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

SU-F-P-39: End-To-End Validation of a 6 MV High Dose Rate Photon Beam, Configured for Eclipse AAA Algorithm Using Golden Beam Data, for SBRT Treatments Using RapidArc

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

Ferreyra, M; Salinas Aranda, F; Dodat, D

Purpose: To use end-to-end testing to validate a 6 MV high dose rate photon beam, configured for Eclipse AAA algorithm using Golden Beam Data (GBD), for SBRT treatments using RapidArc. Methods: Beam data was configured for Varian Eclipse AAA algorithm using the GBD provided by the vendor. Transverse and diagonals dose profiles, PDDs and output factors down to a field size of 2×2 cm2 were measured on a Varian Trilogy Linac and compared with GBD library using 2% 2mm 1D gamma analysis. The MLC transmission factor and dosimetric leaf gap were determined to characterize the MLC in Eclipse. Mechanical andmore » dosimetric tests were performed combining different gantry rotation speeds, dose rates and leaf speeds to evaluate the delivery system performance according to VMAT accuracy requirements. An end-to-end test was implemented planning several SBRT RapidArc treatments on a CIRS 002LFC IMRT Thorax Phantom. The CT scanner calibration curve was acquired and loaded in Eclipse. PTW 31013 ionization chamber was used with Keithley 35617EBS electrometer for absolute point dose measurements in water and lung equivalent inserts. TPS calculated planar dose distributions were compared to those measured using EPID and MapCheck, as an independent verification method. Results were evaluated with gamma criteria of 2% dose difference and 2mm DTA for 95% of points. Results: GBD set vs. measured data passed 2% 2mm 1D gamma analysis even for small fields. Machine performance tests show results are independent of machine delivery configuration, as expected. Absolute point dosimetry comparison resulted within 4% for the worst case scenario in lung. Over 97% of the points evaluated in dose distributions passed gamma index analysis. Conclusion: Eclipse AAA algorithm configuration of the 6 MV high dose rate photon beam using GBD proved efficient. End-to-end test dose calculation results indicate it can be used clinically for SBRT using RapidArc.« 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.

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

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.

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

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

Feasibility study on dosimetry verification of volumetric-modulated arc therapy-based total marrow irradiation.

PubMed

Liang, Yun; Kim, Gwe-Ya; Pawlicki, Todd; Mundt, Arno J; Mell, Loren K

2013-03-04

The purpose of this study was to develop dosimetry verification procedures for volumetric-modulated arc therapy (VMAT)-based total marrow irradiation (TMI). The VMAT based TMI plans were generated for three patients: one child and two adults. The planning target volume (PTV) was defined as bony skeleton, from head to mid-femur, with a 3 mm margin. The plan strategy similar to published studies was adopted. The PTV was divided into head and neck, chest, and pelvic regions, with separate plans each of which is composed of 2-3 arcs/fields. Multiple isocenters were evenly distributed along the patient's axial direction. The focus of this study is to establish a dosimetry quality assurance procedure involving both two-dimensional (2D) and three-dimensional (3D) volumetric verifications, which is desirable for a large PTV treated with multiple isocenters. The 2D dose verification was performed with film for gamma evaluation and absolute point dose was measured with ion chamber, with attention to the junction between neighboring plans regarding hot/cold spots. The 3D volumetric dose verification used commercial dose reconstruction software to reconstruct dose from electronic portal imaging devices (EPID) images. The gamma evaluation criteria in both 2D and 3D verification were 5% absolute point dose difference and 3 mm of distance to agreement. With film dosimetry, the overall average gamma passing rate was 98.2% and absolute dose difference was 3.9% in junction areas among the test patients; with volumetric portal dosimetry, the corresponding numbers were 90.7% and 2.4%. A dosimetry verification procedure involving both 2D and 3D was developed for VMAT-based TMI. The initial results are encouraging and warrant further investigation in clinical trials.

Modelling evolution of air dose rates in river basins in Fukushima Prefecture affected by sediment-sorbed radiocesium redistribution

NASA Astrophysics Data System (ADS)

Malins, A.; Sakuma, K.; Nakanishi, T.; Kurikami, H.; Machida, M.; Kitamura, A.; Yamada, S.

2015-12-01

The radioactive 134Cs and 137Cs isotopes deposited over Fukushima Prefecture by the Fukushima Daiichi nuclear disaster are the predominant radiological concern for the years following the accident. This is because the energetic gamma radiation they emit on decay constitutes the majority of the elevated air dose rates that now afflict the region. Therefore, we developed a tool for calculating air dose rates from arbitrary radiocesium spatial distributions across the land surface and depth profiles within the ground. As cesium is strongly absorbed by clay soils, its primary redistribution mechanism within Fukushima Prefecture is by soil erosion and water-borne sediment transport. Each year between 0.1~1% of the total radiocesium inventory in the river basins neighboring Fukushima Daiichi is eroded from the land surface and enters into water courses, predominantly during typhoon storms. Although this is a small amount in relative terms, in absolute terms it corresponds to terabecquerels of 134Cs and 137Cs redistribution each year and this can affect the air dose rate at locations of high erosion and sediment deposition. This study inputs the results of sediment redistribution simulations into the dose rate evaluation tool to calculate the locations and magnitude of air dose rate changes due to radiocesium redistribution. The dose rate calculations are supported by handheld survey instrument results taken within the Prefecture.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

NOTE: A Monte Carlo study of dose rate distribution around the specially asymmetric CSM3-a 137Cs source

NASA Astrophysics Data System (ADS)

Pérez-Calatayud, J.; Lliso, F.; Ballester, F.; Serrano, M. A.; Lluch, J. L.; Limami, Y.; Puchades, V.; Casal, E.

2001-07-01

The CSM3 137Cs type stainless-steel encapsulated source is widely used in manually afterloaded low dose rate brachytherapy. A specially asymmetric source, CSM3-a, has been designed by CIS Bio International (France) substituting the eyelet side seed with an inactive material in the CSM3 source. This modification has been done in order to allow a uniform dose level over the upper vaginal surface when this `linear' source is inserted at the top of the dome vaginal applicators. In this study the Monte Carlo GEANT3 simulation code, incorporating the source geometry in detail, was used to investigate the dosimetric characteristics of this special CSM3-a 137Cs brachytherapy source. The absolute dose rate distribution in water around this source was calculated and is presented in the form of an along-away table. Comparison of Sievert integral type calculations with Monte Carlo results are discussed.

Interaction of the renin-angiotensin system and the renal nerves in the regulation of rat kidney function.

PubMed Central

Handa, R K; Johns, E J

1985-01-01

Stimulation of the renal sympathetic nerves in pentobarbitone anaesthetized rats achieved a 13% reduction in renal blood flow, did not change glomerular filtration rate, but reduced urine flow by 37%, absolute sodium excretion by 37%, and fractional sodium excretion by 34%. Following inhibition of converting enzyme with captopril (0.38 mmol kg-1 h-1), similar nerve stimulation reduced both renal blood flow and glomerular filtration rate by 16%, and although urine flow and absolute sodium excretion fell by 32 and 31%, respectively, the 18% fall in fractional sodium excretion was significantly less than that observed in the absence of captopril. Renal nerve stimulation at low levels, which did not change either renal blood flow or glomerular filtration rate, reduced urine flow, and absolute and fractional sodium excretions by 25, 26 and 23%, respectively. In animals receiving captopril at 0.38 mmol kg-1 h-1, low-level nerve stimulation caused small increases in glomerular filtration rate of 7% and urine flow of 12%, but did not change either absolute or fractional sodium excretions. At one-fifth the dose of captopril (0.076 mmol kg-1 h-1), low-level nerve stimulation did not change renal haemodynamics but decreased urine flow, and absolute and fractional sodium excretions by 10, 10 and 8%, respectively. These results showed that angiotensin II production was necessary for regulation of glomerular filtration rate in the face of modest neurally induced reductions in renal blood flow and was compatible with an intra-renal site of action of angiotensin II preferentially at the efferent arteriole. They also demonstrated that in the rat the action of the renal nerves to decrease sodium excretion was dependent on angiotensin II. PMID:3005558

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.

Optimal mapping of terrestrial gamma dose rates using geological parent material and aerogeophysical survey data.

PubMed

Rawlins, B G; Scheib, C; Tyler, A N; Beamish, D

2012-12-01

Regulatory authorities need ways to estimate natural terrestrial gamma radiation dose rates (nGy h⁻¹) across the landscape accurately, to assess its potential deleterious health effects. The primary method for estimating outdoor dose rate is to use an in situ detector supported 1 m above the ground, but such measurements are costly and cannot capture the landscape-scale variation in dose rates which are associated with changes in soil and parent material mineralogy. We investigate the potential for improving estimates of terrestrial gamma dose rates across Northern Ireland (13,542 km²) using measurements from 168 sites and two sources of ancillary data: (i) a map based on a simplified classification of soil parent material, and (ii) dose estimates from a national-scale, airborne radiometric survey. We used the linear mixed modelling framework in which the two ancillary variables were included in separate models as fixed effects, plus a correlation structure which captures the spatially correlated variance component. We used a cross-validation procedure to determine the magnitude of the prediction errors for the different models. We removed a random subset of 10 terrestrial measurements and formed the model from the remainder (n = 158), and then used the model to predict values at the other 10 sites. We repeated this procedure 50 times. The measurements of terrestrial dose vary between 1 and 103 (nGy h⁻¹). The median absolute model prediction errors (nGy h⁻¹) for the three models declined in the following order: no ancillary data (10.8) > simple geological classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect. Estimates of airborne radiometric gamma dose rate can significantly improve the spatial prediction of terrestrial dose rate.

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.

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

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

Prescription errors before and after introduction of electronic medication alert system in a pediatric emergency department.

PubMed

Sethuraman, Usha; Kannikeswaran, Nirupama; Murray, Kyle P; Zidan, Marwan A; Chamberlain, James M

2015-06-01

Prescription errors occur frequently in pediatric emergency departments (PEDs).The effect of computerized physician order entry (CPOE) with electronic medication alert system (EMAS) on these is unknown. The objective was to compare prescription errors rates before and after introduction of CPOE with EMAS in a PED. The hypothesis was that CPOE with EMAS would significantly reduce the rate and severity of prescription errors in the PED. A prospective comparison of a sample of outpatient, medication prescriptions 5 months before and after CPOE with EMAS implementation (7,268 before and 7,292 after) was performed. Error types and rates, alert types and significance, and physician response were noted. Medication errors were deemed significant if there was a potential to cause life-threatening injury, failure of therapy, or an adverse drug effect. There was a significant reduction in the errors per 100 prescriptions (10.4 before vs. 7.3 after; absolute risk reduction = 3.1, 95% confidence interval [CI] = 2.2 to 4.0). Drug dosing error rates decreased from 8 to 5.4 per 100 (absolute risk reduction = 2.6, 95% CI = 1.8 to 3.4). Alerts were generated for 29.6% of prescriptions, with 45% involving drug dose range checking. The sensitivity of CPOE with EMAS in identifying errors in prescriptions was 45.1% (95% CI = 40.8% to 49.6%), and the specificity was 57% (95% CI = 55.6% to 58.5%). Prescribers modified 20% of the dosing alerts, resulting in the error not reaching the patient. Conversely, 11% of true dosing alerts for medication errors were overridden by the prescribers: 88 (11.3%) resulted in medication errors, and 684 (88.6%) were false-positive alerts. A CPOE with EMAS was associated with a decrease in overall prescription errors in our PED. Further system refinements are required to reduce the high false-positive alert rates. © 2015 by the Society for Academic Emergency Medicine.

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.

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

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.

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.

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

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.

Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells

PubMed Central

Neumaier, Teresa; Swenson, Joel; Pham, Christopher; Polyzos, Aris; Lo, Alvin T.; Yang, PoAn; Dyball, Jane; Asaithamby, Aroumougame; Chen, David J.; Bissell, Mina J.; Thalhammer, Stefan; Costes, Sylvain V.

2012-01-01

The concept of DNA “repair centers” and the meaning of radiation-induced foci (RIF) in human cells have remained controversial. RIFs are characterized by the local recruitment of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we provide strong evidence for the existence of repair centers. We used live imaging and mathematical fitting of RIF kinetics to show that RIF induction rate increases with increasing radiation dose, whereas the rate at which RIFs disappear decreases. We show that multiple DNA double-strand breaks (DSBs) 1 to 2 μm apart can rapidly cluster into repair centers. Correcting mathematically for the dose dependence of induction/resolution rates, we observe an absolute RIF yield that is surprisingly much smaller at higher doses: 15 RIF/Gy after 2 Gy exposure compared to approximately 64 RIF/Gy after 0.1 Gy. Cumulative RIF counts from time lapse of 53BP1-GFP in human breast cells confirmed these results. The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation. PMID:22184222

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.

Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

PubMed

Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

2015-06-01

In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100,000 members per quarter [95% CI, -0.01 to 0.53]). Opioid dispensing and prescription opioid overdoses decreased substantially after 2 major changes in the pharmaceutical market in late 2010. Pharmaceutical market interventions may have value in combatting the prescription opioid overdose epidemic, but heroin overdose rates continue to increase. Complementary strategies to identify and treat opioid abuse and addiction are urgently needed.

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

Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-11-08

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA.

PubMed

Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab; Rong, Yi

2014-07-08

We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric-modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK-measured and TPS-calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate-based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates.

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.

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.

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

Effect of Remediation Parameters on in-Air Ambient Dose Equivalent Rates When Remediating Open Sites with Radiocesium-contaminated Soil.

PubMed

Malins, Alex; Kurikami, Hiroshi; Kitamura, Akihiro; Machida, Masahiko

2016-10-01

Calculations are reported for ambient dose equivalent rates [H˙*(10)] at 1 m height above the ground surface before and after remediating radiocesium-contaminated soil at wide and open sites. The results establish how the change in H˙*(10) upon remediation depends on the initial depth distribution of radiocesium within the ground, on the size of the remediated area, and on the mass per unit area of remediated soil. The remediation strategies considered were topsoil removal (with and without recovering with a clean soil layer), interchanging a topsoil layer with a subsoil layer, and in situ mixing of the topsoil. The results show the ratio of the radiocesium components of H˙*(10) post-remediation relative to their initial values (residual dose factors). It is possible to use the residual dose factors to gauge absolute changes in H˙*(10) upon remediation. The dependency of the residual dose factors on the number of years elapsed after fallout deposition is analyzed when remediation parameters remain fixed and radiocesium undergoes typical downward migration within the soil column.

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

Simultaneous oral therapeutic and intravenous 14C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin

PubMed Central

Boulton, David W.; Kasichayanula, Sreeneeranj; Keung, Chi Fung (Anther); Arnold, Mark E.; Christopher, Lisa J.; Xu, Xiaohui (Sophia); LaCreta, Frank

2013-01-01

Aim To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C‐microdose/therapeutic oral dosing (i.v.micro + oraltherap). Methods The Fp.o. values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography‐tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively. Results The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap. Conclusions Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability. PMID:22823746

Gafchromic EBT‐XD film: Dosimetry characterization in high‐dose, volumetric‐modulated arc therapy

PubMed Central

Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-01-01

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT‐XD films have been designed for optimal performance in the 40–4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose‐response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high‐dose volumetric‐modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0–4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter‐free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose‐rate dependence. For clinical examinations, we compared the dose distribution measured with EBT‐XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT‐XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ∼3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ∼1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ∼1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film‐ measured and treatment planning system (TPS)‐calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. PACS number(s): 87.56 Fc PMID:27929504

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

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

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.

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

Impact of the vaginal applicator and dummy pellets on the dosimetry parameters of Cs-137 brachytherapy source.

PubMed

Sina, Sedigheh; Faghihi, Reza; Meigooni, Ali S; Mehdizadeh, Simin; Mosleh Shirazi, M Amin; Zehtabian, Mehdi

2011-05-19

In this study, dose rate distribution around a spherical 137Cs pellet source, from a low-dose-rate (LDR) Selectron remote afterloading system used in gynecological brachytherapy, has been determined using experimental and Monte Carlo simulation techniques. Monte Carlo simulations were performed using MCNP4C code, for a single pellet source in water medium and Plexiglas, and measurements were performed in Plexiglas phantom material using LiF TLD chips. Absolute dose rate distribution and the dosimetric parameters, such as dose rate constant, radial dose functions, and anisotropy functions, were obtained for a single pellet source. In order to investigate the effect of the applicator and surrounding pellets on dosimetric parameters of the source, the simulations were repeated for six different arrangements with a single active source and five non-active pellets inside central metallic tubing of a vaginal cylindrical applicator. In commercial treatment planning systems (TPS), the attenuation effects of the applicator and inactive spacers on total dose are neglected. The results indicate that this effect could lead to overestimation of the calculated F(r,θ), by up to 7% along the longitudinal axis of the applicator, especially beyond the applicator tip. According to the results obtained in this study, in a real situation in treatment of patients using cylindrical vaginal applicator and using several active pellets, there will be a large discrepancy between the result of superposition and Monte Carlo simulations.

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

Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure.

PubMed

Poling, A; Cleary, J; Berens, K; Thompson, T

1990-12-01

The purpose of the present study was to examine the effects of haloperidol (0.3-10 mg/kg), molindone (0.3-5.6 mg/kg), mesoridazine (0.3-10) and thioridazine (0.3-25 mg/kg) on the behavior of pigeons exposed to a repeated acquisition procedure. At sufficiently high doses, each of these neuroleptics increased error rates (interfered with learning) and reduced rate of responding. When the drugs were compared on the basis of absolute doses administered, haloperidol disrupted behavior at doses considerably lower than the other drugs. If, however, chlorpromazine equivalent doses were examined, haloperidol was the least disruptive of the four drugs. Comparing the degree of behavioral disruption produced by the four drugs with their relative neuroreceptor affinities for dopamine D-2, cholinergic muscarinic, histamine H1, alpha-1 adrenergic and alpha-2 adrenergic receptors suggests that behavioral disruption cannot be attributed in any simple way to dopamine or acetylcholine receptor blockade. The relationship between the behavioral effects of neuroleptics and their simple neuropharmacological actions must be considered as highly tentative.

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.

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

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.

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.

Carotid endarterectomy--an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Chaturvedi, S; Bruno, A; Feasby, T; Holloway, R; Benavente, O; Cohen, S N; Cote, R; Hess, D; Saver, J; Spence, J D; Stern, B; Wilterdink, J

2005-09-27

To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with <50% stenosis (Level A). For asymptomatic patients with 60 to 99% stenosis, the benefit/risk ratio is smaller compared to symptomatic patients and individual decisions must be made. Endarterectomy can reduce the future stroke rate if the perioperative stroke/death rate is kept low (<3%) (Level A). Low dose aspirin (81 to 325 mg) is preferred for patients before and after carotid endarterectomy to reduce the rate of stroke, myocardial infarction, and death (Level A).

A dual two dimensional electronic portal imaging device transit dosimetry model based on an empirical quadratic formalism

PubMed Central

Metwaly, M; Glegg, M; Baggarley, S P; Elliott, A

2015-01-01

Objective: This study describes a two dimensional electronic portal imaging device (EPID) transit dosimetry model that can predict either: (1) in-phantom exit dose, or (2) EPID transit dose, for treatment verification. Methods: The model was based on a quadratic equation that relates the reduction in intensity to the equivalent path length (EPL) of the attenuator. In this study, two sets of quadratic equation coefficients were derived from calibration dose planes measured with EPID and ionization chamber in water under reference conditions. With two sets of coefficients, EPL can be calculated from either EPID or treatment planning system (TPS) dose planes. Consequently, either the in-phantom exit dose or the EPID transit dose can be predicted from the EPL. The model was tested with two open, five wedge and seven sliding window prostate and head and neck intensity-modulated radiation therapy (IMRT) fields on phantoms. Results were analysed using absolute gamma analysis (3%/3 mm). Results: The open fields gamma pass rates were >96.8% for all comparisons. For wedge and IMRT fields, comparisons between predicted and TPS-computed in-phantom exit dose resulted in mean gamma pass rate of 97.4% (range, 92.3–100%). As for the comparisons between predicted and measured EPID transit dose, the mean gamma pass rate was 97.5% (range, 92.6–100%). Conclusion: An EPID transit dosimetry model that can predict in-phantom exit dose and EPID transit dose was described and proven to be valid. Advances in knowledge: The described model is practical, generic and flexible to encourage widespread implementation of EPID dosimetry for the improvement of patients' safety in radiotherapy. PMID:25969867

Digital holographic interferometry: a novel optical calorimetry technique for radiation dosimetry.

PubMed

Cavan, Alicia; Meyer, Juergen

2014-02-01

To develop and demonstrate the proof-of-principle of a novel optical calorimetry method to determine radiation absorbed dose in a transparent medium. The calorimetric property of water is measured during irradiation by means of an interferometer, which detects temperature-induced changes in the refractive index that can be mathematically related to absorbed dose. The proposed method uses a technique called digital holographic interferometry (DHI), which comprises an optical laser interferometer setup and consecutive physical reconstruction of the recorded wave fronts by means of the Fresnel transform. This paper describes the conceptual framework and provides the mathematical basis for DHI dosimetry. Dose distributions from a high dose rate Brachytherapy source were measured by a prototype optical setup to demonstrate the feasibility of the approach. The developed DHI dosimeter successfully determined absorbed dose distributions in water in the region adjacent to a high dose rate Brachytherapy source. A temperature change of 0.0381 K across a distance of 6.8 mm near the source was measured, corresponding to a dose of 159.3 Gy. The standard deviation in a typical measurement set was ± 3.45 Gy (corresponding to an uncertainty in the temperature value of ± 8.3 × 10(-4) K). The relative dose fall off was in agreement with treatment planning system modeled data. First results with a prototype optical setup and a Brachytherapy source demonstrate the proof-of-principle of the approach. The prototype achieves high spatial resolution of approximately 3 × 10(-4) m. The general approach is fundamentally independent of the radiation type and energy. The sensitivity range determined indicates that the method is predominantly suitable for high dose rate applications. Further work is required to determine absolute dose in all three dimensions.

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.

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

Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA

PubMed Central

Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab

2014-01-01

We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric‐modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK‐measured and TPS‐calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate‐based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3 mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates. PACS numbers: 87.56.Fc, 87.55.kh, 87.55.Qr PMID:25207411

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.

Pixel response-based EPID dosimetry for patient specific QA.

PubMed

Han, Bin; Ding, Aiping; Lu, Minghui; Xing, Lei

2017-01-01

Increasing use of high dose rate, flattening filter free (FFF), and/or small-sized field beams presents a significant challenge to the medical physics community. In this work, we develop a strategy of using a high spatial resolution and high frame rate amorphous silicon flat panel electronic portal imaging device (EPID) for dosimetric measurements of these challenging cases, as well as for conventional external beam therapy. To convert a series of raw EPID-measured radiation field images into water-based dose distribution, a pixel-to-pixel dose-response function of the EPID specific to the linac is essential. The response function was obtained by using a Monte Carlo simulation of the photon transport in the EPID with a comprehensive calibration. After the raw image was converted into the primary incident photon fluence, the fluence was further convolved into a water-based dose distribution of the dynamic field by using a pregenerated pencil-beam kernel. The EPID-based dosimetric measurement technique was validated using beams with and without flattening filter of all energies available in Varian TrueBeam STx™. Both regularly and irregularly shaped fields measured using a PTW 729 ion chamber array in plastic water phantom. The technique was also applied to measure the distribution for a total of 23 treatment plans of different energies to evaluate the accuracy of the proposed approach. The EPID measurements of square fields of 4 × 4 cm 2 to 20 × 20 cm 2 , circular fields of 2-15 cm diameters, rectangular fields of various sizes, and irregular MLC fields were in accordance with measurements using a Farmer chamber and/or ion chamber array. The 2D absolute dose maps generated from EPID raw images agreed with ion chamber measurements to within 1.5% for all fields. For the 23 patient cases examined in this work, the average γ-index passing rate were found to be 99.2 ± 0.6%, 97.4 ± 2.4%, and 72.6 ± 8.4%, respectively, for criterions of 3 mm/3%, 2 mm/2%, and 1 mm/1%. The high spatial resolution and high frame rate EPID provides an accurate and efficient dosimetric tool for QA of modern radiation therapy. Accurate absolute 2D dose maps can be generated from the system for an independent dosimetric verification of treatment delivery. © 2016 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

PubMed

Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W

2017-05-19

The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, p<0.001) and relative increase of 53-125% (median: 82%), and antibody titer to type 2 increasing by 2-32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity. Overall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.

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.

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

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.

[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.

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.

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

A dosimetry technique for measuring kilovoltage cone‐beam CT dose on a linear accelerator using radiotherapy equipment

PubMed Central

Lawford, Catherine E.

2014-01-01

This work develops a technique for kilovoltage cone‐beam CT (CBCT) dosimetry that incorporates both point dose and integral dose in the form of dose length product, and uses readily available radiotherapy equipment. The dose from imaging protocols for a range of imaging parameters and treatment sites was evaluated. Conventional CT dosimetry using 100 mm long pencil chambers has been shown to be inadequate for the large fields in CBCT and has been replaced in this work by a combination of point dose and integral dose. Absolute dose measurements were made with a small volume ion chamber at the central slice of a radiotherapy phantom. Beam profiles were measured using a linear diode array large enough to capture the entire imaging field. These profiles were normalized to absolute dose to form dose line integrals, which were then weighted with radial depth to form the DLPCBCT. This metric is analogous to the standard dose length product (DLP), but derived differently to suit the unique properties of CBCT. Imaging protocols for head and neck, chest, and prostate sites delivered absolute doses of 0.9, 2.2, and 2.9 cGy to the center of the phantom, and DLPCBCT of 28.2, 665.1, and 565.3 mGy.cm, respectively. Results are displayed as dose per 100 mAs and as a function of key imaging parameters such as kVp, mAs, and collimator selection in a summary table. DLPCBCT was found to correlate closely with the dimension of the imaging region and provided a good indication of integral dose. It is important to assess integral dose when determining radiation doses to patients using CBCT. By incorporating measured beam profiles and DLP, this technique provides a CBCT dosimetry in radiotherapy phantoms and allows the prediction of imaging dose for new CBCT protocols. PACS number: 87.57.uq PMID:25207398

A dosimetry technique for measuring kilovoltage cone-beam CT dose on a linear accelerator using radiotherapy equipment.

PubMed

Scandurra, Daniel; Lawford, Catherine E

2014-07-08

This work develops a technique for kilovoltage cone-beam CT (CBCT) dosimetry that incorporates both point dose and integral dose in the form of dose length product, and uses readily available radiotherapy equipment. The dose from imaging protocols for a range of imaging parameters and treatment sites was evaluated. Conventional CT dosimetry using 100 mm long pencil chambers has been shown to be inadequate for the large fields in CBCT and has been replaced in this work by a combination of point dose and integral dose. Absolute dose measurements were made with a small volume ion chamber at the central slice of a radiotherapy phantom. Beam profiles were measured using a linear diode array large enough to capture the entire imaging field. These profiles were normalized to absolute dose to form dose line integrals, which were then weighted with radial depth to form the DLPCBCT. This metric is analogous to the standard dose length product (DLP), but derived differently to suit the unique properties of CBCT. Imaging protocols for head and neck, chest, and prostate sites delivered absolute doses of 0.9, 2.2, and 2.9 cGy to the center of the phantom, and DLPCBCT of 28.2, 665.1, and 565.3mGy.cm, respectively. Results are displayed as dose per 100 mAs and as a function of key imaging parameters such as kVp, mAs, and collimator selection in a summary table. DLPCBCT was found to correlate closely with the dimension of the imaging region and provided a good indication of integral dose. It is important to assess integral dose when determining radiation doses to patients using CBCT. By incorporating measured beam profiles and DLP, this technique provides a CBCT dosimetry in radiotherapy phantoms and allows the prediction of imaging dose for new CBCT protocols.

A Detailed Dosimetric Analysis of Spinal Cord Tolerance in High-Dose Spine Radiosurgery.

PubMed

Katsoulakis, Evangelia; Jackson, Andrew; Cox, Brett; Lovelock, Michael; Yamada, Yoshiya

2017-11-01

Dose-volume tolerance of the spinal cord (SC) in spinal stereotactic radiosurgery (SRS) is difficult to define because radiation myelitis rates are low, and published reports document cases of myelopathy but do not account for the total number of patients treated at given dose-volume combinations who do not have myelitis. This study reports SC toxicity from single-fraction spinal SRS and presents a comprehensive atlas of the incidence of adverse events to examine dose-volume predictors. A prospective database of all patients undergoing single-fraction spinal SRS at our institution between 2004 and 2011 was reviewed. SC toxicity was defined by clinical myelitis with accompanying magnetic resonance imaging (MRI) signal changes that were not attributable to tumor progression. Dose-volume histogram (DVH) atlases were created for these endpoints. Rates of adverse events with 95% confidence limits and probabilities that rates of adverse events were <2% and <5% for myelitis were determined as functions of dose and absolute volume. Information about DVH and myelitis was available for 228 patients treated at 259 sites. The median follow-up time was 14.6 months (range, 0.1-138.3 months). The median prescribed dose to the planning treatment volume was 24 Gy (range, 18-24 Gy). There were 2 cases of radiation myelitis (rate r=0.7%) with accompanying MRI signal changes. Myelitis occurred in 2 patients, with Dmax >13.33 Gy, and minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc were >10.66, 10.9, and 8 Gy, respectively; however, both myelitis cases occurred below the 34th percentile for Dmax and there were 194 DVHs in total with Dmax >13.33 Gy. A median SC Dmax of 13.85 Gy is safe and supports that a Dmax limit of 14 Gy carries a low <1% rate of myelopathy. No dose-volume thresholds or relationships between SC dose and myelitis were apparent. This is the largest study examining dosimetric data and radiation-induced myelitis in de novo spine SRS. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Acellular pertussis vaccines effectiveness over time: A systematic review, meta-analysis and modeling study

PubMed Central

Chit, Ayman; Zivaripiran, Hossein; Shin, Thomas; Lee, Jason K. H.; Tomovici, Antigona; Macina, Denis; Johnson, David R.; Decker, Michael D.; Wu, Jianhong

2018-01-01

Background Acellular pertussis vaccine studies postulate that waning protection, particularly after the adolescent booster, is a major contributor to the increasing US pertussis incidence. However, these studies reported relative (ie, vs a population given prior doses of pertussis vaccine), not absolute (ie, vs a pertussis vaccine naïve population) efficacy following the adolescent booster. We aim to estimate the absolute protection offered by acellular pertussis vaccines. Methods We conducted a systematic review of acellular pertussis vaccine effectiveness (VE) publications. Studies had to comply with the US schedule, evaluate clinical outcomes, and report VE over discrete time points. VE after the 5-dose childhood series and after the adolescent sixth-dose booster were extracted separately and pooled. All relative VE estimates were transformed to absolute estimates. VE waning was estimated using meta-regression modeling. Findings Three studies reported VE after the childhood series and four after the adolescent booster. All booster studies reported relative VE (vs acellular pertussis vaccine-primed population). We estimate initial childhood series absolute VE is 91% (95% CI: 87% to 95%) and declines at 9.6% annually. Initial relative VE after adolescent boosting is 70% (95% CI: 54% to 86%) and declines at 45.3% annually. Initial absolute VE after adolescent boosting is 85% (95% CI: 84% to 86%) and declines at 11.7% (95% CI: 11.1% to 12.3%) annually. Interpretation Acellular pertussis vaccine efficacy is initially high and wanes over time. Observational VE studies of boosting failed to recognize that they were measuring relative, not absolute, VE and the absolute VE in the boosted population is better than appreciated. PMID:29912887

SU-E-T-460: Impact of the LINAC Repetition Rate On a High-Resolution Liquid Ionization Chamber Array for Patient-Specific QA

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

Wang, S; Driewer, J; Zheng, D

2015-06-15

Purpose: The purpose of this study is to investigate the LINAC repetition-rate (dose-rate) dependence of OCTAVIUS 1000SRS liquid ionization chamber (LIC) array for patient specific QA of SRT plans delivered with flattening-filter-free (FFF) beams. Methods: 1) The repetition-rate dependence of 1000SRS was measured in a phantom constructed with 5-cm solid water above and below the array for build-up and backscatter. A 0.3cc calibrated ion chamber was also placed along the central axis 2.3cm below the center chamber of the array for normalizing LINAC output fluctuation. The signals from the center chamber of the array under different repetition rates in themore » range of 400–2400 MU/min for 6xFFF and 10xFFF beams on a Varian TrueBeamSTx LINAC, normalized by the independent chamber readings, were analyzed for the array response dependence on repetition rates. 2) Twelve Step-and-shoot IMRS QA plans (6xFFF and 10xFFF) were delivered to the array under different repetition rates for analysis and comparison. 3) The absolute doses measured by the center chamber were compared to measurements using an independent ionization chamber with the identical setup, taken as the gold standard. 4) The correction factors based on the actual delivery repetition rate were applied to the measurements, and the results were compared again to the gold standard. Results: 1) The 1000SRS array exhibited repetition-rate dependence for FFF beams, up to 5% for 6xFFF and 10% for 10xFFF; 2) The array showed clinically-acceptable repetition-rate dependence for regular flattened beams; 3) This repetition-rate dependence significantly affected the measurement accuracy, thereby affecting IMRS QA results; 4) By applying an empirical repetition-rate correction, the corrected measurements agreed better with the gold standard ion chamber measurements. Conclusion: OCTAVIUS 1000SRS LIC array exhibited considerable repetition-rate dependence for FFF beams, which will affect the accuracy of the absolute QA measurements, especially for IMRS plans with the step-and-shoot technique.« less

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.

Comparison of the myocardial blood flow response to regadenoson and dipyridamole: a quantitative analysis in patients referred for clinical 82Rb myocardial perfusion PET.

PubMed

Goudarzi, Behnaz; Fukushima, Kenji; Bravo, Paco; Merrill, Jennifer; Bengel, Frank M

2011-10-01

Regadenoson is a novel selective A2A adenosine receptor agonist, which is administered as an intravenous bolus at a fixed dose. It is currently not clear if the absolute flow increase in response to this fixed dose is a function of distribution volume in individual patients or if it is generally comparable to the previous standard agents dipyridamole or adenosine, which are dosed based on weight. We used quantitative analysis of clinical 82Rb PET/CT studies to obtain further insights. A total of 104 subjects with normal clinical rest/stress 82Rb perfusion PET/CT were included in a retrospective analysis. To rule out confounding factors, none had evidence of prior cardiac disease, ischaemia or infarction, cardiomyopathy, diabetes with insulin use, calcium score>400, renal disease or other significant systemic disease. A group of 52 patients stressed with regadenoson were compared with a group of 52 patients stressed with dipyridamole before regadenoson became available. The groups were matched for clinical characteristics, risk factors and baseline haemodynamics. Myocardial blood flow (MBF) and myocardial flow reserve (MFR) were quantified using a previously validated retention model, after resampling of dynamic studies from list-mode 82Rb datasets. At rest, heart rate, blood pressure and MBF were comparable between the groups. Regadenoson resulted in a significantly higher heart rate (34±14 vs. 23±10 beats per minute increase from baseline; p<0.01) and rate-pressure product. Patients in the regadenoson group reported less severe symptoms and required less aminophylline. Stress MBF and MFR were not different between the groups (2.2±0.6 vs. 2.1±0.6 ml/min/g, p=0.39, and 2.9±0.8 vs. 2.8±0.7, p=0.31, respectively). In the regadenoson group, there was no correlation between stress flow or MFR and body weight or BMI. Despite its administration at a fixed dose, regadenoson results in an absolute increase in MBF which is comparable to that following dipyridamole administration and is independent of patient distribution volume. This further supports its usefulness as a clinical stress agent.

Dosimetry around metallic ports in tissue expanders in patients receiving postmastectomy radiation therapy: an ex vivo evaluation.

PubMed

Moni, Janaki; Graves-Ditman, Maria; Cederna, Paul; Griffith, Kent; Krueger, Editha A; Fraass, Benedick A; Pierce, Lori J

2004-01-01

Postmastectomy breast reconstruction can be accomplished utilizing tissue expanders and implants. However, in patients who require postoperative radiotherapy, the complication rate with tissue expander/implant reconstruction can exceed 50%. One potential cause of this high complication rate may be the metallic port in the tissue expander producing altered dosimetry in the region of the metallic device. The purpose of this study was to quantify the radiation dose distribution in the vicinity of the metallic port and determine its potential contribution to this extremely high complication rate. The absolute dosimetric effect of the tissue expander's metallic port was quantified using film and thermoluminescent dosimetry (TLD) studies with a single beam incident on a metallic port extracted from an expander. TLD measurements were performed at 11 reproducible positions on an intact expander irradiated with tangential fields. A computed tomography (CT)-based treatment plan without inhomogeneity corrections was used to derive expected doses for all TLD positions. Multiple irradiation experiments were performed for all TLD data. Confidence intervals for the dose at TLD sites with the metallic port in place were compared to the expected dose at the site without the metallic port. Film studies did not reveal a significant component of scatter around the metallic port. TLD studies of the extracted metallic port revealed highest doses within the casing of the metallic port and no consistent increased dose at the surface of the expander. No excess dose due to the metallic port in the expander was noted with the phantom TLD data. Based upon these results, it does not appear that the metallic port in tissue expanders significantly contributes to the high complication rate experienced in patients undergoing tissue expander breast reconstruction and receiving radiation therapy. Strategies designed to reduce the breast reconstruction complication rate in this clinical setting will need to focus on factors other than adjusting the dosimetry around the tissue expander metallic port.

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.

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

Morphine tolerance as a function of ratio schedule: response requirement or unit price?

PubMed

Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A

2005-05-01

Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.

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.

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

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

PubMed Central

Formgren, H.

1976-01-01

1 The effect of metoprolol, a new β1-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β2-adrenoceptor-stimulant. 2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner. 3 At the lower dose levels no influence on FEV1 was noted, and no difference was found between the two active drugs. At the higher dose level FEV1 was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs. 4 Metoprolol and practolol are equally effective β1-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma. PMID:22216522

Carcinoma of the vagina. [Complications following whole-pelvis. gamma. irradiation and radium implant therapy

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

Marcus, R.B. Jr.; Million, R.R.; Daly, J.W.

1978-11-01

Twenty-two patients with Stage I through IV primary vaginal squamous cell carcinomas treated for cure with radiation therapy are reviewed, with particular emphasis on the relationship of dose to complications and local control. All but 2 patients received 4000 to 6000 rad whole pelvis irradiation plus at least one radium application. Local control was 91%, with an absolute 2-year disease-free survival of 82%. The degree of anaplasia was found to influence prognosis, with all local and distant failures resulting from high-grade lesions. The complication rate was modest, with no fistulae or serious bowel complications. An analysis of total dose (externalmore » plus radium) with respect to local failure and complications showed that no major complications occurred at a combined dose below 9000 rad. An analysis of the individual contributions of external irradiation and radium implants showed that all but one very minor complication occurred at a radium dose of 4000 rad or higher. From these data, overall treatment planning and total dose recommendations are made.« less

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

Wen, N; Lu, S; Qin, Y

Purpose: To evaluate the dosimetric uncertainty associated with Gafchromic (EBT3) films and establish an absolute dosimetry protocol for Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT). Methods: EBT3 films were irradiated at each of seven different dose levels between 1 and 15 Gy with open fields, and standard deviations of dose maps were calculated at each color channel for evaluation. A scanner non-uniform response correction map was built by registering and comparing film doses to the reference diode array-based dose map delivered with the same doses. To determine the temporal dependence of EBT3 films, the average correction factors of differentmore » dose levels as a function of time were evaluated up to four days after irradiation. An integrated film dosimetry protocol was developed for dose calibration, calibration curve fitting, dose mapping, and profile/gamma analysis. Patient specific quality assurance (PSQA) was performed for 93 SRS/SBRT treatment plans. Results: The scanner response varied within 1% for the field sizes less than 5 × 5 cm{sup 2}, and up to 5% for the field sizes of 10 × 10 cm{sup 2}. The scanner correction method was able to remove visually evident, irregular detector responses found for larger field sizes. The dose response of the film changed rapidly (∼10%) in the first two hours and plateaued afterwards, ∼3% change between 2 and 24 hours. The mean uncertainties (mean of the standard deviations) were <0.5% over the dose range 1∼15Gy for all color channels for the OD response curves. The percentage of points passing the 3%/1mm gamma criteria based on absolute dose analysis, averaged over all tests, was 95.0 ± 4.2. Conclusion: We have developed an absolute film dose dosimetry protocol using EBT3 films. The overall uncertainty has been established to be approximately 1% for SRS and SBRT PSQA. The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society.« less

A new metric for assessing IMRT modulation complexity and plan deliverability.

PubMed

McNiven, Andrea L; Sharpe, Michael B; Purdie, Thomas G

2010-02-01

To evaluate the utility of a new complexity metric, the modulation complexity score (MCS), in the treatment planning and quality assurance processes and to evaluate the relationship of the metric with deliverability. A multisite (breast, rectum, prostate, prostate bed, lung, and head and neck) and site-specific (lung) dosimetric evaluation has been completed. The MCS was calculated for each beam and the overall treatment plan. A 2D diode array (MapCHECK, Sun Nuclear, Melbourne, FL) was used to acquire measurements for each beam. The measured and planned dose (PINNACLE3, Phillips, Madison, WI) was evaluated using different percent differences and distance to agreement (DTA) criteria (3%/ 3 mm and 2%/ 1 mm) and the relationship between the dosimetric results and complexity (as measured by the MCS or simple beam parameters) assessed. For the multisite analysis (243 plans total), the mean MCS scores for each treatment site were breast (0.92), rectum (0.858), prostate (0.837), prostate bed (0.652), lung (0.631), and head and neck (0.356). The MCS allowed for compilation of treatment site-specific statistics, which is useful for comparing different techniques, as well as for comparison of individual treatment plans with the typical complexity levels. For the six plans selected for dosimetry, the average diode percent pass rate was 98.7% (minimum of 96%) for 3%/3 mm evaluation criteria. The average difference in absolute dose measurement between the planned and measured dose was 1.7 cGy. The detailed lung analysis also showed excellent agreement between the measured and planned dose, as all beams had a diode percentage pass rate for 3%/3 mm criteria of greater than 95.9%, with an average pass rate of 99.0%. The average absolute maximum dose difference for the lung plans was 0.7 cGy. There was no direct correlation between the MCS and simple beam parameters which could be used as a surrogate for complexity level (i.e., number of segments or MU). An evaluation criterion of 2%/ 1 mm reliably allowed for the identification of beams that are dosimetrically robust. In this study we defined a robust beam or plan as one that maintained a diode percentage pass rate greater than 90% at 2%/ 1 mm, indicating delivery that was deemed accurate when compared to the planned dose, even under stricter evaluation criterion. MCS and MU threshold criteria were determined by defining a required specificity of 1.0. A MCS threshold of 0.8 allowed for identification of robust deliverability with a sensitivity of 0.36. In contrast, MU had a lower sensitivity of 0.23 for a threshold of 50 MU. The MCS allows for a quantitative assessment of plan complexity, on a fixed scale, that can be applied to all treatment sites and can provide more information related to dose delivery than simple beam parameters. This could prove useful throughout the entire treatment planning and QA process.

[Effect of substance P on cardiac autonomic nervous function in rats].

PubMed

Deng, Lijun; Li, Jing; Yan, Fuping; Lu, Jie

2009-12-01

Forty SD rats were divided into 5 groups: control group, SP groups (5 microg/kg,10 microg/kg, 20 microg/kg) and spantide II plus SP group. An analysis of heart rate variability (HRV) was used to detect the changes of HRV parameters before and after intravenous injection of SP in order to investigate the effect of substance P on cardiac autonomic nervous function and the corresponding mechanism. (1) There were significant differences in most HRV parameters for the three different doses of SP. Mean heart period (MHP), absolute power of ultra-low frequency and high frequency band (APU, APH), total power (TPV) and ratio of power in ultra-low to high frequency band (RUH) increased, while mean heart rate (MHR) and chaos intensity (HCC) decreased during the 30 minutes. Each peak amplitude of HRV parameters went higher and showed up ahead of the upward doses of SP. (2) Significant change was seen in each of the parameters between spantide II plus SP group and high-dose SP group. These data idicate that, after intravenous injection of different doses of SP, both cardiac sympathetic nervous system activity and parasympathetic nervous system activity increase, and the function of cardiac autonomic nervous becomes instable and unbalanced. The effect of SP may be dose dependent, and it is possibly mediated by neurokinin-1(NK-1) receptor.

Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia in men with LUTS suggestive of BPH: re-evaluation of four controlled clinical studies.

PubMed

Oelke, Matthias; Berges, Richard; Schläfke, Sandra; Burkart, Martin

2014-10-01

To determine the effects of the herbal fixed-dose combination PRO 160/120 (extracts from saw palmetto fruits and stinging nettle roots) on nocturnal voiding frequency, as measured by question 7 of the IPSS questionnaire, in patients with moderate-to-severe LUTS/BPH after 24 weeks of treatment compared to placebo, to the α-blocker tamsulosin, or to the 5α-reductase inhibitor finasteride. The study is about post hoc evaluation of four published randomized, double-blind clinical trials on PRO 160/120, two compared with placebo, one with finasteride and one with tamsulosin. In addition, a pooled data analysis of the two placebo-controlled trials was conducted. We analyzed data from a total of 922 patients with a mean age of 66 years and a mean baseline nocturnal voiding frequency of 2.1. In the pooled analysis of placebo-controlled trials, nocturnal voids improved by 0.8 (29 %) with PRO 160/120 compared to 0.6 (18 %) with placebo (p = 0.015, Wilcoxon test, one-tailed). The 69 % responder rate to PRO 160/120 was significantly superior to the placebo response (52 %; p = 0.003, χ (2)-test, two-tailed). The majority of responders improved by 1 void/night. Absolute improvements and response rates were consistently higher with PRO 160/120 than with placebo over a range of baseline nocturnal voiding frequencies. There were no differences between PRO 160/120 and finasteride or tamsulosin regarding absolute improvement of nocturnal voids or responds rates. PRO 160/120 significantly improved nocturnal voiding frequency compared to placebo and similar to tamsulosin or finasteride.

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

SU-F-T-330: Characterization of the Clinically Released ScandiDos Discover Diode Array for In-Vivo Dose Monitoring

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

Saenz, D; Gutierrez, A

Purpose: The ScandiDos Discover has obtained FDA clearance and is now clinically released. We studied the essential attenuation and beam hardening components as well as tested the diode array’s ability to detect changes in absolute dose and MLC leaf positions. Methods: The ScandiDos Discover was mounted on the heads of an Elekta VersaHD and a Varian 23EX. Beam attenuation measurements were made at 10 cm depth for 6 MV and 18 MV beam energies. The PDD(10) was measured as a metric for the effect on beam quality. Next, a plan consisting of two orthogonal 10 × 10 cm2 fields wasmore » used to adjust the dose per fraction by scaling monitor units to test the absolute dose detection sensitivity of the Discover. A second plan (conformal arc) was then delivered several times independently on the Elekta VersaHD. Artificially introduced MLC position errors in the four central leaves were then added. The errors were incrementally increased from 1 mm to 4 mm and back across seven control points. Results: The absolute dose measured at 10 cm depth decreased by 1.2% and 0.7% for 6 MV and 18 MV beam with the Discover, respectively. Attenuation depended slightly on the field size but only changed the attenuation by 0.1% across 5 × 5 cm{sup 2} and 20 − 20 cm{sup 2} fields. The change in PDD(10) for a 10 − 10 cm{sup 2} field was +0.1% and +0.6% for 6 MV and 18 MV, respectively. Changes in monitor units from −5.0% to 5.0% were faithfully detected. Detected leaf errors were within 1.0 mm of intended errors. Conclusion: A novel in-vivo dosimeter monitoring the radiation beam during treatment was examined through its attenuation and beam hardening characteristics. The device tracked with changes in absolute dose as well as introduced leaf position deviations.« less

A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

PubMed

Díez, P; Aird, E G A; Sander, T; Gouldstone, C A; Sharpe, P H G; Lee, C D; Lowe, G; Thomas, R A S; Simnor, T; Bownes, P; Bidmead, M; Gandon, L; Eaton, D; Palmer, A L

2017-11-09

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192 Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60 Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of  +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

Delivery time comparison for intensity-modulated radiation therapy with/without flattening filter: a planning study

NASA Astrophysics Data System (ADS)

Fu, Weihua; Dai, Jianrong; Hu, Yimin; Han, Dongsheng; Song, Yixin

2004-04-01

The treatment delivery time of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) is generally longer than that of conventional radiotherapy. In theory, removing the flattening filter from the treatment head may reduce the beam-on time by enhancing the output dose rate, and then reduce the treatment delivery time. And in practice, there is a possibility of delivering the required fluence distribution by modulating the unflattened non-uniform fluence distribution. However, the reduction of beam-on time may be discounted by the increase of leaf-travel time and (or) verification-and-recording (V&R) time. Here we investigate the overall effect of flattening filter on the treatment delivery time of IMRT with MLCs implemented in the step and shoot method, as well as with compensators on six hybrid machines. We compared the treatment delivery time with/without flattening filter for ten nasopharynx cases and ten prostate cases by observing the variations of the ratio of the beam-on time, segment number, leaf-travel time and the treatment delivery time with dose rate, leaf speed and V&R time. The results show that, without the flattening filter, the beam-on time reduces for both static MLC and compensator-based techniques; the number of segments and the leaf-travel time increase slightly for the static MLC technique; the relative IMRT treatment delivery time decreases more with lower dose rate, higher leaf speed and shorter V&R overhead time. The absolute treatment delivery time reduction depends on the fraction dose. It is not clinically significant at a fraction dose of 2 Gy for the technique of removing the flattening filter, but becomes significant when the fraction dose is as high as that for radiosurgery.

Feasibility study on the verification of actual beam delivery in a treatment room using EPID transit dosimetry.

PubMed

Baek, Tae Seong; Chung, Eun Ji; Son, Jaeman; Yoon, Myonggeun

2014-12-04

The aim of this study is to evaluate the ability of transit dosimetry using commercial treatment planning system (TPS) and an electronic portal imaging device (EPID) with simple calibration method to verify the beam delivery based on detection of large errors in treatment room. Twenty four fields of intensity modulated radiotherapy (IMRT) plans were selected from four lung cancer patients and used in the irradiation of an anthropomorphic phantom. The proposed method was evaluated by comparing the calculated dose map from TPS and EPID measurement on the same plane using a gamma index method with a 3% dose and 3 mm distance-to-dose agreement tolerance limit. In a simulation using a homogeneous plastic water phantom, performed to verify the effectiveness of the proposed method, the average passing rate of the transit dose based on gamma index was high enough, averaging 94.2% when there was no error during beam delivery. The passing rate of the transit dose for 24 IMRT fields was lower with the anthropomorphic phantom, averaging 86.8% ± 3.8%, a reduction partially due to the inaccuracy of TPS calculations for inhomogeneity. Compared with the TPS, the absolute value of the transit dose at the beam center differed by -0.38% ± 2.1%. The simulation study indicated that the passing rate of the gamma index was significantly reduced, to less than 40%, when a wrong field was erroneously irradiated to patient in the treatment room. This feasibility study suggested that transit dosimetry based on the calculation with commercial TPS and EPID measurement with simple calibration can provide information about large errors for treatment beam delivery.

Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

NASA Astrophysics Data System (ADS)

Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

2016-07-01

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

EXOMARS IRAS (DOSE) radiation measurements.

NASA Astrophysics Data System (ADS)

Federico, C.; Di Lellis, A. M.; Fonte, S.; Pauselli, C.; Reitz, G.; Beaujean, R.

The characterization and the study of the radiations on their interaction with organic matter is of great interest in view of the human exploration on Mars. The Ionizing RAdiation Sensor (IRAS) selected in the frame of the ExoMars/Pasteur ESA mission is a lightweight particle spectrometer combining various techniques of radiation detection in space. It characterizes the first time the radiation environment on the Mars surface, and provide dose and dose equivalent rates as precursor information absolutely necessary to develop ways to mitigate the radiation risks for future human exploration on Mars. The Martian radiation levels are much higher than those found on Earth and they are relatively low for space. Measurements on the surface will show if they are similar or not to those seen in orbit (modified by the presence of ``albedo'' neutrons produced in the regolith and by the thin Martian atmosphere). IRAS consists of a telescope based on segmented silicon detectors of about 40\\userk\\milli\\metre\\user;k diameter and 300\\user;k\\micro\\metre\\user;k thickness, a segmented organic scintillator, and of a thermoluminescence dosimeter. The telescope will continuously monitor temporal variation of the particle count rate, the dose rate, particle and LET (Linear Energy Transfer) spectra. Tissue equivalent BC430 scintillator material will be used to measure the neutron dose. Neutrons are selected by a criteria requiring no signal in the anti-coincidence. Last, the passive thermoluminescence dosimeter, based on LiF:Mg detectors, regardless the on board operation timing, will measure the total dose accumulated during the exposure period and due to beta and gamma radiation, with a responsivity very close to that of a human tissue.

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

Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

PubMed

Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

2013-06-01

Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at p<0.05, and the analysis was performed using SPSS (v16). A total of 354 HIV-infected patients were included. Seventy-five percent (268/354) of patients completed the SD HBVV, an 84% (226/268) returned for the hepatitis B surface antibody evaluation. Only 47.3% (107/226) responded to standard-dose hepatitis B vaccination. Responders had higher absolute numbers (p=0.017) and percentages of CD4 cells (p<0.001) and were more likely to be receiving HAART (p=0.001). There was a 70% (48/69) response rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. 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

Skin contamination dosimeter

DOEpatents

Hamby, David M [Corvallis, OR; Farsoni, Abdollah T [Corvallis, OR; Cazalas, Edward [Corvallis, OR

2011-06-21

A technique and device provides absolute skin dosimetry in real time at multiple tissue depths simultaneously. The device uses a phoswich detector which has multiple scintillators embedded at different depths within a non-scintillating material. A digital pulse processor connected to the phoswich detector measures a differential distribution (dN/dH) of count rate N as function of pulse height H for signals from each of the multiple scintillators. A digital processor computes in real time from the differential count-rate distribution for each of multiple scintillators an estimate of an ionizing radiation dose delivered to each of multiple depths of skin tissue corresponding to the multiple scintillators embedded at multiple corresponding depths within the non-scintillating material.

Linac-based total body irradiation (TBI) with volumetric modulated arc therapy (VMAT)

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.; Okumus, A.; Uzel, O. E.

2017-02-01

To evaluate dose distribution of Volumetric modulated arc therapy (VMAT) planning tecnique using Versa HD® lineer accelerator to deliver Total Body Irradiation (TBI) on the coach. Eight TBI patient's Treatment Planning System (TPS) were performed with dual arc VMAT for each patient. The VMAT-TBI consisted of three isocentres and three dual overlapping arcs. The prescribed dose was 12 Gy. Mean dose to lung and kidney were restricted less than 10 Gy and max. dose to lens were restricted less than 6 Gy. The plans were verified using 2D array and ion chamber. The comparison between calculation and measurement were made by γ-index analysis and absolute dose. An average total delivery time was determined 923±34 seconds and an average MU was determined 2614±228 MUs for dual arc VMAT. Mean dose to lungs was 9.7±0.2 Gy, mean dose to kidneys was 8.8±0.3 Gy, max. dose to lens was 5.5±0.3 Gy and max. dose was 14.6±0.3 Gy, HI of PTV was 1.13±0.2, mean dose to PTV was 12.6±1.5 Gy and mean γ-index pass rate was %97.1±1.9. The results show that the tecnique for TBI using VMAT on the treatment coach is feasible.

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

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

Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network.

PubMed

Cea Soriano, L; Gaist, D; Soriano-Gabarró, M; García Rodríguez, L A

2017-06-01

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use. © 2017 International Society on Thrombosis and Haemostasis.

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.

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.

[The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

PubMed

Leuker, G; Hingst, V

1992-10-01

Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

[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.

Engineering Technology Of Fish Farming Floating Nets Cages On Polka Dot Grouper (Cromileptes Altivelis) Used Artificial Feed Enriched Phytase Enzyme

NASA Astrophysics Data System (ADS)

Samidjan, Istiyanto; Rachmawati, Diana

2018-02-01

One solution is to utilize engineering technology cultivation floating cage net polka dot grouper (ducker grouper), which is given artificial feed enriched with phytase enzymes. The objectives of this study was to examine the use of technology engineering floating net on ducker grouper on artificial feed that is enriched with different dose phytase enzymes to accelerate growth and survival. The research method used ducker grouper fish size 15,5 ± 0,5 cm in the net cages unit (1 m x 1 m x 1 m), 250 fish per cage, using 12 cages. Each net-cages was made of polyethylens netting, mesh size 12.5 mm. with complete randomized design (CRD) 4 treatment and 3 replication were feed Artificial enriched of phytase enzyme with the doses of A (0 FTU · kg-1 diet), B (200 FTU · kg-1 diet), C (500 FTU · kg-1 diet), and D (800 FTU · kg-1 diet) phytase enzyme. Feed was given 2 times a day in the morning and afternoon with 5% biomass per day. Data includes the growth of absolute weight polka dot grouper, FCR, and survival rate analyzed variety and Test Tukey.The result of the research showed that the difference of artificial feeding enriched phytase enzyme significantly (P <0,05) to growth, food conversion ratio (FCR), survival rete of polka dot grouper. The best treatment at C (500 mg / kg of feed) increase growth of absolute weight of 128.75 g, 1.75 (FCR), and a survival rate of 93.5%.

A study of the action of amlodipine on adrenergically regulated sodium handling by the kidney in normotensive and hypertensive rats.

PubMed Central

Johns, E. J.

1988-01-01

1. An investigation was undertaken to examine the effect of calcium channel blockade, induced by amlodipine, on the ability of the renal sympathetic nerves to cause an antidiuresis and anti-natriuresis in normotensive Sprague Dawley and spontaneously hypertensive rats anaesthetized with pentobarbitone. 2. Low frequency renal nerve stimulation in normotensive rats, which did not change renal blood flow, caused a 15% reduction in glomerular filtration rate and was associated with falls in urine flow of 37%, absolute sodium excretion of 47%, and fractional sodium excretion of 38%. The magnitude of these renal excretory changes was unaffected by prior administration of amlodipine at either 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1. Amlodipine given in the higher dose, decreased basal levels of blood pressure and increased basal urine flow and sodium excretion. 3. In spontaneously hypertensive rats, renal nerve stimulation minimally affected renal haemodynamics but decreased urine flow, absolute and fractional sodium excretion by 29%, 31% and 24%, respectively. 4. Similar renal nerve stimulation in spontaneously hypertensive rats given amlodipine at 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1 caused minimal changes in renal haemodynamics and in the excretion of water and sodium. The higher dose of drug resulted in decreased blood pressure and increased basal rates of urine flow and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2967097

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.

Development of a portable graphite calorimeter for radiation dosimetry.

PubMed

Sakama, Makoto; Kanai, Tatsuaki; Fukumura, Akifumi

2008-01-01

We developed and performance-tested a portable graphite calorimeter designed to measure the absolute dosimetry of various beams including heavy-ion beams, based on a flexible and convenient means of measurement. This measurement system is fully remote-controlled by the GPIB system. This system uses a digital PID (Proportional, Integral, Derivative) control method based on the LabVIEW software. It was possible to attain stable conditions in a shorter time by this system. The standard deviation of the measurements using the calorimeter was 0.79% at a dose rate of 0.8 Gy/min in 17 calorimeter runs for a (60)Co photon beam. The overall uncertainties for the absorbed dose to graphite and water of the (60)Co photon beam using the developed calorimeter were 0.89% and 1.35%, respectively. Estimations of the correction factors due to vacuum gaps, impurities in the core, the dose gradient and the radiation profile were included in the uncertainties. The absorbed doses to graphite and water irradiated by the (60)Co photon beam were compared with dosimetry measurements obtained using three ionization chambers. The absorbed doses to graphite and water estimated by the two dosimetry methods agreed within 0.1% and 0.3%, respectively.

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.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

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

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

A pilot study of denileukin diftitox (DD) in combination with high-dose interleukin-2 (IL-2) for patients with metastatic renal cell carcinoma (RCC).

PubMed

Atchison, Elizabeth; Eklund, John; Martone, Brenda; Wang, Lili; Gidron, Adi; Macvicar, Gary; Rademaker, Alfred; Goolsby, Charles; Marszalek, Laura; Kozlowski, James; Smith, Norm; Kuzel, Timothy M

2010-09-01

High-dose (HD) IL-2 is approved to treat renal cell carcinoma (RCC) with modest response rates and significant toxicity. Enhancement of cytotoxic T-cell activity by IL-2 is 1 mechanism of action. IL-2 also stimulates regulatory T lymphocytes (Tregs), which are associated with poor prognosis. Favorable outcomes are associated with greater rebound absolute lymphocyte count (Fumagalli 2003). DD depletes IL-2 receptor (CD25 component) expressing cells. We hypothesized that sequential therapy could complement each other; DD would deplete Tregs so IL-2 could more effectively stimulate proliferation and activity of cytotoxic T lymphocytes. Patients (n=18) received standard HD IL-2 and 1 dose of DD daily for 3 days; periodic flow cytometry and complete blood counts were performed. Group A included 3 patients to assess safety only with DD 6 μg/kg between the IL-2 courses. Group B included 9 patients at 9 μg/kg DD before the IL-2 courses. Group C included 6 patients at 9 μg/kg DD between the IL-2 courses. Efficacy using the RECIST criteria was assessed after the treatment. Fifteen patients from a study of IL-2 without DD served as controls for toxicity comparison and 13 of these for flow cytometry comparisons. No unusual toxicity was noted. For group B/C patients receiving DD, the median decline in Tregs was 56.3% from pre-DD to post-DD (P=0.013). Peak absolute lymphocyte count change from baseline was +9980/μL for group B, +4470/μL for group C, and +4720/μL for the controls (P=0.005 B vs. C). The overall response rate was 5 of 15 (33%); 3 of 9 (33%) and 2 of 6 (33%) for groups B and C, respectively, including 2 patients with sarcomatoid RCC and 1 with earlier sunitinib therapy.

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer

PubMed Central

Janowitz, Tobias; Williams, Edward H.; Marshall, Andrea; Ainsworth, Nicola; Thomas, Peter B.; Sammut, Stephen J.; Shepherd, Scott; White, Jeff; Mark, Patrick B.; Lynch, Andy G.; Jodrell, Duncan I.; Tavaré, Simon; Earl, Helena

2017-01-01

Purpose The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%. Results Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. Conclusion In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care. PMID:28686534

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.

PubMed

Janowitz, Tobias; Williams, Edward H; Marshall, Andrea; Ainsworth, Nicola; Thomas, Peter B; Sammut, Stephen J; Shepherd, Scott; White, Jeff; Mark, Patrick B; Lynch, Andy G; Jodrell, Duncan I; Tavaré, Simon; Earl, Helena

2017-08-20

Purpose The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 ( 51 Cr) EDTA excretion measurements ( 51 Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51 Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%. Results Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)-adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. Conclusion In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.

Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

PubMed

Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

2016-03-07

Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

Scintillating fiber optic dosimeters for breast and prostate brachytherapy

NASA Astrophysics Data System (ADS)

Moutinho, L. M.; Castro, I. F.; Freitas, H.; Melo, J.; Silva, P.; Gonçalves, A.; Peralta, L.; Rachinhas, P. J.; Simões, P. C. P. S.; Pinto, S.; Pereira, A.; Santos, J. A. M.; Costa, M.; Veloso, J. F. C. A.

2017-02-01

Brachytherapy is a radiotherapy modality where the radioactive material is placed close to the tumor, being a common treatment for skin, breast, gynecological and prostate cancers. These treatments can be of low-dose-rate, using isotopes with mean energy of 30 keV, or high-dose-rate, using isotopes such as 192Ir with a mean energy of 380 keV. Currently these treatments are performed in most cases without in-vivo dosimetry for quality control and quality assurance. We developed a dosimeter using small diameter probes that can be inserted into the patient's body using standard brachytherapy needles. By performing real-time dosimetry in breast and prostate brachytherapy it will be possible to perform real-time dose correction when deviations from the treatment plan are observed. The dosimeter presented in this work was evaluated in-vitro. The studies consisted in the characterization of the dosimeter with 500 μm diameter sensitive probes (with a BCF-12 scintillating optical fiber) using an inhouse made gelatin breast phantom with a volume of 566 cm3. A breast brachytherapy treatment was simulated considering a tumor volume of 27 cm3 and a prescribed absolute dose of 5 Gy. The dose distribution was determined by the Inverse Planning Simulated Annealing (IPSA) optimization algorithm (ELEKTA). The dwell times estimated from the experimental measurements are in agreement with the prescribed dwell times, with relative error below 3%. The measured signal-to-noise ratio (SNR) including the stem-effect contribution is below 3%.

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

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

Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage.

PubMed

Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita

2015-10-13

Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

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.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

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

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

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.

SU-E-T-472: A Multi-Dimensional Measurements Comparison to Analyze a 3D Patient Specific QA Tool

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

Ashmeg, S; Jackson, J; Zhang, Y

Purpose: To quantitatively evaluate a 3D patient specific QA tool using 2D film and 3D Presage dosimetry. Methods: A brain IMRT case was delivered to Delta4, EBT2 film and Presage plastic dosimeter. The film was inserted in the solid water slabs at 7.5cm depth for measurement. The Presage dosimeter was inserted into a head phantom for 3D dose measurement. Delta4's Anatomy software was used to calculate the corresponding dose to the film in solid water slabs and to Presage in the head phantom. The results from Anatomy were compared to both calculated results from Eclipse and measured dose from filmmore » and Presage to evaluate its accuracy. Using RIT software, we compared the “Anatomy” dose to the EBT2 film measurement and the film measurement to ECLIPSE calculation. For 3D analysis, DICOM file of “Anatomy” was extracted and imported to CERR software, which was used to compare the Presage dose to both “Anatomy” calculation and ECLIPSE calculation. Gamma criteria of 3% - 3mm and 5% - 5mm was used for comparison. Results: Gamma passing rates of film vs “Anatomy”, “Anatomy” vs ECLIPSE and film vs ECLIPSE were 82.8%, 70.9% and 87.6% respectively when 3% - 3mm criteria is used. When the criteria is changed to 5% - 5mm, the passing rates became 87.8%, 76.3% and 90.8% respectively. For 3D analysis, Anatomy vs ECLIPSE showed gamma passing rate of 86.4% and 93.3% for 3% - 3mm and 5% - 5mm respectively. The rate is 77.0% for Presage vs ECLIPSE analysis. The Anatomy vs ECLIPSE were absolute dose comparison. However, film and Presage analysis were relative comparison Conclusion: The results show higher passing rate in 3D than 2D in “Anatomy” software. This could be due to the higher degrees of freedom in 3D than in 2D for gamma analysis.« less

Development and validation of UPLC-MS/MS assay for quantification of cladrin: Absolute bioavailability and dose proportionality study in rats.

PubMed

Rashid, Mamunur; Singh, Sandeep K; Malik, Mohd Yaseen; Jahan, Sadaf; Chaturvedi, Swati; Taneja, Isha; Raju, Kanumuri Sivarama; Naseem, Zaiba; Gayen, J R; Wahajuddin, Muhammad

2018-04-15

Cladrin, an isoflavone is a major bioactive constituent found in stem bark of Butea monosperma with remarkable osteogenic activity. A speedy and sensitive UPLC coupled tandem mass spectrometry (UPLC-MS/MS) method was developed, validated and successfully applied to bioavailability, blood partitioning, plasma protein binding, intravenous and multiple-dose oral pharmacokinetics of cladrin in rats. Separation was done on C18 column (5.0 μm, 4.6 × 50 mm) using mobile phase containing acetonitrile and 0.10% formic acid in the ratio of 65:35 (v/v) with 0.60 mL/min flow rate. The method was highly sensitive and has a short run time of 2.50 min with an excellent linearity (R 2  > 0.99) in the range of 0.20-200 μg/L. Absolute bioavailability was found to be 16.58, 19.04 and 6.76% at oral doses of 5, 10, and 20 mg/Kg, respectively. Cladrin was rapidly absorbed (T max 3.0 h) with a high apparent volume of distribution (15.03 ± 1.79L/Kg), high clearance (2.27 ± 0.30L/h/Kg) and high plasma protein binding. The present study is a first comprehensive in-vitro as well as the in-vivo preclinical pharmacokinetic report of cladrin giving insights about its drug-likeness and further development as a potential therapeutic agent. Copyright © 2018 Elsevier B.V. All rights reserved.

A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405)

NASA Astrophysics Data System (ADS)

Díez, P.; Aird, E. G. A.; Sander, T.; Gouldstone, C. A.; Sharpe, P. H. G.; Lee, C. D.; Lowe, G.; Thomas, R. A. S.; Simnor, T.; Bownes, P.; Bidmead, M.; Gandon, L.; Eaton, D.; Palmer, A. L.

2017-12-01

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre’s treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres’ calculated dose showed a mean difference (±SD) of  +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

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

Wu, Q

Purpose: According to clinical and research requirement, we develop a function of automatic reading dose of interest from dose volume histogram(DVH), to replace the traditional method with a mouse one by one point, and it's also verified. Methods: The DVH automatic reading function will be developed in an in-house developed radiotherapy information management system(RTIMS), which is based on Apache+PHP+MySQL. A DVH ASCII file is exported from Varian Eclipse V8.6, which includes the following contents: 1. basic information of patient; 2. dose information of plan; 3. dose information of structures, including basic information and dose volume data of target volume andmore » organ at risk. And the default exported dose volume data also includes relative doses by 1% step and corresponding absolute doses and cumulative relative volumes, and the volumes are 4 decimal fraction. Clinically, we often need read the doses of some integer percent volumes, such as D50 and D30. So it couldn't be directly obtained from the above data, but we can use linear interpolation bye the near volumes and doses: Dx=D2−(V2−Vx)*(D2−D1)/(V2−V1), and program a function to search, read and calculate the corresponding data. And the doses of all preseted volume of interest of all structures can be automatically read one by one patient, and saved as a CSV file. To verify it, we select 24 IMRT plans for prostate cancer, and doses of interest are PTV D98/D95/D5/D2, bladder D30/D50, and rectum D25/D50. Two groups of data, using the automatic reading method(ARM) and pointed dose method(PDM), are analyzed with SPSS 16. The absolute difference=D-ARM-D-PDM, relative difference=absolute difference*100%/prescription dose(7600cGy). Results: The differences are as following: PTV D98/D95/D5/D2: −0.04%/− 0.04%/0.13%/0.19%, bladder D30/D50: −0.02%/0.01%, and rectum D25/D50: 0.03%/0.01%. Conclusion: Using this function, the error is very small, and can be neglected. It could greatly improve the efficiency of clinical work. Project supported by the National Natural Science Foundation of China (Grant No.81101694)« less

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.

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.

Field Trial of Attentuated 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

1988-05-18

trial was initiated in Area Sur Oriente and Area Norte, Santiago, Chile,. to compare the relative and absolute’ efficacy of three doses of Ty2la vaccine ...neighboirhood of Area Oriente, Santiago with the broad objective of pr3paring a field area uhere the efficacy of vaccines against Shigella...The high incidence rates of Shisella, ETEC, and EPEC infection make Santa Julia a suitable place for testing the efficacy of vaccines against these

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.

PubMed

Mitra, Souvik; Florez, Ivan D; Tamayo, Maria E; Mbuagbaw, Lawrence; Vanniyasingam, Thuva; Veroniki, Areti Angeliki; Zea, Adriana M; Zhang, Yuan; Sadeghirad, Behnam; Thabane, Lehana

2018-03-27

Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. PROSPERO Identifier: CRD42015015797.

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis.

PubMed

Xu, Ying; Hackett, Maree; Carter, Gregory; Loo, Colleen; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A; Mitchell, Philip B; Rodgers, Anthony

2016-04-01

Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5 mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50 mg intra-nasal spray, another assessed 0.1-0.4 mg/kg i.v., and another assessed 0.1-0.5 mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6-7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2-5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis

PubMed Central

Xu, Ying; Hackett, Maree; Carter, Gregory; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A.; Mitchell, Philip B.; Rodgers, Anthony

2016-01-01

Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1–0.4mg/kg i.v., and another assessed 0.1–0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6–7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2–5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. PMID:26578082

The Effectiveness of a Rater Training Booklet in Increasing Accuracy of Performance Ratings

DTIC Science & Technology

1988-04-01

subjects’ ratings were compared for accuracy. The dependent measure was the absolute deviation score of each individual’s rating from the "true score". The...subjects’ ratings were compared for accuracy. The dependent measure was the absolute deviation score of each individual’s rating from the "true score". The...r IS % _. Findings: The absolute deviation scores of each individual’s ratings from the "true score" provided by subject matter experts were analyzed

Transit dosimetry in IMRT with an a-Si EPID in direct detection configuration

NASA Astrophysics Data System (ADS)

Sabet, Mahsheed; Rowshanfarzad, Pejman; Vial, Philip; Menk, Frederick W.; Greer, Peter B.

2012-08-01

In this study an amorphous silicon electronic portal imaging device (a-Si EPID) converted to direct detection configuration was investigated as a transit dosimeter for intensity modulated radiation therapy (IMRT). After calibration to dose and correction for a background offset signal, the EPID-measured absolute IMRT transit doses for 29 fields were compared to a MatriXX two-dimensional array of ionization chambers (as reference) using Gamma evaluation (3%, 3 mm). The MatriXX was first evaluated as reference for transit dosimetry. The accuracy of EPID measurements was also investigated by comparison of point dose measurements by an ionization chamber on the central axis with slab and anthropomorphic phantoms in a range of simple to complex fields. The uncertainty in ionization chamber measurements in IMRT fields was also investigated by its displacement from the central axis and comparison with the central axis measurements. Comparison of the absolute doses measured by the EPID and MatriXX with slab phantoms in IMRT fields showed that on average 96.4% and 97.5% of points had a Gamma index<1 in head and neck and prostate fields, respectively. For absolute dose comparisons with anthropomorphic phantoms, the values changed to an average of 93.6%, 93.7% and 94.4% of points with Gamma index<1 in head and neck, brain and prostate fields, respectively. Point doses measured by the EPID and ionization chamber were within 3% difference for all conditions. The deviations introduced in the response of the ionization chamber in IMRT fields were<1%. The direct EPID performance for transit dosimetry showed that it has the potential to perform accurate, efficient and comprehensive in vivo dosimetry for IMRT.

Source position verification and dosimetry in HDR brachytherapy using an EPID.

PubMed

Smith, R L; Taylor, M L; McDermott, L N; Haworth, A; Millar, J L; Franich, R D

2013-11-01

Accurate treatment delivery in high dose rate (HDR) brachytherapy requires correct source dwell positions and dwell times to be administered relative to each other and to the surrounding anatomy. Treatment delivery inaccuracies predominantly occur for two reasons: (i) anatomical movement or (ii) as a result of human errors that are usually related to incorrect implementation of the planned treatment. Electronic portal imaging devices (EPIDs) were originally developed for patient position verification in external beam radiotherapy and their application has been extended to provide dosimetric information. The authors have characterized the response of an EPID for use with an (192)Ir brachytherapy source to demonstrate its use as a verification device, providing both source position and dosimetric information. Characterization of the EPID response using an (192)Ir brachytherapy source included investigations of reproducibility, linearity with dose rate, photon energy dependence, and charge build-up effects associated with exposure time and image acquisition time. Source position resolution in three dimensions was determined. To illustrate treatment verification, a simple treatment plan was delivered to a phantom and the measured EPID dose distribution compared with the planned dose. The mean absolute source position error in the plane parallel to the EPID, for dwells measured at 50, 100, and 150 mm source to detector distances (SDD), was determined to be 0.26 mm. The resolution of the z coordinate (perpendicular distance from detector plane) is SDD dependent with 95% confidence intervals of ± 0.1, ± 0.5, and ± 2.0 mm at SDDs of 50, 100, and 150 mm, respectively. The response of the EPID is highly linear to dose rate. The EPID exhibits an over-response to low energy incident photons and this nonlinearity is incorporated into the dose calibration procedure. A distance (spectral) dependent dose rate calibration procedure has been developed. The difference between measured and planned dose is less than 2% for 98.0% of pixels in a two-dimensional plane at an SDD of 100 mm. Our application of EPID dosimetry to HDR brachytherapy provides a quality assurance measure of the geometrical distribution of the delivered dose as well as the source positions, which is not possible with any current HDR brachytherapy verification system.

SU-F-T-307: Peripheral Dose Comparison Between Static and Dynamic Jaw Tracking On a High Definition MLC System

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

Perez-Andujar, A; Cheung, J; Chuang, C

Purpose: To investigate the effect of dynamic and static jaw tracking on patient peripheral doses. Materials and Methods: A patient plan with a large sacral metastasis (volume 800cm3, prescription 600cGyx5) was selected for this study. The plan was created using 2-field RapidArc with jaw tracking enabled (Eclipse, V11.0.31). These fields were then exported and edited in MATLAB with static jaw positions using the control point with the largest field size for each respective arc, but preserving the optimized leaf sequences for delivery. These fields were imported back into Eclipse for dose calculation and comparison and copied to a Rando phantommore » for delivery analysis. Points were chosen in the phantom at depth and on the phantom surface at locations outside the primary radiation field, at distances of 12cm, 20cm, and 30cm from the isocenter. Measurements were acquired with OSLDs placed at these positions in the phantom with both the dynamic and static jaw deliveries for comparison. Surface measurements included an additional 1cm bolus over the OSLDs to ensure electron equilibrium. Results: The static jaw deliveries resulted in cumulative jaw-defined field sizes of 17.3% and 17.4% greater area than the dynamic jaw deliveries for each arc. The static jaw plan resulted in very small differences in calculated dose in the treatment planning system ranging from 0–16cGy. The measured dose differences were larger than calculated, but the differences in absolute dose were small. The measured dose differences at depth (surface) between the two deliveries showed an increase for the static jaw delivery of 2.2%(11.4%), 15.6%(20.0%), and 12.7%(12.7%) for distances of 12cm, 20cm, and 30cm, respectively. Eclipse calculates a difference of 0–3.1% for all of these points. The largest absolute dose difference between all points was 6.2cGy. Conclusion: While we demonstrated larger than expected differences in peripheral dose, the absolute dose differences were small.« 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.

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

Limitations of silicon diodes for clinical electron dosimetry.

PubMed

Song, Haijun; Ahmad, Munir; Deng, Jun; Chen, Zhe; Yue, Ning J; Nath, Ravinder

2006-01-01

This work investigates the relevance of several factors affecting the response of silicon diode dosemeters in depth-dose scans of electron beams. These factors are electron energy, instantaneous dose rate, dose per pulse, photon/electron dose ratio and electron scattering angle (directional response). Data from the literature and our own experiments indicate that the impact of these factors may be up to +/-15%. Thus, the different factors would have to cancel out perfectly at all depths in order to produce true depth-dose curves. There are reports of good agreement between depth-doses measured with diodes and ionisation chambers. However, our measurements with a Scantronix electron field detector (EFD) diode and with a plane-parallel ionisation chamber show discrepancies both in the build-up and in the low-dose regions, with a ratio up to 1.4. Moreover, the absolute sensitivity of two diodes of the same EFD model was found to differ by a factor of 3, and this ratio was not constant but changed with depth between 5 and 15% in the low-dose regions of some clinical electron beams. Owing to these inhomogeneities among diodes even of the same model, corrections for each factor would have to be diode-specific and beam-specific. All these corrections would have to be determined using parallel plane chambers, as recommended by AAPM TG-25, which would be unrealistic in clinical practice. Our conclusion is that in general diodes are not reliable in the measurement of depth-dose curves of clinical electron beams.

The fading American dream: Trends in absolute income mobility since 1940.

PubMed

Chetty, Raj; Grusky, David; Hell, Maximilian; Hendren, Nathaniel; Manduca, Robert; Narang, Jimmy

2017-04-28

We estimated rates of "absolute income mobility"-the fraction of children who earn more than their parents-by combining data from U.S. Census and Current Population Survey cross sections with panel data from de-identified tax records. We found that rates of absolute mobility have fallen from approximately 90% for children born in 1940 to 50% for children born in the 1980s. Increasing Gross Domestic Product (GDP) growth rates alone cannot restore absolute mobility to the rates experienced by children born in the 1940s. However, distributing current GDP growth more equally across income groups as in the 1940 birth cohort would reverse more than 70% of the decline in mobility. These results imply that reviving the "American dream" of high rates of absolute mobility would require economic growth that is shared more broadly across the income distribution. Copyright © 2017, American Association for the Advancement of Science.

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.

Poster - Thurs Eve-43: Verification of dose calculation with tissue inhomogeneity using MapCHECK.

PubMed

Korol, R; Chen, J; Mosalaei, H; Karnas, S

2008-07-01

MapCHECK (Sun Nuclear, Melbourne, FL) with 445 diode detectors has been used widely for routine IMRT quality assurance (QA) 1 . However, routine IMRT QA has not included the verification of inhomogeneity effects. The objective of this study is to use MapCHECK and a phantom to verify dose calculation and IMRT delivery with tissue inhomogeneity. A phantom with tissue inhomogeneities was placed on top of MapCHECK to measure the planar dose for an anterior beam with photon energy 6 MV or 18 MV. The phantom was composed of a 3.5 cm thick block of lung equivalent material and solid water arranged side by side with a 0.5 cm slab of solid water on the top of the phantom. The phantom setup including MapCHECK was CT scanned and imported into Pinnacle 8.0d for dose calculation. Absolute dose distributions were compared with gamma criteria 3% for dose difference and 3 mm for distance-to-agreement. The results are in good agreement between the measured and calculated planar dose with 88% pass rate based on the gamma analysis. The major dose difference was at the lung-water interface. Further investigation will be performed on a custom designed inhomogeneity phantom with inserts of varying densities and effective depth to create various dose gradients at the interface for dose calculation and delivery verification. In conclusion, a phantom with tissue inhomogeneities can be used with MapCHECK for verification of dose calculation and delivery with tissue inhomogeneity. © 2008 American Association of Physicists in Medicine.

Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.

PubMed

1996-09-07

Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Development of a PET cyclotron based irradiation setup for proton radiobiology

NASA Astrophysics Data System (ADS)

Ghithan, Sharif; Crespo, Paulo; do Carmo, S. J. C.; Ferreira Marques, Rui; Fraga, F. A. F.; Simões, Hugo; Alves, Francisco; Rachinhas, P. J. B. M.

2015-02-01

An out-of-yoke irradiation setup using the proton beam from a cyclotron that ordinary produces radioisotopes for positron emission tomography (PET) has been developed, characterized, calibrated and validated. The current from a 20 μm thick aluminum transmission foil is readout by home-made transimpedance electronics, providing online dose information. The main monitoring variables, delivered in real-time, include beam current, integrated charge and dose rate. Hence the dose and integrated current delivered at a given instant to an experimental setup can be computer-controlled with a shutter. In this work, we report on experimental results and Geant4 simulations of a setup which exploits for the first time the 18 MeV proton beam from a PET cyclotron to irradiate a selected region of a target using the developed irradiation system. By using this system, we are able to deliver a homogeneous beam on targets with 18 mm diameter, allowing to achieve the controlled irradiation of cell cultures located in biological multi-well dishes of 16 mm diameter. We found that the magnetic field applied inside the cyclotron plays a major role for achieving the referred to homogeneity. The quasi-Gaussian curve obtained by scanning the magnet current and measuring the corresponding dose rate must be measured before any irradiation procedure, with the shutter closed. At the optimum magnet current, which corresponds to the center of the Gaussian, a homogenous dose is observed over the whole target area. Making use of a rotating disk with a slit of 0.5 mm at a radius of 150 mm, we could measure dose rates on target ranging from 500 mGy/s down to 5 mGy/s. For validating the developed irradiation setup, several Gafchromic® EBT2 films were exposed to different values of dose. The absolute dose in the irradiated films were assessed in the 2D film dosimetry system of the Department of Radiotherapy of Coimbra University Hospital Center with a precision better than 2%. In the future, we plan to irradiate small animals, cell cultures, or other materials or samples.

Subcutaneous Administration of Otelixizumab is Limited by Injection Site Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.

PubMed

MacDonald, A; Ambery, P; Donaldson, J; Hicks, K; Keymeulen, B; Parkin, J

2016-05-01

Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously. We investigated single- and repeat-dose subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in small cohorts of patients with type 1 diabetes. Transient reductions in free or unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were observed in the blood of these patients during treatment, consistent with the known mechanism of action of otelixizumab and other anti-CD3 monoclonal antibodies. This was despite the very low systemic exposure of antibodies measured during the same time period. With the exception of sporadic headaches, other symptoms associated with cytokine release syndrome, such as fever, nausea, vomiting, myalgia, and arthralgia, were absent in treated patients. However, treatment-related injection site reactions were consistently observed. The reactions were erythematous and their sizes were dose-dependent; in some cases, reactions persisted for up to 2 weeks following the start of treatment. While patients responded well to topical corticosteroid treatment and prophylaxis reduced the intensity of injection site reactions, the reactions were considered dose-limiting and higher doses were not investigated. © Georg Thieme Verlag KG Stuttgart · New York.

Design and statistical considerations for studies evaluating the efficacy of a single dose of the human papillomavirus (HPV) vaccine.

PubMed

Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H

2018-05-01

Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.

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

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

Absolute Bioavailability and Pharmacokinetics of Linezolid in Hospitalized Patients Given Enteral Feedings

PubMed Central

Beringer, Paul; Nguyen, Megan; Hoem, Nils; Louie, Stan; Gill, Mark; Gurevitch, Michael; Wong-Beringer, Annie

2005-01-01

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens which are common causes of infections in hospitalized patients. Many such patients rely on the intravenous or enteral route for nutrition and drug administration. Therefore, the bioavailability of linezolid administered enterally in the presence of enteral feedings in hospitalized patients was examined. Eighteen subjects were assessed in a randomized single-dose crossover study; 12 received continuous enteral feedings, while 6 did not (controls). Both groups received linezolid 600 mg intravenously and orally (control) or enterally, with the alternate route of administration separated by a 24-h washout period. Pharmacokinetic parameters derived from noncompartmental and compartmental analysis incorporating linear and nonlinear elimination pathways were compared between groups: F, Ka, Vs, K23, K32, Vmax, Km, and K20 (bioavailability, absorption rate constant, volume of central compartment normalized to body weight, intercompartmental rate constants, maximum velocity, Michaelis-Menten constant, and elimination rate constant, respectively). Pharmacokinetic (PK) data were available from 17 patients. The linezolid oral suspension was rapidly and completely absorbed by either the oral or enteral route of administration. Bioavailability was unaltered in the presence of enteral feedings. PK estimates remain similar regardless of the model applied. At the therapeutic dose used, only slight nonlinearity in elimination was observed. A linezolid oral suspension may be administered via the enteral route to hospitalized patients without compromise in its excellent bioavailability and rapid rate of absorption. Compartmental pharmacokinetic analysis offers a more flexible study application, since bioavailability (F) can be estimated directly with intermixed intravenous/oral doses without a need for a washout period. PMID:16127039

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.

Validation of GPU based TomoTherapy dose calculation engine.

PubMed

Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

2012-04-01

The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) < 1. The worst case observed in the phantom had 0.22% voxels violating the criterion. In patient cases, the worst percentage of voxels violating the criterion was 0.57%. For absolute point dose verification, all cases agreed with measurement to within ±3% with average error magnitude within 1%. All cases passed the acceptance criterion that more than 95% of the pixels have Γ(3%, 3 mm) < 1 in film measurement, and the average passing pixel percentage is 98.5%-99%. The GPU dose engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

Effect of tissue composition on dose distribution in brachytherapy with various photon emitting sources

PubMed Central

Ghorbani, Mahdi; Salahshour, Fateme; Haghparast, Abbas; Knaup, Courtney

2014-01-01

Purpose The aim of this study is to compare the dose in various soft tissues in brachytherapy with photon emitting sources. Material and methods 103Pd, 125I, 169Yb, 192Ir brachytherapy sources were simulated with MCNPX Monte Carlo code, and their dose rate constant and radial dose function were compared with the published data. A spherical phantom with 50 cm radius was simulated and the dose at various radial distances in adipose tissue, breast tissue, 4-component soft tissue, brain (grey/white matter), muscle (skeletal), lung tissue, blood (whole), 9-component soft tissue, and water were calculated. The absolute dose and relative dose difference with respect to 9-component soft tissue was obtained for various materials, sources, and distances. Results There was good agreement between the dosimetric parameters of the sources and the published data. Adipose tissue, breast tissue, 4-component soft tissue, and water showed the greatest difference in dose relative to the dose to the 9-component soft tissue. The other soft tissues showed lower dose differences. The dose difference was also higher for 103Pd source than for 125I, 169Yb, and 192Ir sources. Furthermore, greater distances from the source had higher relative dose differences and the effect can be justified due to the change in photon spectrum (softening or hardening) as photons traverse the phantom material. Conclusions The ignorance of soft tissue characteristics (density, composition, etc.) by treatment planning systems incorporates a significant error in dose delivery to the patient in brachytherapy with photon sources. The error depends on the type of soft tissue, brachytherapy source, as well as the distance from the source. PMID:24790623

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.

Effects of resistance or aerobic exercise training on total and regional body composition in sedentary overweight middle-aged adults.

PubMed

Donges, Cheyne E; Duffield, Rob

2012-06-01

The purpose of this study was to examine the effects of 10 weeks of aerobic endurance training (AET), resistance exercise training (RET), or a control (CON) condition on absolute and relative fat mass (FM) or fat-free mass (FFM) in the total body (TB) and regions of interest (ROIs) of sedentary overweight middle-aged males and females. Following prescreening, 102 subjects underwent anthropometric measurements, dual-energy X-ray absorptiometry, and strength and aerobic exercise testing. Randomized subjects (male RET, n = 16; female RET, n = 19; male AET, n = 16; and female AET, n = 25) completed supervised and periodized exercise programs (AET, 30-50 min cycling at 70%-75% maximal heart rate; RET, 2-4 sets × 8-10 repetitions of 5-7 exercises at 70%-75% 1 repetition maximum) or a nonexercising control condition (male CON, n = 13 and female CON, n = 13). Changes in absolute and relative TB-FM and TB-FFM and ROI-FM and ROI-FFM were determined. At baseline, and although matched for age and body mass index, males had greater strength, aerobic fitness, body mass, absolute and relative TB-FFM and ROI-FFM, but reduced absolute and relative TB-FM and ROI-FM, compared with females (p < 0.05). After training, both female exercise groups showed equivalent or greater relative improvements in strength and aerobic fitness than did the male exercise groups (p < 0.05); however, the male exercise groups increased TB-FFM and reduced TB-FM more than did the female exercise groups (p < 0.05). Male AET altered absolute FM more than male RET altered absolute FFM, thus resulting in a greater enhancement of relative FFM. Despite equivalent or greater responses to RET or AET by female subjects, the corresponding respective increases in FFM or reductions in FM were lower than those in males, indicating that a biased dose-response relationship exists between sexes following 10 weeks of exercise training.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

PubMed

van Rein, N; Biedermann, J S; van der Meer, F J M; Cannegieter, S C; Wiersma, N; Vermaas, H W; Reitsma, P H; Kruip, M J H A; Lijfering, W M

2017-07-01

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials. © 2017 International Society on Thrombosis and Haemostasis.

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)

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

Koay, Eugene J.; Lege, David; Mohan, Radhe

Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in termsmore » of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans.« less

Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer.

PubMed

Koay, Eugene J; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D; Chang, Joe Y

2012-12-01

To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm(3) adaptive and 86.4 cm(3) nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V(70), 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-F-BRE-07: Experimental Validation of a Lung SBRT Technique Using a Novel, True Volumetric Plenoptic-Plastic-Scintillator Detector

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

Goulet, M; Rilling, M; Gingras, L

2014-06-15

Purpose: Lung SBRT is being used by an increasing number of clinics, including our center which recently treated its first patient. In order to validate this technique, the 3D dose distribution of the SBRT plan was measured using a previously developed 3D detector based on plenoptic camera and plastic scintillator technology. The excellent agreement between the detector measurement and the expected dose from the treatment planning system Pinnacle{sup 3} shows great promise and amply justify the development of the technique. Methods: The SBRT treatment comprised 8 non-coplanar 6MV photon fields with a mean field size of 12 cm{sup 2} atmore » isocentre and a total prescription dose of 12Gy per fraction for a total of 48Gy. The 3D detector was composed of a 10×10×10 cm{sup 2} EJ-260 water-equivalent plastic scintillator embedded inside a truncated cylindrical acrylic phantom of 10cm radius. The scintillation light was recorded using a static R5 light-field camera and the 3D dose was reconstructed at a 2mm resolution in all 3 dimensions using an iterative backprojection algorithm. Results: The whole 3D dose distribution was recorded at a rate of one acquisition per second. The mean absolute dose difference between the detector and Pinnacle{sup 3} was 1.3% over the region with more than 10% of the maximum dose. 3D gamma tests performed over the same region yield passing rates of 98.8% and 96.6% with criteria of 3%/1mm and 2%/1mm, respectively. Conclusion: Experimental results showed that our beam modeling and treatment planning system calculation was adequate for the safe administration of small field/high dose techniques such as SBRT. Moreover, because of the real-time capability of the detector, further validation of small field rotational, dynamic or gated technique can be monitored or verified by this system.« less

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.

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

Risk of ischemic heart disease in women after radiotherapy for breast cancer.

PubMed

Darby, Sarah C; Ewertz, Marianne; McGale, Paul; Bennet, Anna M; Blom-Goldman, Ulla; Brønnum, Dorthe; Correa, Candace; Cutter, David; Gagliardi, Giovanna; Gigante, Bruna; Jensen, Maj-Britt; Nisbet, Andrew; Peto, Richard; Rahimi, Kazem; Taylor, Carolyn; Hall, Per

2013-03-14

Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

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

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.

Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model.

PubMed

Sörenby, Anne K; Kumagai-Braesch, Makiko; Sharma, Amit; Hultenby, Kjell R; Wernerson, Annika M; Tibell, Annika B

2008-07-27

Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.

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).

Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery

PubMed Central

He, Pengbo; Li, Qiang; Liu, Xinguo; Dai, Zhongying; Zhao, Ting; Fu, Tingyan; Shen, Guosheng; Ma, Yuanyuan; Huang, Qiyan; Yan, Yuanlin

2014-01-01

Purpose: To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. Methods: In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standard BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%–50% duty cycles (DCs) that were synchronized with the synchrotron’s flat-top phase. Results: All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39–4.65, 2.39–4.59, 1.73–3.50, and 1.73–3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. Conclusions: The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique. PMID:25370622

Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery

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

He, Pengbo; Ma, Yuanyuan; Huang, Qiyan

Purpose: To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. Methods: In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standardmore » BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%–50% duty cycles (DCs) that were synchronized with the synchrotron’s flat-top phase. Results: All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39–4.65, 2.39–4.59, 1.73–3.50, and 1.73–3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. Conclusions: The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique.« less

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.

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

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.

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

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

Levy, R.P.

1991-01-01

An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute [gamma]-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures.« less

Measuring neutron spectra in radiotherapy using the nested neutron spectrometer.

PubMed

Maglieri, Robert; Licea, Angel; Evans, Michael; Seuntjens, Jan; Kildea, John

2015-11-01

Out-of-field neutron doses resulting from photonuclear interactions in the head of a linear accelerator pose an iatrogenic risk to patients and an occupational risk to personnel during radiotherapy. To quantify neutron production, in-room measurements have traditionally been carried out using Bonner sphere systems (BSS) with activation foils and TLDs. In this work, a recently developed active detector, the nested neutron spectrometer (NNS), was tested in radiotherapy bunkers. The NNS is designed for easy handling and is more practical than the traditional BSS. Operated in current-mode, the problem of pulse pileup due to high dose-rates is overcome by measuring current, similar to an ionization chamber. In a bunker housing a Varian Clinac 21EX, the performance of the NNS was evaluated in terms of reproducibility, linearity, and dose-rate effects. Using a custom maximum-likelihood expectation-maximization algorithm, measured neutron spectra at various locations inside the bunker were then compared to Monte Carlo simulations of an identical setup. In terms of dose, neutron ambient dose equivalents were calculated from the measured spectra and compared to bubble detector neutron dose equivalent measurements. The NNS-measured spectra for neutrons at various locations in a treatment room were found to be consistent with expectations for both relative shape and absolute magnitude. Neutron fluence-rate decreased with distance from the source and the shape of the spectrum changed from a dominant fast neutron peak near the Linac head to a dominant thermal neutron peak in the moderating conditions of the maze. Monte Carlo data and NNS-measured spectra agreed within 30% at all locations except in the maze where the deviation was a maximum of 40%. Neutron ambient dose equivalents calculated from the authors' measured spectra were consistent (one standard deviation) with bubble detector measurements in the treatment room. The NNS may be used to reliably measure the neutron spectrum of a radiotherapy beam in less than 1 h, including setup and data unfolding. This work thus represents a new, fast, and practical method for neutron spectral measurements in radiotherapy.

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

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

Free Radical Chemistry of Disinfection Byproducts 2: Rate Constants and Degradation Mechanism of Trichloronitromethane (Chloropicrin)

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

B. J. Mincher; S. K. Cole; W. J. Cooper

2007-02-01

Absolute rate constants for the free-radical-induced degradation of trichloronitromethane (TCNM, chloropicrin) were determined using electron pulse radiolysis and transient absorption spectroscopy. Rate constants for hydroxyl radical, OH, and hydrated electron, eaq-, reactions were (4.97 ± 0.28) × 107 M-1 s-1 and (2.13 ± 0.03) × 1010 M-1 s-1, respectively. It appears that the OH adds to the nitro-group, while the eaq- reacts via dissociative electron attachment to give two carbon centered radicals. The mechanisms of these free radical reactions with TCNM were investigated, using 60Co gamma irradiation at various absorbed doses, measuring the disappearance of TCNM and the appearance ofmore » the product nitrate and chloride ions. The rate constants and mechanistic data were combined in a kinetic computer model that was used to describe the major free radical pathways for the destruction of TCNM in solution. These data are applicable to other advanced oxidation/reduction processes.« less

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Pharmaceutical container/closure integrity. I: Mass spectrometry-based helium leak rate detection for rubber-stoppered glass vials.

PubMed

Kirsch, L E; Nguyen, L; Moeckly, C S

1997-01-01

The development of mass spectrometry-based leak detection for pharmaceutical container integrity was undertaken to provide an alternative to microbial challenge testing. Standard 10-mL vials were modified to contain pinholes (0.5 to 10 microns) by affixing micropipettes with epoxy into 2-mm vial side wall holes. The absolute leak rate was determined using vials that were sealed in a tracer (helium) environment with butyl rubber stoppers and crimps. Alternatively leak rates were determined using vials that were sealed in room air and exposed to tracer under pressure (charging or bombing). Tracer leak rates were measured with mass spectrometry leak rate detectors. The absolute leak rate was correlated the squared nominal leak radius which suggested that the mode of gas flow through the glass pipette leaks was more turbulent than viscous even at low leak rates typically associated with viscous flow. The minimum observed absolute leak rate was about 10(-6.6) std cc/sec and was likely due to helium permeation through the rubber stoppers. Heat-stressed rubber stoppers did not affect the baseline absolute leak rate. Adsorption of helium tracer to the test unit surfaces was found to confound baseline leak rate measurement reliability but was eliminated as a source of variation by exposing the test units to ambient air for > or = 12 hours. The absolute leak rate and the leak rate measured after charging were related in a mathematically predictable way.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

PubMed

Seagle, Brandon-Luke L; Shahabi, Shohreh

2017-04-01

To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

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

Using two detectors concurrently to monitor ambient dose equivalent rates in vehicle surveys of radiocesium contaminated land.

PubMed

Takeishi, Minoru; Shibamichi, Masaru; Malins, Alex; Kurikami, Hiroshi; Murakami, Mitsuhiro; Saegusa, Jun; Yoneya, Masayuki

2017-10-01

In response to the accident at Tokyo Electric Power Company's Fukushima Dai-ichi Nuclear Power Plant (FDNPP), vehicle-borne monitoring was used to map radiation levels for radiological protection of the public. By convention measurements from vehicle-borne surveys are converted to the ambient dose equivalent rate at 1 m height in the absence of the vehicle. This allows for comparison with results from other types of survey, including surveys with hand-held or airborne instruments. To improve the accuracy of the converted results from vehicle-borne surveys, we investigated combining measurements from two detectors mounted on the vehicle at different heights above the ground. A dual-detector setup was added to a JAEA monitoring car and compared against hand-held survey meter measurements in Fukushima Prefecture. The results obtained by combining measurements from two detectors were within ±20% of the hand-held reference measurements. The mean absolute percentage deviation from the reference measurements was 7.2%. The combined results from the two detectors were more accurate than those from either the roof-mounted detector, or the detector inside the vehicle, taken alone. One issue with vehicle-borne surveys is that ambient dose equivalent rates above roads are not necessarily representative of adjacent areas. This is because radiocesium is often deficient on asphalt surfaces, as it is easily scrubbed off by rain, wind and vehicle tires. To tackle this issue, we investigated mounting heights for vehicle-borne detectors using Monte Carlo gamma-ray simulations. When radiocesium is deficient on a road compared to the adjacent land, mounting detectors high on vehicles yields results closer to the values adjacent to the road. The ratio of ambient dose equivalent rates reported by detectors mounted at different heights in a dual-detector setup indicates whether radiocesium is deficient on the road compared to the adjacent land. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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

Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702).

PubMed

Nishio, Teiji; Shirato, Hiroki; Ishikawa, Masayori; Miyabe, Yuki; Kito, Satoshi; Narita, Yuichirou; Onimaru, Rikiya; Ishikura, Satoshi; Ito, Yoshinori; Hiraoka, Masahiro

2014-05-01

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤ 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

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.

Patient-specific quality assurance for the delivery of (60)Co intensity modulated radiation therapy subject to a 0.35-T lateral magnetic field.

PubMed

Li, H Harold; Rodriguez, Vivian L; Green, Olga L; Hu, Yanle; Kashani, Rojano; Wooten, H Omar; Yang, Deshan; Mutic, Sasa

2015-01-01

This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging-guided RT device. The program consisted of: (1) a 1-dimensional multipoint ionization chamber measurement using a customized 15-cm(3) cube-shaped phantom; (2) 2-dimensional (2D) radiographic film measurement using a 30- × 30- × 20-cm(3) phantom with multiple inserted ionization chambers; (3) quasi-3D diode array (ArcCHECK) measurement with a centrally inserted ionization chamber; (4) 2D fluence verification using machine delivery log files; and (5) 3D Monte Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Ionization chamber measurements agreed well with treatment planning system (TPS)-computed doses in all phantom geometries where the mean ± SD difference was 0.0% ± 1.3% (n=102; range, -3.0%-2.9%). Film measurements also showed excellent agreement with the TPS-computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30; range, 87.4%-100%). For ArcCHECK measurements, the mean ± SD passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34; range, 95.8%-100%). 2D fluence maps with a resolution of 1 × 1 mm(2) showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18; range, 97.0%-100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. We developed a dosimetry program for ViewRay's patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay's IMRT QA. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Calorimetry of electron beams and the calibration of dosimeters at high doses

NASA Astrophysics Data System (ADS)

Humphreys, J. C.; McLaughlin, W. L.

Graphite or metal calorimeters are used to make absolute dosimetric measurements of high-energy electron beams. These calibrated beams are then used to calibrate several types of dosimeters for high-dose applications such as medical-product sterilization, polymer modification, food processing, or electronic-device hardness testing. The electron beams are produced either as continuous high-power beams at approximately 4.5 MeV by d.c. type accelerators or in the energy range of approximately 8 to 50 MeV using pulsed microwave linear accelerators (linacs). The continuous beams are generally magnetically scanned to produce a broad, uniform radiation environment for the processing of materials of extended lateral dimensions. The higher-energy pulsed beams may also be scanned for processing applications or may be used in an unscanned, tightly-focused mode to produce maximum absorbed dose rates such as may be required for electronic-device radiation hardness testing. The calorimeters are used over an absorbed dose range of 10 2 to 10 4 Gy. Intercomparison studies are reported between National Institute of Standards and Technology (NIST) and UK National Physical Laboratory (NPL) graphite disk calorimeters at high doses, using the NPL 10-MeV linac, and agreement was found within 1.5%. It was also shown that the electron-beam responses of radiochromic film dosimeters and alanine pellet dosimeters can be accurately calibrated by comparison with calorimeter readings.

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.

Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung.

PubMed

Dolovich, M A

2000-06-01

A number of studies in the literature support the use of fine aerosols of drug, inhaled at low IFRs to target peripheral airways, with the objective of improving clinical responses to inhaled therapy (Fig. 8). Attempts have been made to separate response due to changes in total administered dose or the surface concentration of the dose from response due to changes in site of deposition--both are affected by the particle size of the aerosol, with IFR additionally influencing the latter. The tools for measuring dose and distribution have improved over the last 10-15 years, and thus we should expect greater accuracy in these measurements for assessing drug delivery to the lung. There are still issues, though, in producing radiolabeled (99m)technetium aerosols that are precise markers for the pharmaceutical product being tested and in quantitating absolute doses deposited in the lung. PET isotopes may provide the means for directly labelling a drug and perhaps can offer an alternative for making these measurements in the future, but deposition measurements should not be used in isolation; protocols should incorporate clinical tests to provide parallel therapeutic data in response to inhalation of the drug by the various patient populations being studied.

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.

19 CFR 132.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... indicated: (a) Absolute (or quantitative) quotas. “Absolute (or quantitative) quotas” are those which permit... for consumption of merchandise subject to quota are permitted. Some absolute quotas limit the entry or... absolute or a tariff-rate quota. (f) Quota priority. “Quota priority” is the precedence granted to one...

19 CFR 132.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... indicated: (a) Absolute (or quantitative) quotas. “Absolute (or quantitative) quotas” are those which permit... for consumption of merchandise subject to quota are permitted. Some absolute quotas limit the entry or... absolute or a tariff-rate quota. (f) Quota priority. “Quota priority” is the precedence granted to one...

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.

SU-F-T-09: In Phantom Full-Implant Validation of Plastic Scintillation Detectors for in Vivo Dosimetry During Low Dose Rate Brachytherapy

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

Therriault-Proulx, F; Bruno, T; Beddar, S

Purpose: To validate in a water phantom the use of plastic scintillation detectors to measure dose to the urethra and the rectal wall during a clinically realistic low dose rate (LDR) brachytherapy implant. Methods: A template was designed to replicate a clinically realistic LDR brachytherapy prostate implant inside a water phantom. Twenty-two catheters were inserted, including one mimicking the urethra and another the rectal wall. The needles inserted in the remaining 20 catheters were composed of thin-walled nylon tubes in which I-125 radioactive seeds (Air Kerma Strengths of (0.328±0.020)U) were abutted together with plastic spacers to replicate a typical loading.more » A plastic scintillation detector (PSD) with a 5-mm long × 1-mm diameter sensitive element was first placed inside the urethra and 1-second measurements were performed for 60s after each needle implant. Measurements were also performed at multiple positions along the urethra once all the needles were inserted. The procedure was then repeated with the PSD placed at the rectal wall. Results: Individual dose-rates ranging from 0.07µGy/s to 1.5µGy/s were measured after each needle implant. The average absolute relative differences were (6.2±3.6)% and (6.9±6.5)% to the values calculated with the TG-43 formalism, for the urethra and rectal wall respectively. These results are within expectations from the error uncertainty budget once accounting for uncertainties in seeds’ strength and positioning. Interestingly, the PSD allowed for unplanned error detection as the study was performed. Finally, the measured dose after the full implant at different positions along the mimicked organs at risk were in agreement with TG-43 values for all of the positions tested. Conclusion: Plastic scintillation detectors could be used as in vivo detectors for LDR brachytherapy as they would provide accurate dose information after each needle implant as well as along the organs at risk at the end of the implant.« less

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.

Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.

PubMed Central

Ohnishi, A; Orita, Y; Okahara, R; Fujihara, H; Inoue, T; Yamamura, Y; Yabuuchi, Y; Tanaka, T

1993-01-01

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men. Images PMID:8254021

SU-E-T-50: Automatic Validation of Megavoltage Beams Modeled for Clinical Use in Radiation Therapy

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

Melchior, M; Salinas Aranda, F; 21st Century Oncology, Ft. Myers, FL

2014-06-01

Purpose: To automatically validate megavoltage beams modeled in XiO™ 4.50 (Elekta, Stockholm, Sweden) and Varian Eclipse™ Treatment Planning Systems (TPS) (Varian Associates, Palo Alto, CA, USA), reducing validation time before beam-on for clinical use. Methods: A software application that can automatically read and analyze DICOM RT Dose and W2CAD files was developed using MatLab integrated development environment.TPS calculated dose distributions, in DICOM RT Dose format, and dose values measured in different Varian Clinac beams, in W2CAD format, were compared. Experimental beam data used were those acquired for beam commissioning, collected on a water phantom with a 2D automatic beam scanningmore » system.Two methods were chosen to evaluate dose distributions fitting: gamma analysis and point tests described in Appendix E of IAEA TECDOC-1583. Depth dose curves and beam profiles were evaluated for both open and wedged beams. Tolerance parameters chosen for gamma analysis are 3% and 3 mm dose and distance, respectively.Absolute dose was measured independently at points proposed in Appendix E of TECDOC-1583 to validate software results. Results: TPS calculated depth dose distributions agree with measured beam data under fixed precision values at all depths analyzed. Measured beam dose profiles match TPS calculated doses with high accuracy in both open and wedged beams. Depth and profile dose distributions fitting analysis show gamma values < 1. Relative errors at points proposed in Appendix E of TECDOC-1583 meet therein recommended tolerances.Independent absolute dose measurements at points proposed in Appendix E of TECDOC-1583 confirm software results. Conclusion: Automatic validation of megavoltage beams modeled for their use in the clinic was accomplished. The software tool developed proved efficient, giving users a convenient and reliable environment to decide whether to accept or not a beam model for clinical use. Validation time before beam-on for clinical use was reduced to a few hours.« less

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

The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial

PubMed Central

2011-01-01

Background Our phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) revealed the efficacy in reducing the decline of vital capacity (VC) and increasing the progression-free survival (PFS) time by pirfenidone. Recently, marginal decline in forced VC (FVC) has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC. Methods Improvement ratings based on 5% change in absolute VC, i.e., "improved (VC ≥ 5% increase)", "stable (VC < 5% change)", and "worsened (VC ≥ 5% decrease)" at month 3, 6, 9 and 12 were compared between high-dose pirfenidone (1800 mg/day; n = 108) and placebo (n = 104) groups, and (high-dose and low-dose (1200 mg/day; n = 55)) pirfenidone (n = 163) and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering "worsened" and "non-worsened (improved and stable)" of the ratings at months 3 and 12 as "positive" and "negative", respectively, and the positive and negative predictive values of the ratings were calculated in each group. Results In the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive/negative predictive values in placebo and pirfenidone groups were 86.1%/50.8% and 87.1%/71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year. Conclusions The efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF. Trial Registration This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121). PMID:21756364

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

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

Lichtenstein, A.H.; Cohn, J.S.; Hachey, D.L.

1990-09-01

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of (5,5,5,-2H3)leucine, (4,4,4,-2H3)valine, and (6,6-2H2,1,2-13C2)lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine)more » mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.« less

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

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.

19 CFR 132.5 - Merchandise imported in excess of quota quantities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... quantities. (a) Absolute quota merchandise. Absolute quota merchandise imported in excess of the quantity... merchandise. Merchandise imported in excess of either an absolute or a tariff-rate quota may be held for the...

19 CFR 132.5 - Merchandise imported in excess of quota quantities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... quantities. (a) Absolute quota merchandise. Absolute quota merchandise imported in excess of the quantity... merchandise. Merchandise imported in excess of either an absolute or a tariff-rate quota may be held for the...

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 .).

Poster - Thur Eve - 03: LDR to HDR: RADPOS applications in brachytherapy.

PubMed

Cherpak, A J; Cygler, J E; Kertzscher, G; E, C; Perry, G

2012-07-01

The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor and either one or five MOSFET dosimeters. The feasibility of using the system for quality control has been explored for a range of radiotherapy treatment techniques including most recently transperineal interstitial permanent prostate brachytherapy and high dose rate (HDR) treatments. Dose and position information was collected by a RADPOS array detector inside a Foley catheter within patients' urethra during permanent seed implantation. Ten patients were studied, and average displacement during implantation was Δr = (1.4-5.1) mm, with movements up to 9.7 mm due to the removal of the transrectal ultrasound probe. Maximum integral dose in the prostatic urethra ranged from 110-195 Gy, and it was found that the dose can change up to 63 cGy (62.0%) depending on whether the rectal probe is in place. For HDR, a RADPOS detector was first calibrated with an Ir-192 source. A treatment was then simulated using a total of 50 dwell positions in 5 catheters in an acrylic phantom. Dwell positions ranged from 1 to 10 cm away from the RADPOS detector and dose was measured for each source position. An average calibration coefficient of 0.74±0.11 cGy/mV was calculated for the detector and the average absolute difference between measured values and expected dose was 0.7±5.4 cGy (5±20%). The demonstrated accuracy of RADPOS dose measurements along with its ability to simultaneously measure displacement makes it a powerful tool for brachytherapy treatments, where high dose gradients can present unique in vivo dosimetry challenges. © 2012 American Association of Physicists in Medicine.

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.

SU-E-J-85: Leave-One-Out Perturbation (LOOP) Fitting Algorithm for Absolute Dose Film Calibration

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

Chu, A; Ahmad, M; Chen, Z

2014-06-01

Purpose: To introduce an outliers-recognition fitting routine for film dosimetry. It cannot only be flexible with any linear and non-linear regression but also can provide information for the minimal number of sampling points, critical sampling distributions and evaluating analytical functions for absolute film-dose calibration. Methods: The technique, leave-one-out (LOO) cross validation, is often used for statistical analyses on model performance. We used LOO analyses with perturbed bootstrap fitting called leave-one-out perturbation (LOOP) for film-dose calibration . Given a threshold, the LOO process detects unfit points (“outliers”) compared to other cohorts, and a bootstrap fitting process follows to seek any possibilitiesmore » of using perturbations for further improvement. After that outliers were reconfirmed by a traditional t-test statistics and eliminated, then another LOOP feedback resulted in the final. An over-sampled film-dose- calibration dataset was collected as a reference (dose range: 0-800cGy), and various simulated conditions for outliers and sampling distributions were derived from the reference. Comparisons over the various conditions were made, and the performance of fitting functions, polynomial and rational functions, were evaluated. Results: (1) LOOP can prove its sensitive outlier-recognition by its statistical correlation to an exceptional better goodness-of-fit as outliers being left-out. (2) With sufficient statistical information, the LOOP can correct outliers under some low-sampling conditions that other “robust fits”, e.g. Least Absolute Residuals, cannot. (3) Complete cross-validated analyses of LOOP indicate that the function of rational type demonstrates a much superior performance compared to the polynomial. Even with 5 data points including one outlier, using LOOP with rational function can restore more than a 95% value back to its reference values, while the polynomial fitting completely failed under the same conditions. Conclusion: LOOP can cooperate with any fitting routine functioning as a “robust fit”. In addition, it can be set as a benchmark for film-dose calibration fitting performance.« less

Pharmacokinetics of hERG Channel Blocking Voacangine in Wistar Rats Applying a Validated LC-ESI-MS/MS Method.

PubMed

Mair, Christina E; de Miranda Silva, Carolina; Grienke, Ulrike; Kratz, Jadel M; Carreño, Fernando; Zimmermann, Estevan Sonego; de Araújo, Bibiana Verlindo; Dalla Costa, Teresa; Rollinger, Judith M

2016-07-01

Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-à-go-go-related gene channel blocker in vitro. Blockage of this channel might imply possible cardiotoxicity. Therefore, the aim of this study was to characterise voacangine in vivo to assess its pharmacokinetics and to estimate if further studies to investigate its cardiotoxic risk are required. Male Wistar rats received different doses of voacangine as a pure compound and as a hydro-ethanolic extract of V. africana root bark with a quantified amount of 9.71 % voacangine. For the obtained data, a simultaneous population pharmacokinetics model was successfully developed, comprising a two-compartment model for i. v. dosing and a one-compartmental model with two first-order absorption rates for oral dosing. The absolute bioavailability of voacangine was determined to be 11-13 %. Model analysis showed significant differences in the first absorption rate constant for voacangine administered as a pure compound and voacangine from the extract of V. africana. Taking into account the obtained low bioavailability of voacangine, its cardiotoxic risk might be neglectable in healthy consumers, but may have a serious impact in light of drug/drug interactions and impaired health conditions. Georg Thieme Verlag KG Stuttgart · New York.

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

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

PubMed

King, B H; Wright, D M; Handen, B L; Sikich, L; Zimmerman, A W; McMahon, W; Cantwell, E; Davanzo, P A; Dourish, C T; Dykens, E M; Hooper, S R; Jaselskis, C A; Leventhal, B L; Levitt, J; Lord, C; Lubetsky, M J; Myers, S M; Ozonoff, S; Shah, B G; Snape, M; Shernoff, E W; Williamson, K; Cook, E H

2001-06-01

To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Effect of Mass Flow on Stack Eductor Performance.

DTIC Science & Technology

1984-06-01

absolute viscosity, lbf-sec/ft2 - density, Ibm/ft 3 "function of" ENGLISH LETTER SYMBOLS 2 A - area, in , ft B - atmospheric pressure, in Hg c - sonic... absolute temperature ratio T* - tertiary flow to primary flow absolute temperature t ratio - secondary -o primary mass flow rate ratio W* - tertiary to...secondary to primary absolute Tp temperature ratio TiL tertiary to primary absolute -TE temperature ratio secondary to primary flow density ratio

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.

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

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

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.

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

Poster — Thur Eve — 22: A water calorimeter for low-energy particle beams

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

Renaud, J; Sarfehnia, A; Seuntjens, J

2014-08-15

In this work, the feasibility of absolute dose to water measurements in low-energy electron beams using a water calorimeter specifically developed for shallow measurements is established. The calorimeter design consists of a cylindrical glass vessel encased in a block of expanded polystyrene. The vessel has a front window thickness of 1.1 mm, a 4 cm radius, and is 2.5 cm in depth. The vessel-block assembly sits inside a thermally-insulated box and is air-cooled to an operating temperature of 4 °C. Radiation-induced thermal gradients were simulated in a geometric model of the calorimeter using a finite element analysis software package. 52more » absorbed dose to water measurements were performed in a 6 and 8 MeV electron beam (z{sub max} of 1.32 and 1.76 cm, respectively) for 60 seconds at a repetition rate of 400 MU/min and an SSD of 120 cm. Within the vessel, the depth of measurement was set to 1.08 cm relative to the inner front window. The average measured dose to water was 59.6 ± 0.2 cGy/100 MU (6 MeV), and 63.7 ± 0.3 cGy/100 MU (8 MeV). The associated heat transfer corrections were determined to be 1.026 ± 0.003 and 1.017 ± 0.004 for the 6 and 8 MeV beams, respectively. The most significant source of uncertainty in this study was the repeatability (type A, 0.42%). It is expected that performing fewer consecutive measurements under higher dose rate conditions will improve the stability of the thermal background, thereby improving the repeatability and reducing the overall standard uncertainty.« less

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

Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

PubMed

Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

2016-08-01

The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

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

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

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

PubMed

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Hadsell, M; Holcombe, C; Chin, E

Introduction: As diagnostic techniques become more sensitive and targeting methods grow in accuracy, target volumes continue to shrink and SBRT becomes more prevalent. Due to this fact, patient-specific QA must also enhance resolution and accuracy in order to verify dose delivery in these volumes. It has been suggested that when measuring small fields at least two separate detectors be used to verify delivered dose. Therefore, we have instituted a secondary patient QA verification for small (<3cm) SBRT fields using Gafchromic EBT2 film. Methods: Films were cross-calibrated using a Farmer chamber in plastic water at reference conditions as defined by TG-51.more » Films were scanned, and an RGB calibration curve was created according to best practices published by Ashland, Inc. Four SBRT cases were evaluated both with the Scandidos Delta4 and with EBT2 films sandwiched in plastic water. Raw values obtained from the film were converted to dose using an in-house algorithm employing all three color channels to increase accuracy and dosimetric range. Gamma and dose profile comparisons to Eclipse dose calculations were obtained using RIT and compared to values obtained with the Delta4. Results: Film gamma pass rates at 2% and 2mm were similar to those obtained with the Delta4. However, dose difference histograms showed better absolute dose agreement, with the average mean film dose agreeing with calculation to 0.3% and the Delta4 only agreeing to 3.1% across the cases. Additionally, films provided more resolution than the Delta4 and thus their dose profiles better succeeded in diagnosing dose calculation inaccuracies. Conclusion: We believe that the implementation of secondary patient QA using EBT2 film analyzed with all three color channels is an invaluable tool for evaluation of small SBRT fields. Furthermore, we have shown that this method can sometimes provide a more detailed and faithful reproduction of plan dose than the Delta4.« less

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.

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

An open source solution for an in-house built dynamic platform for the validation of stereotactic ablative body radiotherapy for VMAT and IMRT.

PubMed

Munoz, Luis; Ziebell, Amy; Morton, Jason; Bhat, Madhava

2016-12-01

An in-house solution for the verification of dose delivered to a moving phantom as required for the clinical implementation of lung stereotactic ablative body radiation therapy was developed. The superior-inferior movement required to simulate tumour motion during a normal breathing cycle was achieved via the novel use of an Arduino Uno™, a low-cost open-source microcontroller board connected to a high torque servo motor. Slow CT imaging was used to acquire the image set and a 4D cone beam CT (4D-CBCT) verified the efficacy of contoured margins before treatment on the moving phantom. Treatment fields were delivered to a section of a CIRS™ anthropomorphic phantom. Dose verification to the dynamic phantom with Gafchromic EBT3 film using 3 %-1 mm gamma analysis acceptance criteria registered an absolute dose pass rate for IMRT and VMAT of 98 and 96.6 %, respectively. It was verified that 100 % of the PTV received the prescribed dose of 12 Gy per fraction using the dynamic phantom, and no major discrepancy between planned and measured results due to interplay between multileaf collimator sequences and target motion was observed. This study confirmed that the use of an in-house solution using open source hardware and software with existing quality assurance equipment was appropriate in validating a new treatment technique.

Absolute Sea-level Changes Derived from Integrated Geodetic Datasets (1955-2016) in the Caribbean Sea

NASA Astrophysics Data System (ADS)

Yang, L.; Wang, G.; Liu, H.

2017-12-01

Rising sea level has important direct impacts on coastal and island regions such as the Caribbean where the influence of sea-level rise is becoming more apparent. The Caribbean Sea is a semi-enclosed sea adjacent to the landmasses of South and Central America to the south and west, and the Greater Antilles and the Lesser Antilles separate it from the Atlantic Ocean to the north and east. The work focus on studying the relative and absolute sea-level changes by integrating tide gauge, GPS, and satellite altimetry datasets (1955-2016) within the Caribbean Sea. Further, the two main components of absolute sea-level change, ocean mass and steric sea-level changes, are respectively studied using GRACE, temperature, and salinity datasets (1955-2016). According to the analysis conducted, the sea-level change rates have considerable temporal and spatial variations, and estimates may be subject to the techniques used and observation periods. The average absolute sea-level rise rate is 1.8±0.3 mm/year for the period from 1955 to 2015 according to the integrated tide gauge and GPS observations; the average absolute sea-level rise rate is 3.5±0.6 mm/year for the period from 1993 to 2016 according to the satellite altimetry observations. This study shows that the absolute sea-level change budget in the Caribbean Sea is closed in the periods from 1955 to 2016, in which ocean mass change dominates the absolute sea-level rise. The absolute sea-level change budget is also closed in the periods from 2004 to 2016, in which steric sea-level rise dominates the absolute sea-level rise.

The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors: 1950 – 2001

PubMed Central

Hsu, Wan-Ling; Preston, Dale L.; Soda, Midori; Sugiyama, Hiromi; Funamoto, Sachiyo; Kodama, Kazunori; Kimura, Akiro; Kamada, Nanao; Dohy, Hiroo; Tomonaga, Masao; Iwanaga, Masako; Miyazaki, Yasushi; Cullings, Harry M.; Suyama, Akihiko; Ozasa, Kotaro; Shore, Roy E.; Mabuchi, Kiyohiko

2013-01-01

A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This paper presents analyses of radiation effects on leukemia, lymphoma, and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry-based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma, and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose response relationship and, to the extent the data allowed, to investigate variation in the excess risks with sex, attained age, exposure age, and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a non-linear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this non-linearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to – 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma. PMID:23398354

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

Characterization of a prototype MR-compatible Delta4 QA system in a 1.5 tesla MR-linac

NASA Astrophysics Data System (ADS)

de Vries, J. H. W.; Seravalli, E.; Houweling, A. C.; Woodings, S. J.; van Rooij, R.; Wolthaus, J. W. H.; Lagendijk, J. J. W.; Raaymakers, B. W.

2018-01-01

To perform patient plan quality assurance (QA) on a newly installed MR-linac (MRL) it is necessary to have an MR-compatible QA device. An MR compatible device (MR-Delta4) has been developed together with Scandidos AB (Uppsala, Sweden). The basic characteristics of the detector response, such as short-term reproducibility, dose linearity, field size dependency, dose rate dependency, dose-per-pulse dependency and angular dependency, were investigated for the clinical Delta4-PT as well as for the MR compatible version. All tests were performed with both devices on a conventional linac and the MR compatible device was tested on the MRL as well. No statistically significant differences were found in the short-term reproducibility (<0.1%), dose linearity (⩽0.5%), field size dependency (<2.0% for field sizes larger than 5  ×  5 cm2), dose rate dependency (<1.0%) or angular dependency for any phantom/linac combination. The dose-per-pulse dependency (<0.8%) was found to be significantly different between the two devices. This difference can be explained by the fact that the diodes in the clinical Delta4-PT were irradiated with a much larger dose than the MR-Delta4-PT ones. The absolute difference between the devices (<0.5%) was found to be small, so no clinical impact is expected. For both devices, the results were consistent with the characteristics of the Delta4-PT device reported in the literature (Bedford et al 2009 Phys. Med. Biol. 54 N167-76 Sadagopan et al 2009 J. Appl. Clin. Med. Phys. 10 2928). We found that the characteristics of the MR compatible Delta4 phantom were found to be comparable to the clinically used one. Also, the found characteristics do not differ from the previously reported characteristics of the commercially available non-MR compatible Delta4-PT phantom. Therefore, the MR compatible Delta4 prototype was found to be safe and effective for use in the 1.5 tesla magnetic field of the Elekta MR-linac

A quantified dosing ALD reactor with in-situ diagnostics for surface chemistry studies

NASA Astrophysics Data System (ADS)

Larrabee, Thomas J.

A specialized atomic layer deposition (ALD) reactor has been constructed to serve as an instrument to simultaneously study the surface chemistry of the ALD process, and perform ALD as is conventionally done in continuum flow of inert gas. This reactor is uniquely useful to gain insight into the ALD process because of the combination of its precise, controllable, and quantified dosing/microdosing capability; its in-situ quadrupole mass spectrometer for gas composition analysis; its pair of highly-sensitive in-situ quartz crystal microbalances (QCMs); and its complete spectrum of pressures and operating conditions --- from viscous to molecular flow regimes. Control of the dose is achieved independently of the conditions by allowing a reactant gas to fill a fixed volume and measured pressure, which is held at a controlled temperature, and subsequently dosed into the system by computer controlled pneumatic valves. Absolute reactant exposure to the substrate and QCMs is unambiguously calculated from the molecular impingement flux, and its relationship to dose size is established, allowing means for easily intentionally reproducing specific exposures. Methods for understanding atomic layer growth and adsorption phenomena, including the precursor sticking probability, dynamics of molecular impingement, size of dose, and other operating variables are for the first time quantitatively related to surface reaction rates by mass balance. Extensive characterization of the QCM as a measurement tool for adsorption under realistic ALD conditions has been examined, emphasizing the state-of-the-art and importance of QCM system features required. Finally, the importance of dose-quantification and microdosing has been contextualized in view of the ALD literature, underscoring the significance of more precise condition specification in establishing a better basis for reactor and reactant comparison.

Estimation of total rate of formation of nitric oxide in the rat.

PubMed Central

Sakinis, A; Wennmalm, A

1998-01-01

Nitric oxide (NO) is a powerful mediator with important actions in several organ systems. NO is synthesized during the enzymatic conversion of l-arginine and molecular oxygen to L-citrulline. About 90% of the NO formed is degraded to nitrate. Utilizing this information we have developed a method for assessment of the total rate of formation of NO in the rat. Male Wistar rats were kept in a closed-cage system allowing controlled breathing of a mixture of 18O2 and 16O2 in N2 for up to 5h. Blood samples for mass spectrometric analysis of nitrate residues with varying numbers of 18O atoms incorporated were drawn before and during the exposure to 18O2. By comparing the relative incorporation of 18O into nitrate residues to the 16O2/18O2 ratio in the breathing gas mixture in the cage system it was possible to calculate the absolute rate of NO formation in the animal. The rate of formation of NO in anaesthetized rats ranged from 0.33 to 0.85 micromol.kg-1.h-1. The rate of formation did not differ significantly in rats which were awake during the experiment (range 0.36-0.72 micromol.kg-1.h-1). The L-arginine analogue Nomega-nitro-L-arginine methyl ester (L-NAME) dose-dependently inhibited the formation of NO, at a dose of 100mg/kg by more than 99%. The technique presented allows estimation of the total rate of formation of NO in vivo in rats. Application of the technique may yield important information about the physiological and pathophysiological roles of NO. It may also be utilized to evaluate the effect of pharmacological treatment on NO formation. PMID:9461552

Validation of the flooding dose technique to determine fractional rates of protein synthesis in a model bivalve species, the blue mussel (Mytilus edulis L.).

PubMed

McCarthy, Ian D; Nicholls, Ruth; Malham, Shelagh K; Whiteley, Nia M

2016-01-01

For the first time, use of the flooding dose technique using (3)H-Phenylalanine is validated for measuring whole-animal and tissue-specific rates of protein synthesis in the blue mussel Mytilus edulis (61mm shell length; 4.0g fresh body mass). Following injection, the phenylalanine-specific radioactivities in the gill, mantle and whole-animal free pools were elevated within one hour and remained elevated and stable for up to 6h following injection of (3)H-phenylalanine into the posterior adductor muscle. Incorporation of (3)H-phenylalanine into body protein was linear over time following injection and the non-significant intercepts for the regressions suggested incorporation into body protein occurred rapidly after injection. These results validate the technique for measuring rates of protein synthesis in mussels. There were no differences in the calculated rates following 1-6h incubation in gill, mantle or whole-animal and fractional rates of protein synthesis from the combined time course data were 9.5±0.8%d(-1) for the gill, 2.5±0.3%d(-1) for the mantle and 2.6±0.3%d(-1) for the whole-animal, respectively (mean values±SEM). The whole-animal absolute rate of protein synthesis was calculated as 18.9±0.6mg protein day(-1). The use of this technique in measuring one of the major components of maintenance metabolism and growth will provide a valuable and convenient tool in furthering our understanding of the protein metabolism and energetics of this keystone marine invertebrate and its ability to adjust and respond to fluctuations, such as that expected as a result of climate change. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

TU-G-BRD-04: A Round Robin Dosimetry Intercomparison of Gamma Stereotactic Radiosurgery Calibration Protocols

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

Drzymala, R; Alvarez, P; Bednarz, G

2015-06-15

Purpose: The purpose of this multi-institutional study was to compare two new gamma stereotactic radiosurgery (GSRS) dosimetry protocols to existing calibration methods. The ultimate goal was to guide AAPM Task Group 178 in recommending a standard GSRS dosimetry protocol. Methods: Nine centers (ten GSRS units) participated in the study. Each institution made eight sets of dose rate measurements: six with two different ionization chambers in three different 160mm-diameter spherical phantoms (ABS plastic, Solid Water and liquid water), and two using the same ionization chambers with a custom in-air positioning jig. Absolute dose rates were calculated using a newly proposed formalismmore » by the IAEA working group for small and non-standard radiation fields and with a new air-kerma based protocol. The new IAEA protocol requires an in-water ionization chamber calibration and uses previously reported Monte-Carlo generated factors to account for the material composition of the phantom, the type of ionization chamber, and the unique GSRS beam configuration. Results obtained with the new dose calibration protocols were compared to dose rates determined by the AAPM TG-21 and TG-51 protocols, with TG-21 considered as the standard. Results: Averaged over all institutions, ionization chambers and phantoms, the mean dose rate determined with the new IAEA protocol relative to that determined with TG-21 in the ABS phantom was 1.000 with a standard deviation of 0.008. For TG-51, the average ratio was 0.991 with a standard deviation of 0.013, and for the new in-air formalism it was 1.008 with a standard deviation of 0.012. Conclusion: Average results with both of the new protocols agreed with TG-21 to within one standard deviation. TG-51, which does not take into account the unique GSRS beam configuration or phantom material, was not expected to perform as well as the new protocols. The new IAEA protocol showed remarkably good agreement with TG-21. Conflict of Interests: Paula Petti, Josef Novotny, Gennady Neyman and Steve Goetsch are consultants for Elekta Instrument A/B; Elekta Instrument AB, PTW Freiburg GmbH, Standard Imaging, Inc., and The Phantom Laboratory, Inc. loaned equipment for use in these experiments; The University of Wisconsin Accredited Dosimetry Calibration Laboratory provided calibration services.« less

Patient-specific quality assurance for the delivery of 60Co intensity modulated radiation therapy subject to a 0.35 T lateral magnetic field

PubMed Central

Li, H. Harold; Rodriguez, Vivian L.; Green, Olga L.; Hu, Yanle; Kashani, Rojano; Wooten, H. Omar; Yang, Deshan; Mutic, Sasa

2014-01-01

Purpose This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging guided radiation therapy device. Methods and materials The program consisted of the following components: 1) one-dimensional multipoint ionization chamber measurement using a customized 15 cm3 cubic phantom, 2) two-dimensional (2D) radiographic film measurement using a 30×30×20 cm3 phantom with multiple inserted ionization chambers, 3) quasi- three-dimensional (3D) diode array (ArcCHECK) measurement with a centrally inserted ionization chamber, 4) 2D fluence verification using machine delivery log files, and 5) 3D Monte-Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Results The ionization chamber measurements agreed well with treatment planning system (TPS) computed doses in all phantom geometries where the mean difference (mean ± SD) was 0.0% ± 1.3% (n=102, range, −3.0 % to 2.9%). The film measurements also showed excellent agreement with the TPS computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30, range, 87.4% to 100%). For ArcCHECK measurements, the mean passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34, range, 95.8% to 100%). 2D fluence maps with a resolution of 1×1 mm2 showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18, range, 97.0% to100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. Conclusions We have developed a dosimetry program for ViewRay’s patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay’s IMRT QA. PMID:25442343

SU-E-T-410: Evaluation of Treatment Modalities for Stereotactic Lung Radiation Therapy: A Phantom Study

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

Mohatt, D; Malhotra, H

Purpose: To evaluate and verify the accuracy of alternative treatment modalities for stereotactic lung therapy with end-to-end testing. We compared three dimensional conformal therapy (3DCRT), dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment using 6 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photons. Methods: A QUASAR respiratory motion phantom was utilized with custom ion chamber and gafchromatic EBT2 film inserts. The phantom contained a low density lung medium with a cylindrical polystyrene tumor (35 cc). Pseudo representative structures for various organs at risk (OAR) were created. Allmore » treatment plans were created using Eclipse ver. 11 using the same image and structure sets, and delivered via Varian TrueBeam STx linear accelerator equipped with high definition MLC. Evaluation of plan quality followed ROTG 0813 criterion for conformity index (CI100%), high dose spillage, D2cm, and R50%. Results: All treatment plans met the OAR dose constraints per protocol and could be delivered without any beam hold offs or other interlocks and hence were deemed clinically safe. For equivalent beam energies, target conformity was improved for all modalities when switching to FFF mode. Treatment efficiency increased for VMAT FFF by a factor of 3–4 over IMRT, and up to factor of 7 when compared to 3DCRT. Pass rates were > 97% for all treatment using gamma criteria of 3%, 3mm. Absolute dose at iso-center was verified with ion chamber, and found to be within 2% of the treatment planning system. Conclusion: The higher dose rate associated with FFF not only reduces delivery times, but in most cases enhances plan quality. The one modality with succeeding best results for all RTOG criterions was VMAT 6 MV FFF. This end-to-end testing provides necessary confidence in the entire dose delivery chain for lung SBRT patients.« less

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.

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.

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

Absolute Humidity and the Seasonality of Influenza (Invited)

NASA Astrophysics Data System (ADS)

Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

2010-12-01

Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

Towards quantitative [18F]FDG-PET/MRI of the brain: Automated MR-driven calculation of an image-derived input function for the non-invasive determination of cerebral glucose metabolic rates.

PubMed

Sundar, Lalith Ks; Muzik, Otto; Rischka, Lucas; Hahn, Andreas; Rausch, Ivo; Lanzenberger, Rupert; Hienert, Marius; Klebermass, Eva-Maria; Füchsel, Frank-Günther; Hacker, Marcus; Pilz, Magdalena; Pataraia, Ekaterina; Traub-Weidinger, Tatjana; Beyer, Thomas

2018-01-01

Absolute quantification of PET brain imaging requires the measurement of an arterial input function (AIF), typically obtained invasively via an arterial cannulation. We present an approach to automatically calculate an image-derived input function (IDIF) and cerebral metabolic rates of glucose (CMRGlc) from the [18F]FDG PET data using an integrated PET/MRI system. Ten healthy controls underwent test-retest dynamic [18F]FDG-PET/MRI examinations. The imaging protocol consisted of a 60-min PET list-mode acquisition together with a time-of-flight MR angiography scan for segmenting the carotid arteries and intermittent MR navigators to monitor subject movement. AIFs were collected as the reference standard. Attenuation correction was performed using a separate low-dose CT scan. Assessment of the percentage difference between area-under-the-curve of IDIF and AIF yielded values within ±5%. Similar test-retest variability was seen between AIFs (9 ± 8) % and the IDIFs (9 ± 7) %. Absolute percentage difference between CMRGlc values obtained from AIF and IDIF across all examinations and selected brain regions was 3.2% (interquartile range: (2.4-4.3) %, maximum < 10%). High test-retest intravariability was observed between CMRGlc values obtained from AIF (14%) and IDIF (17%). The proposed approach provides an IDIF, which can be effectively used in lieu of AIF.

19 CFR 132.13 - Quotas after opening.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Customs custody until Headquarters has determined the quantity entitled to the quota rate. (ii) Absolute. Except as provided for in § 142.21 (e)(2) and (g) of this chapter, absolute quota merchandise shall not... merchandise shall not be released until Customs has determined the quantity entitled to absolute quota status...

19 CFR 132.13 - Quotas after opening.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Customs custody until Headquarters has determined the quantity entitled to the quota rate. (ii) Absolute. Except as provided for in § 142.21 (e)(2) and (g) of this chapter, absolute quota merchandise shall not... merchandise shall not be released until Customs has determined the quantity entitled to absolute quota status...

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.

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

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

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.

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

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

Levy, R.P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

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

Levy, Richard P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform

PubMed Central

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2011-01-01

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP’s treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min−1 at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth–dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5–7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important. PMID:19687532

Role of Hematopoietic Growth Factors as Adjuncts in the Treatment of Chronic Hepatitis C Patients

PubMed Central

Danish, Fazal A.; Koul, Salman S.; Subhani, Fazal R.; Rabbani, Ahemd E.; Yasmin, Saeeda

2008-01-01

Drug-induced hematotoxicity is the most common reason for reducing the dose or withdrawing ribavirin (RBV) and interferon (IFN) therapy in chronic hepatitis C, which leads to the elimination of a possible cure for the patient. Traditionally, severe anemia and neutropenia have been considered as absolute contraindications to start antiviral therapy. This has not however, been the case since the advent of adjunct therapy with hematopoietic growth factors (erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF)). Some recent landmark studies have used this adjunct therapy to help avoid antiviral dose reductions. Although the addition of this adjunct therapy has been shown to significantly increase the overall cost of the treatment, this extra cost is worth bearing if the infection is cured at the end of the day. Although more studies are needed to refine the true indications of this adjunct therapy, determine the best dose regimen, quantify the average extra cost and determine whether or not the addition of this therapy increases the sustained virological response rates achieved, the initial reports are encouraging. Therefore, although not recommended on a routine basis, some selected patients may be given the benefits of these factors. This article reviews the current literature on this subject and makes a few recommendations to help develop local guidelines. PMID:19568529

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform.

PubMed

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2009-09-07

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min(-1) at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth-dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5-7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important.

Radar prediction of absolute rain fade distributions for earth-satellite paths and general methods for extrapolation of fade statistics to other locations

NASA Technical Reports Server (NTRS)

Goldhirsh, J.

1982-01-01

The first absolute rain fade distribution method described establishes absolute fade statistics at a given site by means of a sampled radar data base. The second method extrapolates absolute fade statistics from one location to another, given simultaneously measured fade and rain rate statistics at the former. Both methods employ similar conditional fade statistic concepts and long term rain rate distributions. Probability deviations in the 2-19% range, with an 11% average, were obtained upon comparison of measured and predicted levels at given attenuations. The extrapolation of fade distributions to other locations at 28 GHz showed very good agreement with measured data at three sites located in the continental temperate region.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

Seasonal influenza vaccine dose distribution in 157 countries (2004-2011).

PubMed

Palache, Abraham; Oriol-Mathieu, Valerie; Abelin, Atika; Music, Tamara

2014-11-12

Globally there are an estimated 3-5 million cases of severe influenza illness every year, resulting in 250,000-500,000 deaths. At the World Health Assembly in 2003, World Health Organization (WHO) resolved to increase influenza vaccine coverage rates (VCR) for high-risk groups, particularly focusing on at least 75% of the elderly by 2010. But systematic worldwide data have not been available to assist public health authorities to monitor vaccine uptake and review progress toward vaccination coverage targets. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply task force (IFPMA IVS) developed a survey methodology to assess global influenza vaccine dose distribution. The current survey results represent 2011 data and demonstrate the evolution of the absolute number distributed between 2004 and 2011 inclusive, and the evolution in the per capita doses distributed in 2008-2011. Global distribution of IFPMA IVS member doses increased approximately 86.9% between 2004 and 2011, but only approximately 12.1% between 2008 and 2011. The WHO's regions in Eastern Mediterranean (EMRO), Southeast Asian (SEARO) and Africa (AFRO) together account for about 47% of the global population, but only 3.7% of all IFPMA IVS doses distributed. While distributed doses have globally increased, they have decreased in EURO and EMRO since 2009. Dose distribution can provide a reasonable proxy of vaccine utilization. Based on the dose distribution, we conclude that seasonal influenza VCR in many countries remains well below the WHA's VCR targets and below the recommendations of the Council of the European Union in EURO. Inter- and intra-regional disparities in dose distribution trends call into question the impact of current vaccine recommendations at achieving coverage targets. Additional policy measures, particularly those that influence patients adherence to vaccination programs, such as reimbursement, healthcare provider knowledge, attitudes, practices, and communications, are required for VCR targets to be met and benefit public health. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Trends in Racial and Ethnic Disparities in Infant Mortality Rates in the United States, 1989–2006

PubMed Central

Rossen, Lauren M.; Schoendorf, Kenneth C.

2014-01-01

Objectives. We sought to measure overall disparities in pregnancy outcome, incorporating data from the many race and ethnic groups that compose the US population, to improve understanding of how disparities may have changed over time. Methods. We used Birth Cohort Linked Birth–Infant Death Data Files from US Vital Statistics from 1989–1990 and 2005–2006 to examine multigroup indices of racial and ethnic disparities in the overall infant mortality rate (IMR), preterm birth rate, and gestational age–specific IMRs. We calculated selected absolute and relative multigroup disparity metrics weighting subgroups equally and by population size. Results. Overall IMR decreased on the absolute scale, but increased on the population-weighted relative scale. Disparities in the preterm birth rate decreased on both the absolute and relative scales, and across equally weighted and population-weighted indices. Disparities in preterm IMR increased on both the absolute and relative scales. Conclusions. Infant mortality is a common bellwether of general and maternal and child health. Despite significant decreases in disparities in the preterm birth rate, relative disparities in overall and preterm IMRs increased significantly over the past 20 years. PMID:24028239

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.

Preparation and characterization of poly(methyl methacrylate) and poly(maleic anhydride-co-diallyl phthalate) grafted carbon black through γ-ray irradiation

NASA Astrophysics Data System (ADS)

Bo, Yang; Cui, Jiayang; Cai, Yangben; Xu, Shiai

2016-02-01

In this study, the grafting polymerization of methyl methacrylate (MMA) monomer and maleic anhydride/diallyl phthalate (MAH/DAP) co-monomer onto the surface of carbon black (CB) were carried out at room temperature and normal pressure by γ-ray irradiation. The surface chemistry of grafted CBs were characterized by infrared spectroscopy (IR), thermo-gravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). The results show that there are some remanent polymers on the surface of modified CBs after extract for 48 h, indicating that poly(methyl methacrylate) (PMMA) and poly(MAH-co-DAP) have been successfully grafted onto the surface of CB without using initiator due to the high energy of γ-ray irradiation. Dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) reveal that the grafted CBs have smaller average aggregate size and better dispersibility than that of CB in absolute ethanol. In addition, it was found that the amount of oxygen groups and the irradiation doses/dose rates have little effect on the grafting degree of CB.

Dosimetric evaluation of a novel high dose rate (HDR) intraluminal / interstitial brachytherapy applicator for gastrointestinal and bladder cancers

PubMed Central

Aghamiri, Seyyed Mahmoud Reza; Najarian, Siamak; Jaberi, Ramin

2010-01-01

High dose rate (HDR) brachytherapy is one of the accepted treatment modalities in gastro‐intestinal tract and bladder carcinomas. Considering the shortcoming of contact brachytherapy routinely used in gastrointestinal tract in treatment of big tumors or invasive method of bladder treatment, an intraluminal applicator with the capability of insertion into the tumor depth seems to be useful. This study presents some dosimetric evaluations to introduce this applicator to the clinical use. The radiation attenuation characteristics of the applicator were evaluated by means of two dosimetric methods including well‐type chamber and radiochromic film. The proposed 110 cm long applicator has a flexible structure made of stainless steel for easy passage through lumens and a needle tip to drill into big tumors. The 2 mm diameter of the applicator is thick enough for source transition, while easy passage through any narrow lumen such as endoscope or cystoscope working channel is ensured. Well‐chamber results showed an acceptably low attenuation of this steel springy applicator. Performing absolute dosimetry resulted in a correlation coefficient of R=0.9916(p‐value≈10−7) between standard interstitial applicator and the one proposed in this article. This study not only introduces a novel applicator with acceptable attenuation but also proves the response independency of the GAFCHROMIC EBT films to energy. By applying the dose response of the applicator in the treatment planning software, it can be used as a new intraluminal / interstitial applicator. PACS number: 87.53.Bn, 87.53.Jw, 29.40.Cs

Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions.

PubMed

Gajjar, Rachna M; Kasting, Gerald B

2014-11-15

The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each (14)C-radiolabed compound were tested - 5, 10, 20, and 40μLcm(-2), corresponding to specific doses ranging in mass from 5.0 to 63mgcm(-2). The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, Ksc, and modest changes to the diffusion coefficients, Dsc, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Absolute and Relative Reliability of Percentage of Syllables Stuttered and Severity Rating Scales

ERIC Educational Resources Information Center

Karimi, Hamid; O'Brian, Sue; Onslow, Mark; Jones, Mark

2014-01-01

Purpose: Percentage of syllables stuttered (%SS) and severity rating (SR) scales are measures in common use to quantify stuttering severity and its changes during basic and clinical research conditions. However, their reliability has not been assessed with indices measuring both relative and absolute reliability. This study was designed to provide…

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

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.

Assessing the dose values received by patients during conventional radiography X-ray examinations and the technical condition of the equipment used for this purpose.

PubMed

Bekas, Marcin; Pachocki, Krzysztof A; Waśniewska, Elżbieta; Bogucka, Dagmara; Magiera, Andrzej

2014-01-01

X-ray examination is associated with patient exposure to ionizing radiation. Dose values depend on the type of medical procedure used, the X-ray unit technical condition and exposure conditions selected. The aim of this study was to determine the dose value received by patients during certain conventional radiography X-ray examinations and to assess the technical condition of medical equipment used for this purpose. The study covered the total number of 118 conventional diagnostic X-ray units located in the Masovian Voivodeship. The methodology used to assess the conventional diagnostic X-ray unit technical condition and the measurement of the radiation dose rate received by patients are based on test procedures developed by the Department of Radiation Protection and Radiobiology of the National Institute of Public Health - National Institute of Hygiene (Warszawa, Poland) accredited for compliance with PN-EN 17025 standard by the Polish Centre for Accreditation. It was found that 84.7% of X-ray units fully meet the criteria set out in the Polish legislation regarding the safe use of ionizing radiation in medicine, while 15.3% of the units do not meet some of them. The broadest dose value range was recorded for adult patients. Particularly, during lateral (LATl) lumbar spine radiography the recorded entrance surface dose (ESD) values ranged from 283.5 to 7827 µGy (mean: 2183.3 µGy). It is absolutely necessary to constantly monitor the technical condition of all X-ray units, because it affects population exposure to ionizing radiation. Furthermore, it is essential to raise radiographers' awareness of the effects that ionizing radiation exposure can have on the human body.

Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

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

Constine, Louis S.; Department of Pediatrics, James P. Wilmot Cancer Center at University of Rochester, Rochester, NY; Tarbell, Nancy

2008-09-01

Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. Withmore » 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.« less

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients.

PubMed

Ellebaek, Eva; Iversen, Trine Zeeberg; Junker, Niels; Donia, Marco; Engell-Noerregaard, Lotte; Met, Özcan; Hölmich, Lisbet Rosenkrantz; Andersen, Rikke Sick; Hadrup, Sine Reker; Andersen, Mads Hald; thor Straten, Per; Svane, Inge Marie

2012-08-21

Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3-4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

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.

Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose.

PubMed

Constine, Louis S; Tarbell, Nancy; Hudson, Melissa M; Schwartz, Cindy; Fisher, Susan G; Muhs, Ann G; Basu, Swati K; Kun, Larry E; Ng, Andrea; Mauch, Peter; Sandhu, Ajay; Culakova, Eva; Lyman, Gary; Mendenhall, Nancy

2008-09-01

Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Dosimetric evaluation of magnetic resonance-generated synthetic CT for radiation treatment of rectal cancer.

PubMed

Wang, Hesheng; Du, Kevin; Qu, Juliet; Chandarana, Hersh; Das, Indra J

2018-01-01

The purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer. This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer. The plans were recalculated on CT with the same monitor units (MUs) as that of synCT. Dose-volume metrics of planning target volume (PTV) and organs at risk (OARs) as well as gamma analysis of dose distributions were evaluated to quantify the difference between synCT and CT plans. All plans were calculated using the analytical anisotropic algorithm (AAA). The VMAT plans on synCT and CT were also calculated using the Acuros XB algorithm for comparison with the AAA calculation. Medians of absolute differences in PTV metrics between synCT and CT plans were 0.2%, 0.2% and 0.3% for 4F, O4F and VMAT respectively. No significant differences were observed in OAR dose metrics including bladder V40Gy, mean dose in bladder, bowel V45Gy and femoral head V30Gy in any techniques. Gamma analysis with 2%/2mm dose difference/distance to agreement criteria showed median passing rates of 99.8% (range: 98.5 to 100%), 99.9% (97.2 to 100%), and 99.9% (99.4 to 100%) for 4F, O4F and VMAT, respectively. Using Acuros XB dose calculation, 2%/2mm gamma analysis generated a passing rate of 99.2% (97.7 to 99.9%) for VMAT plans. SynCT enabled dose calculation equivalent to conventional CT for treatment planning of 3D conformal treatment as well as VMAT of rectal cancer. The dosimetric agreement between synCT and CT calculated doses demonstrated the potential of MR-only treatment planning for rectal cancer using MR generated synCT.

(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.

MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

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

Brady, S; Kaufman, R

Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculatemore » their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced.« less

Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions

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

Gajjar, Rachna M.; Kasting, Gerald B., E-mail: Gerald.Kasting@uc.edu

The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each {sup 14}C-radiolabed compound were tested — 5, 10, 20, and 40 μL cm{sup −2}, corresponding to specific doses ranging in mass from 5.0 tomore » 63 mg cm{sup −2}. The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, K{sub sc}, and modest changes to the diffusion coefficients, D{sub sc}, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions. - Highlights: • Human skin absorption of small doses of VOCs was measured in vitro in a fume hood. • The VOCs tested were ethanol, acetone, benzene and 1,2-dichloroethane. • Fraction of dose absorbed for all compounds at all doses tested was less than 0.3%. • The more aggressive VOCs absorbed at higher levels than diffusion model predictions. • We conclude that even small exposures to VOCs temporarily alter skin permeability.« less

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.

SU-F-BRA-11: An Experimental Commissioning Test of Brachytherapy MBDCA Dosimetry, Based On a Commercial Radiochromic Gel/optical CT System

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

Pappas, E; Karaiskos, P; Zourari, K

2015-06-15

Purpose: To implement a 3D dose verification procedure of Model-Based Dose Calculation Algorithms (MBDCAs) for {sup 192}Ir HDR brachytherapy, based on a novel Ferrous Xylenol-orange gel (FXG) and optical CT read-out. Methods: The TruView gel was employed for absolute dosimetry in conjunction with cone-beam optical CT read-out with the VISTA scanner (both from Modus Medical Inc, London, ON, Canada). A multi-catheter skin flap was attached to a cylindrical PETE jar (d=9.6cm, h=16cm) filled with FXG, which served as both the dosimeter and the water equivalent phantom of bounded dimensions. X- ray CT image series of the jar with flap attachedmore » was imported to Oncentra Brachy v.4.5. A treatment plan consisting of 8 catheters and 56 dwell positions was generated, and Oncentra-ACE MBDCA as well as TG43 dose results were exported for further evaluation. The irradiation was carried out with a microSelecton v2 source. The FXG dose-response, measured via an electron irradiation of a second dosimeter from the same batch, was linear (R2>0.999) at least up to 12Gy. A MCNP6 input file was prepared from the DICOM-RT plan data using BrachyGuide to facilitate Monte Carlo (MC) simulation dosimetry in the actual experimental geometry. Agreement between experimental (reference) and calculated dose distributions was evaluated using the 3D gamma index (GI) method with criteria (5%-2mm applied locally) determined from uncertainty analysis. Results: The TG-43 GI failed, as expected, in the majority of voxels away from the flap (pass rate 59% for D>0.8Gy, corresponding to 10% of prescribed dose). ACE performed significantly better (corresponding pass rate 92%). The GI evaluation for the MC data (corresponding pass rate 97%) failed mainly at low dose points of increased uncertainty. Conclusion: FXG gel/optical CT is an efficient method for level-2 commissioning of brachytherapy MBDCAs. Target dosimetry is not affected from uncertainty introduced by TG43 assumptions in 192Ir skin brachytherapy. Research co-financed by the ESF and Greek funds through the Operational Program Education and Lifelong Learning Investing in Knowledge Society of the NSRF. Research Funding Program: Aristeia. Modus Medical Devices Inc. provided a TruView dosimeter batch and Nucletron, and Elekta company, provided access to Oncentra Brachy v4.5, for research purposes.« less

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.

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

Multi-centre audit of VMAT planning and pre-treatment verification.

PubMed

Jurado-Bruggeman, Diego; Hernández, Victor; Sáez, Jordi; Navarro, David; Pino, Francisco; Martínez, Tatiana; Alayrach, Maria-Elena; Ailleres, Norbert; Melero, Alejandro; Jornet, Núria

2017-08-01

We performed a multi-centre intercomparison of VMAT dose planning and pre-treatment verification. The aims were to analyse the dose plans in terms of dosimetric quality and deliverability, and to validate whether in-house pre-treatment verification results agreed with those of an external audit. The nine participating centres encompassed different machines, equipment, and methodologies. Two mock cases (prostate and head and neck) were planned using one and two arcs. A plan quality index was defined to compare the plans and different complexity indices were calculated to check their deliverability. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit (global 3D gamma, absolute dose differences, 10% of maximum dose threshold). Log-file analysis was performed to look for delivery errors. All centres fulfilled the dosimetric goals but plan quality and delivery complexity were heterogeneous and uncorrelated, depending on the manufacturer and the planner's methodology. Pre-treatment verifications results were within tolerance in all cases for gamma 3%-3mm evaluation. Nevertheless, differences between the external audit and in-house measurements arose due to different equipment or methodology, especially for 2%-2mm criteria with differences up to 20%. No correlation was found between complexity indices and verification results amongst centres. All plans fulfilled dosimetric constraints, but plan quality and complexity did not correlate and were strongly dependent on the planner and the vendor. In-house measurements cannot completely replace external audits for credentialing. Copyright © 2017 Elsevier B.V. All rights reserved.

A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Cucinotta, Francis A.

2010-01-01

After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

Prevalence of risk factors for acquiring measles during the 2011 outbreak in Quebec and impact of the province-wide school-based vaccination campaign on population immunity.

PubMed

Billard, Marie-Noëlle; De Serres, Gaston; Gariépy, Marie-Claude; Boulianne, Nicole; Toth, Eveline; Landry, Monique; Skowronski, Danuta M

2017-01-01

A large measles outbreak occurred in Quebec, Canada, in 2011. Although nearly two-thirds of the cases occurred in only two health districts, a mass vaccination campaign targeting all Quebec elementary and high school students without valid two-dose history was undertaken to prevent future outbreaks. We compared rates of non-vaccination and age at first measles vaccine dose among students in the two most-affected districts and the rest of the province and estimated the improvement in overall student measles immunity due to the mass school-based vaccination campaign. Data were extracted from the provincial vaccination registry for students in kindergarten to grade 11 during the 2011/2012 school year. A telephone survey was conducted in three sub-groups: students whose first measles vaccine dose recorded in the vaccination registry was received during the 2011 school vaccination campaign; students with no dose recorded in the registry whose parents refused receipt during the school campaign; and students with no dose recorded in the registry and no information about parental consent/refusal during the school campaign. Neither the prevalence of being non-vaccinated nor a younger age at first pediatric dose were higher in the two most-affected districts versus the rest of the province. The school campaign vaccinated nearly 8% of all students including 7% who previously received at least one dose. Before the outbreak, 3% of students were not vaccinated and one-third of these (1%/3%) were vaccinated during the campaign. The campaign likely increased the absolute school population immunity by just 1.7%. The concentration of measles cases in the two most-affected health districts during the large Quebec outbreak is not explained by more students who were unvaccinated or who had received their first vaccine dose at a younger age. The vaccination campaign reached one-third of unvaccinated students and only marginally improved population immunity.

SU-E-T-10: A Clinical Implementation and the Dosimetric Evidence in High Dose Rate Vaginal Multichannel Applicator Brachytherapy

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

Syh, J; Syh, J; Patel, B

2015-06-15

Purpose: The multichannel cylindrical applicator has a distinctive modification of the traditional single channel cylindrical applicator. The novel multichannel applicator has additional peripheral channels that provide more flexibility both in treatment planning process and outcomes. To protect by reducing doses to adjacent organ at risk (OAR) while maintaining target coverage with inverse plan optimization are the goals for such novel Brachytherapy device. Through a series of comparison and analysis of reults in more than forty patients who received HDR Brachytherapy using multichannel vaginal applicator, this procedure has been implemented in our institution. Methods: Multichannel planning was CT image based. Themore » CTV of 5mm vaginal cuff rind with prescribed length was well reconstructed as well as bladder and rectum. At least D95 of CTV coverage is 95% of prescribed dose. Multichannel inverse plan optimization algorithm not only shapes target dose cloud but set dose avoids to OAR’s exclusively. The doses of D2cc, D5cc and D5; volume of V2Gy in OAR’s were selected to compare with single channel results when sole central channel is only possibility. Results: Study demonstrates plan superiorly in OAR’s doe reduction in multi-channel plan. The D2cc of the rectum and bladder were showing a little lower for multichannel vs. single channel. The V2Gy of the rectum was 93.72% vs. 83.79% (p=0.007) for single channel vs. multichannel respectively. Absolute reduced mean dose of D5 by multichannel was 17 cGy (s.d.=6.4) and 44 cGy (s.d.=15.2) in bladder and rectum respectively. Conclusion: The optimization solution in multichannel was to maintain D95 CTV coverage while reducing the dose to OAR’s. Dosimetric advantage in sparing critical organs by using a multichannel applicator in HDR Brachytherapy treatment of the vaginal cuff is so promising and has been implemented clinically.« less

SU-F-T-513: Dosimetric Validation of Spatially Fractionated Radiotherapy Using Gel Dosimetry

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

Papanikolaou, P; Watts, L; Kirby, N

2016-06-15

Purpose: Spatially fractionated radiation therapy, also known as GRID therapy, is used to treat large solid tumors by irradiating the target to a single dose of 10–20Gy through spatially distributed beamlets. We have investigated the use of a 3D gel for dosimetric characterization of GRID therapy. Methods: GRID therapy is an external beam analog of volumetric brachytherapy, whereby we produce a distribution of hot and cold dose columns inside the tumor volume. Such distribution can be produced with a block or by using a checker-like pattern with MLC. We have studied both types of GRID delivery. A cube shaped acrylicmore » phantom was filled with polymer gel and served as a 3D dosimeter. The phantom was scanned and the CT images were used to produce two plans in Pinnacle, one with the grid block and one with the MLC defined grid. A 6MV beam was used for the plan with a prescription of 1500cGy at dmax. The irradiated phantom was scanned in a 3T MRI scanner. Results: 3D dose maps were derived from the MR scans of the gel dosimeter and were found to be in good agreement with the predicted dose distribution from the RTP system. Gamma analysis showed a passing rate of 93% for 5% dose and 2mm DTA scoring criteria. Both relative and absolute dose profiles are in good agreement, except in the peripheral beamlets where the gel measured slightly higher dose, possibly because of the changing head scatter conditions that the RTP is not fully accounting for. Our results have also been benchmarked against ionization chamber measurements. Conclusion: We have investigated the use of a polymer gel for the 3D dosimetric characterization and evaluation of GRID therapy. Our results demonstrated that the planning system can predict fairly accurately the dose distribution for GRID type therapy.« less

Long-term outcome of accelerated partial breast irradiation using a multilumen balloon applicator in a patient with existing breast implants.

PubMed

Akhtari, Mani; Nitsch, Paige L; Bass, Barbara L; Teh, Bin S

2015-01-01

Accelerated partial breast irradiation is now an accepted component of breast-conserving therapy. However, data regarding long-term outcomes of patients treated with multilumen catheter systems who have existing breast implants are limited. We report the treatment and outcome of our patient who had existing bilateral silicone subpectoral implants at the time of presentation. Ultrasound-guided core needle biopsy of the right breast showed infiltrating mucinous carcinoma. Right breast lumpectomy revealed an 8 mm area of infiltrating ductal carcinoma with mucinous features and nuclear grade 1. A 4-5 cm Contura (Bard Biopsy Systems, Tempe, AZ) device was placed, and she was treated over the course of 5 days twice daily to a dose of 34 Gy using a high-dose-rate iridium-192 source. The planning target volume for evaluation was 73.9 cc. The percentage of the planning target volume for evaluation receiving 90%, 95%, and 100% of the prescribed dose was 99.9%, 99.3%, and 97.8%, respectively. The total implant volume was 234.5 cc and received a mean dose of 15.4 Gy and a maximum dose of 72.8 Gy. The percentage of implant volume receiving 50%, 75%, 100%, and 200% of the prescribed dose was 31.1%, 16.5%, 8.6%, 2.0%, and 0%, respectively. Maximum skin dose was 97% of the prescribed dose. With a followup of nearly 5 years, she continues to be cancer free with minimal late toxicities and good to excellent cosmetic outcome. Accelerated partial breast irradiation using a multilumen balloon applicator in patients with existing breast implants can safely be performed with excellent long-term cosmetic outcome. Further studies are needed to establish the absolute dosimetric tolerance of breast implants. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

A graphite calorimeter for absolute measurements of absorbed dose to water: application in medium-energy x-ray filtered beams.

PubMed

Pinto, M; Pimpinella, M; Quini, M; D'Arienzo, M; Astefanoaei, I; Loreti, S; Guerra, A S

2016-02-21

The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) has designed and built a graphite calorimeter that, in a water phantom, has allowed the determination of the absorbed dose to water in medium-energy x-rays with generating voltages from 180 to 250 kV. The new standard is a miniaturized three-bodies calorimeter, with a disc-shaped core of 21 mm diameter and 2 mm thickness weighing 1.134 g, sealed in a PMMA waterproof envelope with air-evacuated gaps. The measured absorbed dose to graphite is converted into absorbed dose to water by means of an energy-dependent conversion factor obtained from Monte Carlo simulations. Heat-transfer correction factors were determined by FEM calculations. At a source-to-detector distance of 100 cm, a depth in water of 2 g cm(-2), and at a dose rate of about 0.15 Gy min(-1), results of calorimetric measurements of absorbed dose to water, D(w), were compared to experimental determinations, D wK, obtained via an ionization chamber calibrated in terms of air kerma, according to established dosimetry protocols. The combined standard uncertainty of D(w) and D(wK) were estimated as 1.9% and 1.7%, respectively. The two absorbed dose to water determinations were in agreement within 1%, well below the stated measurement uncertainties. Advancements are in progress to extend the measurement capability of the new in-water-phantom graphite calorimeter to other filtered medium-energy x-ray qualities and to reduce the D(w) uncertainty to around 1%. The new calorimeter represents the first implementation of in-water-phantom graphite calorimetry in the kilovoltage range and, allowing independent determinations of D(w), it will contribute to establish a robust system of absorbed dose to water primary standards for medium-energy x-ray beams.

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.

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

Absolute instabilities of travelling wave solutions in a Keller-Segel model

NASA Astrophysics Data System (ADS)

Davis, P. N.; van Heijster, P.; Marangell, R.

2017-11-01

We investigate the spectral stability of travelling wave solutions in a Keller-Segel model of bacterial chemotaxis with a logarithmic chemosensitivity function and a constant, sublinear, and linear consumption rate. Linearising around the travelling wave solutions, we locate the essential and absolute spectrum of the associated linear operators and find that all travelling wave solutions have parts of the essential spectrum in the right half plane. However, we show that in the case of constant or sublinear consumption there exists a range of parameters such that the absolute spectrum is contained in the open left half plane and the essential spectrum can thus be weighted into the open left half plane. For the constant and sublinear consumption rate models we also determine critical parameter values for which the absolute spectrum crosses into the right half plane, indicating the onset of an absolute instability of the travelling wave solution. We observe that this crossing always occurs off of the real axis.

Setup and Calibration of SLAC's Peripheral Monitoring Stations

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

Cooper, C.

2004-09-03

The goals of this project were to troubleshoot, repair, calibrate, and establish documentation regarding SLAC's (Stanford Linear Accelerator Center's) PMS (Peripheral Monitoring Station) system. The PMS system consists of seven PMSs that continuously monitor skyshine (neutron and photon) radiation levels in SLAC's environment. Each PMS consists of a boron trifluoride (BF{sub 3}) neutron detector (model RS-P1-0802-104 or NW-G-20-12) and a Geiger Moeller (GM) gamma ray detector (model TGM N107 or LND 719) together with their respective electronics. Electronics for each detector are housed in Nuclear Instrument Modules (NIMs) and are plugged into a NIM bin in the station. All communicationmore » lines from the stations to the Main Control Center (MCC) were tested prior to troubleshooting. To test communication with MCC, a pulse generator (Systron Donner model 100C) was connected to each channel in the PMS and data at MCC was checked for consistency. If MCC displayed no data, the communication cables to MCC or the CAMAC (Computer Automated Measurement and Control) crates were in need of repair. If MCC did display data, then it was known that the communication lines were intact. All electronics from each station were brought into the lab for troubleshooting. Troubleshooting usually consisted of connecting an oscilloscope or scaler (Ortec model 871 or 775) at different points in the circuit of each detector to record simulated pulses produced by a pulse generator; the input and output pulses were compared to establish the location of any problems in the circuit. Once any problems were isolated, repairs were done accordingly. The detectors and electronics were then calibrated in the field using radioactive sources. Calibration is a process that determines the response of the detector. Detector response is defined as the ratio of the number of counts per minute interpreted by the detector to the amount of dose equivalent rate (in mrem per hour, either calculated or measured). Detector response for both detectors is dependent upon the energy of the incident radiation; this trend had to be accounted for in the calibration of the BF{sub 3} detector. Energy dependence did not have to be taken into consideration when calibrating the GM detectors since GM detector response is only dependent on radiation energy below 100 keV; SLAC only produces a spectrum of gamma radiation above 100 keV. For the GM detector, calibration consisted of bringing a {sup 137}Cs source and a NIST-calibrated RADCAL Radiation Monitor Controller (model 9010) out to the field; the absolute dose rate was determined by the RADCAL device while simultaneously irradiating the GM detector to obtain a scaler reading corresponding to counts per minute. Detector response was then calculated. Calibration of the BF{sub 3} detector was done using NIST certified neutron sources of known emission rates and energies. Five neutron sources ({sup 238}PuBe, {sup 238}PuB, {sup 238}PuF4, {sup 238}PuLi and {sup 252}Cf) with different energies were used to account for the energy dependence of the response. The actual neutron dose rate was calculated by date-correcting NIST source data and considering the direct dose rate and scattered dose rate. Once the total dose rate (sum of the direct and scattered dose rates) was known, the response vs. energy curve was plotted. The first station calibrated (PMS6) was calibrated with these five neutron sources; all subsequent stations were calibrated with one neutron source and the energy dependence was assumed to be the same.« less

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.

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 Typology for Charting Socioeconomic Mortality Gradients: "Go Southwest".

PubMed

Blakely, Tony; Disney, George; Atkinson, June; Teng, Andrea; Mackenbach, Johan P

2017-07-01

Holistic depiction of time-trends in average mortality rates, and absolute and relative inequalities, is challenging. We outline a typology for situations with falling average mortality rates (m↓; e.g., cardiovascular disease), rates stable over time (m-; e.g., some cancers), and increasing average mortality rates (m↑; e.g., suicide in some contexts). If we consider inequality trends on both the absolute (a) and relative (r) scales, there are 13 possible combination of m, a, and r trends over time. They can be mapped to graphs with relative inequality (log relative index of inequality [RII]; r) on the y axis, log average mortality rate on the x axis (m), and absolute inequality (slope index of inequality; SII; a) as contour lines. We illustrate this by plotting adult mortality trends: (1) by household income from 1981 to 2011 for New Zealand, and (2) by education for European countries. Types range from the "best" m↓a↓r↓ (average, absolute, and relative inequalities all decreasing; southwest movement in graphs) to the "worst" m↑a↑r↑ (northeast). Mortality typologies in New Zealand (all-cause, cardiovascular disease, nonlung cancer, and unintentional injury) were all m↓r↑ (northwest), but variable with respect to absolute inequality. Most European typologies were m↓r↑ types (northwest; e.g., Finland), but with notable exceptions of m-a↑r↑ (north; e.g., Hungary) and "best" or southwest m↓a↓r↓ for Spain (Barcelona) females. Our typology and corresponding graphs provide a convenient way to summarize and understand past trends in inequalities in mortality, and hold potential for projecting future trends and target setting.

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

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...

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.

Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial.

PubMed

Kato, Eri Toda; Giugliano, Robert P; Ruff, Christian T; Koretsune, Yukihiro; Yamashita, Takeshi; Kiss, Robert Gabor; Nordio, Francesco; Murphy, Sabina A; Kimura, Tetsuya; Jin, James; Lanz, Hans; Mercuri, Michele; Braunwald, Eugene; Antman, Elliott M

2016-05-20

Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age. Twenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients. Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

Gout and subsequent erectile dysfunction: a population-based cohort study from England.

PubMed

Abdul Sultan, Alyshah; Mallen, Christian; Hayward, Richard; Muller, Sara; Whittle, Rebecca; Hotston, Matthew; Roddy, Edward

2017-06-06

An association has been suggested between gout and erectile dysfunction (ED), however studies quantifying the risk of ED amongst gout patients are lacking. We aimed to precisely determine the population-level absolute and relative rate of ED reporting among men with gout over a decade in England. We utilised the UK-based Clinical Practice Research Datalink to identify 9653 men with incident gout age- and practice-matched to 38,218 controls. Absolute and relative rates of incident ED were calculated using Cox regression models. Absolute rates within specific time periods before and after gout diagnosis were compared to control using a Poisson regression model. Overall, the absolute rate of ED post-gout diagnosis was 193 (95% confidence interval (CI): 184-202) per 10,000 person-years. This corresponded to a 31% (hazard ratio (HR): 1.31 95%CI: 1.24-1.40) increased relative risk and 0.6% excess absolute risk compared to those without gout. We did not observe statistically significant differences in the risk of ED among those prescribed ULT within 1 and 3 years after gout diagnosis. Compared to those unexposed, the risk of ED was also high in the year before gout diagnosis (relative rate = 1.63 95%CI 1.27-2.08). Similar findings were also observed for severe ED warranting pharmacological intervention. We have shown a statistically significant increased risk of ED among men with gout. Our findings will have important implications in planning a multidisciplinary approach to managing patients with gout.

SU-E-T-509: Inter-Observer and Inter-Modality Contouring Analysis for Organs at Risk for HDR Gynecological Brachytherapy

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

Sadeghi, P; Smith, W; Tom Baker Cancer Centre, Calgary, AB

2015-06-15

Purpose This study quantifies errors associated with MR-guided High Dose Rate (HDR) gynecological brachytherapy. Uncertainties in this treatment results from contouring, organ motion between imaging and treatment delivery, dose calculation, and dose delivery. We focus on interobserver and inter-modality variability in contouring and the motion of organs at risk (OARs) in the time span between the MR and CT scans (∼1 hour). We report the change in organ volume and position of center of mass (CM) between the two imaging modalities. Methods A total of 8 patients treated with MR-guided HDR brachytherapy were included in this study. Two observers contouredmore » the bladder and rectum on both MR and CT scans. The change in OAR volume and CM position between the MR and CT imaging sessions on both image sets were calculated. Results The absolute mean bladder volume change between the two imaging modalities is 67.1cc. The absolute mean inter-observer difference in bladder volume is much lower at 15.5cc (MR) and 11.0cc (CT). This higher inter-modality volume difference suggests a real change in the bladder filling between the two imaging sessions. Change in Rectum volume inter-observer standard error of means (SEM) is 3.18cc (MR) and 3.09cc (CT), while the inter-modality SEM is 3.65cc (observer 1), and 2.75cc (observer 2). The SEM for rectum CM position in the superior-inferior direction was approximately three times higher than in other directions for both the inter—observer (0.77 cm, 0.92 cm for observers 1 and 2, respectively) and inter-modality (0.91 cm, 0.95 cm for MR and CT, respectively) variability. Conclusion Bladder contours display good consistency between different observers on both CT and MR images. For rectum contouring the highest inconsistency stems from the observers’ choice of the superior-inferior borders. A complete analysis of a larger patient cohort will enable us to separate the true organ motion from the inter-observer variability.« less

Reduced dose measurement of absolute myocardial blood flow using dynamic SPECT imaging in a porcine model

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

Timmins, Rachel; Klein, Ran; Petryk, Julia

Purpose: Absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements provide important additional information over traditional relative perfusion imaging. Recent advances in camera technology have made this possible with single-photon emission tomography (SPECT). Low dose protocols are desirable to reduce the patient radiation risk; however, increased noise may reduce the accuracy of MBF measurements. The authors studied the effect of reducing dose on the accuracy of dynamic SPECT MBF measurements. Methods: Nineteen 30–40 kg pigs were injected with 370 + 1110 MBq of Tc-99m sestamibi or tetrofosmin or 37 + 111 MBq of Tl-201 at rest + stress.more » Microspheres were injected simultaneously to measure MBF. The pigs were imaged in list-mode for 11 min starting at the time of injection using a Discovery NM 530c camera (GE Healthcare). Each list file was modified so that 3/4, 1/2, 1/4, 1/8, 1/16, and 1/32 of the original counts were included in the projections. Modified projections were reconstructed with CT-based attenuation correction and an energy window-based scatter correction and analyzed with FlowQuant kinetic modeling software using a 1-compartment model. A modified Renkin-Crone extraction function was used to convert the tracer uptake rate K1 to MBF values. The SPECT results were compared to those from microspheres. Results: Correlation between SPECT and microsphere MBF values for the full injected activity was r ≥ 0.75 for all 3 tracers and did not significantly degrade over all count levels. The mean MBF and MFR and the standard errors in the estimates were not significantly worse than the full-count data at 1/4-counts (Tc99m-tracers) and 1/2-counts (Tl-201). Conclusions: Dynamic SPECT measurement of MBF and MFR in pigs can be performed with 1/4 (Tc99m-tracers) or 1/2 (Tl-201) of the standard injected activity without significantly reducing accuracy and precision.« less

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-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.

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

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

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

2012-08-01

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trialsmore » showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.« less

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

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

PubMed Central

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events. PMID:27490468

Dose monitoring in Partial Liquid Ventilation by infrared measurement of expired perfluorochemicals.

PubMed

Mazzoni, M; Nugent, L; Klein, D; Hoffman, J; Sekins, K M; Flaim, S F

1999-01-01

Patients undergoing Partial Liquid Ventilation (PLV) with the perfluorochemical liquid perflubron (PFB) continuously evaporate the drug from the lung during ventilatory expiration. In this study, two infrared (IR) devices, a modified industrial analyzer ("experimental prototype") and a custom-designed device suitable for use in a clinical environment ("clinical prototype"), were calibrated and validated on the bench to measure a range of PFB concentrations (CPFB) in a gas stream. PFB loss from the lung (area under the CPFB-vs-time-curve) could be correlated during PLV simulation with changes in tidal volume, breathing rate, and variable CPFB-vs-time profiles. The two IR devices produced nearly identical measurements for the same CPFB standards (maximum deviation = 1.5%). The experimental IR prototype was tested in 17 anesthetized, paralyzed, and ventilated swine (42-53 kg) to quantify the total amount and rate of evaporate loss of PFB over 12 hours of PLV, both with and without periodic supplemental PFB doses. The residual PFB volumes in the animal lungs at the end of the study, as determined by a gravimetric postmortem lung method, were found to agree on average for all animals to within 10% of the residual PFB volume as predicted by the IR approach. Furthermore, the IR signal of CPFB does not appear to correlate with the absolute amount of PFB in the lungs, but may reflect the relative proportion of PFB-wetted airway and alveolar surface. The authors conclude that IR quantitation of PFB evaporative loss is acceptably accurate for extended periods of PLV and may be a useful tool in the clinic for PFB dose monitoring and maintenance, thereby helping to optimize PLV treatment.

Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12 904 patients.

PubMed

Jay, M A; Thomas, B M; Nandi, R; Howard, R F

2017-02-01

Children with neurodevelopmental disabilities may be at risk of opioid-induced respiratory depression. We aimed to quantify the risks and effectiveness of morphine nurse-controlled analgesia (morphine-NCA) for postoperative pain in children with neurodevelopmental disabilities. We carried out a retrospective cohort study of 12 904 children who received postoperative i.v. morphine-NCA. Subjects were divided into a neurodevelopmental disability group and a control group. Rates of clinical satisfaction, respiratory depression, and serious adverse events were obtained, and statistical analysis, including multilevel logistic regression using Bayesian inference, was performed. Of 12 904 patients, 2390 (19%) had neurodevelopmental disabilities. There were 88 instances of respiratory depression and 52 serious adverse events; there were no opioid-related deaths. The cumulative incidence of respiratory depression in the neurodevelopmental disability group was 1.09% vs 0.59% in the control group [odds ratio 1.8 (98% chance that the true odds ratio was >1)]. A significant interaction between postoperative morphine dose and neurodevelopmental disabilities was observed, with higher risk of respiratory depression with increasing dose. Satisfaction with morphine-NCA was very high overall, although children with neurodevelopmental disabilities were 1% more likely to have infusions rated as fair or poor (3.3 vs 2.1%, χ 2 P<0.001). Children with neurodevelopmental disabilities were 1.8 times more likely to suffer respiratory depression, absolute risk difference 0.5%; opioid-induced respiratory depression in this group may relate to increased sensitivity to dose-relate respiratory effects of morphine. Morphine-NCA as described was an acceptable technique for children with and without neurodevelopmental disabilities. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Absolute calorimetric calibration of low energy brachytherapy sources

NASA Astrophysics Data System (ADS)

Stump, Kurt E.

In the past decade there has been a dramatic increase in the use of permanent radioactive source implants in the treatment of prostate cancer. A small radioactive source encapsulated in a titanium shell is used in this type of treatment. The radioisotopes used are generally 125I or 103Pd. Both of these isotopes have relatively short half-lives, 59.4 days and 16.99 days, respectively, and have low-energy emissions and a low dose rate. These factors make these sources well suited for this application, but the calibration of these sources poses significant metrological challenges. The current standard calibration technique involves the measurement of ionization in air to determine the source air-kerma strength. While this has proved to be an improvement over previous techniques, the method has been shown to be metrologically impure and may not be the ideal means of calbrating these sources. Calorimetric methods have long been viewed to be the most fundamental means of determining source strength for a radiation source. This is because calorimetry provides a direct measurement of source energy. However, due to the low energy and low power of the sources described above, current calorimetric methods are inadequate. This thesis presents work oriented toward developing novel methods to provide direct and absolute measurements of source power for low-energy low dose rate brachytherapy sources. The method is the first use of an actively temperature-controlled radiation absorber using the electrical substitution method to determine total contained source power of these sources. The instrument described operates at cryogenic temperatures. The method employed provides a direct measurement of source power. The work presented here is focused upon building a metrological foundation upon which to establish power-based calibrations of clinical-strength sources. To that end instrument performance has been assessed for these source strengths. The intent is to establish the limits of the current instrument to direct further work in this field. It has been found that for sources with powers above approximately 2 muW the instrument is able to determine the source power in agreement to within less than 7% of what is expected based upon the current source strength standard. For lower power sources, the agreement is still within the uncertainty of the power measurement, but the calorimeter noise dominates. Thus, to provide absolute calibration of lower power sources additional measures must be taken. The conclusion of this thesis describes these measures and how they will improve the factors that limit the current instrument. The results of the work presented in this thesis establish the methodology of active radiometric calorimetey for the absolute calibration of radioactive sources. The method is an improvement over previous techniques in that there is no reliance upon the thermal properties of the materials used or the heat flow pathways on the source measurements. The initial work presented here will help to shape future refinements of this technique to allow lower power sources to be calibrated with high precision and high accuracy.

Simulator-Based Angiography and Endovascular Neurosurgery Curriculum: A Longitudinal Evaluation of Performance Following Simulator-Based Angiography Training.

PubMed

Pannell, J Scott; Santiago-Dieppa, David R; Wali, Arvin R; Hirshman, Brian R; Steinberg, Jeffrey A; Cheung, Vincent J; Oveisi, David; Hallstrom, Jon; Khalessi, Alexander A

2016-08-29

This study establishes performance metrics for angiography and neuroendovascular surgery procedures based on longitudinal improvement in individual trainees with differing levels of training and experience. Over the course of 30 days, five trainees performed 10 diagnostic angiograms, coiled 10 carotid terminus aneurysms in the setting of subarachnoid hemorrhage, and performed 10 left middle cerebral artery embolectomies on a Simbionix Angio Mentor™ simulator. All procedures were nonconsecutive. Total procedure time, fluoroscopy time, contrast dose, heart rate, blood pressures, medications administered, packing densities, the number of coils used, and the number of stent-retriever passes were recorded. Image quality was rated, and the absolute value of technically unsafe events was recorded. The trainees' device selection, macrovascular access, microvascular access, clinical management, and the overall performance of the trainee was rated during each procedure based on a traditional Likert scale score of 1=fail, 2=poor, 3=satisfactory, 4=good, and 5=excellent. These ordinal values correspond with published assessment scales on surgical technique. After performing five diagnostic angiograms and five embolectomies, all participants demonstrated marked decreases in procedure time, fluoroscopy doses, contrast doses, and adverse technical events; marked improvements in image quality, device selection, access scores, and overall technical performance were additionally observed (p < 0.05). Similarly, trainees demonstrated marked improvement in technical performance and clinical management after five coiling procedures (p < 0.05). However, trainees with less prior experience deploying coils continued to experience intra-procedural ruptures up to the eighth embolization procedure; this observation likely corresponded with less tactile procedural experience to an exertion of greater force than appropriate for coil placement. Trainees across all levels of training and prior experience demonstrated a significant performance improvement after completion of our simulator curriculum consisting of five diagnostic angiograms, five embolectomy cases, and 10 aneurysm coil embolizations.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate.

PubMed

Drost, Sarah A; Wentzell, Jason R; Giguère, Pierre; McLurg, Darcy L; Sabloff, Mitchell; Kanji, Salmaan; Nguyen, Tiffany T

2017-06-01

Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high-dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance. Retrospective cohort study. Hematology service of a large university-affiliated teaching hospital in Ottawa, Canada. Sixty-five adults with 150 HDMTX exposures who had elective admissions for HDMTX between September 1, 2014, and December 18, 2015, were included. Thirty-four patients (with 79 HDMTX exposures) had their urine alkalinized to a pH of 8 or higher, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH of 7 or higher, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015. Data related to patient demographics, urine alkalinization, MTX serum concentration monitoring, hospital length of stay, and renal function were collected retrospectively from patients' electronic health records. Lowering the urine pH threshold from 8 to 7 did not significantly affect hospital length of stay (absolute difference 3.5 hrs, 95% confidence interval -4.0 to 10.9) or clearance of MTX (elimination rate constant 0.058 in the pH of 7 or higher group vs 0.064 in the pH of 8 or higher group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH of 7 or higher group vs 10.1% in the pH of 8 or higher group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed MTX elimination. No significant differences in HDMTX-associated hospital length of stay, MTX clearance, or rates of nephrotoxicity were noted between patients in the urine pH of 7 or higher and 8 or higher groups. Interacting medications and higher MTX dose were associated with delayed MTX elimination, suggesting that a closer review of interacting medications before HDMTX administration may be warranted. © 2017 Pharmacotherapy Publications, Inc.

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

Effect of the absolute statistic on gene-sampling gene-set analysis methods.

PubMed

Nam, Dougu

2017-06-01

Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.

A calibration method for patient specific IMRT QA using a single therapy verification film

PubMed Central

Shukla, Arvind Kumar; Oinam, Arun S.; Kumar, Sanjeev; Sandhu, I.S.; Sharma, S.C.

2013-01-01

Aim The aim of the present study is to develop and verify the single film calibration procedure used in intensity-modulated radiation therapy (IMRT) quality assurance. Background Radiographic films have been regularly used in routine commissioning of treatment modalities and verification of treatment planning system (TPS). The radiation dosimetery based on radiographic films has ability to give absolute two-dimension dose distribution and prefer for the IMRT quality assurance. However, the single therapy verification film gives a quick and significant reliable method for IMRT verification. Materials and methods A single extended dose rate (EDR 2) film was used to generate the sensitometric curve of film optical density and radiation dose. EDR 2 film was exposed with nine 6 cm × 6 cm fields of 6 MV photon beam obtained from a medical linear accelerator at 5-cm depth in solid water phantom. The nine regions of single film were exposed with radiation doses raging from 10 to 362 cGy. The actual dose measurements inside the field regions were performed using 0.6 cm3 ionization chamber. The exposed film was processed after irradiation using a VIDAR film scanner and the value of optical density was noted for each region. Ten IMRT plans of head and neck carcinoma were used for verification using a dynamic IMRT technique, and evaluated using the gamma index method with TPS calculated dose distribution. Results Sensitometric curve has been generated using a single film exposed at nine field region to check quantitative dose verifications of IMRT treatments. The radiation scattered factor was observed to decrease exponentially with the increase in the distance from the centre of each field region. The IMRT plans based on calibration curve were verified using the gamma index method and found to be within acceptable criteria. Conclusion The single film method proved to be superior to the traditional calibration method and produce fast daily film calibration for highly accurate IMRT verification. PMID:24416558

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation.

PubMed

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B; Bass, Barbara L; Miltenburg, Darlene M; Butler, E Brian; Teh, Bin S

2015-12-01

Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate (192)Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes.

Methods for estimation of radiation risk in epidemiological studies accounting for classical and Berkson errors in doses.

PubMed

Kukush, Alexander; Shklyar, Sergiy; Masiuk, Sergii; Likhtarov, Illya; Kovgan, Lina; Carroll, Raymond J; Bouville, Andre

2011-02-16

With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)(-1), R = λ(0) + EAR D, where λ(0) is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes=fiQi(mes)/Mi(mes). Here, Qi(mes) is the measured content of radioiodine in the thyroid gland of person i at time t(mes), Mi(mes) is the estimate of the thyroid mass, and f(i) is the normalizing multiplier. The Q(i) and M(i) are measured with multiplicative errors Vi(Q) and ViM, so that Qi(mes)=Qi(tr)Vi(Q) (this is classical measurement error model) and Mi(tr)=Mi(mes)Vi(M) (this is Berkson measurement error model). Here, Qi(tr) is the true content of radioactivity in the thyroid gland, and Mi(tr) is the true value of the thyroid mass. The error in f(i) is much smaller than the errors in ( Qi(mes), Mi(mes)) and ignored in the analysis. By means of Parametric Full Maximum Likelihood and Regression Calibration (under the assumption that the data set of true doses has lognormal distribution), Nonparametric Full Maximum Likelihood, Nonparametric Regression Calibration, and by properly tuned SIMEX method we study the influence of measurement errors in thyroid dose on the estimates of λ(0) and EAR. The simulation study is presented based on a real sample from the epidemiological studies. The doses were reconstructed in the framework of the Ukrainian-American project on the investigation of Post-Chernobyl thyroid cancers in Ukraine, and the underlying subpolulation was artificially enlarged in order to increase the statistical power. The true risk parameters were given by the values to earlier epidemiological studies, and then the binary response was simulated according to the dose-response model.

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation

PubMed Central

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B.; Bass, Barbara L.; Miltenburg, Darlene M.; Butler, E. Brian

2015-01-01

Purpose Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. Material and methods We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate 192Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. Results After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Conclusions Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. PMID:26816499

Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

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

Boukheris, Houda; Stovall, Marilyn; Gilbert, Ethel S.

Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 casesmore » of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.« less

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

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

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.

Febuxostat for treating chronic gout

PubMed Central

Tayar, Jean H; Lopez-Olivo, Maria Angeles; Suarez-Almazor, Maria E

2014-01-01

Background Gout is the most common inflammatory arthritis in men over 40 years and has an increasing prevalence among postmenopausal women. Lowering serum uric acid levels remains one of the primary goals in the treatment of chronic gout. In clinical trials, febuxostat has been shown to be effective in lowering serum uric acid levels to < 6.0 mg/dL. Objectives To evaluate the benefits and harms of febuxostat for chronic gout. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, and International Pharmaceutical Abstracts from inception to July 2011. The ClinicalTrials.gov website was searched for references to trials of febuxostat. Our search did not include any restrictions. Selection criteria Two authors independently reviewed the search results and disagreements were resolved by discussion. We included any controlled clinical trial or open label trial (OLT) using febuxostat at any dose. Data collection and analysis Data and risk of bias were independently extracted by two authors and summarised in a meta-analysis. Continuous data were expressed as mean difference and dichotomous data as risk ratio (RR). Main results Four randomised trials and two OLTs with 3978 patients were included. Risk of bias differed by outcome, ranging from low to high risk of bias. Included studies failed to report on five to six of the nine outcome measures recommended by OMERACT. Patients taking febuxostat 120 mg and 240 mg reported more frequent gout flares than in the placebo group at 4 to 28 weeks (RR 1.7; 95% CI 1.3 to 2.3, and RR 2.6; 95% CI 1.8 to 3.7 respectively). No statistically significant differences were observed at 40 mg and 80 mg. Compared to placebo, patients on febuxostat 40 mg were 40.1 times more likely to achieve serum uric acid levels < 6.0 mg/dL at 4 weeks (95% CI 2.5 to 639), with an absolute treatment benefit of 56% (95% CI 37% to 71%). For febuxostat 80 mg and 120 mg, patients were 68.9 and 80.7 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit compared to placebo (95% CI 13.8 to 343.9, 95% CI 16.0 to 405.5), respectively; with an absolute treatment benefit of 75% and 87% (95% CI 68 to 80% and 81 to 91%), respectively. Total discontinuation rates were significantly higher in the febuxostat 80 mg group compared to placebo (RR 1.4; 95% CI 1.0 to 2.0, absolute risk increase 11%; 95% CI 3 to 19%). No other differences were observed. When comparing allopurinol to febuxostat at 24 to 52 weeks, the number of gout flares was not significantly different between the two groups, except for febuxostat 240 mg (RR 2.3; 95% CI 1.7 to 3.0). Patients on febuxostat 40 mg showed no statistically significant differences in benefits or harms. Patients on febuxostat 80 mg and 120 mg were 1.8 and 2.2 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit (95% CI 1.6 to 2.2, 95% CI 1.9 to 2.5) with an absolute treatment benefit of 29% and 44% (95% CI 25% to 33%, 95% CI 38% to 50%), respectively, at 24 to 52 weeks. Total discontinuation rates were higher for febuxostat 80 mg and 120 mg compared to allopurinol (RR 1.5; 95% CI 1.2 to 1.8, absolute risk increase 11%; 95% CI 6% to 16%; and RR 2.6; 95% CI 2.0 to 3.3, absolute risk increase 20%; 95% CI 3% to 14%, respectively). Discontinuations due to adverse events were similar across groups. Total adverse events were lower for febuxostat 80 mg and 120 mg compared with allopurinol (RR 0.93; 95% CI 0.87 to 0.99, absolute risk increase 6%; 95% CI 0.7% to 11%; and RR 0.90; 95% CI 0.84 to 0.96, absolute risk increase 8%; 95% CI 3% to 13%, respectively). No other relevant differences were noted. After 3 years of follow-up there were no statistically significant differences regarding effectiveness and harms between febuxostat 80 mg or 120 mg and allopurinol groups (adverse event rate per 100 patient-years 227, 216, and 246, respectively). Authors’ conclusions Although the incidence of gout flares requiring treatment may be increased in patients taking febuxostat compared to placebo or allopurinol during early treatment, no such increase in gout flares was observed in the long-term follow-up study when compared to allopurinol. Febuxostat at any dose was shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and reducing serum uric acid levels in the period from baseline to final visit when compared to placebo and to allopurinol. However, the grade of evidence ranged from low to high, which indicates that further research is needed. PMID:23152264

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.

In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis.

PubMed

Linares, Oscar A; Schiesser, William E; Fudin, Jeffrey; Pham, Thien C; Bettinger, Jeffrey J; Mathew, Roy O; Daly, Annemarie L

2015-01-01

There is a need to have a model to study methadone's losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model). We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone's overall intradialytic mass transfer rate coefficient, km ; and, methadone's removal rate, j ME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. The ODE/PDE model revealed a significant increase in the change of methadone's mass transfer with increased dialysate flow rate, %Δkm =18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11). This was accompanied by a small significant increase in methadone's mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11). The ODE/PDE model accurately predicted methadone's removal during dialysis. The absolute value of the prediction errors for methadone's extraction and throughput were less than 2%. ODE/PDE modeling of methadone's hemodialysis is a new approach to study methadone's removal, in particular, and opioid removal, in general, in patients with end-stage renal disease on hemodialysis. ODE/PDE modeling accurately quantified the fundamental phenomena of methadone's mass transfer during hemodialysis. This methodology may lead to development of optimally designed intradialytic opioid treatment protocols, and allow dynamic monitoring of outflow plasma opioid concentrations for model predictive control during dialysis in humans.

Absolute and Relative Training Load and Its Relation to Fatigue in Football

PubMed Central

Zurutuza, Unai; Castellano, Julen; Echeazarra, Ibon; Casamichana, David

2017-01-01

The aim of the study was to assess the relationship of external and internal training load (TL) indicators with the objective and subjective fatigue experienced by 15 semi-professional football players, over eight complete weeks of the competition period in the 2015–2016 season, which covered microcycles from 34th to 41st. The maximum heart rate (HRmax) and maximum speed (Vmax) of all the players were previously measured in specific tests. The TL was monitored via questionnaires on rating of perceived exertion (RPE), pulsometers and GPS devices, registering the variables: total distance (TD), player load 2D (PL2D), TD at >80% of the Vmax (TD80), TD in deceleration at < -2 m⋅sec-2 (TDD <-2), TD in acceleration >2 m⋅sec-2 (TDA >2), Edwards (ED), time spent at between 50 and 80% (50–80% HRmax), 80–90% (80–90% HRmax), and >90% of the HRmax (>90% HRmax), and RPE both respiratory/thoracic (RPEres) and leg/muscular (RPEmus). All the variables were analyzed taking into account both the absolute values accumulated over the week and the normalized values in relation to individual mean competition values. Neuromuscular fatigue was measured objectively using the countermovement jump test and subjectively via the Total Quality Recovery (TQR) scale questionnaire. Analytical correlation techniques were later applied within the general linear model. There is a correlation between the fatigue experienced by the player, assessed objectively and subjectively, and the load accumulated over the week, this being assessed in absolute and relative terms. Specifically, the load relative to competition correlated with the physical variables TD (-0.279), PL2D (-0.272), TDD < -2 (-0.294), TDA >2 (-0.309), and sRPEmus (-0.287). The variables related to heart rate produced a higher correlation with TQR. There is a correlation between objectively and subjectively assessed fatigue and the accumulated TL of a player over the week, with a higher sensitivity being shown when compared to the values related to the demands of competition. Monitoring load and assessing fatigue, we are closer to knowing what the prescription of an adequate dose of training should be in order for a player to be as fresh as possible and in top condition for a match. Normalizing training demands with respect to competition could be an appropriate strategy for individualizing player TL. PMID:28634456

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.

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-578: Characterization of Vidar DosimetryPro Advantage RED Scanner with Application to SBRT and SRS QA

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

Dumas, M; Wen, N

Purpose: To use Gafchromic EBT3 film to quantify key dosimetric characteristics of the Vidar DosimetryPro Advantage RED film scanner for use in SBRT/SRS QA, by analyzing scanner uniformity and dose sensitivity. Method: Gafchromic EBT3 film was used in this study. Films were irradiated using 6MV FFF and 10MV FFF beams from a Varian Edge linear accelerator, with setup of 100cm SAD at depth 5 cm. Nine doses were delivered per film, with calibration dose ranges of 1–10 Gy and 3–24 Gy for 6MV FFF, and 3–27 Gy for 10MV FFF. Films were scanned with the long side of the filmmore » parallel to the detector array. Dose calibration curves were fitted to a 3rd degree polynomial. The derivative of a calibration curve was taken to determine the scanner’s sensitivity per dose delivered (OD/Gy). Scanner non-uniformity was calculated in 2 dimensions by taking the mean of standard deviation in each row and column. Absolute dose SRS/SBRT Gamma analyses were performed with passing criteria of 3% and 1mm DTA. For comparison, Gamma analyses were also performed using an Epson Expression 10000 XL. Results: Uniformity for the Vidar scanner was 0.37% +/− 0.03% in the perpendicular to scan direction and 0.67% +/− 0.05% in the parallel to scan direction, with an overall uniformity of 0.52% +/− 0.03%. Epson red channel uniformity was 0.85% +/− 0.05% and 0.88% +/− 0.08% for the green channel. The Vidar average dose sensitivity from 1–10 Gy was 0.112 OD/Gy and 0.061 OD/Gy for 3–24 Gy. SBRT/SRS Gamma pass rates were 97.8 +/− 1.4 for Vidar and 97.5 +/− 1.4 for Epson. Conclusion: The Vidar scanner has 41% less non-uniformity compared to Epson XL10000 green channel. The dose sensitivity is 2–3 time greater for the Vidar scanner compared to the Epson in the SRS/SBRT dose range of 5–24 Gy.« less

Does unilateral laparoscopic diathermy adjusted to ovarian volume increase the chances of ovulation in women with polycystic ovary syndrome?

PubMed

Sunj, M; Canic, T; Baldani, D P; Tandara, M; Jeroncic, A; Palada, I

2013-09-01

Does unilateral volume-adjusted laparoscopic diathermy increase the chances of ovulation in women with polycystic ovary syndrome (PCOS)? Although unilateral laparoscopic ovarian drilling (ULOD) using adjusted thermal doses was more efficient than bilateral laparoscopic ovarian drilling (BLOD) using fixed doses, the chances of ovulation were improved in patients irrespective of the technique used. The adjustment of the thermal dose to ovarian volume in BLOD increases ovulation and pregnancy rates compared with fixed-dose treatment, but BLOD causes the formation of adhesions, particularly on the left ovary, and increases the risk of damage to ovarian tissue. In contrast, ULOD with a fixed thermal dose minimizes the risk of ovarian tissue damage, and can increase the activity in both right and left ovaries, although this varies in humans and in other species. This prospective, longitudinal, study, between September 2009 and January 2013, included 96 infertile women with PCOS who were unresponsive to clomiphene citrate treatment and had underwent either ULOD or BLOD. After surgery, the groups were followed up for 6 months to assess ovulatory response. Patients were assigned to two groups; one group underwent laparoscopic ovarian drilling of the right ovary alone, while both ovaries were treated in the second group. The ULOD group (n = 49) received thermal doses adjusted to the volume of the right ovary (60 J/cm³). The BLOD group (n = 47) received fixed doses of 600 J per ovary, regardless of its volume. The two treatment groups were matched by the number of participants, age and baseline parameters. The ovulation rate during the first menstrual cycle after LOD was significantly higher in the ULOD group than in the BLOD group [73 versus 49%; absolute risk reduction (ARR), -0.25; 95% confidence interval (CI), -0.44 to -0.03; P = 0.014]. Treatment with ULOD on the right ovary significantly increased the chances of ovulation in patients with a larger right ovary compared with those who had a smaller right ovary (100 versus 36%; ARR, -0.64; 95% CI, -0.84 to -0.37; P = 0.004). Interestingly, the chances of ovulation were also significantly higher in patients in the BLOD group who had a larger right ovary compared with those who had a smaller right ovary (88 versus 33%; ARR, -0.55; 95% CI, -0.73 to -0.28; P = 0.002). The pregnancy rate was also significantly higher in patients with a larger right ovary compared with those with a smaller right ovary, regardless of the treatment group. The 6-month follow-up was too short to demonstrate any long-term differences in the ovulation rates. Future research should therefore extend the follow-up beyond 6 months. Another limitation is that ULOD was used to treat only the right ovary. Future studies should investigate whether ULOD treatment of the larger ovary, whether left or right, would significantly increase the ovulation rate. This study represents an advance in the determination of the optimal laparoscopic treatment for women with PCOS, as it was shown that improved results can be achieved using less thermal energy in volume-adjusted ULOD.

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

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

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

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming.

PubMed

Isbister, G K; Jayamanne, S; Mohamed, F; Dawson, A H; Maduwage, K; Gawarammana, I; Lalloo, D G; de Silva, H J; Scorgie, F E; Lincz, L F; Buckley, N A

2017-04-01

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Gender equality and women's absolute status: a test of the feminist models of rape.

PubMed

Martin, Kimberly; Vieraitis, Lynne M; Britto, Sarah

2006-04-01

Feminist theory predicts both a positive and negative relationship between gender equality and rape rates. Although liberal and radical feminist theory predicts that gender equality should ameliorate rape victimization, radical feminist theorists have argued that gender equality may increase rape in the form of male backlash. Alternatively, Marxist criminologists focus on women's absolute socioeconomic status rather than gender equality as a predictor of rape rates, whereas socialist feminists combine both radical and Marxist perspectives. This study uses factor analysis to overcome multicollinearity limitations of past studies while exploring the relationship between women's absolute and relative socioeconomic status on rape rates in major U.S. cities using 2000 census data. The findings indicate support for both the Marxist and radical feminist explanations of rape but no support for the ameliorative hypothesis. These findings support a more inclusive socialist feminist theory that takes both Marxist and radical feminist hypotheses into account.

SU-F-T-32: Evaluation of the Performance of a Multiple-Array-Diode Detector for Quality Assurance Tests in High-Dose-Rate Brachytherapy with Ir-192 Source

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

Harpool, K; De La Fuente Herman, T; Ahmad, S

Purpose: To evaluate the performance of a two-dimensional (2D) array-diode- detector for geometric and dosimetric quality assurance (QA) tests of high-dose-rate (HDR) brachytherapy with an Ir-192-source. Methods: A phantom setup was designed that encapsulated a two-dimensional (2D) array-diode-detector (MapCheck2) and a catheter for the HDR brachytherapy Ir-192 source. This setup was used to perform both geometric and dosimetric quality assurance for the HDR-Ir192 source. The geometric tests included: (a) measurement of the position of the source and (b) spacing between different dwell positions. The dosimteric tests include: (a) linearity of output with time, (b) end effect and (c) relative dosemore » verification. The 2D-dose distribution measured with MapCheck2 was used to perform the previous tests. The results of MapCheck2 were compared with the corresponding quality assurance testes performed with Gafchromic-film and well-ionization-chamber. Results: The position of the source and the spacing between different dwell-positions were reproducible within 1 mm accuracy by measuring the position of maximal dose using MapCheck2 in contrast to the film which showed a blurred image of the dwell positions due to limited film sensitivity to irradiation. The linearity of the dose with dwell times measured from MapCheck2 was superior to the linearity measured with ionization chamber due to higher signal-to-noise ratio of the diode readings. MapCheck2 provided more accurate measurement of the end effect with uncertainty < 1.5% in comparison with the ionization chamber uncertainty of 3%. Although MapCheck2 did not provide absolute calibration dosimeter for the activity of the source, it provided accurate tool for relative dose verification in HDR-brachytherapy. Conclusion: The 2D-array-diode-detector provides a practical, compact and accurate tool to perform quality assurance for HDR-brachytherapy with an Ir-192 source. The diodes in MapCheck2 have high radiation sensitivity and linearity that is superior to Gafchromic-films and ionization chamber used for geometric and dosimetric QA in HDR-brachytherapy, respectively.« less

Mathematical models of cervical cancer prevention in Latin America and the Caribbean.

PubMed

Goldie, Sue J; Diaz, Mireia; Constenla, Dagna; Alvis, Nelson; Andrus, Jon Kim; Kim, Sun-Young

2008-08-19

Using population and epidemiologic data for 33 countries in Latin America and the Caribbean (LAC), a model-based approach estimated averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (I$/DALY averted) for human papillomavirus (HPV) vaccination of young adolescent girls. Absolute reduction in lifetime cancer risk varied between countries, depending on incidence, proportion attributable to HPV-16 and 18, and population age-structure; for example, with 70% coverage, cancer reduction ranged from 40% in Mexico to more than 50% in Argentina. Screening of women over age 30 three times per lifetime, after vaccinating them as pre-adolescents, is expected to provide a relative increase of 25% to 30% in mortality reduction. Countries with the highest risk of cancer (age-standardized rate > 33.6) accounted for only 34% of deaths averted with vaccination, highlighting why a regional universal vaccination approach will be most effective in reducing the overall global burden. At I$25 per vaccinated girl ($5 per dose), for all 33 countries, the cost per DALY averted is less than I$400; at I$10 ($2 per dose) the vaccine is cost saving in 26 out of 33 countries. For all countries, ratios become less attractive (i.e., increase) as the cost of the vaccine increases. For example, at current vaccine prices ($120 per dose), the cost per DALY averted is I$7,300 in Mexico, I$3,700 in Nicaragua, and I$6,300 in Costa Rica. Vaccine price has an even greater effect on predicted affordability. For the 33 countries, vaccinating 5 consecutive birth cohorts at 70% coverage would cost $360 million at $5.00 per dose, $811 million at $12.25 per dose, and $1.26 billion at $19.50 per dose. In the LAC region, if effective delivery mechanisms can achieve high coverage rates in young adolescent girls, vaccination against HPV-16 and 18 will provide similar health value for resources invested as other new vaccines such as rotavirus. If the cost per vaccinated girl is less than I$25 HPV-16/18 vaccination would be very cost-effective in all 33 countries; for it to be affordable, costs may need to be lower.

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.

Effect of Sameera Pannaga Rasa (arsenomercurial formulation) in the management of Tamaka Shwasa (bronchial asthma) - Randomized double blind clinical study

PubMed Central

Mashru, Mayur; Galib, R.; Shukla, Vinay J.; Ravishankar, B.; Prajapati, Pradeep Kumar

2013-01-01

Asthma represents a profound world-wide public health problem. The most effective anti-asthmatic drugs currently available include β2-agonists and glucocorticoids which can controls asthma in about 90-95% of patients. In Ayurveda, this miserable condition is comparable with Tamaka Shwasa type of Shwasa Roga. In the present study, 52 patients were treated with Sameera Pannaga Rasa at a dose of 30 mg twice a day for 4 weeks along with Nagavallidala (leaf of Piper betel Linn.) The results were assessed in terms of clinical recovery, symptomatic relief, pulmonary function improvement and on subjective and objective parameters. A significant improvement in subjective parameters, control on asthma, recurrence of asthma, increase in peak expiratory flow rate, considerable decrease in total and absolute, acute eosinophil count and erythrocyte sedimentation rate were observed. Overall marked improvement was found in 33.33%, moderate improvement in 44.44% and mild improvement in 20.00% was observed. The study reveals that Sameera Pannaga Rasa can be used as an effective drug in bronchial asthma. PMID:24696570

Effect of Sameera Pannaga Rasa (arsenomercurial formulation) in the management of Tamaka Shwasa (bronchial asthma) - Randomized double blind clinical study.

PubMed

Mashru, Mayur; Galib, R; Shukla, Vinay J; Ravishankar, B; Prajapati, Pradeep Kumar

2013-10-01

Asthma represents a profound world-wide public health problem. The most effective anti-asthmatic drugs currently available include β2-agonists and glucocorticoids which can controls asthma in about 90-95% of patients. In Ayurveda, this miserable condition is comparable with Tamaka Shwasa type of Shwasa Roga. In the present study, 52 patients were treated with Sameera Pannaga Rasa at a dose of 30 mg twice a day for 4 weeks along with Nagavallidala (leaf of Piper betel Linn.) The results were assessed in terms of clinical recovery, symptomatic relief, pulmonary function improvement and on subjective and objective parameters. A significant improvement in subjective parameters, control on asthma, recurrence of asthma, increase in peak expiratory flow rate, considerable decrease in total and absolute, acute eosinophil count and erythrocyte sedimentation rate were observed. Overall marked improvement was found in 33.33%, moderate improvement in 44.44% and mild improvement in 20.00% was observed. The study reveals that Sameera Pannaga Rasa can be used as an effective drug in bronchial asthma.

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.

Dose-rate effects on the radiation-induced oxidation of electric cable used in nuclear power plants

NASA Astrophysics Data System (ADS)

Reynolds, A. B.; Bell, R. M.; Bryson, N. M. N.; Doyle, T. E.; Hall, M. B.; Mason, L. R.; Quintric, L.; Terwilliger, P. L.

1995-01-01

Dose-rate effects were measured for typical ethylene propylene rubber (EPR) and crosslinked polyethylene (XLPE) electric cable used in nuclear power plants. The radiation source was the 60Co Irradiation Facility at the University of Virginia. Dose rates were varied from 5 Gy/h to 2500 Gy/h. It was found that there is little or no dose-rate effect at low doses for four of the five EPR cable products tested from 2500 Gy/h down to dose rates of 5 Gy/h but perhaps a small dose-rate effect at high doses for dose rates above 340 Gy/h. A small dose-rate exists for the fifth EPR above 340 Gy/h at all doses. A dose-rate effect exists above 40 Gy/h for two of the three XLPE cable products tested, but there is no dose-rate for these XLPE's between 40 Gy/h and 5 Gy/h. These results indicate that the dose-rate effects observed are due to oxygen diffusion effects during heterogeneous aging and suggest that there is no dose-rate effect for either EPR or XLPE during homogeneous aging.

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

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats.

PubMed

Codrons, Valérie; Vanderbist, Francis; Verbeeck, Roger K; Arras, Mohammed; Lison, Dominique; Préat, Véronique; Vanbever, Rita

2003-05-01

The aim of this work was to prepare and characterize inhalation dry powders of human parathyroid hormone (PTH), as well as to assess their efficacy for systemic delivery of the peptide and safety in rats. The powders were prepared by spray-drying using PTH, sugars, dipalmitoylphosphatidylcholine, and/or albumin. They presented an average primary particle diameter of 4.5 microm and tap density of 0.06 g/cm(3), a mass median aerodynamic diameter between 3.9 and 5.9 microm, and reached up to 98% emitted dose and up to 61% fine particle fraction in the multi-stage liquid impinger using a Spinhaler inhaler device. Varying the airflow rate from 30 to 100 L/min had limited influence on the aerodynamic behavior of the aerosols. The absolute PTH bioavailability was 21% after intratracheal administration of the powder formed of PTH/albumin/lactose/dipalmitoylphosphatidylcholine and 18% after subcutaneous injection in rats. Equilibrium dialysis revealed a 78% binding of PTH to albumin and the withdrawal of albumin from the powder increased absolute bioavailability after inhalation from 21 to 34%. No acute inflammation appeared in the lung up to 48 h after a single inhalation. The increased bioavailability of the optimized powder aerosol of PTH makes it a promising alternative to subcutaneous injection. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:938-950, 2003

Polyculture Engineering technology of larasati red tilapia (Oreochromis niloticus) and white shrimp (Litopenaeus vannamei) based for protease enzyme

NASA Astrophysics Data System (ADS)

Samidjan, I.; Rachmawati, D.

2018-04-01

The objective is polyculture technology of red tilapia larasati fish and white shrimp with different combinations density. The material is saline red tilapia larasati 3.29 ± 0.018 g and white shrimp with initial weight 1.39 ± 0.025 g. Seeds are density of red tilapia larasati larvae 5 and 10 larvae / m2 fish. And white shrimp 5 larvae / m2 and 10 larvae / m2. An artificial feed used enzyme dose of 2.25 g / kg. The experimental using complete randomized design 4 treatments and 3 replications that is given seeds 5 larvae / m2 larvae red tilapia larasati and given 5 larvae / m2 white shrimp (A), 5 larvae / m2 red tilapia) and 10 m2 / m2 of white shrimp (B), 10 m2 larvae and 5 m2 white shrimp (C), 10 m2 larvae and 10 m2 white shrimp (D)). The data were growth of absolute weight, survival rate, FCR, and water quality data (temperature, salinity, pH, O2, NO2, NH3). Data were analyzed of variance (F test). The results showed significantly effect (P <0.01) on the growth. The highest absolute growth in D treatment were red tilapia larasati (185.75 ± 0.50g) and white shrimp (25.25 ± 0.95 g).

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats.

PubMed

Yakubu, M T; Afolayan, A J

2009-08-01

The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100mg/kg body weight group. The number of litters was not statistically different (P>0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follicle-stimulating hormone significantly increased in the 25 and 50mg/kg body weight groups, whereas the estradiol concentration decreased significantly at all the doses. The extract dose of 100mg/kg body weight decreased the serum testosterone and progesterone levels in male rats. The prolactin concentration was not affected by all the doses. All the indices of reproduction, maternal, embryo/fetotoxic, teratogenic, and reproductive hormones in the female rats were not statistically different from that of their control except the resorption index, which increased at the dose of 100mg/kg body weight of the extract. Histologic examination of the cross section of rat testes that received the extract at all the doses investigated revealed well-preserved seminiferous tubules with normal amount of stroma, normal population of spermatogenic and supporting cells, as well as normal spermatocytes within the lumen. The results revealed that the aqueous extract of Bulbine natalensis stem at doses of 25 and 50mg/kg body weight enhanced the success rate of mating and fertility due to increased libido as well as the levels of reproductive hormones in male rats. The absence of alterations in the reproductive parameters of female rats at doses of 25 and 50mg/kg body weight of Bulbine natalensis stem extract suggest that the extract is "safe" for use at these doses by females during the organogenic period of pregnancy, whereas the extract dose of 100mg/kg body weight portends a negative effect on some reproductive functions of male and female rats.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

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

Absolute rate constants for the reaction of OH with cyclopentane and cycloheptane from 233 to 351 K.

PubMed

Gennaco, Michael A; Huang, Yi-wen; Hannun, Reem A; Dransfield, Timothy J

2012-12-27

Absolute rate constant measurements for the reactions of OH with cyclopentane and cycloheptane in the gas phase in 6-8 Torr of nitrogen from 233 to 351 K in the Harvard University High-Pressure Flow System (HPFS) are reported. Hydroxyl concentrations were measured using laser-induced fluorescence, and alkane concentrations were measured using Fourier transform infrared spectroscopy. Results were fit to a modified Arrhenius equation based on transition state theory (ignoring tunneling): k(T) = B e(-E(a)/T)/T(1 - e(-1.44ν(1)/T))(2)(1 - e(-1.44ν(2)/T)), with ν(1) and ν(2) bending frequencies set to 280 and 500 cm(-1) . Results were as follows for E(a) (K) and k (298) (10(-12) cm(3) s(-1)): cyclopentane, 460 ± 32, 4.85; cycloheptane, 319 ± 36, 9.84. This work represents the second absolute temperature-dependent rate constant measurement reported for cycloheptane, and the third absolute temperature-dependent rate constant measurement reported near room temperature for the reaction of OH and cyclopentane. For the title reactions, the reaction barriers reported here are in agreement with the reaction barrier previously reported for cyclohexane and considerably higher than the barrier previously reported for cyclo-octane, a result that is not predicted by our current understanding of hydrocarbon reactivity.

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.

DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Shin, Cheol Min; Lee, Yoon Jin; Kim, Jong-Min; Lee, Jee Young; Kim, Kyung-Joon; Choi, Yoon Jin; Kim, Nayoung; Lee, Dong Ho

2018-04-21

To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

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

Entrenched geographical and socioeconomic disparities in child mortality: trends in absolute and relative inequalities in Cambodia.

PubMed

Jimenez-Soto, Eliana; Durham, Jo; Hodge, Andrew

2014-01-01

Cambodia has made considerable improvements in mortality rates for children under the age of five and neonates. These improvements may, however, mask considerable disparities between subnational populations. In this paper, we examine the extent of the country's child mortality inequalities. Mortality rates for children under-five and neonates were directly estimated using the 2000, 2005 and 2010 waves of the Cambodian Demographic Health Survey. Disparities were measured on both absolute and relative scales using rate differences and ratios, and where applicable, slope and relative indices of inequality by levels of rural/urban location, regions and household wealth. Since 2000, considerable reductions in under-five and to a lesser extent in neonatal mortality rates have been observed. This mortality decline has, however, been accompanied by an increase in relative inequality in both rates of child mortality for geography-related stratifying markers. For absolute inequality amongst regions, most trends are increasing, particularly for neonatal mortality, but are not statistically significant. The only exception to this general pattern is the statistically significant positive trend in absolute inequality for under-five mortality in the Coastal region. For wealth, some evidence for increases in both relative and absolute inequality for neonates is observed. Despite considerable gains in reducing under-five and neonatal mortality at a national level, entrenched and increased geographical and wealth-based inequality in mortality, at least on a relative scale, remain. As expected, national progress seems to be associated with the period of political and macroeconomic stability that started in the early 2000s. However, issues of quality of care and potential non-inclusive economic growth might explain remaining disparities, particularly across wealth and geography markers. A focus on further addressing key supply and demand side barriers to accessing maternal and child health care and on the social determinants of health will be essential in narrowing inequalities.

Changing ethnic inequalities in mortality in New Zealand over 30 years: linked cohort studies with 68.9 million person-years of follow-up.

PubMed

Disney, George; Teng, Andrea; Atkinson, June; Wilson, Nick; Blakely, Tony

2017-01-01

Internationally, ethnic inequalities in mortality within countries are increasingly recognized as a public health concern. But few countries have data to monitor such inequalities. We aimed to provide a detailed description of ethnic inequalities (Māori [indigenous], Pacific, and European/Other) in mortality for a country with high quality ethnicity data, using both standard and novel visualization methods. Cohort studies of the entire New Zealand population were conducted, using probabilistically-linked Census and mortality data from 1981 to 2011 (68.9 million person years). Absolute (standardized rate difference) and relative (standardized rate ratio) inequalities were calculated, in 1-74-year-olds, for Māori and Pacific peoples in comparison to European/Other. All-cause mortality rates were highest for Māori, followed by Pacific peoples then European/Other, and declined in all three ethnic groups over time. Pacific peoples experienced the slowest annual percentage fall in mortality rates, then Māori, with European/Other having the highest percentage falls - resulting in widening relative inequalities. Absolute inequalities, however, for both Māori and Pacific males compared to European/Other have been falling since 1996. But for females, only Māori absolute inequalities (compared with European/Other) have been falling. Regarding cause of death, cancer is becoming a more important contributor than cardiovascular disease (CVD) to absolute inequalities, especially for Māori females. We found declines in all-cause mortality rates, over time, for each ethnic group of interest. Ethnic mortality inequalities are generally stable or even falling in absolute terms, but have increased on a relative scale. The drivers of these inequalities in mortality are transitioning over time, away from CVD to cancer and diabetes; such transitions are likely in other countries, and warrant further research. To address these inequalities, policymakers need to enhance prevention activities and health care delivery, but also support wider improvements in educational achievement and socioeconomic position for highest need populations.

Changing ethnic inequalities in mortality in New Zealand over 30 years: linked cohort studies with 68.9 million person-years of follow-up.

PubMed

Disney, George; Teng, Andrea; Atkinson, June; Wilson, Nick; Blakely, Tony

2017-04-26

Internationally, ethnic inequalities in mortality within countries are increasingly recognized as a public health concern. But few countries have data to monitor such inequalities. We aimed to provide a detailed description of ethnic inequalities (Māori [indigenous], Pacific, and European/Other) in mortality for a country with high quality ethnicity data, using both standard and novel visualization methods. Cohort studies of the entire New Zealand population were conducted, using probabilistically-linked Census and mortality data from 1981 to 2011 (68.9 million person years). Absolute (standardized rate difference) and relative (standardized rate ratio) inequalities were calculated, in 1-74-year-olds, for Māori and Pacific peoples in comparison to European/Other. All-cause mortality rates were highest for Māori, followed by Pacific peoples then European/Other, and declined in all three ethnic groups over time. Pacific peoples experienced the slowest annual percentage fall in mortality rates, then Māori, with European/Other having the highest percentage falls - resulting in widening relative inequalities. Absolute inequalities, however, for both Māori and Pacific males compared to European/Other have been falling since 1996. But for females, only Māori absolute inequalities (compared with European/Other) have been falling. Regarding cause of death, cancer is becoming a more important contributor than cardiovascular disease (CVD) to absolute inequalities, especially for Māori females. We found declines in all-cause mortality rates, over time, for each ethnic group of interest. Ethnic mortality inequalities are generally stable or even falling in absolute terms, but have increased on a relative scale. The drivers of these inequalities in mortality are transitioning over time, away from CVD to cancer and diabetes; such transitions are likely in other countries, and warrant further research. To address these inequalities, policymakers need to enhance prevention activities and health care delivery, but also support wider improvements in educational achievement and socioeconomic position for highest need populations.

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.

Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer.

PubMed

Abo-Madyan, Yasser; Aziz, Muhammad Hammad; Aly, Moamen M O M; Schneider, Frank; Sperk, Elena; Clausen, Sven; Giordano, Frank A; Herskind, Carsten; Steil, Volker; Wenz, Frederik; Glatting, Gerhard

2014-03-01

Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED). Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk. Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively. Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Area-under-the-curve monitoring of cyclosporine therapy: Performance of different assay methods and their target concentrations

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

Grevel, J.; Napoli, K.L.; Gibbons, S.

1990-01-01

The measurement of areas under the concentration-time curve (AUC) was recently introduced as an alternative to trough level monitoring of cyclosporine therapy. The AUC is divided by the oral dosing interval to calculate an average concentration. All measurements are performed at clinical steady state. The initial evaluation of AUC monitoring showed advantages over trough level monitoring with concentrations of cyclosporine measured in serum by the polyclonal radioimmunoassay of Sandoz. This assay technique is no longer available and the following assays were performed in parallel during up to 173 AUC determinations in 51 consecutive renal transplant patients: polyclonal fluorescence polarization immunoassaymore » of Abbott in serum, specific and nonspecific monoclonal radioimmunoassays using {sup 3}H and {sup 125}I tracers in serum and whole blood, and high performance liquid chromatography in whole blood. Both trough levels and average concentrations at steady state measured by those different techniques were significantly correlated with the oral dose. The best correlation (r2 = 0.54) was shown by average concentrations measured in whole blood by the specific monoclonal radioimmunoassay of Sandoz ({sup 3}H tracer). This monitoring technique was also associated with the smallest absolute error between repeated observations in the same patient while the oral dose rate remained the same or was changed. Both allegedly specific monoclonal radioimmunoassays (with {sup 3}H and {sup 125}I tracer) measured significantly higher concentrations than the liquid chromatography.« less

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.

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.

Channel specific rate constants for reactions of O(1D) with HCl and HBr

NASA Technical Reports Server (NTRS)

Wine, P. H.; Wells, J. R.; Ravishankara, A. R.

1986-01-01

The absolute rate coefficients and product yields for reactions of O(1D) with HCl(1) and HBr(2) at 287 K are presently determined by means of the time-resolved resonance fluorescence detection of O(3P) and H(2S) in conjunction with pulsed laser photolysis of O3/HX/He mixtures. Total rate coefficients for O(1D) removal are found to be, in units of 10 to the -10th cu cm/molecule per sec, k(1) = 1.50 + or - 0.18 and k(2) 1.48 + or - 0.16; the absolute accuracy of these rate coefficients is estimated to be + or - 20 percent.

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.

Aircraft noise-induced awakenings are more reasonably predicted from relative than from absolute sound exposure levels.

PubMed

Fidell, Sanford; Tabachnick, Barbara; Mestre, Vincent; Fidell, Linda

2013-11-01

Assessment of aircraft noise-induced sleep disturbance is problematic for several reasons. Current assessment methods are based on sparse evidence and limited understandings; predictions of awakening prevalence rates based on indoor absolute sound exposure levels (SELs) fail to account for appreciable amounts of variance in dosage-response relationships and are not freely generalizable from airport to airport; and predicted awakening rates do not differ significantly from zero over a wide range of SELs. Even in conjunction with additional predictors, such as time of night and assumed individual differences in "sensitivity to awakening," nominally SEL-based predictions of awakening rates remain of limited utility and are easily misapplied and misinterpreted. Probabilities of awakening are more closely related to SELs scaled in units of standard deviates of local distributions of aircraft SELs, than to absolute sound levels. Self-selection of residential populations for tolerance of nighttime noise and habituation to airport noise environments offer more parsimonious and useful explanations for differences in awakening rates at disparate airports than assumed individual differences in sensitivity to awakening.

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

Ultrahigh-Repetition Pulse Train with Absolute-Phase Control Produced by AN Adiabatic Raman Process

NASA Astrophysics Data System (ADS)

Katsuragawa, M.; Suzuki, T.; Shiraga, K.; Arakawa, M.; Onose, T.; Yokoyama, K.; Hong, F. L.; Misawa, K.

2010-02-01

We describe the generation of an ultrahigh-repetition-rate train of ultrashort pulses on the basis of an adiabatic Raman process. We also describe recent progress in studies toward the ultimate regime: realization of an ultrahigh-repetition-rate train of monocycle pulses with control of the absolute phase. We comment on the milestones expected in the near future in terms of the study of such novel light sources and the new field of optical science stimulated by their development.

Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers.

PubMed

Crevoisier, C; Delisle, M C; Joseph, I; Foletti, G

2003-01-01

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C(max) 11.0 vs. 14.9 ng.ml(-1)) and time to reach maximum concentration (t(max) 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C(max) 9.9 ng.ml(-1); t(max) 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC(0- infinity ) 620 vs. 561 ng.h.ml(-1)). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V(Z)) were 55 ml.min(-1) and 180 liters, respectively. In conclusion, the observed differences in C(max) and t(max) after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients, but therapeutic response would be expected to be less predictable and to occur later in the case of i.m. administration. Copyright 2003 S. Karger AG, Basel

Novel, full 3D scintillation dosimetry using a static plenoptic camera.

PubMed

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-08-01

Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm(3) EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle(3) was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions.

Novel, full 3D scintillation dosimetry using a static plenoptic camera

PubMed Central

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-01-01

Purpose: Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm3 EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. Results: The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle3 was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Conclusions: Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions. PMID:25086549

[Measurements of vancomycin concentrations in the blood - a method of personalization the antibiotic therapy in patients with chronic kidney disease].

PubMed

Pondel, Joanna; Krajewski, Piotr; Królikowska, Natalia; Tobiasz, Aleksandra; Augustyniak-Bartosik, Hanna; Hurkacz, Magdalena

2017-04-21

Therapeutic Drug Monitoring is a recognized method of personalizing treatment, having particular application in patients with chronic kidney disease who have frequent infections, requiring administration of vancomycin. International guidelines indicate the need to adjust the dose of the drug to the state of renal function. The recommended therapeutic ranges of minimum and maximum levels should be achieved in order to increase the effectiveness and safety of treatment. The aim of this study was to evaluate the usefulness of measuring the concentration of vancomycin in patients with chronic kidney disease due to bacterial infection. The study included 96 adult patients with chronic kidney disease of varying severity treated with vancomycin Patients were divided into 3 groups: treated by haemodialysis (hd), after renal transplantations (ktx), do not require renal replacement therapy (nef). In subjects were examined the minimum and maximum concentrations of vancomycin in steady-state and were compared with recommended therapeutic ranges. Statistically significant decrease of inflammatory markers was observed only in patients treated with dialysis. In the other groups not significant changes in values of inflammatory parameters were confirmed. Trough concentrations of vancomycin marked in patients were consistent with the recommendation of EUCAST, but exceeded the value recommended by the manufacturers of the drug. Considering absolute values of the minimum concentrations, only about 50% of patients achieved the therapeutic range (58% for recommendation EUCAST and 36% for the manufacturer's instructions). Peak concentration values indicated in dialyzed patients were below the prescribed range of 20-50 mg/l and averaged 17.7 mg / l. In the other subgroups they were correct. The rating of the absolute values of the peak concentrations of vancomycin also showed that only 46% (64% in the ktx, 30% - hd and 53% - nef) was within the recommended range, while 50% were classified as concentrations of sub-therapeutic (36% in the ktx, 42% of the nef group and 65% in hd). Vancomycin concentrations measured in patients with chronic kidney disease, both minimum and maximum, were not fully comply with the recommended therapeutic ranges, despite the use of doses determined based on a calculation of glomerular filtration rate. This points to the need for particularly careful monitoring of therapy and analysis of antibiotic concentrations to improve the effectiveness and reduce the incidence of undesirable consequences of treatment.

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

Randomized trial of a dual-hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor-augmented pump therapy.

PubMed

Jacobs, P G; El Youssef, J; Reddy, R; Resalat, N; Branigan, D; Condon, J; Preiser, N; Ramsey, K; Jones, M; Edwards, C; Kuehl, K; Leitschuh, J; Rajhbeharrysingh, U; Castle, J R

2016-11-01

To test whether adjusting insulin and glucagon in response to exercise within a dual-hormone artificial pancreas (AP) reduces exercise-related hypoglycaemia. In random order, 21 adults with type 1 diabetes (T1D) underwent three 22-hour experimental sessions: AP with exercise dosing adjustment (APX); AP with no exercise dosing adjustment (APN); and sensor-augmented pump (SAP) therapy. After an overnight stay and 2 hours after breakfast, participants exercised for 45 minutes at 60% of their maximum heart rate, with no snack given before exercise. During APX, insulin was decreased and glucagon was increased at exercise onset, while during SAP therapy, subjects could adjust dosing before exercise. The two primary outcomes were percentage of time spent in hypoglycaemia (<3.9 mmol/L) and percentage of time spent in euglycaemia (3.9-10 mmol/L) from the start of exercise to the end of the study. The mean (95% confidence interval) times spent in hypoglycaemia (<3.9 mmol/L) after the start of exercise were 0.3% (-0.1, 0.7) for APX, 3.1% (0.8, 5.3) for APN, and 0.8% (0.1, 1.4) for SAP therapy. There was an absolute difference of 2.8% less time spent in hypoglycaemia for APX versus APN (p = .001) and 0.5% less time spent in hypoglycaemia for APX versus SAP therapy (p = .16). Mean time spent in euglycaemia was similar across the different sessions. Adjusting insulin and glucagon delivery at exercise onset within a dual-hormone AP significantly reduces hypoglycaemia compared with no adjustment and performs similarly to SAP therapy when insulin is adjusted before exercise. © 2016 John Wiley & Sons Ltd.

A dosimetric evaluation of the Eclipse AAA algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery

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

Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel

2014-07-01

The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [AAA]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1 cc) were planned (Eclipse, AAA, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2Dmore » dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1 mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46 mm. According to our results, we conclude that the Eclipse/AAA algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.« less

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

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.

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

Gadolinium-Based Contrast Agents in Kidney Disease: Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists.

PubMed

Schieda, Nicola; Blaichman, Jason I; Costa, Andreu F; Glikstein, Rafael; Hurrell, Casey; James, Matthew; Jabehdar Maralani, Pejman; Shabana, Wael; Tang, An; Tsampalieros, Anne; van der Pol, Christian; Hiremath, Swapnil

2018-05-01

Use of gadolinium-based contrast agents (GBCAs) in renal impairment is controversial, with physician and patient apprehension in acute kidney injury (AKI), chronic kidney disease (CKD), and dialysis because of concerns regarding nephrogenic systemic fibrosis (NSF). The position that GBCAs are absolutely contraindicated in AKI, CKD stage 4 or 5 (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m 2 ) and dialysis-dependent patients is outdated, and may limit access to clinically necessary contrast-enhanced MRI examinations. Following a comprehensive review of the literature and reported NSF cases to date, a committee of radiologists and nephrologists developed clinical practice guidelines to assist physicians in making decisions regarding GBCA administrations. In patients with mild-to-moderate CKD (eGFR ≥30 and <60 mL/min/1.73 m 2 ), administration of standard doses of GBCA is safe and no additional precautions are necessary. In patients with AKI, with severe CKD (eGFR <30 mL/min/1.73 m 2 ), or on dialysis, administration of GBCAs should be considered individually and alternative imaging modalities utilized whenever possible. If GBCAs are necessary, newer GBCAs may be administered with patient consent obtained by a physician (or their delegate), citing an exceedingly low risk (much less than 1%) of developing NSF. Standard GBCA dosing should be used; half or quarter dosing is not recommended and repeat injections should be avoided. Dialysis-dependent patients should receive dialysis; however, initiating dialysis or switching from peritoneal to hemodialysis to reduce the risk of NSF is unproven. Use of a macrocyclic ionic instead of macrocyclic nonionic GBCA or macrocyclic instead of newer linear GBCA to further prevent NSF is unproven. Gadopentetate dimeglumine, gadodiamide, and gadoversetamide remain absolutely contraindicated in patients with AKI, with stage 4 or 5 CKD, or on dialysis. The panel agreed that screening for renal disease is important but less critical when using macrocyclic and newer linear GBCAs. Monitoring for and reporting of potential cases of NSF in patients with AKI or CKD who have received GBCAs is recommended. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Validation of absolute axial neutron flux distribution calculations with MCNP with 197Au(n,γ)198Au reaction rate distribution measurements at the JSI TRIGA Mark II reactor.

PubMed

Radulović, Vladimir; Štancar, Žiga; Snoj, Luka; Trkov, Andrej

2014-02-01

The calculation of axial neutron flux distributions with the MCNP code at the JSI TRIGA Mark II reactor has been validated with experimental measurements of the (197)Au(n,γ)(198)Au reaction rate. The calculated absolute reaction rate values, scaled according to the reactor power and corrected for the flux redistribution effect, are in good agreement with the experimental results. The effect of different cross-section libraries on the calculations has been investigated and shown to be minor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

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.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

PubMed

Berwanger, Otavio; Santucci, Eliana Vieira; de Barros E Silva, Pedro Gabriel Melo; Jesuíno, Isabella de Andrade; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Santos, Renato Hideo Nakagawa; Laranjeira, Ligia Nasi; Egydio, Flávia de Mattos; Borges de Oliveira, Juliana Aparecida; Dall Orto, Frederico Toledo Campo; Beraldo de Andrade, Pedro; Bienert, Igor Ribeiro de Castro; Bosso, Carlos Eduardo; Mangione, José Armando; Polanczyk, Carisi Anne; Sousa, Amanda Guerra de Moraes Rego; Kalil, Renato Abdala Karam; Santos, Luciano de Moura; Sposito, Andrei Carvalho; Rech, Rafael Luiz; Sousa, Antônio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; Giraldez, Roberto Rocha Corrêa Veiga; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo Moraes Rego; Alexander, John Hunter; Granger, Christopher Bull; Lopes, Renato Delascio

2018-04-03

The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. clinicaltrials.gov Identifier: NCT01448642.

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.

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 development of a 6 to 7 MeV photon field for instrument calibration

NASA Astrophysics Data System (ADS)

Duvall, K. C.; Soares, C. G.; Heaton, H. T.; Seltzer, S. M.

1985-05-01

A photon source has been developed at the National Bureau of Standards to measure the response of radiological survey instruments to high-energy photons. The 19F(p, αγ) 16 O reaction has been used to produce a 6 to 7 MeV photon field with a fairly uniform photon flux density of approximately 3 × 10 3 cm -2 s -1 at one meter from the source. The photon flux density is obtained from measurements with a 3 × 3 inch 2 Nal detector whose absolute response has been determined by a Monte Carlo calculation. The spectral characteristics of the high-energy photons have been determined from measurements with a large volume high purity germanium detector. The absorbed dose rate to water was measured with LiF thermoluminescent dosimeters (TLDs) at several depths in a 30 × 30 × 30 cm 3 Lucite phantom. It is planned to compare absorbed dose determinations from the TLD measurements with those computed from spectral measurements. The response of six commercial radiological survey instruments has been measured behind various thicknesses of plastic absorber. The results indicate that approximately 2.5 cm of plastic in front of these instruments is sufficient to discriminate against the associated high-energy electron contamination.

Development and evaluation of a novel microemulsion formulation of elacridar to improve its bioavailability

PubMed Central

Sane, Ramola; Mittapalli, Rajendar K.; Elmquist, William F.

2014-01-01

The study objective was to develop a formulation of elacridar to overcome its dissolution-rate limited bioavailability. Elacridar is a P-gp and BCRP inhibitor that has been used to improve the brain distribution of drugs that are substrates of P-gp and BCRP. The chronic use of elacridar is restricted due to poor solubility leading to poor oral bioavailability. A microemulsion formulation using Cremophor EL, Carbitol and Captex 355 (6:3:1) was developed. The elacridar microemulsion was effective in the inhibition of P-gp and Bcrp in MDCKII-transfected cells. FVBn mice were used to determine the bioavailability of elacridar after a 10 mg/kg dose of elacridar in the microemulsion, intraperitoneally and orally; and the absolute bioavailability was determined to be 1.3 and 0.47, respectively. Co-administration of elacridar microemulsion intraperitoneally with oral erlotinib in FVBn mice improved the erlotinib brain penetration three-fold. The current study shows that a microemulsion formulation of elacridar is effective in improving the bioavailability of elacridar and is an effective inhibitor of P-gp and Bcrp; in-vitro and in-vivo. It offers an alternative to the suspension and allows a decrease in the dose required to achieve a significant inhibitory effect at the blood-brain barrier. PMID:23334925

Projected cancer risks potentially related to past, current, and future practices in paediatric CT in the United Kingdom, 1990-2020.

PubMed

Journy, Neige M Y; Lee, Choonsik; Harbron, Richard W; McHugh, Kieran; Pearce, Mark S; Berrington de González, Amy

2017-01-03

To project risks of developing cancer and the number of cases potentially induced by past, current, and future computed tomography (CT) scans performed in the United Kingdom in individuals aged <20 years. Organ doses were estimated from surveys of individual scan parameters and CT protocols used in the United Kingdom. Frequencies of scans were estimated from the NHS Diagnostic Imaging Dataset. Excess lifetime risks (ELRs) of radiation-related cancer were calculated as cumulative lifetime risks, accounting for survival probabilities, using the RadRAT risk assessment tool. In 2000-2008, ELRs ranged from 0.3 to 1 per 1000 head scans and 1 to 5 per 1000 non-head scans. ELRs per scan were reduced by 50-70% in 2000-2008 compared with 1990-1995, subsequent to dose reduction over time. The 130 750 scans performed in 2015 in the United Kingdom were projected to induce 64 (90% uncertainty interval (UI): 38-113) future cancers. Current practices would lead to about 300 (90% UI: 230-680) future cancers induced by scans performed in 2016-2020. Absolute excess risks from single exposures would be low compared with background risks, but even small increases in annual CT rates over the next years would substantially increase the number of potential subsequent cancers.

Exposure of school children to polycyclic aromatic hydrocarbons, heavy metals and radionuclides in the urban soil of Kragujevac city, Central Serbia.

PubMed

Stajic, J M; Milenkovic, B; Pucarevic, M; Stojic, N; Vasiljevic, I; Nikezic, D

2016-03-01

The concentrations of radionuclides, polycyclic aromatic hydrocarbons (PAHs) and heavy metals were measured in soil samples collected from school backyards and playgrounds in Kragujevac, one of the largest cities of Central Serbia. The activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs were determined using the HPGe semiconductor detector. The average values were 34.6, 44.7, 428.9 and 45.1 Bq kg(-1), respectively. The correlation between the activity concentrations of (226)Ra in the soil samples and the results of the previous measurement of (222)Rn concentrations in the indoor air was examined. The absorbed dose rates, the annual effective doses and excess lifetime cancer risk were also estimated. The activity concentrations of (226)Ra and (232)Th have shown normal distribution. The collected soil samples were analysed for PAHs by HPLC. All analysed soil samples contained PAHs, and their total amounts (for 15 measured compounds) were found to be between 0.038 and 3.136 mg kg(-1) of absolutely dry soil (a.d.s). In addition the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn were measured in the fourteen soil samples collected from the playgrounds of kindergartens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

40 CFR 1065.345 - Vacuum-side leak verification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... zero flow, or by detecting the dilution of a known concentration of span gas when it flows through the.... Measure and record the absolute pressure of the trapped gas and optionally the system absolute temperature... pressure and optionally temperature. (4) Calculate the leak flow rate based on an assumed value of zero for...

40 CFR 1065.345 - Vacuum-side leak verification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... zero flow, or by detecting the dilution of a known concentration of span gas when it flows through the.... Measure and record the absolute pressure of the trapped gas and optionally the system absolute temperature... pressure and optionally temperature. (4) Calculate the leak flow rate based on an assumed value of zero for...

40 CFR 1065.345 - Vacuum-side leak verification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... zero flow, or by detecting the dilution of a known concentration of span gas when it flows through the.... Measure and record the absolute pressure of the trapped gas and optionally the system absolute temperature... pressure and optionally temperature. (4) Calculate the leak flow rate based on an assumed value of zero for...

40 CFR 1065.345 - Vacuum-side leak verification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... zero flow, or by detecting the dilution of a known concentration of span gas when it flows through the.... Measure and record the absolute pressure of the trapped gas and optionally the system absolute temperature... pressure and optionally temperature. (4) Calculate the leak flow rate based on an assumed value of zero for...

40 CFR 1065.345 - Vacuum-side leak verification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... zero flow, or by detecting the dilution of a known concentration of span gas when it flows through the.... Measure and record the absolute pressure of the trapped gas and optionally the system absolute temperature... pressure and optionally temperature. (4) Calculate the leak flow rate based on an assumed value of zero for...

Zeta potential response of human erythrocyte membranes to the modulators of Gardos channel activity under low rate β-radiation.

PubMed

Zhirnov, V V; Iakovenko, I N; Voitsitskiy, V M; Khyzhnyak, S V; Zubrikova-Chugainova, O G; Gorobetz, V A

2015-12-01

Study of human erythrocyte DP response under modification by activators and blockers of the functional state of Ca2+-dependent K+ channels under low rate β-radiation. Erythrocytes were isolated from the donor blood. The zeta potential was computed from the value of the cell electrophoretic mobility. The investigated drugs preliminary introduced in cellular suspensions, and then aliquote of 90Sr(NO3)2 solution to get the final activity concentration of 44,4kBq⋅l-1. The radioisotope radiation of 90Sr/90Y (RR, 15 μGy⋅h-1) increases an absolute value of erythrocyte membranes DP (DPab), and its action is reversible. It specifies the effect is mediated by non-ionizing part of the RR. Dibutyril-cAMP dose-independent increases DPab of erythrocyte membranes in the concentration range of 1-100 мкМ, but RR does not amplify this effect. Anaprilin increases dose-independent DPab in concentrations 10 and 100 μМ. The effect of maximal concentration of anaprilin (100 μМ) decreases by RR. Clotrimazol increases DPab of erythrocyte membranes in the concentration range of 0,1-10 μМ relatively control, while its maximal concentration - decreases, and the minimal level does not reliably influence on this index The action of сlotrimazol on DP in concentrations of 10-100 μМ is abolished by RR, and is not changed in the range of 0,1-1,0 μМ. Nitrendipine raises DPab of erythrocyte membranes in all of range of concentrations, and RR amplifies the effect of the drug. 1. There is a threshold of the biological action on cells for the ionizing component of radioisotope radiation determined by efficiency of operation their antioxidant system.2. At dose rates below a threshold, the action of ionizing radiation is mediated by its non-ionizing component, and is reversible, and therefore is determined only in the field of radiation. V. V. Zhirnov, I. N. Iakovenko, V.M. Voitsitskiy, S. V. Khyzhnyak, О. G. Zubrikova-Chugainova, V.A. Gorobetz.

Secondary Electron Emission From Solar Cell Coverslides And Its Effect On Absolute Vehicle Charging

NASA Astrophysics Data System (ADS)

Ferguson, Dale C.

2011-10-01

It has often been stated that earthed conductive solar cell coverslides are the best way to prevent electrostatic discharges on space solar arrays in GEO. While it is true that such coverslides will prevent differential charging on the solar arrays, it will be shown through NASCAP- 2k simulations that the secondary electron emission of such coverslides is very important for absolute vehicle charging. In particular, carbon nanotube coatings, due to the extremely low secondary electron emission from carbon, may exacerbate absolute vehicle charging. However, if they are earthed, because of their conductivity they may minimize differential charging and the possibility of arcing elsewhere on the spacecraft. Such results may also be true for insulative coverslides if spacecraft thermal blankets are made of materials with high secondary electron emission. Finally, photoemission from coverslides is investigated, with regard to anti-reflection coatings. Surfaces which reflect UV can have low photoemission, while those that absorb may have higher photoemission rates. Thus, anti-reflection coatings may lead to higher absolute spacecraft charging rates. NASCAP-2k simulations will be used to investigate these dependences for realistic spacecraft.

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

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.

Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Assessing the health effects associated with occupational radiation exposure in Korean radiation workers: protocol for a prospective cohort study.

PubMed

Seo, Songwon; Lim, Wan Young; Lee, Dal Nim; Kim, Jung Un; Cha, Eun Shil; Bang, Ye Jin; Lee, Won Jin; Park, Sunhoo; Jin, Young Woo

2018-03-30

The cancer risk of radiation exposure in the moderate-to-high dose range has been well established. However, the risk remains unclear at low-dose ranges with protracted low-dose rate exposure, which is typical of occupational exposure. Several epidemiological studies of Korean radiation workers have been conducted, but the data were analysed retrospectively in most cases. Moreover, groups with relatively high exposure, such as industrial radiographers, have been neglected. Therefore, we have launched a prospective cohort study of all Korean radiation workers to assess the health effects associated with occupational radiation exposure. Approximately 42 000 Korean radiation workers registered with the Nuclear Safety and Security Commission from 2016 to 2017 are the initial target population of this study. Cohort participants are to be enrolled through a nationwide self-administered questionnaire survey between 24 May 2016 and 30 June 2017. As of 31 March 2017, 22 982 workers are enrolled in the study corresponding to a response rate of 75%. This enrolment will be continued at 5-year intervals to update information on existing study participants and recruit newly hired workers. Survey data will be linked with the national dose registry, the national cancer registry, the national vital statistics registry and national health insurance data via personal identification numbers. Age-specific and sex-specific standardised incidence and mortality ratios will be calculated for overall comparisons of cancer risk. For dose-response assessment, excess relative risk (per Gy) and excess absolute risk (per Gy) will be estimated with adjustments for birth year and potential confounders, such as lifestyle factors and socioeconomic status. This study has received ethical approval from the institutional review board of the Korea Institute of Radiological and Medical Sciences (IRB No. K-1603-002-034). All participants provided written informed consent prior to enrolment. The findings of the study will be disseminated through scientific peer-reviewed journals and be provided to the public, including radiation workers, via the study website (http://www.rhs.kr/) and onsite radiation safety education. © 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.

What Risk? (edited by Roger Bate)

NASA Astrophysics Data System (ADS)

Behrman, E. J.

1999-07-01

Roger Bate, Ed. Butterworth-Heinemann: Oxford, UK. 329 pp. Cloth (1997): ISBN 0-7506-3810-9. 56.95. Paper (1999): ISBN 0 7506 4228 9. 29.95. A train carrying radioactive waste had begun its trip in New York and was close to its destination in California. As it stopped, the engineer called to a bystander, "Congratulations." "What for?" said the man. "You get to die. We calculated that each person along the route would receive one-millionth of the lethal dose of radioactivity. No one has died yet and you are the millionth person." "But I have received only one-millionth of the lethal dose." "That doesn't matter, it's a question of statistics." (This story is paraphrased from Rockwell's piece in The Scientist, March 16, 1998, p 7.) What Risk? contains 15 chapters (by 19 authors) arranged in five categories: methodology, science, science policy, commentaries, and perception. It deals in different ways, broadly speaking, with the problems raised by this anecdote. It would make a splendid textbook for high-school students or college undergraduates for a course dealing with pitfalls in extrapolation, unexpected variables, the proper use of statistics, political correctness and absolute safety, evaluation of the scientific literature, and the interplay of science and politics. Each article has an extensive reference list. Among the specific risks discussed are asbestos, benzene, environmental (secondhand) tobacco smoke, dioxin, ionizing radiation, and carcinogens. Some general principles emerge. (i) Since all organisms have repair mechanisms against environmental damage, there are thresholds for all damaging agents. Therefore, extrapolation from high dose rates to very low levels does not make sense. (ii) Doses and dose rates should not be confused. (iii) There are very large species differences in response to damaging agents. (iv) Unrecognized variables lurk everywhere. (v) The costs of enforcing demonstrably false standards are huge. Here are some illustrations. Nilsson's article on environmental tobacco smoke (ETS) concludes that the dangers are about one order of magnitude less than those currently used for regulatory purposes. The errors arise from misclassification of smoking status, inappropriate controls, confounding factors having to do with lifestyle, and, possibly, heredity. Looked at another way, a child's intake of benzo[a]pyrene during 10 hours from ETS is estimated to be about 250 times less than the amount ingested from eating one grilled sausage. Munby and Weetman's article on benzene and leukemia concludes that the risk of leukemia from nonindustrial exposure is probably zero. The slope of the hypothetically linear dose-effect curve currently in use is too large, the effect at low doses is overestimated, and the linear extrapolation to zero is not justified. The current standard for air quality is about six orders of magnitude below human toxicity levels. Ames and Gold, in the chapter Pollution, Pesticides and Cancer Misconceptions, give a fine summary of the difficulties with animal cancer tests. "Rodent carcinogens are not rare. Half of all chemicals tested in standard high dose animal cancer tests, whether occurring naturally or produced synthetically, are 'carcinogens'. There are high dose effects in these rodent cancer tests that are not relevant to low dose human exposures... Though 99.9 percent of the chemicals humans ingest are natural, the focus of regulatory policy is on synthetic chemicals." For example, more than 1000 chemicals have been identified in coffee: 27 have been tested and 19 are rodent carcinogens at the high levels at which these tests are carried out. Dioxin has been called the most toxic chemical known to man. Máller shows that this is not true by any measure. Part of the confusion is based on the fact that guinea pigs are killed by doses thousands of times less than those which affect humans. The chief symptom of dioxin exposure in humans is acne. The chapter that most surprised me was that by Jaworowski on ionizing radiation. First, the extrapolation of data on the survivors of the Hiroshima and Nagasaki bombings involves dose rates on the order of 5000 mSv/year. For these dose rates, the effects are well established. The average natural dose rate (from the unperturbed environment) is about 2.4 mSv/year. Average additional levels resulting from the Chernobyl accident in Central Europe were about 0.01 mSv/year. So, are there measurable effects at these low dose rates? The linear extrapolation model says yes. But there is no evidence to support this model. Indeed, the author refers to a large body of literature (more than 1000 publications) which is said to show that not only are these low dose rates not harmful, but they are actually beneficial. Examples: people in houses with higher than average radon levels show a lower mortality from lung cancer. The number of birth defects in Hungary in the two years following Chernobyl was smaller than in the years preceding it. At low dose rates, the incidence of neoplasms in irradiated mice is lower than in nonirradiated controls. There are other examples. This literature should be critically examined. Then there is the question of cost. Funds are limited. Are we spending our money wisely? Ames and Gold give some numbers that suggest not. The average toxin control program costs 60 times more per life-year saved than an injury prevention program and 150 times more than a health care program. Chemical educators could do much for humanity by encouraging study of the material in this book.

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

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

PubMed Central

Papi, A; Dokic, D; Tzimas, W; Mészáros, I; Olech-Cudzik, A; Koroknai, Z; McAulay, K; Mersmann, S; Dalvi, PS; Overend, T

2017-01-01

Purpose To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. Patients and methods COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. Results In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. Conclusion FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments. PMID:28740376

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial.

PubMed

Papi, A; Dokic, D; Tzimas, W; Mészáros, I; Olech-Cudzik, A; Koroknai, Z; McAulay, K; Mersmann, S; Dalvi, P S; Overend, T

2017-01-01

To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. COPD patients with forced expiratory volume in 1 s (FEV 1 ) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P ≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P =0.084). Pre- and post-dose FEV 1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM ( P ≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P =0.077). There were more St George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P ≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM ( P ≤0.066). Acute β 2 -agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.