatment planning. In comparison to other algorithms for the calculation of dose distributions, Monte Carlo methods have the capability of improving the accuracy of dose calculations - especially under complex circumstances (e.g. consideration of inhomogeneities). However, there is a lack of knowledge of how accurate the results of Monte Carlo calculations are on an absolute basis. A practical verification of the calculations can be performed by direct comparison with the results of a benchmark experiment. This work presents such a benchmark experiment and compares its results (with detailed consideration of measurement uncertainty) with the results of Monte Carlo calculations using the well-established Monte Carlo code EGSnrc. The experiment was designed to have parallels to external beam radiation therapy with respect to the type and energy of the radiation, the materials used and the kind of dose measurement. Because the properties of the beam have to be well known in order to compare the results of the experiment and the simulation on an absolute basis, the benchmark experiment was performed using the research electron accelerator of the Physikalisch-Technische Bundesanstalt (PTB), whose beam was accurately characterized in advance. The benchmark experiment and the corresponding Monte Carlo simulations were carried out for two different types of ionization chambers and the results were compared. Considering the uncertainty, which is about 0.7 % for the experimental values and about 1.0 % for the Monte Carlo simulation, the results of the simulation and the experiment coincide. Copyright © 2015. Published by Elsevier GmbH.

Cardiac Side-effects From Breast Cancer Radiotherapy.

PubMed

Taylor, C W; Kirby, A M

2015-11-01

Breast cancer radiotherapy reduces the risk of cancer recurrence and death. However, it usually involves some radiation exposure of the heart and analyses of randomised trials have shown that it can increase the risk of heart disease. Estimates of the absolute risks of radiation-related heart disease are needed to help oncologists plan each individual woman's treatment. The risk for an individual woman varies according to her estimated cardiac radiation dose and her background risk of ischaemic heart disease in the absence of radiotherapy. When it is known, this risk can then be compared with the absolute benefit of the radiotherapy. At present, many UK cancer centres are already giving radiotherapy with mean heart doses of less than 3 Gy and for most women the benefits of the radiotherapy will probably far outweigh the risks. Technical approaches to minimising heart dose in breast cancer radiotherapy include optimisation of beam angles, use of multileaf collimator shielding, intensity-modulated radiotherapy, treatment in a prone position, treatment in deep inspiration (including the use of breath-hold and gating techniques), proton therapy and partial breast irradiation. The multileaf collimator is suitable for many women with upper pole left breast cancers, but for women with central or lower pole cancers, breath-holding techniques are now recommended in national UK guidelines. Ongoing work aims to identify ways of irradiating pan-regional lymph nodes that are effective, involve minimal exposure of organs at risk and are feasible to plan, deliver and verify. These will probably include wide tangent-based field-in-field intensity-modulated radiotherapy or arc radiotherapy techniques in combination with deep inspiratory breath-hold, and proton beam irradiation for women who have a high predicted heart dose from intensity-modulated radiotherapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The influence of diltiazem and nifedipine on renal function in the rat.

PubMed Central

Johns, E. J.

1985-01-01

The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone-anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. Diltiazem was infused at 5, 10 and 20 micrograms kg-1 min-1. Blood pressure did not change following 5 micrograms kg-1 min-1 diltiazem but was significantly reduced, by 12 mmHg, after 10 micrograms kg-1 min-1 and by 17 mmHg after 20 micrograms kg-1 min-1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 micrograms kg-1 min-1 diltiazem, 20% and 24% respectively, by 10 micrograms kg-1 min-1 diltiazem, but were unchanged by 20 micrograms kg-1 min-1. Infusion of nifedipine at 0.5, 1.0 and 2.0 micrograms kg-1 min-1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 microgram kg-1 min-1 only, while g.f.r. did not change at any dose. Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 microgram kg-1 min-1 nifedipine, 127%, 197% and 194% respectively, by 1.0 microgram kg-1 min-1, while these variables remained unchanged by a dose of 2.0 micrograms kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3986432

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebert, Martin A., E-mail: Martin.Ebert@health.wa.gov.au; School of Physics, University of Western Australia, Perth, Western Australia; Foo, Kerwyn

Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with amore » comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.« less

Evaluation of detector array technology for the verification of advanced intensity-modulated radiotherapy

NASA Astrophysics Data System (ADS)

Hussien, Mohammad

Purpose: Quality assurance (QA) for intensity modulated radiotherapy (IMRT) has evolved substantially. In recent years, various ionization chamber or diode detector arrays have become commercially available, allowing pre-treatment absolute dose verification with near real-time results. This has led to a wide uptake of this technology to replace point dose and film dosimetry and to facilitate QA streamlining. However, arrays are limited by their spatial resolution giving rise to concerns about their response to clinically relevant deviations. The common factor in all commercial array systems is the reliance on the gamma index (γ) method to provide the quantitative evaluation of the measured dose distribution against the Treatment Planning System (TPS) calculated dose distribution. The mathematical definition of the gamma index presents computational challenges that can cause a variation in the calculation in different systems. The purpose of this thesis was to evaluate the suitability of detector array systems, combined with their implementation of the gamma index, in the verification and dosimetry audit of advanced IMRT. Method: The response of various commercial detector array systems (Delta4®, ArcCHECK®, and the PTW 2D-Array seven29™ and OCTAVIUS II™ phantom combination, Gafchromic® EBT2 and composite EPID measurements) to simulated deliberate changes in clinical IMRT and VMAT plans was evaluated. The variability of the gamma index calculation in the different systems was also evaluated by comparing against a bespoke Matlab-based gamma index analysis software. A novel methodology for using a commercial detector array in a dosimetry audit of rotational radiotherapy was then developed. Comparison was made between measurements using the detector array and those performed using ionization chambers, alanine and radiochromic film. The methodology was developed as part of the development of a national audit of rotational radiotherapy. Ten cancer centres were asked to create a rotational radiotherapy treatment plan for a three-dimensional treatment-planning-system (3DTPS) test and audited. Phantom measurements using a commercial 2D ionization chamber (IC) array were compared with measurements using 0.125cm3 ion chamber, Gafchromic film and alanine pellets in the same plane. Relative and absolute gamma index (γ) comparisons were made for Gafchromic film and 2D-Array planes respectively. A methodology for prospectively deriving appropriate gamma index acceptance criteria for detector array systems, via simulation of deliberate changes and receiver operator characteristic (ROC) analysis, has been developed. Results: In the event of clinically relevant delivery introduced changes, the detector array systems evaluated are able to detect some of these changes if suitable gamma index passing criteria, such as 2%/2mm, are used. Different computational approaches can produce variability in the calculation of the gamma index between different software implementations. For the same passing criteria, different devices and software combinations exhibit varying levels of agreement with the Matlab predicted gamma index analysis. This work has found that it is suitable to use a detector array in a dosimetry audit of rotational radiotherapy in place of standard systems of dosimetry such as ion chambers, alanine and film. Comparisons between individual detectors within the 2D-Array against the corresponding ion chamber and alanine measurement showed a statistically significant concordance correlation coefficient (ρc>0.998, p<0.001) with mean difference of -1.1%±1.1% and -0.8%±1.1%, respectively, in a high dose PTV. In the γ comparison between the 2D-Array and film it was found that the 2D-Array was more likely to fail in planes where there was a dose discrepancy due to the absolute analysis performed. A follow-up analysis of the library of measured data during the audit found that additional metrics such as the mean gamma index or dose differences over regions of interest can be gleaned from the measured dose distributions. Conclusions: It is important to understand the response and limitations of the gamma index analysis combined with the equipment and software in use. For the same pass-rate criteria, different devices and software combinations exhibit varying levels of agreement with the predicted γ analysis. It has been found that using a commercial detector array for a dosimetry audit of rotational radiotherapy is suitable in place of standard systems of dosimetry. A methodology for being able to prospectively ascertain appropriate gamma index acceptance criteria for the detector array system in use, via simulation of deliberate changes and ROC analysis, has been developed. It has been shown that setting appropriate tolerances can be achieved and should be performed as the methodology takes into account the configuration of the commercial system as well as the software implementation of the gamma index.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

The technical implementation of an IMPT system for research purpose

NASA Astrophysics Data System (ADS)

Nguyen, T. T. C.; Nguyen, B. T.; Mai, N. V.

2018-03-01

Because of their superior distribution, proton beams is the state-of-the-art modality in radiation therapy. There is a variety of researchers about proton therapy to utilize it. In this paper, we introduce a Matlab-based platform to develop and prototype proton treatment planning using LAP and CERR. Planning workflow to make an IMPT plan is described in details and demonstrated by a prostate case. The results showed that most of the dose criteria are satisfied, except for bladder and rectum, 2% of the volume of each organ receiving the least dose of 77.5 Gy (RBE) instead of 76 Gy(RBE) as dose requirements suggested by ICRU 78. As a result, planners absolutely can implement Intensity Modulated Proton Therapy plans by LAP and CERR for research purpose.

Patient-specific CT dosimetry calculation: a feasibility study.

PubMed

Fearon, Thomas; Xie, Huchen; Cheng, Jason Y; Ning, Holly; Zhuge, Ying; Miller, Robert W

2011-11-15

Current estimation of radiation dose from computed tomography (CT) scans on patients has relied on the measurement of Computed Tomography Dose Index (CTDI) in standard cylindrical phantoms, and calculations based on mathematical representations of "standard man". Radiation dose to both adult and pediatric patients from a CT scan has been a concern, as noted in recent reports. The purpose of this study was to investigate the feasibility of adapting a radiation treatment planning system (RTPS) to provide patient-specific CT dosimetry. A radiation treatment planning system was modified to calculate patient-specific CT dose distributions, which can be represented by dose at specific points within an organ of interest, as well as organ dose-volumes (after image segmentation) for a GE Light Speed Ultra Plus CT scanner. The RTPS calculation algorithm is based on a semi-empirical, measured correction-based algorithm, which has been well established in the radiotherapy community. Digital representations of the physical phantoms (virtual phantom) were acquired with the GE CT scanner in axial mode. Thermoluminescent dosimeter (TLDs) measurements in pediatric anthropomorphic phantoms were utilized to validate the dose at specific points within organs of interest relative to RTPS calculations and Monte Carlo simulations of the same virtual phantoms (digital representation). Congruence of the calculated and measured point doses for the same physical anthropomorphic phantom geometry was used to verify the feasibility of the method. The RTPS algorithm can be extended to calculate the organ dose by calculating a dose distribution point-by-point for a designated volume. Electron Gamma Shower (EGSnrc) codes for radiation transport calculations developed by National Research Council of Canada (NRCC) were utilized to perform the Monte Carlo (MC) simulation. In general, the RTPS and MC dose calculations are within 10% of the TLD measurements for the infant and child chest scans. With respect to the dose comparisons for the head, the RTPS dose calculations are slightly higher (10%-20%) than the TLD measurements, while the MC results were within 10% of the TLD measurements. The advantage of the algebraic dose calculation engine of the RTPS is a substantially reduced computation time (minutes vs. days) relative to Monte Carlo calculations, as well as providing patient-specific dose estimation. It also provides the basis for a more elaborate reporting of dosimetric results, such as patient specific organ dose volumes after image segmentation.

Effect of a single prophylactic preoperative oral antibiotic dose on surgical site infection following complex dermatological procedures on the nose and ear: a prospective, randomised, controlled, double-blinded trial.

PubMed

Rosengren, Helena; Heal, Clare F; Buttner, Petra G

2018-04-19

There is limited published research studying the effect of antibiotic prophylaxis on surgical site infection (SSI) in dermatological surgery, and there is no consensus for its use in higher-risk cases. The objective of this study was to determine the effectiveness of a single oral preoperative 2 g dose of cephalexin in preventing SSI following flap and graft dermatological closures on the nose and ear. Prospective double-blinded, randomised, placebo-controlled trial testing for difference in infection rates. Primary care skin cancer clinics in North Queensland, Australia, were randomised to 2 g oral cephalexin or placebo 40-60 min prior to skin incision. 154 consecutive eligible patients booked for flap or graft closure following skin cancer excision on the ear and nose. 2 g dose of cephalexin administered 40-60 min prior to surgery. Overall 8/69 (11.6%) controls and 1/73 (1.4%) in the intervention group developed SSI (p=0.015; absolute SSI reduction 10.2%; number needed to treat (NNT) for benefit 9.8, 95% CI 5.5 to 45.5). In males, 7/44 controls and 0/33 in the intervention group developed SSI (p=0.018; absolute SSI reduction 15.9%; NNT for benefit 6.3, 95% CI 3.8 to 19.2). SSI was much lower in female controls (1/25) and antibiotic prophylaxis did not further reduce this (p=1.0). There was no difference between the study groups in adverse symptoms attributable to high-dose antibiotic administration (p=0.871). A single oral 2 g dose of cephalexin given before complex skin closure on the nose and ear reduced SSI. ANZCTR 365115; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SU-G-206-06: Analytic Dose Function for CT Scans in Infinite Cylinders as a Function of Scan Length and Cylinder Radius

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakalyar, D; Feng, W; McKenney, S

Purpose: The radiation dose absorbed at a particular radius ρ within the central plane of a long cylinder following a CT scan is a function of the length of the scan L and the cylinder radius R along with kVp and cylinder composition. An analytic function was created that that not only expresses these dependencies but is integrable in closed form over the area of the central plane. This feature facilitates explicit calculation of the planar average dose. The “approach to equilibrium” h(L) discussed in the TG111 report is seamlessly included in this function. Methods: For a cylindrically symmetric radiationmore » field, Monte Carlo calculations were performed to compute the dose distribution to long polyethylene cylinders for scans of varying L for cylinders ranging in radius from 5 to 20 cm. The function was developed from the resultant Monte Carlo data. In addition, the function was successfully fit to data taken from measurements on the 30 cm diameter ICRU/TG200 phantom using a real-time dosimeter. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. There are competing effects as the beam penetrates the cylinder from the outside: attenuation, resulting in a decrease; scatter, abruptly increasing at the circumference. This competition may result in an absolute maximum between the center and outer edge leading to a “gull wing” shape for the radial dependence. For the smallest cylinders, scatter may dominate to the extent that there is an absolute maximum at the center. Conclusion: An integrable, analytic function has been developed that provides the radial dependency of dose for the central plane of a scan of length L for cylinders of varying diameter. Equivalently, we have developed h(L,R,ρ).« less

Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk.

PubMed

Ilett, Kenneth F; Paech, Michael J; Page-Sharp, Madhu; Sy, Sherwin K; Kristensen, Judith H; Goy, Raymond; Chua, Sebastian; Christmas, Tracey; Scott, Karen L

2008-05-01

There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant. We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk. To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant. Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2-4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied. RESULTS At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) microg kg(-1) day(-1) and 30 (28, 32) microg kg(-1) day(-1), and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores. The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.

Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging.

PubMed

Burghelea, Manuela; Verellen, Dirk; Poels, Kenneth; Gevaert, Thierry; Depuydt, Tom; Tournel, Koen; Hung, Cecilia; Simon, Viorica; Hiraoka, Masahiro; de Ridder, Mark

2015-07-15

The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques.

PubMed

Chen, Ligong; Schiffer, Jarad M; Dalton, Shannon; Sabourin, Carol L; Niemuth, Nancy A; Plikaytis, Brian D; Quinn, Conrad P

2014-11-01

Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined. The immunological and survival data were from 114 vaccinated and 23 control animals exposed to Bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. The vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (AVA) (BioThrax) at 0, 1, and 6 months. The immune responses were modulated by administering a range of vaccine dilutions. Together with the vaccine dilution dose and interval between the first vaccination and challenge, each of 80 immune response variables to anthrax toxin protective antigen (PA) at every available study time point was analyzed as a potential COP by logistic regression penalized by least absolute shrinkage and selection operator (LASSO) or elastic net. The anti-PA IgG level at the last available time point before challenge (last) and lymphocyte stimulation index (SI) at months 2 and 6 were identified consistently as a COP. Anti-PA IgG levels and lethal toxin neutralization activity (TNA) at months 6 and 7 (peak) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 also had statistically significant positive correlations with survival. The ratio of interleukin 4 (IL-4) mRNA to IFN-γ mRNA at month 6 also had a statistically significant negative correlation with survival. TNA had lower accuracy as a COP than did anti-PA IgG response. Following the 3-i.m. priming with AVA, the anti-PA IgG responses at the time of exposure or at month 7 were practicable and accurate metrics for correlating vaccine-induced immunity with protection against inhalation anthrax. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A comparison of terbutaline and fenoterol unit dose vials in treating children with acute asthmatic attacks.

PubMed

Lin, Yung-Zen; Huang, Fu-Yuan

2002-01-01

To compare the bronchodilation and adverse effects of two commercially marketed short-acting beta2-adrenergic agonists, terbutaline (Bricanyl, 5.0 mg/2ml) and fenoterol (Berotec,1.25 mg/2ml) unit dose vials (UDV), 108 acute asthmatic children, aged 5 to 14, were randomly enrolled into this study. Nebulization treatment for 10 minutes using an air compressor nebulizer was performed after measurements of baseline spirometry, SaO2, blood pressure and pulse rate. Same measurements were repeated at 0, 5, 15 and 30 minutes after the end of the nebulization treatment. The blood pressure was also monitored immediately and 30 minutes after treatment. Almost all the spirometric parameters of both treatments at various time points significantly improved. The pulse rate significantly increased at 15 and 30 min. The SaO2 significantly increased at 30 min. The systolic blood pressure significantly decreased immediately (terbutaline only) and at 30 min (fenoterol only). No significant change was found in diastolic blood pressure. When the laboratory parameters at the same time points were compared. Significant better results for fenoterol treatment were found in FEV, at 30 min (p = 0.048), PEF at 15 and 30 min (p = 0.049 and p = 0.027, respectively), FEF25-75% at 30 min (p = 0.033), mean absolute increase of PEF at 15 min (p = 0.034) and 30 min (p = 0.021), FEF25-75% at 30 min (p = 0.046), and in mean percent increase of FEF25-75% at 30 min (p = 0.047). The adverse effects for both groups were almost equal and around 21%. In conclusion, both terbutaline and fenoterol UDV nebulization treatments are effective in treating acute asthmatic children. The adverse effects are nearly equal. The fenoterol UDV nebulization treatment shows a little better result in improving pulmonary function than does terbutaline.

Useful marker of oscillatory lung function in methacholine challenge test-comparison of reactance and resistance with dose-response slope.

PubMed

Yoon, Jung Won; Shin, Youn Ho; Jee, Hye Mi; Chang, Sun Jung; Baek, Ji Hyeon; Choi, Sun Hee; Kim, Hyeong Yun; Han, Man Yong

2014-06-01

There are few studies focusing on the comparison of resistance (Rrs) and reactance (Xrs) in impulse oscillometry system (IOS) in the bronchial challenge test using dose-response slope (DRS), a quantitative index of bronchial hyperresponsiveness. We conducted a case-control study of 144 asthmatic and 218 non-asthmatic children to compare the diagnostic accuracy of two-point linear DRS for FEV1 , Rrs5 , and Xrs5 (DRS_FEV1 , DRS_Rrs5 , and DRS_Xrs5 ) and assessed various diagnostic cut-off points of provocation concentrations (PC) using receiver operating characteristic (ROC) curves. DRS_FEV1 had a stronger correlation with DRS_Xrs5 (r = 0.739, P < 0.001) than with DRS_Rrs5 (r = 0.652, P < 0.001) and the area under the ROC curves of DRS_Xrs5 (0.737) was similar to that of DRS_FEV1 (0.732) and higher than that of DRS_Rrs5 (0.668). The area under the ROC curves in order of greater value was as follows: absolute change of Xrs5 (Abs_Xrs5 ) (0.759) > percent change of FEV1 (Pch_FEV1 ) (0.735) > Pch_Xrs5 (0.727) > Abs_Rrs5 (0.690) > Pch_Rrs5 (0.630). PC78 _Xrs5 and PC0.17 _Xrs5 of IOS showed considerably good sensitivity and specificity comparable to those of PC20 _FEV1 by spirometry. Additional 18 (13%) children who showed normal spirometric measures were identified as asthmatics with the use of IOS. The utility of the DRS_Xrs5 to differentiate asthmatics from controls was comparable to that of the DRS_FEV1 and better than that of the DRS_Rrs5 . In addition, IOS could detect additional asthmatic patients who did not show positive responses in spirometry. © 2013 Wiley Periodicals, Inc.

High heat flux measurements and experimental calibrations/characterizations

NASA Technical Reports Server (NTRS)

Kidd, Carl T.

1992-01-01

Recent progress in techniques employed in the measurement of very high heat-transfer rates in reentry-type facilities at the Arnold Engineering Development Center (AEDC) is described. These advances include thermal analyses applied to transducer concepts used to make these measurements; improved heat-flux sensor fabrication methods, equipment, and procedures for determining the experimental time response of individual sensors; performance of absolute heat-flux calibrations at levels above 2,000 Btu/cu ft-sec (2.27 kW/cu cm); and innovative methods of performing in-situ run-to-run characterizations of heat-flux probes installed in the test facility. Graphical illustrations of the results of extensive thermal analyses of the null-point calorimeter and coaxial surface thermocouple concepts with application to measurements in aerothermal test environments are presented. Results of time response experiments and absolute calibrations of null-point calorimeters and coaxial thermocouples performed in the laboratory at intermediate to high heat-flux levels are shown. Typical AEDC high-enthalpy arc heater heat-flux data recently obtained with a Calspan-fabricated null-point probe model are included.

Completely optical orientation determination for an unstabilized aerial three-line camera

NASA Astrophysics Data System (ADS)

Wohlfeil, Jürgen

2010-10-01

Aerial line cameras allow the fast acquisition of high-resolution images at low costs. Unfortunately the measurement of the camera's orientation with the necessary rate and precision is related with large effort, unless extensive camera stabilization is used. But also stabilization implicates high costs, weight, and power consumption. This contribution shows that it is possible to completely derive the absolute exterior orientation of an unstabilized line camera from its images and global position measurements. The presented approach is based on previous work on the determination of the relative orientation of subsequent lines using optical information from the remote sensing system. The relative orientation is used to pre-correct the line images, in which homologous points can reliably be determined using the SURF operator. Together with the position measurements these points are used to determine the absolute orientation from the relative orientations via bundle adjustment of a block of overlapping line images. The approach was tested at a flight with the DLR's RGB three-line camera MFC. To evaluate the precision of the resulting orientation the measurements of a high-end navigation system and ground control points are used.

Communicating data about the benefits and harms of treatment: a randomized trial.

PubMed

Woloshin, Steven; Schwartz, Lisa M

2011-07-19

Despite limited evidence, it is often asserted that natural frequencies (for example, 2 in 1000) are the best way to communicate absolute risks. To compare comprehension of treatment benefit and harm when absolute risks are presented as natural frequencies, percents, or both. Parallel-group randomized trial with central allocation and masking of investigators to group assignment, conducted through an Internet survey in September 2009. (ClinicalTrials.gov registration number: NCT00950014) National sample of U.S. adults randomly selected from a professional survey firm's research panel of about 30,000 households. 2944 adults aged 18 years or older (all with complete follow-up). Tables presenting absolute risks in 1 of 5 numeric formats: natural frequency (x in 1000), variable frequency (x in 100, x in 1000, or x in 10,000, as needed to keep the numerator >1), percent, percent plus natural frequency, or percent plus variable frequency. Comprehension as assessed by 18 questions (primary outcome) and judgment of treatment benefit and harm. The average number of comprehension questions answered correctly was lowest in the variable frequency group and highest in the percent group (13.1 vs. 13.8; difference, 0.7 [95% CI, 0.3 to 1.1]). The proportion of participants who "passed" the comprehension test (≥13 correct answers) was lowest in the natural and variable frequency groups and highest in the percent group (68% vs. 73%; difference, 5 percentage points [CI, 0 to 10 percentage points]). The largest format effect was seen for the 2 questions about absolute differences: the proportion correct in the natural frequency versus percent groups was 43% versus 72% (P < 0.001) and 73% versus 87% (P < 0.001). Even when data were presented in the percent format, one third of participants failed the comprehension test. Natural frequencies are not the best format for communicating the absolute benefits and harms of treatment. The more succinct percent format resulted in better comprehension: Comprehension was slightly better overall and notably better for absolute differences. Attorney General Consumer and Prescriber Education grant program, the Robert Wood Johnson Pioneer Program, and the National Cancer Institute.

Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors – Differences in excess relative and absolute risk from female breast cancer

DOE PAGES

Little, Mark P.; McElvenny, Damien M.

2016-06-10

There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the UK, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. The objectives here, compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. As a result, we observed significant ( p≤ 0.01)more » dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are approximate 15-fold and 5- fold elevations, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data there are approximate 20-fold and 10-fold elevations, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least 5-fold that of many other malignancies. In conclusion, there is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding.« less

Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors – Differences in excess relative and absolute risk from female breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, Mark P.; McElvenny, Damien M.

There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the UK, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. The objectives here, compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. As a result, we observed significant ( p≤ 0.01)more » dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are approximate 15-fold and 5- fold elevations, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data there are approximate 20-fold and 10-fold elevations, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least 5-fold that of many other malignancies. In conclusion, there is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding.« less

Synergistic inhibition in vivo of bone marrow myeloid progenitors by myelosuppressive chemokines and chemokine-accelerated recovery of progenitors after treatment of mice with Ara-C.

PubMed

Broxmeyer, Hal E; Pelus, Louis M; Kim, Chang H; Hangoc, Giao; Cooper, Scott; Hromas, Robert

2006-08-01

Selected chemokines suppress proliferation of hematopoietic progenitor cells (HPCs) in vitro; some of these have demonstrated inhibition of myelopoiesis in vivo. Because myelosuppressive chemokines synergize in vitro with other myelosuppressive chemokines, we sought to determine whether additional chemokines active in vitro were myelosuppressive in vivo and whether combinations of myelosuppressive chemokines synergized in vivo to dampen myelopoiesis. We also evaluated three chemokines in vivo for myeloprotection against Ara-C-induced decreases in HPCs. C3H/HeJ mice were used for analysis of in vivo influence of chemokines, with the end points being effects on absolute numbers and cycling status of HPCs. When used alone, CCL2, CCL3, CCL19, CCL20, CXCL4, CXCL5, CXCL8, CXCL9, and XCL1 caused dose-dependent significant decreases in absolute numbers and cycling status of HPCs in vivo. The following combinations of two chemokines resulted in in vivo myelosuppression at concentrations much lower than that induced by each chemokine alone: CCL3 plus either CXCL8 or CXCL4, CXCL8 plus CXCL4, CCL2 plus either CCL20 or CXCL9, CCL20 plus CXCL9, CXCL5 plus either XCL1 or CCL19, XCL1 plus CCL19, and CCL3 plus CCL19. Also, mice injected with CXCL8, CXCL4, or the chimeric CXCL8/CXCL4 protein CXCL8M1 manifested accelerated recovery of absolute numbers of HPCs in response to the toxic effects of Ara-C administration. A number of chemokines shown previously to manifest inhibitory effects in vitro for proliferation of HPCs are now demonstrated to also induce myelosuppression in vivo. Moreover, combinations of low dosages of two myelosuppressive chemokines when administered together demonstrate synergistic suppression in vivo. Additionally, chemokines, including a CXCL8M1 chimeric protein previously shown to manifest enhanced suppression of HPC proliferation in vitro and in vivo, accelerate HPC recovery after treatment of mice with Ara-C. These results may be of use for future clinical utility of chemokines in a myelosuppressive/myeloprotective setting.

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

PubMed

Xin, Yong; Wang, Jia-Yang; Li, Liang; Tang, Tian-You; Liu, Gui-Hong; Wang, Jian-She; Xu, Yu-Mei; Chen, Yong; Zhang, Long-Zhen

2012-01-01

To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Golden beam data for proton pencil-beam scanning.

PubMed

Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Gomà, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B; Kooy, Hanne M

2012-03-07

Proton, as well as other ion, beams applied by electro-magnetic deflection in pencil-beam scanning (PBS) are minimally perturbed and thus can be quantified a priori by their fundamental interactions in a medium. This a priori quantification permits an optimal reduction of characterizing measurements on a particular PBS delivery system. The combination of a priori quantification and measurements will then suffice to fully describe the physical interactions necessary for treatment planning purposes. We consider, for proton beams, these interactions and derive a 'Golden' beam data set. The Golden beam data set quantifies the pristine Bragg peak depth-dose distribution in terms of primary, multiple Coulomb scatter, and secondary, nuclear scatter, components. The set reduces the required measurements on a PBS delivery system to the measurement of energy spread and initial phase space as a function of energy. The depth doses are described in absolute units of Gy(RBE) mm² Gp⁻¹, where Gp equals 10⁹ (giga) protons, thus providing a direct mapping from treatment planning parameters to integrated beam current. We used these Golden beam data on our PBS delivery systems and demonstrated that they yield absolute dosimetry well within clinical tolerance.

The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women.

PubMed

Zajic, Stefan; Rossenu, Stefaan; Hreniuk, David; Kesisoglou, Filippos; McCrea, Jacqueline; Liu, Fang; Sun, Li; Witter, Rose; Gauthier, Don; Helmy, Roy; Joss, Darrick; Ni, Tong; Stoltz, Randall; Stone, Julie; Stoch, S Aubrey

2016-09-01

A stable-label i.v./oral study design was conducted to investigate the pharmacokinetics (PK) of odanacatib. Healthy, postmenopausal women received oral doses of unlabeled odanacatib administered simultaneously with a reference of 1 mg i.v. stable (13)C-labeled odanacatib. The absolute bioavailability of odanacatib was 30% at 50 mg (the phase 3 dose) and 70% at 10 mg, which is consistent with solubility-limited absorption. Odanacatib exposure (area under the curve from zero to infinity) increased by 15% and 63% when 50 mg was administered with low-fat and high-fat meals, respectively. This magnitude of the food effect is unlikely to be clinically important. The volume of distribution was ∼100 liters. The clearance was ∼0.8 l/h (13 ml/min), supporting that odanacatib is a low-extraction ratio drug. Population PK modeling indicated that 88% of individuals had completed absorption of >80% bioavailable drug within 24 hours, with modest additional absorption after 24 hours and periodic fluctuations in plasma concentrations contributing to late values for time to Cmax in some subjects. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Performance analysis of a film dosimetric quality assurance procedure for IMRT with regard to the employment of quantitative evaluation methods.

PubMed

Winkler, Peter; Zurl, Brigitte; Guss, Helmuth; Kindl, Peter; Stuecklschweiger, Georg

2005-02-21

A system for dosimetric verification of intensity-modulated radiotherapy (IMRT) treatment plans using absolute calibrated radiographic films is presented. At our institution this verification procedure is performed for all IMRT treatment plans prior to patient irradiation. Therefore clinical treatment plans are transferred to a phantom and recalculated. Composite treatment plans are irradiated to a single film. Film density to absolute dose conversion is performed automatically based on a single calibration film. A software application encompassing film calibration, 2D registration of measurement and calculated distributions, image fusion, and a number of visual and quantitative evaluation utilities was developed. The main topic of this paper is a performance analysis for this quality assurance procedure, with regard to the specification of tolerance levels for quantitative evaluations. Spatial and dosimetric precision and accuracy were determined for the entire procedure, comprising all possible sources of error. The overall dosimetric and spatial measurement uncertainties obtained thereby were 1.9% and 0.8 mm respectively. Based on these results, we specified 5% dose difference and 3 mm distance-to-agreement as our tolerance levels for patient-specific quality assurance for IMRT treatments.

Systematic review of the incremental costs of interventions that increase immunization coverage.

PubMed

Ozawa, Sachiko; Yemeke, Tatenda T; Thompson, Kimberly M

2018-05-10

Achieving and maintaining high vaccination coverage requires investments, but the costs and effectiveness of interventions to increase coverage remain poorly characterized. We conducted a systematic review of the literature to identify peer-reviewed studies published in English that reported interventions aimed at increasing immunization coverage and the associated costs and effectiveness of the interventions. We found limited information in the literature, with many studies reporting effectiveness estimates, but not providing cost information. Using the available data, we developed a cost function to support future programmatic decisions about investments in interventions to increase immunization coverage for relatively low and high-income countries. The cost function estimates the non-vaccine cost per dose of interventions to increase absolute immunization coverage by one percent, through either campaigns or routine immunization. The cost per dose per percent increase in absolute coverage increased with higher baseline coverage, demonstrating increasing incremental costs required to reach higher coverage levels. Future studies should evaluate the performance of the cost function and add to the database of available evidence to better characterize heterogeneity in costs and generalizability of the cost function. Copyright © 2018. Published by Elsevier Ltd.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.