Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

PubMed

Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

2012-06-01

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

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

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

Cao, N; Young, L; Parvathaneni, U

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

Radiation dose delivery verification in the treatment of carcinoma-cervix

NASA Astrophysics Data System (ADS)

Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

2015-06-01

The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

2000-05-01

We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

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

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

Qin, Y; Gardner, S; Huang, Y

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

SU-E-T-113: Dose Distribution Using Respiratory Signals and Machine Parameters During Treatment

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

Imae, T; Haga, A; Saotome, N

Purpose: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. Treatment plans for lung tumors using stereotactic body radiotherapy (SBRT) are calculated with planning computed tomography (CT) images only exhale phase. Purpose of this study is to evaluate dose distribution by reconstructing from only the data such as respiratory signals and machine parameters acquired during treatment. Methods: Phantom and three patients with lung tumor underwent CT scans for treatment planning. They were treated by VMAT while acquiring projection images to derive their respiratory signals and machine parameters including positions ofmore » multi leaf collimators, dose rates and integrated monitor units. The respiratory signals were divided into 4 and 10 phases and machine parameters were correlated with the divided respiratory signals based on the gantry angle. Dose distributions of each respiratory phase were calculated from plans which were reconstructed from the respiratory signals and the machine parameters during treatment. The doses at isocenter, maximum point and the centroid of target were evaluated. Results and Discussion: Dose distributions during treatment were calculated using the machine parameters and the respiratory signals detected from projection images. Maximum dose difference between plan and in treatment distribution was −1.8±0.4% at centroid of target and dose differences of evaluated points between 4 and 10 phases were no significant. Conclusion: The present method successfully evaluated dose distribution using respiratory signals and machine parameters during treatment. This method is feasible to verify the actual dose for moving target.« less

Bombesin and G-17 dose responses in duodenal ulcer and controls.

PubMed

Hirschowitz, B I; Tim, L O; Helman, C A; Molina, E

1985-11-01

Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: an exaggerated release of gastrin with bombesin stimulation, and a defective inhibition of acid and pepsin secretion with higher doses of bombesin.

Validation and uncertainty analysis of a pre-treatment 2D dose prediction model

NASA Astrophysics Data System (ADS)

Baeza, Jose A.; Wolfs, Cecile J. A.; Nijsten, Sebastiaan M. J. J. G.; Verhaegen, Frank

2018-02-01

Independent verification of complex treatment delivery with megavolt photon beam radiotherapy (RT) has been effectively used to detect and prevent errors. This work presents the validation and uncertainty analysis of a model that predicts 2D portal dose images (PDIs) without a patient or phantom in the beam. The prediction model is based on an exponential point dose model with separable primary and secondary photon fluence components. The model includes a scatter kernel, off-axis ratio map, transmission values and penumbra kernels for beam-delimiting components. These parameters were derived through a model fitting procedure supplied with point dose and dose profile measurements of radiation fields. The model was validated against a treatment planning system (TPS; Eclipse) and radiochromic film measurements for complex clinical scenarios, including volumetric modulated arc therapy (VMAT). Confidence limits on fitted model parameters were calculated based on simulated measurements. A sensitivity analysis was performed to evaluate the effect of the parameter uncertainties on the model output. For the maximum uncertainty, the maximum deviating measurement sets were propagated through the fitting procedure and the model. The overall uncertainty was assessed using all simulated measurements. The validation of the prediction model against the TPS and the film showed a good agreement, with on average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis respectively, with a low dose threshold of 10%. The maximum and overall uncertainty of the model is dependent on the type of clinical plan used as input. The results can be used to study the robustness of the model. A model for predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used clinically and its uncertainties can be taken into account.

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

PubMed Central

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

2015-01-01

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

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

PubMed

Davidson, Scott E; Cui, Jing; Kry, Stephen; Deasy, Joseph O; Ibbott, Geoffrey S; Vicic, Milos; White, R Allen; Followill, David S

2016-08-01

A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.

Comparison of GATE/GEANT4 with EGSnrc and MCNP for electron dose calculations at energies between 15 keV and 20 MeV.

PubMed

Maigne, L; Perrot, Y; Schaart, D R; Donnarieix, D; Breton, V

2011-02-07

The GATE Monte Carlo simulation platform based on the GEANT4 toolkit has come into widespread use for simulating positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging devices. Here, we explore its use for calculating electron dose distributions in water. Mono-energetic electron dose point kernels and pencil beam kernels in water are calculated for different energies between 15 keV and 20 MeV by means of GATE 6.0, which makes use of the GEANT4 version 9.2 Standard Electromagnetic Physics Package. The results are compared to the well-validated codes EGSnrc and MCNP4C. It is shown that recent improvements made to the GEANT4/GATE software result in significantly better agreement with the other codes. We furthermore illustrate several issues of general interest to GATE and GEANT4 users who wish to perform accurate simulations involving electrons. Provided that the electron step size is sufficiently restricted, GATE 6.0 and EGSnrc dose point kernels are shown to agree to within less than 3% of the maximum dose between 50 keV and 4 MeV, while pencil beam kernels are found to agree to within less than 4% of the maximum dose between 15 keV and 20 MeV.

The effect of dose heterogeneity on radiation risk in medical imaging.

PubMed

Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

2013-06-01

The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations

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

Davidson, Scott E., E-mail: sedavids@utmb.edu

Purpose: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who usesmore » these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today’s modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. Methods: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Results: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. Conclusions: A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.« less

Calculation of absorbed dose and biological effectiveness from photonuclear reactions in a bremsstrahlung beam of end point 50 MeV.

PubMed

Gudowska, I; Brahme, A; Andreo, P; Gudowski, W; Kierkegaard, J

1999-09-01

The absorbed dose due to photonuclear reactions in soft tissue, lung, breast, adipose tissue and cortical bone has been evaluated for a scanned bremsstrahlung beam of end point 50 MeV from a racetrack accelerator. The Monte Carlo code MCNP4B was used to determine the photon source spectrum from the bremsstrahlung target and to simulate the transport of photons through the treatment head and the patient. Photonuclear particle production in tissue was calculated numerically using the energy distributions of photons derived from the Monte Carlo simulations. The transport of photoneutrons in the patient and the photoneutron absorbed dose to tissue were determined using MCNP4B; the absorbed dose due to charged photonuclear particles was calculated numerically assuming total energy absorption in tissue voxels of 1 cm3. The photonuclear absorbed dose to soft tissue, lung, breast and adipose tissue is about (0.11-0.12)+/-0.05% of the maximum photon dose at a depth of 5.5 cm. The absorbed dose to cortical bone is about 45% larger than that to soft tissue. If the contributions from all photoparticles (n, p, 3He and 4He particles and recoils of the residual nuclei) produced in the soft tissue and the accelerator, and from positron radiation and gammas due to induced radioactivity and excited states of the nuclei, are taken into account the total photonuclear absorbed dose delivered to soft tissue is about 0.15+/-0.08% of the maximum photon dose. It has been estimated that the RBE of the photon beam of 50 MV acceleration potential is approximately 2% higher than that of conventional 60Co radiation.

SU-D-304-07: Application of Proton Boron Fusion Reaction to Radiation Therapy

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

Jung, J; Yoon, D; Shin, H

Purpose: we present the introduction of a therapy method using the proton boron fusion reaction. The purpose of this study is to verify the theoretical validity of proton boron fusion therapy using Monte Carlo simulations. Methods: After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton’s maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here we show thatmore » the effectiveness of the proton boron fusion therapy (PBFT) was verified using Monte Carlo simulations. Results: We found that a dramatic increase by more than half of the proton’s maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton’s maximum dose point was located within the boron uptake region (BUR). In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. Conclusion: This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

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

Vikraman, S; Ramu, M; Karrthick, Kp

Purpose: The purpose of this study was to validate the advent of COMPASS 3D dosimetry as a routine pre treatment verification tool with commercially available CMS Monaco and Oncentra Masterplan planning system. Methods: Twenty esophagus patients were selected for this study. All these patients underwent radical VMAT treatment in Elekta Linac and plans were generated in Monaco v5.0 with MonteCarlo(MC) dose calculation algorithm. COMPASS 3D dosimetry comprises an advanced dose calculation algorithm of collapsed cone convolution(CCC). To validate CCC algorithm in COMPASS, The DICOM RT Plans generated using Monaco MC algorithm were transferred to Oncentra Masterplan v4.3 TPS. Only finalmore » dose calculations were performed using CCC algorithm with out optimization in Masterplan planning system. It is proven that MC algorithm is an accurate algorithm and obvious that there will be a difference with MC and CCC algorithms. Hence CCC in COMPASS should be validated with other commercially available CCC algorithm. To use the CCC as pretreatment verification tool with reference to MC generated treatment plans, CCC in OMP and CCC in COMPASS were validated using dose volume based indices such as D98, D95 for target volumes and OAR doses. Results: The point doses for open beams were observed <1% with reference to Monaco MC algorithms. Comparisons of CCC(OMP) Vs CCC(COMPASS) showed a mean difference of 1.82%±1.12SD and 1.65%±0.67SD for D98 and D95 respectively for Target coverage. Maximum point dose of −2.15%±0.60SD difference was observed in target volume. The mean lung dose of −2.68%±1.67SD was noticed between OMP and COMPASS. The maximum point doses for spinal cord were −1.82%±0.287SD. Conclusion: In this study, the accuracy of CCC algorithm in COMPASS 3D dosimetry was validated by compared with CCC algorithm in OMP TPS. Dose calculation in COMPASS is feasible within < 2% in comparison with commercially available TPS algorithms.« less

Dosimetric impact of applicator displacement during high dose rate (HDR) Cobalt-60 brachytherapy for cervical cancer: A planning study

NASA Astrophysics Data System (ADS)

Yong, J. S.; Ung, N. M.; Jamalludin, Z.; Malik, R. A.; Wong, J. H. D.; Liew, Y. M.; Ng, K. H.

2016-02-01

We investigated the dosimetric impact of applicator displacement on dose specification during high dose rate (HDR) Cobalt-60 (Co-60) brachytherapy for cervical cancer through a planning study. Eighteen randomly selected HDR full insertion plans were restrospectively studied. The tandem and ovoids were virtually shifted translationally and rotationally in the x-, y- and z-axis directions on the treatment planning system. Doses to reference points and volumes of interest in the plans with shifted applicators were compared with the original plans. The impact of dose displacement on 2D (point-based) and 3D (volume-based) treatment planning techniques was also assessed. A ±2 mm translational y-axis applicator shift and ±4° rotational x-axis applicator shift resulted in dosimetric changes of more than 5% to organs at risk (OAR) reference points. Changes to the maximum doses to 2 cc of the organ (D2cc) in 3D planning were statistically significant and higher than the reference points in 2D planning for both the rectum and bladder (p<0.05). Rectal D2cc was observed to be the most sensitive to applicator displacement among all dose metrics. Applicator displacement that is greater than ±2 mm translational y-axis and ±4° rotational x-axis resulted in significant dose changes to the OAR. Thus, steps must be taken to minimize the possibility of applicator displacement during brachytherapy.

The effects of spatial sampling choices on MR temperature measurements.

PubMed

Todd, Nick; Vyas, Urvi; de Bever, Josh; Payne, Allison; Parker, Dennis L

2011-02-01

The purpose of this article is to quantify the effects that spatial sampling parameters have on the accuracy of magnetic resonance temperature measurements during high intensity focused ultrasound treatments. Spatial resolution and position of the sampling grid were considered using experimental and simulated data for two different types of high intensity focused ultrasound heating trajectories (a single point and a 4-mm circle) with maximum measured temperature and thermal dose volume as the metrics. It is demonstrated that measurement accuracy is related to the curvature of the temperature distribution, where regions with larger spatial second derivatives require higher resolution. The location of the sampling grid relative temperature distribution has a significant effect on the measured values. When imaging at 1.0 × 1.0 × 3.0 mm(3) resolution, the measured values for maximum temperature and volume dosed to 240 cumulative equivalent minutes (CEM) or greater varied by 17% and 33%, respectively, for the single-point heating case, and by 5% and 18%, respectively, for the 4-mm circle heating case. Accurate measurement of the maximum temperature required imaging at 1.0 × 1.0 × 3.0 mm(3) resolution for the single-point heating case and 2.0 × 2.0 × 5.0 mm(3) resolution for the 4-mm circle heating case. Copyright © 2010 Wiley-Liss, Inc.

SU-F-BRE-16: VMAT Commissioning and Quality Assurance (QA) of An Elekta Synergy-STM Linac Using ICOM Test HarnessTM

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

Nguyen, A; Ironwood CRC, Phoenix, AZ; Rajaguru, P

2014-06-15

Purpose: To establish a set of tests based on the iCOM software that can be used to commission and perform periodic QA of VMAT delivery on the Elekta Synergy-S, commonly known as the Beam Modulator (BM). Methods: iCOM is used to create and deliver customized treatment fields to characterize the system in terms of 1) MLC positioning accuracy under static and dynamic delivery with full gantry rotation, 2) MLC positioning with known errors, 3) Maximum dose rate, 4) Maximum MLC speed, 5) Maximum gantry speed, 6) Synchronization: gantry speed versus dose rate, and 7) Synchronization: MLC speed versus dose rate.more » The resulting images were captured on the iView GT and exported in DICOM format to Dosimetry Check™ system for visual and quantitative analysis. For the initial commissioning phase, the system tests described should be supplemented with extensive patient QAs covering all clinically relevant treatment sites. Results: The system performance test suite showed that on our Synergy-S, MLC positioning was accurate under both static and dynamic deliveries. Intentional errors of 1 mm were also easily identified on both static and dynamic picket fence tests. Maximum dose rate was verified with stop watch to be consistently between 475-480 MU/min. Maximum gantry speed and MLC speed were 5.5 degree/s and 2.5 cm/s respectively. After accounting for beam flatness, both synchronization tests, gantry versus dose rate and MLC speed versus dose rate, were successful as the fields were uniform across the strips and there were no obvious cold/hot spots. Conclusion: VMAT commissioning and quality assurance should include machine characterization tests in addition to patient QAs. Elekta iCOM is a valuable tool for the design of customized VMAT field with specific MU, MLC leaf positions, dose rate, and indirect control of MLC and gantry speed at each of its control points.« less

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

Single toxin dose-response models revisited

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

Demidenko, Eugene, E-mail: eugened@dartmouth.edu

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the fourmore » models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.« less

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

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

PubMed Central

Loghin, Corina; Haber, Harry; Beasley, Charles M; Kothare, Prajakti A; Kauffman, Lynnette; April, John; Jin, Ling; Allen, Albert J; Mitchell, Malcolm I

2013-01-01

Aim The effects of atomoxetine (20 and 60 mg twice daily), 400 mg moxifloxacin and placebo on QTc in 131 healthy CYP2D6 poor metabolizer males were compared. Methods Atomoxetine doses were selected to result in plasma concentrations that approximated expected plasma concentrations at both the maximum recommended dose and at a supratherapeutic dose in CYP2D6 extensive metabolizers. Ten second electrocardiograms were obtained for time-matched baseline on days −2 and −1, three time points after dosing on day 1 for moxifloxacin and five time points on day 7 for atomoxetine and placebo. Maximum mean placebo-subtracted change from baseline model-corrected QT (QTcM) on day 7 was the primary endpoint. Results QTcM differences for atomoxetine 20 and 60 mg twice daily were 0.5 ms (upper bound of the one-sided 95% confidence interval 2.2 ms) and 4.2 ms (upper bound of the one-sided 95% confidence interval 6.0 ms), respectively. As plasma concentration of atomoxetine increased, a statistically significant increase in QTc was observed. The moxifloxacin difference from placebo met the a priori definition of non-inferiority. Maximum mean placebo-subtracted change from baseline QTcM for moxifloxacin was 4.8 ms and this difference was statistically significant. Moxifloxacin plasma concentrations were below the concentrations expected from the literature. However, the slope of the plasma concentration−QTc change observed was consistent with the literature. Conclusion Atomoxetine was not associated with a clinically significant change in QTc. However, a statistically significant increase in QTc was associated with increasing plasma concentrations. PMID:22803597

The influence of plan modulation on the interplay effect in VMAT liver SBRT treatments.

PubMed

Hubley, Emily; Pierce, Greg

2017-08-01

Volumetric modulated arc therapy (VMAT) uses multileaf collimator (MLC) leaves, gantry speed, and dose rate to modulate beam fluence, producing the highly conformal doses required for liver radiotherapy. When targets that move with respiration are treated with a dynamic fluence, there exists the possibility for interplay between the target and leaf motions. This study employs a novel motion simulation technique to determine if VMAT liver SBRT plans with an increase in MLC leaf modulation are more susceptible to dosimetric differences in the GTV due to interplay effects. For ten liver SBRT patients, two VMAT plans with different amounts of MLC leaf modulation were created. Motion was simulated using a random starting point in the respiratory cycle for each fraction. To isolate the interplay effect, motion was also simulated using four specific starting points in the respiratory cycle. The dosimetric differences caused by different starting points were examined by subtracting resultant dose distributions from each other. When motion was simulated using random starting points for each fraction, or with specific starting points, there were significantly more dose differences in the GTV (maximum 100cGy) for more highly modulated plans, but the overall plan quality was not adversely affected. Plans with more MLC leaf modulation are more susceptible to interplay effects, but dose differences in the GTV are clinically negligible in magnitude. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

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

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

[An investigation of ionizing radiation dose in a manufacturing enterprise of ion-absorbing type rare earth ore].

PubMed

Zhang, W F; Tang, S H; Tan, Q; Liu, Y M

2016-08-20

Objective: To investigate radioactive source term dose monitoring and estimation results in a manufacturing enterprise of ion-absorbing type rare earth ore and the possible ionizing radiation dose received by its workers. Methods: Ionizing radiation monitoring data of the posts in the control area and supervised area of workplace were collected, and the annual average effective dose directly estimated or estimated using formulas was evaluated and analyzed. Results: In the control area and supervised area of the workplace for this rare earth ore, α surface contamination activity had a maximum value of 0.35 Bq/cm 2 and a minimum value of 0.01 Bq/cm 2 ; β radioactive surface contamination activity had a maximum value of 18.8 Bq/cm 2 and a minimum value of 0.22 Bq/cm 2 . In 14 monitoring points in the workplace, the maximum value of the annual average effective dose of occupational exposure was 1.641 mSv/a, which did not exceed the authorized limit for workers (5 mSv/a) , but exceeded the authorized limit for general personnel (0.25 mSv/a) . The radionuclide specific activity of ionic mixed rare earth oxides was determined to be 0.9. Conclusion: The annual average effective dose of occupational exposure in this enterprise does not exceed the authorized limit for workers, but it exceeds the authorized limit for general personnel. We should pay attention to the focus of the radiation process, especially for public works radiation.

SU-F-T-389: Validation in 4D Dosimetry Using Dynamic Phantom

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

Lin, C; Lin, C; Tu, P

2016-06-15

Purpose: Tumor motion due to respiration causes the uncertainties during the radiotherapy. This study aims to find the differences between planning dose by treatment planning and the received dose using dynamic phantom. Methods: Respiratory motion was simulated by the DYNAMIC THORAX PHANTOM (Model 008A). 4D-CT scans and maximum intensity projection (MIP) images for GTV were acquired for analysis. The amplitude of craniocaudal tumor motion including 2mm, 5mm, 10mm and 20mm with 3cm2 tumor size were performed in this study. The respiratory cycles of 4-seconds and 6-seconds were included as the different breathing modes. IMRT, VAMT, and Tomotherapy were utilized formore » treatment planning. Ion chamber and EBT3 were used to measure the point dose and planar dose. Dose distributions with different amplitudes, respiratory cycles, and planning techniques were all measured and compared to calculations. Results: The variations between the does measurements and calculation dose by treatment planning system were found in both point dose and dose distribution. The 0.83% and 5.46 % differences in dose average were shown on phantom with motions using 2mm amplitude in 4 second respiratory cycle, and 20mm amplitude in 4 second respiratory cycle, respectively. The most point dose overestimation as compared of the calculations was shown the plan generated by Tomotherapy. The underestimations of planar dose as compared of calculations was found in the 100% coverage doses for GTV. Conclusion: The loss of complete (100%) GTV coverage was the predominant effect of respiratory motion observed in this study. Motion amplitude and treatment planning system were the major factors leading the dose measurement variation as compared of planning calculations.« less

Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

PubMed

Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

2012-01-01

Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

NASA Astrophysics Data System (ADS)

Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

2011-02-01

Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

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

Park, J; Kim, J; Park, S

Purpose: To investigate exposure outside the treatment field when treating breast cancer with tri-Co-60 magnetic resonance (MR) image guided radiation therapy (IGRT) system. Methods: A total of 7 patients who treated with accelerated partial breast irradiation (APBI) technique were selected prospectively for this study (prescription dose = 38.5 Gy in 10 fractions). Every patient treated with two plans, one was an initial plan and the other was an adaptive plan generated after finishing 5 fractions (a total of 14 plans). Every plan was calculated with and without magnetic field in the treatment planning system. The EBT3 films were attached onmore » the front and the back of 1 cm bolus, and then it was placed on the patient body vertically to cover patient’s jaw and shoulder. After measurements, the maximum point dose and the mean dose of whole area of EBT3 film were acquired. Results: In the treatment plan with magnetic field, low dose stream outside the patient body was observed, almost reaching the patient’s jaw or shoulder, while it was not observed without magnetic field. The average values of the measured maximum and mean doses at the front of bolus were 30.1 ± 11.1 cGy (7.8% of the daily dose) and 14.7 ± 3.3 cGy (3.8%), respectively. At the back of bolus, those values were 6.0 ± 1.9 cGy (1.6%) and 5.1 ± 1.6 cGy (1.3%), respectively. The largest maximum dose at the front was 54.2 cGy (14.1%) while it was 20.7 cGy (5.4%) at the back. The average decrease of the maximum dose by the bolus was 24.0 ± 11.0 cGy. Conclusion: Due to magnetic field, dose stream outside the patient body can be generated during breast cancer treatment with the tri-Co-60 MR-IGRT system. Since this dose stream irradiated skin outside the treatment field, it should be shielded. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01054192).« less

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

PubMed

Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

2018-04-23

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in {sup 131}I-NaI treatments of differentiated thyroid cancer

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

Mínguez, Pablo, E-mail: pablo.minguezgabina@osakid

Purpose: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). Methods: Eighteen DTC patients were administered 1.11 GBq of {sup 131}I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3–7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimatedmore » using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. Results: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2–176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2–145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. Conclusions: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.« less

SU-E-T-72: A Retrospective Correlation Analysis On Dose-Volume Control Points and Treatment Outcomes

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

Roy, A; Nohadani, O; Refaat, T

2015-06-15

Purpose: To quantify correlation between dose-volume control points and treatment outcomes. Specifically, two outcomes are analyzed: occurrence of radiation induced dysphagia and target complications. The results inform the treatment planning process when competing dose-volume criteria requires relaxations. Methods: 32 patients, treated with whole-field sequential intensity modulated radiation therapy during 2009–2010 period, are considered for this study. Acute dysphagia that is categorized into 3 grades is observed on all patients. 3 patients are observed in grade 1, 17 patients in grade 2, and 12 patients in grade 3. Ordinal logistic regression is employed to establish correlations between grades of dysphagia andmore » dose to cervico-thoracic esophagus. Particularly, minimum (Dmin), mean (Dmean), and maximum (Dmax) dose control points are analyzed. Additionally, target complication, which includes local-regional recurrence and/or distant metastasis, is observed on 4 patients. Binary logistic regression is used to quantify correlation between target complication and four dose control points. Namely, ICRU recommended dose control points, D2, D50, D95, and D98 are analyzed. Results: For correlation with dysphagia, Dmin on cervico-thoracic esophagus is statistically significant (p-value = 0.005). Additionally, Dmean on cervico-thoracic esophagus is also significant in association with dysphagia (p-value = 0.012). However, no correlation was observed between Dmax and dysphagia (p-value = 0.263). For target complications, D50 on the target is a statistically significant dose control point (p-value = 0.032). No correlations were observed between treatment complications and D2 (p-value = 0.866), D95 (p-value = 0.750), and D98 (p-value = 0.710) on the target. Conclusion: Significant correlations are observed between radiation induced dysphagia and Dmean (and Dmin) to cervico-thoracic esophagus. Additionally, correlation between target complications and median dose to target (D50) is observed. Quantification of these correlations can inform treatment planners when any competing objectives requires relaxation of target D50 or Dmean (or Dmin) to cervico-thoracic esophagus.« less

Estimation of external dose by car-borne survey in Kerala, India.

PubMed

Hosoda, Masahiro; Tokonami, Shinji; Omori, Yasutaka; Sahoo, Sarata Kumar; Akiba, Suminori; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Nair, Raghu Ram; Jayalekshmi, Padmavathy Amma; Sebastian, Paul; Iwaoka, Kazuki; Akata, Naofumi; Kudo, Hiromi

2015-01-01

A car-borne survey was carried out in Kerala, India to estimate external dose. Measurements were made with a 3-in × 3-in NaI(Tl) scintillation spectrometer from September 23 to 27, 2013. The routes were selected from 12 Panchayats in Karunagappally Taluk which were classified into high level, mid-level and low level high background radiation (HBR) areas. A heterogeneous distribution of air kerma rates was seen in the dose rate distribution map. The maximum air kerma rate, 2.1 μGy/h, was observed on a beach sand surface. 232Th activity concentration for the beach sand was higher than that for soil and grass surfaces, and the range of activity concentration was estimated to be 0.7-2.3 kBq/kg. The contribution of 232Th to air kerma rate was over 70% at the measurement points with values larger than 0.34 μGy/h. The maximum value of the annual effective dose in Karunagappally Taluk was observed around coastal areas, and it was estimated to be 13 mSv/y. More than 30% of all the annual effective doses obtained in this survey exceeded 1 mSv/y.

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

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison

PubMed Central

Melchert, Corinna; Kovács, György

2016-01-01

Purpose This study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer. Material and methods We analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms. Results There was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01). Conclusions Compared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer. PMID:27648082

Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

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

Stephans, Kevin L., E-mail: stephak@ccf.org; Djemil, Toufik; Diaconu, Claudiu

2014-09-01

Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose andmore » 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus.« less

Esophageal dose tolerance to hypofractionated stereotactic body radiation therapy: risk factors for late toxicity.

PubMed

Stephans, Kevin L; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A; Xia, Ping; Woody, Neil M; Greskovich, John; Makkar, Vinit; Videtic, Gregory M M

2014-09-01

To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus. Copyright © 2014 Elsevier Inc. All rights reserved.

Uncertainties in Assesment of the Vaginal Dose for Intracavitary Brachytherapy of Cervical Cancer using a Tandem-ring Applicator

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

Berger, Daniel; Dimopoulos, Johannes; Georg, Petra

2007-04-01

Purpose: The vagina has not been widely recognized as organ at risk in brachytherapy for cervical cancer. No widely accepted dose parameters are available. This study analyzes the uncertainties in dose reporting for the vaginal wall using tandem-ring applicators. Methods and Materials: Organ wall contours were delineated on axial magnetic resonance (MR) slices to perform dose-volume histogram (DVH) analysis. Different DVH parameters were used in a feasibility study based on 40 magnetic resonance imaging (MRI)-based treatment plans of different cervical cancer patients. Dose to the most irradiated, 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, and at defined pointsmore » on the ring surface and at 5-mm tissue depth were reported. Treatment-planning systems allow different methods of dose point definition. Film dosimetry was used to verify the maximum dose at the surface of the ring applicator in an experimental setup. Results: Dose reporting for the vagina is extremely sensitive to geometrical uncertainties with variations of 25% for 1 mm shifts. Accurate delineation of the vaginal wall is limited by the finite pixel size of MRI and available treatment-planning systems. No significant correlation was found between dose-point and dose-volume parameters. The DVH parameters were often related to noncontiguous volumes and were not able to detect very different situations of spatial dose distributions inside the vaginal wall. Deviations between measured and calculated doses were up to 21%. Conclusions: Reporting either point dose values or DVH parameters for the vaginal wall is based on high inaccuracies because of contouring and geometric positioning. Therefore, the use of prospective dose constraints for individual treatment plans is not to be recommended at present. However, for large patient groups treated within one protocol correlation with vaginal morbidity can be evaluated.« less

Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin.

PubMed

Stockis, Armel; van Lier, Jan Jaap; Cawello, Willi; Kumke, Thomas; Eckhardt, Klaus

2013-07-01

The aim of this study was to evaluate the effect of the antiepileptic drug lacosamide on the pharmacokinetics and pharmacodynamics of the anticoagulant warfarin. In this open-label, two-treatment crossover study, 16 healthy adult male volunteers were randomized to receive a single 25-mg dose of warfarin alone in one period and lacosamide 200 mg twice daily on days 1-9 with a single 25 mg dose of warfarin coadministered on day 3 in the other period. There was a 2-week washout between treatments. Pharmacokinetic end points were area under the plasma concentration-time curve (AUC(0,last) and AUC(0,∞) ) and maximum plasma concentration (Cmax ) for S- and R-warfarin. Pharmacodynamic end points were area under the international normalized ratio (INR)-time curve (AUCINR ), maximum INR (INRmax ), maximum prothrombin time (PTmax ) and area under the PT-time curve (AUCPT ). Following warfarin and lacosamide coadministration, Cmax and AUC of S- and R-warfarin, as well as peak value and AUC of PT and INR, were equivalent to those after warfarin alone. In particular, the AUC(0,∞) ratio (90% confidence interval) for coadministration of warfarin and lacosamide versus warfarin alone was 0.97 (0.94-1.00) for S-warfarin and 1.05 (1.02-1.09) for R-warfarin, and the AUCINR ratio was 1.04 (1.01-1.06). All participants completed the study. Coadministration of lacosamide 400 mg/day did not alter the pharmacokinetics of warfarin 25 mg or the anticoagulation level. These results suggest that there is no need for dose adjustment of warfarin when coadministered with lacosamide. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

SU-E-T-259: Particle Swarm Optimization in Radial Dose Function Fitting for a Novel Iodine-125 Seed

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

Wu, X; Duan, J; Popple, R

2014-06-01

Purpose: To determine the coefficients of bi- and tri-exponential functions for the best fit of radial dose functions of the new iodine brachytherapy source: Iodine-125 Seed AgX-100. Methods: The particle swarm optimization (PSO) method was used to search for the coefficients of the biand tri-exponential functions that yield the best fit to data published for a few selected radial distances from the source. The coefficients were encoded into particles, and these particles move through the search space by following their local and global best-known positions. In each generation, particles were evaluated through their fitness function and their positions were changedmore » through their velocities. This procedure was repeated until the convergence criterion was met or the maximum generation was reached. All best particles were found in less than 1,500 generations. Results: For the I-125 seed AgX-100 considered as a point source, the maximum deviation from the published data is less than 2.9% for bi-exponential fitting function and 0.2% for tri-exponential fitting function. For its line source, the maximum deviation is less than 1.1% for bi-exponential fitting function and 0.08% for tri-exponential fitting function. Conclusion: PSO is a powerful method in searching coefficients for bi-exponential and tri-exponential fitting functions. The bi- and tri-exponential models of Iodine-125 seed AgX-100 point and line sources obtained with PSO optimization provide accurate analytical forms of the radial dose function. The tri-exponential fitting function is more accurate than the bi-exponential function.« less

Proposal for a New Prognostic Score for Linac-Based Radiosurgery in Cerebral Arteriovenous Malformations

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

Milker-Zabel, Stefanie, E-mail: Stefanie_Milker-Zabel@med.uni-heidelberg.de; Kopp-Schneider, Annette; Wiesbauer, Hannah

2012-06-01

Purpose: We evaluate patient-, angioma-, and treatment-specific factors for successful obliteration of cerebral arteriovenous malformations (AVM) to develop a new appropriate score to predict patient outcome after linac-based radiosurgery (RS). Methods and Materials: This analysis in based on 293 patients with cerebral AVM. Mean age at treatment was 38.8 years (4-73 years). AVM classification according Spetzler-Martin was 55 patients Grade I (20.5%), 114 Grade II (42.5%), 79 Grade III (29.5%), 19 Grade IV (7.1%), and 1 Grade V (0.4%). Median maximum AVM diameter was 3.0 cm (range, 0.3-10 cm). Median dose prescribed to the 80% isodose was 18 Gy (range,more » 12-22 Gy). Eighty-five patients (29.1%) had prior partial embolization; 141 patients (51.9%) experienced intracranial hemorrhage before RS. Median follow-up was 4.2 years. Results: Age at treatment, maximum diameter, nidus volume, and applied dose were significant factors for successful obliteration. Under presumption of proportional hazard in the dose range between 12 and 22 Gy/80% isodose, an increase of obliteration rate of approximately 25% per Gy was seen. On the basis of multivariate analysis, a prediction score was calculated including AVM maximum diameter and age at treatment. The prediction error up to the time point 8 years was 0.173 for the Heidelberg score compared with the Kaplan-Meier value of 0.192. An increase of the score of 1 point results in a decrease of obliteration chance by a factor of 0.447. Conclusion: The proposed score is linac-based radiosurgery-specific and easy to handle to predict patient outcome. Further validation on an independent patient cohort is necessary.« less

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PubMed

Fröhlich, Georgina; Agoston, Péter; Lövey, József; Somogyi, András; Fodor, János; Polgár, Csaba; Major, Tibor

2010-07-01

To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

SU-E-T-395: Evaluation of Multiple Brain Metastases Stereotactic Treatment Planning in Cyberknife Versus Linac

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

Vikraman, S; Rajesh, Thiyagarajan; Karrthick, Kp

2015-06-15

Purpose: The purpose of this study was to evaluate multiple brain metastases stereotactic treatment planning of Cyberknife versus linac using dose volume based indices. Methods: Fifteen multiple brain metastases patients were taken for this study from Cyberknife Multiplan TPSv4.6.0. All these patients underwent stereotactic treatment in Cyberknife. For each patient VMAT stereotactic treatment plan was generated in MONACO TPSv5.0 using Elekta beam modulator MLC and matched the delivered plan. A median dose of 8.5Gy(range 7–12Gy) per fraction was prescribed. Tumor volume was in the range of 0.06–4.33cc. Treatment plan quality was critically evaluated by comparing DVH indices such as D98,more » D95, CI, and HI for target volumes. Maximum point doses and volume doses were evaluated for critical organs. Results: For each case, target coverage of D98 was achieved with 100% prescription dose with SD of 0.29% and 0.41% in Linac and Cyberknife respectively. The average conformity index(CI) of 1.26±0.0796 SD for Cyberknife and 1.92±0.60SD for linac were observed. Better homogeneity Index (HI) of 1.17±0.09SD was observed in linac as compared to Cyberknife HI of 1.24±0.05SD.All the critical organ doses were well within tolerance limit in both linac and Cyberknife plans. There is no significant difference of maximum point doses for brainstem and optic chiasm. Treatment time and number of monitor units are more in Cyberknife compared to linac. The average volume receiving 12Gy in whole brain was 6% and 12% for Cyberknife and linac respectively. 1000cc of whole brain received 60% lesser dose in Linac compared to Cyberknife in all cases. Conclusion: The study shows that dosimetrically comparable plans are achievable Cyberknife and Linac. However, a better conformity, target coverage, lesser OAR dose is achieved with Cyberknife due to greater degrees of freedom with robotic gantry and smaller collimator for multiple targets.« less

A gradient of radioactive contamination in Dolon village near the SNTS and comparison of computed dose values with instrumental estimates for the 29 August, 1949 nuclear test.

PubMed

Stepanenko, Valeriy F; Hoshi, Masaharu; Dubasov, Yuriy V; Sakaguchi, Aya; Yamamoto, Masayoshi; Orlov, Mark Y; Bailiff, Ian K; Ivannikov, Alexander I; Skvortsov, Valeriy G; Iaskova, Elena K; Kryukova, Irina G; Zhumadilov, Kassym S; Endo, Satoru; Tanaka, Kenichi; Apsalikov, Kazbek N; Gusev, Boris I

2006-02-01

Spatial distributions of soil contamination by 137Cs (89 sampling points) and 239+240Pu (76 points) near and within Dolon village were analyzed. An essential exponential decrease of contamination was found in Dolon village: the distance of a half reduction in contamination is about 0.87-1.25 km (in a northwest-southeast direction from the supposed centerline of the radioactive trace). This fact is in agreement with the available exposure rate measurements near Dolon (September 1949 archive data): on the basis of a few measurements the pattern of the trace was estimated to comprise a narrow 2 km corridor of maximum exposure rate. To compare computed external doses in air with local dose estimates by retrospective luminescence dosimetry (RLD) the gradient of radioactive soil contamination within the village was accounted for. The computed dose associated with the central axis of the trace was found to be equal to 2260 mGy (calculations based on archive exposure rate data). Local doses near the RLD sampling points (southeast of the village) were calculated to be in the range 466-780 mGy (averaged value: 645+/-70 mGy), which is comparable with RLD data (averaged value 460+/-92 mGy with range 380-618 mGy). A comparison of the computed mean dose in the settlement with dose estimates by ESR tooth enamel dosimetry makes it possible to estimate the "upper level" of the "shielding and behavior" factor in dose reduction for inhabitants of Dolon village which was found to be 0.28+/-0.068.

Clinical implementation and evaluation of the Acuros dose calculation algorithm.

PubMed

Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

2017-09-01

The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose-to-medium by Acuros XB (Acuros_D m,m ) was 4.3% on patient plans at the isocenter, and maximum difference between D 100 calculated by AAA and by Acuros_D m,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_D m,m were more than 3%. Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_D w,m were generally less than the dose differences between AAA and Acuros_D m,m . Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose-to-water or dose-to-medium) should be used in clinics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Willingness to pay for a 4% chlorhexidine (7.1% chlorhexidine digluconate) product for umbilical cord care in rural Bangladesh: a contingency valuation study

PubMed Central

2013-01-01

Background Recent trials in Bangladesh, Nepal, and Pakistan have shown that chlorhexidine is an effective antiseptic for umbilical cord care compared to existing community-based cord care practices. Because of the aggregate reduction in neonatal mortality in these trials, interest is high in introducing a 7.1% chlorhexidine digluconate liquid or gel that delivers 4% chlorhexidine for umbilical cord care in Bangladesh and elsewhere. Methods In 2010, we conducted a household survey applying a contingent valuation method with 1717 eligible couples (pregnant women or women with a first child younger than 6 months old, and their husbands) in the rural subdistricts of Abhoynagar and Mirsarai in Bangladesh to assess their willingness to pay for three types of umbilical cord care products at different price points. Each respondent was asked about willingness to pay prefixed prices for any one of three 7.1% chlorhexidine digluconate products: 1) a single-dose liquid, 2) a multi-dose liquid, or 3) a gel formulation. Each also reported the maximum price they were independently willing to pay for their selected product. We compared participant willingness-to-pay responses to the prefixed prices with their independently reported maximum prices for each type of the product separately. The comparison identified to what extent the respondents’ positive responses to the prefixed prices matched their independently reported maximum prices. Results This cross matching revealed that willingness to pay the prefixed prices was 41% for the single-dose liquid, 33% for the multi-dose liquid, and 31% for the gel formulation. Although the majority of the respondents were unwilling to pay the prefixed prices, all were willing to pay some amount and reported they could borrow money if necessary. Subsequent analysis of responses to the multi-dose liquid showed borrowing money would not be required if the unit price was Bangladeshi taka 15–25. Conclusions A unit price of Bangladeshi taka 15–25 (US$0.21–0.35) for multi-dose 7.1% chlorhexidine digluconate liquid would be affordable to the primary target population in Bangladesh. Although a large market demand could be generated if the product were available at this price point, subsidization may be required to achieve optimal coverage, especially among poorer families. PMID:24139384

Willingness to pay for a 4% chlorhexidine (7.1% chlorhexidine digluconate) product for umbilical cord care in rural Bangladesh: a contingency valuation study.

PubMed

Coffey, Patricia S; Metzler, Mutsumi; Islam, Ziaul; Koehlmoos, Tracey P

2013-10-18

Recent trials in Bangladesh, Nepal, and Pakistan have shown that chlorhexidine is an effective antiseptic for umbilical cord care compared to existing community-based cord care practices. Because of the aggregate reduction in neonatal mortality in these trials, interest is high in introducing a 7.1% chlorhexidine digluconate liquid or gel that delivers 4% chlorhexidine for umbilical cord care in Bangladesh and elsewhere. In 2010, we conducted a household survey applying a contingent valuation method with 1717 eligible couples (pregnant women or women with a first child younger than 6 months old, and their husbands) in the rural subdistricts of Abhoynagar and Mirsarai in Bangladesh to assess their willingness to pay for three types of umbilical cord care products at different price points. Each respondent was asked about willingness to pay prefixed prices for any one of three 7.1% chlorhexidine digluconate products: 1) a single-dose liquid, 2) a multi-dose liquid, or 3) a gel formulation. Each also reported the maximum price they were independently willing to pay for their selected product. We compared participant willingness-to-pay responses to the prefixed prices with their independently reported maximum prices for each type of the product separately. The comparison identified to what extent the respondents' positive responses to the prefixed prices matched their independently reported maximum prices. This cross matching revealed that willingness to pay the prefixed prices was 41% for the single-dose liquid, 33% for the multi-dose liquid, and 31% for the gel formulation. Although the majority of the respondents were unwilling to pay the prefixed prices, all were willing to pay some amount and reported they could borrow money if necessary. Subsequent analysis of responses to the multi-dose liquid showed borrowing money would not be required if the unit price was Bangladeshi taka 15-25. A unit price of Bangladeshi taka 15-25 (US$0.21-0.35) for multi-dose 7.1% chlorhexidine digluconate liquid would be affordable to the primary target population in Bangladesh. Although a large market demand could be generated if the product were available at this price point, subsidization may be required to achieve optimal coverage, especially among poorer families.

SU-E-T-206: Comparison of EBT and EBT3 RadioChromic Films in Radiation Field of Parotid Cancer Radiotherapy

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

Toosi, T Bahreyni; Mianaei, F Khorshidi; Ghorbani, M

Purpose: The aim of the current study is to compare EBT and EBT3 RadioChromic films in dosimetry of radiotherapy fields for treatment of parotid cancer. Methods: The calibrations of EBT and EBT3 films were performed with the same setups for doses ranging from 0.2 Gy to 5 Gy using 6 MV photon beam of a Siemens Primus linac. These films were scanned in color mode (RGB) by a Microtek (1000XL) scanner and the red color channel data was extracted. Treatment planning for parotid cancer radiation therapy was performed on a RANDO phantom. Skin dose was measured at different points inmore » the right anterior oblique (RAO) and right posterior oblique (RPO) fields by EBT and EBT3 films. Results: Dosimetry was performed with the same conditions for the two film types for calibration and in-phantom in parotid cancer radiotherapy. The measured net optical density (NOD) in EBT film was in some extent higher than that from EBT3 film. The minimum difference between these two films under calibration conditions was about 2.9% (for 0.2 Gy). However, the maximum difference was 35.5% (for 0.5 Gy). In the therapeutic fields of parotid cancer radiotherapy at different points, the measured dose from EBT film was higher than the EBT3 film. In these fields the minimum and maximum measured dose differences were 16.0% and 25.5%, respectively. Conclusion: With the same irradiation and reading conditions, EBT film demonstrates higher NOD than the EBT3 film. This effect may be related to the higher sensitivity of EBT film over EBT3 film. However, the obtained dose differences between these two films in low dose range can be due to the differences in fitting functions applied following the calibration process.« less

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

PubMed

Ferris, Matthew J; Zhong, Jim; Switchenko, Jeffrey M; Higgins, Kristin A; Cassidy, Richard J; McDonald, Mark W; Eaton, Bree R; Patel, Kirtesh R; Steuer, Conor E; Baddour, H Michael; Miller, Andrew H; Bruner, Deborah W; Xiao, Canhua; Beitler, Jonathan J

2018-01-01

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients. At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed. Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores. In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

PubMed

Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

2017-08-01

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids

PubMed Central

Guerreros, Alfredo G.; Brockhaus, Florian; Pethe, Abhijit; Kay, Richard A.; Townley, Robert G.

2017-01-01

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS). Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d.) or twice-daily (2, 25, 75 or 150 mg b.i.d.) fevipiprant (n=782), montelukast 10 mg q.d. (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d. Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d. and 75 mg b.i.d. groups, with no clinically meaningful differences between q.d. and b.i.d. Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments. Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. PMID:28838980

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

PubMed Central

Zheng, Yuanshui

2015-01-01

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

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

Vostrotin, Vadim; Birchall, Alan; Zhdanov, Alexey

The distribution of calculated internal doses was determined for 8043 Mayak Production Associate (Mayak PA) workers according to the epidemiological cohorts and groups of raw data used as well as the type of industrial compounds of inhaled aerosols. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185585 mGy, with a median value of 31 mGy and a maximum of 8980 mGy maximum. The ranges of relative standard uncertainty were: from 40 to 2200% for accumulated lung dose,more » from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-18% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to lognormal. The accumulated internal plutonium dose to systemic organs was close to a log-triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar-interstitial region, liver, bone surface cells and red bone marrow, calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8-13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.8 in median value, while accumulated doses to systemic organs increased by 6-12% in median value.« less

Commissioning Varian enhanced dynamic wedge in the PINNACLE treatment planning system using Gafchromic EBT film.

PubMed

Fontanarosa, Davide; Orlandini, Lucia Clara; Andriani, Italo; Bernardi, Luca

2009-10-01

In external photon beam therapies, the technique of dynamic wedge is a well established method for dose inhomogeneity compensation. The introduction of the enhanced dynamic wedge (EDW) on Varian LINACs considerably improved the pre-existing techniques. In the process of commissioning a Varian LINAC into a PINNACLE3 treatment planning system (TPS), the user is required to import quite a few measurements of EDW profiles and percentage depth doses (PDDs). Standard measurement devices like ionization chambers in a water phantom are not the most indicated ones for this situation where each measurement point is obtained by integrating during the entire exposure: Measurements would result to be a very laborious and time consuming operation, most of the times not practically possible. The goal of the present work is to introduce an alternative and hands-on procedure to perform the measurements using a combination of GafchromicTM EBT films, irradiated sideways in one single shot for both profiles and PDDs, and a single standard ionization chamber. The scanned profiles obtained at different depths have easily been imported in the TPS; for the PDD measurements, a correction was proven necessary to account for a "self-shielding" effect introduced by the presence of the films themselves, when irradiated sideways, resulting in an underestimation of the dose at deeper depths. A correction curve was derived comparing TPS open field validated measurements with the curves extracted from GafchromicTM EBT films. Finally, the curve was applied to all the wedged fields PDD measurements and could minimize the errors. The comparison for the 15 MV photon beam between the measured and the calculated 48 profiles and 12 PDDs (field sizes from 5 x 5 to 20 x 20 cm2, wedge angles ranging from 15 degrees to 60 degrees) was acceptable. The confidence limit (CL) was used as fit indicator, as suggested by the ESTRO Booklet No. 7: For the investigated PDDs the maximum value was 6.40 in the build up region and 2.83 beyond the maximum dose point; regarding cross beam profiles, the CLs were below 3 for 85% of the points within the field and for 96% of the points outside the field; in the penumbra region, a more appropriate parameter to evaluate the agreement between calculated and measured doses is the distance to agreement; only 73% of the profiles had CLs below 15, but for the remaining ones, distance-to-agreement values were within 3 mm. A hundred ionization chamber point dose measurements (for square and elongated fields at different depth and for points in field and out of field) were performed in a water phantom and 98 of them confirmed the TPS calculations with differences lower than 3% and considerably lower in most of the cases. This article gives valuable guidance and insight to other physicists attempting to approach EDW commissioning in the PINNACLE TPS software using Gafchromic EBT films.

A Monte Carlo calculation model of electronic portal imaging device for transit dosimetry through heterogeneous media

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

Yoon, Jihyung; Jung, Jae Won, E-mail: jungj@ecu.edu; Kim, Jong Oh

2016-05-15

Purpose: To develop and evaluate a fast Monte Carlo (MC) dose calculation model of electronic portal imaging device (EPID) based on its effective atomic number modeling in the XVMC code. Methods: A previously developed EPID model, based on the XVMC code by density scaling of EPID structures, was modified by additionally considering effective atomic number (Z{sub eff}) of each structure and adopting a phase space file from the EGSnrc code. The model was tested under various homogeneous and heterogeneous phantoms and field sizes by comparing the calculations in the model with measurements in EPID. In order to better evaluate themore » model, the performance of the XVMC code was separately tested by comparing calculated dose to water with ion chamber (IC) array measurement in the plane of EPID. Results: In the EPID plane, calculated dose to water by the code showed agreement with IC measurements within 1.8%. The difference was averaged across the in-field regions of the acquired profiles for all field sizes and phantoms. The maximum point difference was 2.8%, affected by proximity of the maximum points to penumbra and MC noise. The EPID model showed agreement with measured EPID images within 1.3%. The maximum point difference was 1.9%. The difference dropped from the higher value of the code by employing the calibration that is dependent on field sizes and thicknesses for the conversion of calculated images to measured images. Thanks to the Z{sub eff} correction, the EPID model showed a linear trend of the calibration factors unlike those of the density-only-scaled model. The phase space file from the EGSnrc code sharpened penumbra profiles significantly, improving agreement of calculated profiles with measured profiles. Conclusions: Demonstrating high accuracy, the EPID model with the associated calibration system may be used for in vivo dosimetry of radiation therapy. Through this study, a MC model of EPID has been developed, and their performance has been rigorously investigated for transit dosimetry.« less

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150 μg/L) well water arsenic levels--an exploration of the dose-response Poisson analysis.

PubMed

Lamm, Steven H; Robbins, Shayhan A; Zhou, Chao; Lu, Jun; Chen, Rusan; Feinleib, Manning

2013-02-01

To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study.

PubMed

Zhao, Yue; Ruan, Xiangyan; Mueck, Alfred O

2017-06-01

There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS). Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3 months. All patients got LTZ on day 3 for 5 d in combination with Hp-HMG, starting with 75 IU from cycle day 7 and maintained for up to 3 d. The maximum dose was 150 IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events. Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen. LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.

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

PubMed

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

2007-08-21

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

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI-LINAC systems.

PubMed

Gargett, Maegan; Oborn, Brad; Metcalfe, Peter; Rosenfeld, Anatoly

2015-02-01

MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named "magic plate," for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. geant4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-line and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm(3)) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm(2) area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm(2) photon field size. The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI-linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI–LINAC systems

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

Gargett, Maegan, E-mail: mg406@uowmail.edu.au; Rosenfeld, Anatoly; Oborn, Brad

2015-02-15

Purpose: MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named “magic plate,” for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. Methods: GEANT4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-linemore » and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm{sup 3}) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm{sup 2} area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm{sup 2} photon field size. Results: The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. Conclusions: A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI–linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.« less

Engineering design constraints of the lunar surface environment

NASA Technical Reports Server (NTRS)

Morrison, D. A.

1992-01-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

Engineering design constraints of the lunar surface environment

NASA Astrophysics Data System (ADS)

Morrison, D. A.

1992-02-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

PubMed Central

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-01-01

Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

PubMed

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-12-01

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biological end points were assessed; growth responses were the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude. The average low-dose maximum stimulation was approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hormetic curve approaching the estimated no observable effect level for the particular end point. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the hormetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitative scheme is presented for future application to the database. PMID:9539030

Cosmic Radiation Exposure of Future Hypersonic Flight Missions.

PubMed

Koops, L

2017-06-15

Cosmic radiation exposure in air traffic grows with flight altitude, geographical latitude and flight time. For future high-speed intercontinental point-to-point travel, the trade-off between reduced flight time and enhanced dose rate at higher flight altitudes is investigated. Various representative (partly) hypersonic cruise missions are considered and in dependence on solar activity the integral route dose is calculated for envisaged flight profiles and trajectories. Our results are compared to those for corresponding air connections served by present day subsonic airliners. During solar maximum, we find a significant reduction in route dose for all considered high-speed missions compared to the subsonic reference. However, during solar minimum, comparable or somewhat larger doses result on transpolar trajectories with (partly) hypersonic cruise at Mach 5. Both solar activity and routing are hence found to determine, whether passengers can profit from shorter flight times in terms of radiation exposure, despite of altitude-induced higher dose rates. Yet, aircrews with fixed number of block hours are always subject to larger annual doses, which in the considered cases take values up to five times the reference. We comment on the implications of our results for route planning and aviation decision-making in the absence of radiation shielding solutions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of full width at half maximum and penumbra of different Gamma Knife models.

PubMed

Asgari, Sepideh; Banaee, Nooshin; Nedaie, Hassan Ali

2018-01-01

As a radiosurgical tool, Gamma Knife has the best and widespread name recognition. Gamma Knife is a noninvasive intracranial technique invented and developed by Swedish neurosurgeon Lars Leksell. The first commercial Leksell Gamma Knife entered the therapeutic armamentarium at the University of Pittsburgh in the United States on August 1987. Since that time, different generation of Gamma Knife developed. In this study, the technical points and dosimetric parameters including full width at half maximum and penumbra on different generation of Gamma Knife will be reviewed and compared. The results of this review study show that the rotating gamma system provides a better dose conformity.

Experimental determination of the effective point of measurement of cylindrical ionization chambers for high-energy photon and electron beams.

PubMed

Huang, Yanxiao; Willomitzer, Christian; Zakaria, Golam Abu; Hartmann, Guenther H

2010-01-01

Measurements of depth-dose curves in water phantom using a cylindrical ionization chamber require that its effective point of measurement is located at the measuring depth. Recommendations for the position of the effective point of measurement with respect to the central axis valid for high-energy electron and photon beams are given in dosimetry protocols. According to these protocols, the use of a constant shift P(eff) is currently recommended. However, this is still based on a very limited set of experimental results. It is therefore expected that an improved knowledge of the exact position of the effective point of measurement will further improve the accuracy of dosimetry. Recent publications have revealed that the position of the effective point of measurement is indeed varying with beam energy, field size and also with chamber geometry. The aim of this study is to investigate whether the shift of P(eff) can be taken to be constant and independent from the beam energy. An experimental determination of the effective point of measurement is presented based on a comparison between cylindrical chambers and a plane-parallel chamber using conventional dosimetry equipment. For electron beams, the determination is based on the comparison of halfvalue depth R(50) between the cylindrical chamber of interest and a well guarded plane-parallel Roos chamber. For photon beams, the depth of dose maximum, d(max), the depth of 80% dose, d(80), and the dose parameter PDD(10) were used. It was again found that the effective point of measurement for both, electron and photon beams Dosimetry, depends on the beam energy. The deviation from a constant value remains very small for photons, whereas significant deviations were found for electrons. It is therefore concluded that use of a single upstream shift value from the centre of the cylindrical chamber as recommended in current dosimetry protocols is adequate for photons, however inadequate for accurate electron beam dosimetry.

Comparison of 2D and 3D Imaging and Treatment Planning for Postoperative Vaginal Apex High-Dose Rate Brachytherapy for Endometrial Cancer

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

Russo, James K.; Armeson, Kent E.; Richardson, Susan, E-mail: srichardson@radonc.wustl.edu

2012-05-01

Purpose: To evaluate bladder and rectal doses using two-dimensional (2D) and 3D treatment planning for vaginal cuff high-dose rate (HDR) in endometrial cancer. Methods and Materials: Ninety-one consecutive patients treated between 2000 and 2007 were evaluated. Seventy-one and 20 patients underwent 2D and 3D planning, respectively. Each patient received six fractions prescribed at 0.5 cm to the superior 3 cm of the vagina. International Commission on Radiation Units and Measurements (ICRU) doses were calculated for 2D patients. Maximum and 2-cc doses were calculated for 3D patients. Organ doses were normalized to prescription dose. Results: Bladder maximum doses were 178% ofmore » ICRU doses (p < 0.0001). Two-cubic centimeter doses were no different than ICRU doses (p = 0.22). Two-cubic centimeter doses were 59% of maximum doses (p < 0.0001). Rectal maximum doses were 137% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 87% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 64% of maximum doses (p < 0.0001). Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final bladder dose to within 10% for 44%, 59%, 83%, 82%, and 89% of patients by using the ICRU dose, and for 45%, 55%, 80%, 85%, and 85% of patients by using the maximum dose, and for 37%, 68%, 79%, 79%, and 84% of patients by using the 2-cc dose. Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final rectal dose to within 10% for 100%, 100%, 100%, 100%, and 100% of patients by using the ICRU dose, and for 60%, 65%, 70%, 75%, and 75% of patients by using the maximum dose, and for 68%, 95%, 84%, 84%, and 84% of patients by using the 2-cc dose. Conclusions: Doses to organs at risk vary depending on the calculation method. In some cases, final dose accuracy appears to plateau after the third fraction, indicating that simulation and planning may not be necessary in all fractions. A clinically relevant level of accuracy should be determined and further research conducted to address this issue.« less

Dose calculation with respiration-averaged CT processed from cine CT without a respiratory surrogate

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

Riegel, Adam C.; Ahmad, Moiz; Sun Xiaojun

2008-12-15

Dose calculation for thoracic radiotherapy is commonly performed on a free-breathing helical CT despite artifacts caused by respiratory motion. Four-dimensional computed tomography (4D-CT) is one method to incorporate motion information into the treatment planning process. Some centers now use the respiration-averaged CT (RACT), the pixel-by-pixel average of the ten phases of 4D-CT, for dose calculation. This method, while sparing the tedious task of 4D dose calculation, still requires 4D-CT technology. The authors have recently developed a means to reconstruct RACT directly from unsorted cine CT data from which 4D-CT is formed, bypassing the need for a respiratory surrogate. Using RACTmore » from cine CT for dose calculation may be a means to incorporate motion information into dose calculation without performing 4D-CT. The purpose of this study was to determine if RACT from cine CT can be substituted for RACT from 4D-CT for the purposes of dose calculation, and if increasing the cine duration can decrease differences between the dose distributions. Cine CT data and corresponding 4D-CT simulations for 23 patients with at least two breathing cycles per cine duration were retrieved. RACT was generated four ways: First from ten phases of 4D-CT, second, from 1 breathing cycle of images, third, from 1.5 breathing cycles of images, and fourth, from 2 breathing cycles of images. The clinical treatment plan was transferred to each RACT and dose was recalculated. Dose planes were exported at orthogonal planes through the isocenter (coronal, sagittal, and transverse orientations). The resulting dose distributions were compared using the gamma ({gamma}) index within the planning target volume (PTV). Failure criteria were set to 2%/1 mm. A follow-up study with 50 additional lung cancer patients was performed to increase sample size. The same dose recalculation and analysis was performed. In the primary patient group, 22 of 23 patients had 100% of points within the PTV pass {gamma} criteria. The average maximum and mean {gamma} indices were very low (well below 1), indicating good agreement between dose distributions. Increasing the cine duration generally increased the dose agreement. In the follow-up study, 49 of 50 patients had 100% of points within the PTV pass the {gamma} criteria. The average maximum and mean {gamma} indices were again well below 1, indicating good agreement. Dose calculation on RACT from cine CT is negligibly different from dose calculation on RACT from 4D-CT. Differences can be decreased further by increasing the cine duration of the cine CT scan.« less

TH-EF-BRB-02: Feasibility of Optimization for Dynamic Trajectory Radiotherapy

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

Fix, MK; Frei, D; Volken, W

2016-06-15

Purpose: Over the last years, volumetric modulated arc therapy (VMAT) has been widely introduced into clinical routine using a coplanar delivery technique. However, VMAT might be improved by including dynamic couch and collimator rotations, leading to dynamic trajectory radiotherapy (DTRT). In this work the feasibility and the potential benefit of DTRT was investigated. Methods: A general framework for the optimization was developed using the Eclipse Scripting Research Application Programming Interface (ESRAPI). Based on contoured target and organs at risk (OARs), the structures are extracted using the ESRAPI. Sampling potential beam directions, regularly distributed on a sphere using a Fibanocci-lattice, themore » fractional volume-overlap of each OAR and the target is determined and used to establish dynamic gantry-couch movements. Then, for each gantry-couch track the most suitable collimator angle is determined for each control point by optimizing the area between the MLC leaves and the target contour. The resulting dynamic trajectories are used as input to perform the optimization using a research version of the VMAT optimization algorithm and the ESRAPI. The feasibility of this procedure was tested for a clinically motivated head and neck case. Resulting dose distributions for the VMAT plan and for the dynamic trajectory treatment plan were compared based on DVH-parameters. Results: While the DVH for the target is virtually preserved, improvements in maximum dose for the DTRT plan were achieved for all OARs except for the inner-ear, where maximum dose remains the same. The major improvements in maximum dose were 6.5% of the prescribed dose (66 Gy) for the parotid and 5.5% for the myelon and the eye. Conclusion: The result of this work suggests that DTRT has a great potential to reduce dose to OARs with similar target coverage when compared to conventional VMAT treatment plans. This work was supported by Varian Medical Systems. This work was supported by Varian Medical Systems.« less

SU-F-T-269: Preliminary Experience of Kuwait Cancer Control Center (KCCC) On IMRT Treatment Planning and Pre-Treatment Verification

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

Sethuraman, TKR; Sherif, M; Subramanian, N

Purpose: The complexity of IMRT delivery requires pre-treatment quality assurance and plan verification. KCCC has implemented IMRT clinically in few sites and will extend to all sites. Recently, our Varian linear accelerator and Eclipse planning system were upgraded from Millennium 80 to 120 Multileaf Collimator (MLC) and from v8.6 to 11.0 respectively. Our preliminary experience on the pre-treatment quality assurance verification is discussed. Methods: Eight Breast, Three Prostate and One Hypopharynx cancer patients were planned with step and shoot IMRT. All breast cases were planned before the upgrade with 60% cases treated. The ICRU 83 recommendations were followed for themore » dose prescription and constraints to OAR for all cases. Point dose measurement was done with CIRS cylindrical phantom and PTW 0.125 cc ionization chamber. Measured dose was compared with calculated dose at the point of measurement. Map CHECK diode array phantom was used for the plan verification. Planned and measured doses were compared by applying gamma index of 3% (dose difference) / 3 mm DTA (average distance to agreement). For all cases, a plan is considered to be successful if more than 95% of the tested diodes pass the gamma test. A prostate case was chosen to compare the plan verification before and after the upgrade. Results: Point dose measurement results were in agreement with the calculated doses. The maximum deviation observed was 2.3%. The passing rate of average gamma index was measured higher than 97% for the plan verification of all cases. Similar result was observed for plan verification of the chosen prostate case before and after the upgrade. Conclusion: Our preliminary experience from the obtained results validates the accuracy of our QA process and provides confidence to extend IMRT to all sites in Kuwait.« less

Investigation of photon beam models in heterogeneous media of modern radiotherapy.

PubMed

Ding, W; Johnston, P N; Wong, T P Y; Bubb, I F

2004-06-01

This study investigates the performance of photon beam models in dose calculations involving heterogeneous media in modern radiotherapy. Three dose calculation algorithms implemented in the CMS FOCUS treatment planning system have been assessed and validated using ionization chambers, thermoluminescent dosimeters (TLDs) and film. The algorithms include the multigrid superposition (MGS) algorithm, fast Fourier Transform Convolution (FFTC) algorithm and Clarkson algorithm. Heterogeneous phantoms used in the study consist of air cavities, lung analogue and an anthropomorphic phantom. Depth dose distributions along the central beam axis for 6 MV and 10 MV photon beams with field sizes of 5 cm x 5 cm and 10 cm x 10 cm were measured in the air cavity phantoms and lung analogue phantom. Point dose measurements were performed in the anthropomorphic phantom. Calculated results with three dose calculation algorithms were compared with measured results. In the air cavity phantoms, the maximum dose differences between the algorithms and the measurements were found at the distal surface of the air cavity with a 10 MV photon beam and a 5 cm x 5 cm field size. The differences were 3.8%. 24.9% and 27.7% for the MGS. FFTC and Clarkson algorithms. respectively. Experimental measurements of secondary electron build-up range beyond the air cavity showed an increase with decreasing field size, increasing energy and increasing air cavity thickness. The maximum dose differences in the lung analogue with 5 cm x 5 cm field size were found to be 0.3%. 4.9% and 6.9% for the MGS. FFTC and Clarkson algorithms with a 6 MV photon beam and 0.4%. 6.3% and 9.1% with a 10 MV photon beam, respectively. In the anthropomorphic phantom, the dose differences between calculations using the MGS algorithm and measurements with TLD rods were less than +/-4.5% for 6 MV and 10 MV photon beams with 10 cm x 10 cm field size and 6 MV photon beam with 5 cm x 5 cm field size, and within +/-7.5% for 10 MV with 5 cm x 5 cm field size, respectively. The FFTC and Clarkson algorithms overestimate doses at all dose points in the lung of the anthropomorphic phantom. In conclusion, the MGS is the most accurate dose calculation algorithm of investigated photon beam models. It is strongly recommended for implementation in modern radiotherapy with multiple small fields when heterogeneous media are in the treatment fields.

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.

Early photosensitizer uptake kinetics predict optimum drug-light interval for photodynamic therapy

NASA Astrophysics Data System (ADS)

Sinha, Lagnojita; Elliott, Jonathan T.; Hasan, Tayyaba; Pogue, Brian W.; Samkoe, Kimberley S.; Tichauer, Kenneth M.

2015-03-01

Photodynamic therapy (PDT) has shown promising results in targeted treatment of cancerous cells by developing localized toxicity with the help of light induced generation of reactive molecular species. The efficiency of this therapy depends on the product of the intensity of light dose and the concentration of photosensitizer (PS) in the region of interest (ROI). On account of this, the dynamic and variable nature of PS delivery and retention depends on many physiological factors that are known to be heterogeneous within and amongst tumors (e.g., blood flow, blood volume, vascular permeability, and lymph drainage rate). This presents a major challenge with respect to how the optimal time and interval of light delivery is chosen, which ideally would be when the concentration of PS molecule is at its maximum in the ROI. In this paper, a predictive algorithm is developed that takes into consideration the variability and dynamic nature of PS distribution in the body on a region-by-region basis and provides an estimate of the optimum time when the PS concentration will be maximum in the ROI. The advantage of the algorithm lies in the fact that it predicts the time in advance as it takes only a sample of initial data points (~12 min) as input. The optimum time calculated using the algorithm estimated a maximum dose that was only 0.58 +/- 1.92% under the true maximum dose compared to a mean dose error of 39.85 +/- 6.45% if a 1 h optimal light deliver time was assumed for patients with different efflux rate constants of the PS, assuming they have the same plasma function. Therefore, if the uptake values of PS for the blood and the ROI is known for only first 12 minutes, the entire curve along with the optimum time of light radiation can be predicted with the help of this algorithm.

Conformal Stereotactic Radiosurgery With Multileaf Collimation.

DTIC Science & Technology

1992-01-01

Hartmann, W. Schlegel, V. Sturm, B. Kober, 0. Pastyr, W.J. Lorenz, "Cerebral radiation surgery using moving field irradiation at a linear ac ...Kober, 0. Pastyr, W.J. Lorenz, "Cerebral radiation surgery using moving field irradiation at a linear ac - celerator facility," Int. J. Radiation...scattered photons), off-axis ratios (for points off of the central axis of the incident beam), percent depth dose or tissue maximum ratio (to ac - count for

Radiation exposure in interventional radiology

NASA Astrophysics Data System (ADS)

Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array.

PubMed

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0-16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array

PubMed Central

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

Introduction: The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. Materials and Methods: QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. Results: The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0–16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Conclusion: Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall. PMID:28974858

System Design Verification for Closed Loop Control of Oxygenation With Concentrator Integration.

PubMed

Gangidine, Matthew M; Blakeman, Thomas C; Branson, Richard D; Johannigman, Jay A

2016-05-01

Addition of an oxygen concentrator into a control loop furthers previous work in autonomous control of oxygenation. Software integrates concentrator and ventilator function from a single control point, ensuring maximum efficiency by placing a pulse of oxygen at the beginning of the breath. We sought to verify this system. In a test lung, fraction of inspired oxygen (FIO2) levels and additional data were monitored. Tests were run across a range of clinically relevant ventilator settings in volume control mode, for both continuous flow and pulse dose flow oxygenation. Results showed the oxygen concentrator could maintain maximum pulse output (192 mL) up to 16 breaths per minute. Functionality was verified across ranges of tidal volumes and respiratory rates, with and without positive end-expiratory pressure, in continuous flow and pulse dose modes. For a representative test at respiratory rate 16 breaths per minute, tidal volume 550 mL, without positive end-expiratory pressure, pulse dose oxygenation delivered peak FIO2 of 76.83 ± 1.41%, and continuous flow 47.81 ± 0.08%; pulse dose flow provided a higher FIO2 at all tested setting combinations compared to continuous flow (p < 0.001). These tests verify a system that provides closed loop control of oxygenation while integrating time-coordinated pulse-doses from an oxygen concentrator. This allows the most efficient use of resources in austere environments. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

POLYMERIZATION OF /cap alpha/-METHYLSTYRENE BY ELECTRON IRRADIATION (in German)

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

Braun, D.; Heufer, G.; Seufert, W.

1964-01-01

Ampoules of alpha -methylstyrene sealed under vacuum were irradiated with 1-Mev electrons in a type JS Van de Graaff generator; comparative experiments with gamma rays were carried out with a /sup 60/Co source of 3000 deg C. High doses of electrons (ca. 10/sup 8/ rad) are necessary for polymerization. The conversion is graphed as a function of dose at 0 deg C; it reaches a maximum plateau of 65% at 4 x 10/sup 8/ rad; this may point to radiolysis of the polymer at doses above this. Polymerization conversion increases with decreasing dose rate, when dose and temperature are heldmore » constant; and conversion increases with decreasing temperature (22% at --22 deg C; 10% at 15 deg C; <1% at 60 deg C), as has been found with gamma rays. In the solid state between --40 deg C and --80 deg C the maximum yield is only about 5%. The molecular weights of all poly- alpha -methylstyrenes thus formed lie between 3000 and 12,000, independently of dose rate and temperature. All polymethylstyrenes formed in the liquid state have approximately the same tacticity independent of temperature (isotactic about 20%; syndiotactic about 80%). This corresponds to the tacticity of polymers formed cationically with Lewis acids. In the solid state the tacticity is: isotactic 38%, syndiotactic, 62%, comparable with the tacticity of anionic polymerization. In the liquid state the tacticity and the sensitivity towards water indicate a cationic mechanism for the reaction. NMR studies also indicate a cationic mechanism. (BBB)« less

SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9 Radioactive Eye Plaque Using MCNP5.

PubMed

Aryal, P; Molloy, J

2012-06-01

To show the effect of gold backing on dose rates for the USC #9 radioactive eye plaque. An I125 source (IsoAid model IAI-125A) and gold backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was simulated with and without gold backing. Dose rates were calculated in two orthogonal planes. Dose calculation points were structured in two orthogonal planes that bisect the center of the source. A 2×2 cm matrix of spherical points of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion particle histories were tracked. Dose differences with and without the gold backing were analyzed using Matlab. The gold backing produced a 3% increase in the dose rate near the source surface (<1mm) relative to that without the backing. This was presumably caused by fluorescent photons from the gold. At distances between 1 and 2 cm, the gold backing reduced the dose rate by up to 12%, which we attribute to a lack of scatter resulting from the attenuation from the gold. Dose differences were most pronounced in the radial direction near the source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3 mm off axis at a distance of 1 mm from the source surface. These effects were less pronounced in the perpendicular dimension near the source tip, where maximum dose decreases of 2% were noted. I 125 sources embedded directly into gold troughs display dose differences of 2 - 90%, relative to doses without the gold backing. This is relevant for certain types of plaques used in treatment of ocular melanoma. Large dose reductions can be observed and may have implications for scleral dose reduction. © 2012 American Association of Physicists in Medicine.

Dosimetric Analysis of Radiation-induced Gastric Bleeding

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

Feng, Mary, E-mail: maryfeng@umich.edu; Normolle, Daniel; Pan, Charlie C.

2012-09-01

Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at amore » median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.« less

Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

PubMed

Saiyed, Salim M; Greco, Peter J; Fernandes, Glenn; Kaelber, David C

2017-11-01

All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DEMAT: A multi-institutional dosimetry audit of rotational and static intensity-modulated radiotherapy.

PubMed

Lafond, Caroline; Chiavassa, Sophie; Bertaut, Cindy; Boussion, Nicolas; Chapel, Nathalie; Chapron, Lucie; Coste, Frédéric; Crespin, Sylvain; Dy, Gilles; Faye, Papa Abdoulaye; Leleu, Cyril; Bouvier, Jeanne; Madec, Ludovic; Mesgouez, Jérôme; Palisson, Jérémy; Vela, Anthony; Delpon, Grégory

2016-05-01

Static beam intensity-modulated-radiation-therapy (IMRT) and/or Volumetric-Modulated-Arc-Therapy (VMAT) are now available in many regional radiotherapy departments. The aim of this multi-institutional audit was to design a new methodology based on radiochromic films to perform an independent quality control. A set of data were sent to all participating centres for two clinical localizations: prostate and Head and Neck (H&N) cancers. The agreement between calculations and measurements was verified in the Octavius phantom (PTW) by point measurements using ionization chambers and by 2D measurements using EBT3 radiochromic films. Due to uncertainties in the whole procedure, criteria were set to 5% and 3% in local dose and 3mm in distance excluding doses lower than 10% of the maximum doses. No normalization point or area was used for the quantitative analysis. 13 radiotherapy centres participated in this audit involving 28 plans (12 IMRT, 16 VMAT). For point measurements, mean errors were -0.18±1.54% and 0.00±1.58% for prostate and H&N cases respectively. For 2D measurements with 5%/3mm criteria, gamma map analysis showed a pixel pass rate higher than 95% for prostate and H&N. Mean gamma index was lower than 0.4 for prostate and 0.5 for H&N. Both techniques yielded similar results. This study showed the feasibility of an independent quality control by peers for conventional IMRT and VMAT. Results from all participating centres were found to be in good agreement. This regional study demonstrated the feasibility of our new methodology based on radiochromic films without dose normalization on a specific point. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL)

PubMed Central

Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

2014-01-01

Background & objectives: With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Methods: Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. Results: In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Interpretation & conclusions: Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus transverse diameter on the axial surface, percutaneous puncture depth, and angulation in patients, with a significant lower radiation exposure, who are to be treated by MPCNL, and can be used as an alternative localization method. PMID:24820832

Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL).

PubMed

Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

2014-03-01

With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus transverse diameter on the axial surface, percutaneous puncture depth, and angulation in patients, with a significant lower radiation exposure, who are to be treated by MPCNL, and can be used as an alternative localization method.

Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region.

PubMed

Abusaris, Huda; Hoogeman, M; Nuyttens, Joost J

2012-12-01

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy(3) (range: 42-420 Gy(3)). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy(3), 98 Gy(3) and 113 Gy(3), respectively. No grades 5, 4 and 3 acute and late toxicity was observed. re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Cargo and Container X-Ray Inspection with Intra-Pulse Multi-Energy Method for Material Discrimination

NASA Astrophysics Data System (ADS)

Saverskiy, Aleksandr Y.; Dinca, Dan-Cristian; Rommel, J. Martin

The Intra-Pulse Multi-Energy (IPME) method of material discrimination mitigates main disadvantages of the traditional "interlaced" approach: ambiguity caused by sampling different regions of cargo and reduction of effective scanning speed. A novel concept of creating multi-energy probing pulses using a standing-wave structure allows maintaining a constant energy spectrum while changing the time duration of each sub-pulse and thus enables adaptive cargo inspection. Depending on the cargo density, the dose delivered to the inspected object is optimized for best material discrimination, maximum material penetration, or lowest dose to cargo. A model based on Monte-Carlo simulation and experimental reference points were developed for the optimization of inspection conditions.

A mathematical approach to beam matching

PubMed Central

Manikandan, A; Nandy, M; Gossman, M S; Sureka, C S; Ray, A; Sujatha, N

2013-01-01

Objective: This report provides the mathematical commissioning instructions for the evaluation of beam matching between two different linear accelerators. Methods: Test packages were first obtained including an open beam profile, a wedge beam profile and a depth–dose curve, each from a 10×10 cm2 beam. From these plots, a spatial error (SE) and a percentage dose error were introduced to form new plots. These three test package curves and the associated error curves were then differentiated in space with respect to dose for a first and second derivative to determine the slope and curvature of each data set. The derivatives, also known as bandwidths, were analysed to determine the level of acceptability for the beam matching test described in this study. Results: The open and wedged beam profiles and depth–dose curve in the build-up region were determined to match within 1% dose error and 1-mm SE at 71.4% and 70.8% for of all points, respectively. For the depth–dose analysis specifically, beam matching was achieved for 96.8% of all points at 1%/1 mm beyond the depth of maximum dose. Conclusion: To quantify the beam matching procedure in any clinic, the user needs to merely generate test packages from their reference linear accelerator. It then follows that if the bandwidths are smooth and continuous across the profile and depth, there is greater likelihood of beam matching. Differentiated spatial and percentage variation analysis is appropriate, ideal and accurate for this commissioning process. Advances in knowledge: We report a mathematically rigorous formulation for the qualitative evaluation of beam matching between linear accelerators. PMID:23995874

A thorough QT study to evaluate the effects of therapeutic and supratherapeutic doses of delafloxacin on cardiac repolarization.

PubMed

Litwin, Jeffrey S; Benedict, Michael S; Thorn, Michael D; Lawrence, Laura E; Cammarata, Sue K; Sun, Eugene

2015-01-01

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ΔΔQTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ΔΔQTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Thorough QT Study To Evaluate the Effects of Therapeutic and Supratherapeutic Doses of Delafloxacin on Cardiac Repolarization

PubMed Central

Benedict, Michael S.; Thorn, Michael D.; Lawrence, Laura E.; Cammarata, Sue K.; Sun, Eugene

2015-01-01

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ΔΔQTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ΔΔQTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug. PMID:25845864

Estimation Of Organ Doses From Solar Particle Events For Future Space Exploration Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.

2006-01-01

Radiation protection practices define the effective dose as a weighted sum of equivalent dose over major organ sites for radiation cancer risks. Since a crew personnel dosimeter does not make direct measurement of the effective dose, it has been estimated with skin-dose measurements and radiation transport codes for ISS and STS missions. If sufficient protection is not provided near solar maximum, the radiation risk can be significant due to exposure to sporadic solar particle events (SPEs) as well as to the continuous galactic cosmic radiation (GCR) on future exploratory-class and long-duration missions. For accurate estimates of overall fatal cancer risks from SPEs, the specific doses at various blood forming organs (BFOs) were considered, because proton fluences and doses vary considerably across marrow regions. Previous estimates of BFO doses from SPEs have used an average body-shielding distribution for the bone marrow based on the computerized anatomical man model (CAM). With the development of an 82-point body-shielding distribution at BFOs, the mean and variance of SPE doses in the major active marrow regions (head and neck, chest, abdomen, pelvis and thighs) will be presented. Consideration of the detailed distribution of bone marrow sites is one of many requirements to improve the estimation of effective doses for radiation cancer risks.

Predicting Chest Wall Pain From Lung Stereotactic Body Radiotherapy for Different Fractionation Schemes

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

Woody, Neil M.; Videtic, Gregory M.M.; Stephans, Kevin L.

Purpose: Recent studies with two fractionation schemes predicted that the volume of chest wall receiving >30 Gy (V30) correlated with chest wall pain after stereotactic body radiation therapy (SBRT) to the lung. This study developed a predictive model of chest wall pain incorporating radiobiologic effects, using clinical data from four distinct SBRT fractionation schemes. Methods and Materials: 102 SBRT patients were treated with four different fractionations: 60 Gy in three fractions, 50 Gy in five fractions, 48 Gy in four fractions, and 50 Gy in 10 fractions. To account for radiobiologic effects, a modified equivalent uniform dose (mEUD) model calculatedmore » the dose to the chest wall with volume weighting. For comparison, V30 and maximum point dose were also reported. Using univariable logistic regression, the association of radiation dose and clinical variables with chest wall pain was assessed by uncertainty coefficient (U) and C statistic (C) of receiver operator curve. The significant associations from the univariable model were verified with a multivariable model. Results: 106 lesions in 102 patients with a mean age of 72 were included, with a mean of 25.5 (range, 12-55) months of follow-up. Twenty patients reported chest wall pain at a mean time of 8.1 (95% confidence interval, 6.3-9.8) months after treatment. The mEUD models, V30, and maximum point dose were significant predictors of chest wall pain (p < 0.0005). mEUD improved prediction of chest wall pain compared with V30 (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.11). The mEUD with moderate weighting (a = 5) better predicted chest wall pain than did mEUD without weighting (a = 1) (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.14). Body mass index (BMI) was significantly associated with chest wall pain (p = 0.008). On multivariable analysis, mEUD and BMI remained significant predictors of chest wall pain (p = 0.0003 and 0.03, respectively). Conclusion: mEUD with moderate weighting better predicted chest wall pain than did V30, indicating that a small chest wall volume receiving a high radiation dose is responsible for chest wall pain. Independently of dose to the chest wall, BMI also correlated with chest wall pain.« less

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

Carver, R; Popple, R; Benhabib, S

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

Pharmacokinetics of a concentrated buprenorphine formulation in red-tailed hawks (Buteo jamaicensis).

PubMed

Gleeson, Molly D; Guzman, David Sanchez-Migallon; Knych, Heather K; Kass, Philip H; Drazenovich, Tracy L; Hawkins, Michelle G

2018-01-01

OBJECTIVE To determine the pharmacokinetics and sedative effects of 2 doses of a concentrated buprenorphine formulation after SC administration to red-tailed hawks (Buteo jamaicensis). ANIMALS 6 adult red-tailed hawks. PROCEDURES Concentrated buprenorphine (0.3 mg/kg, SC) was administered to all birds. Blood samples were collected at 10 time points over 24 hours after drug administration to determine plasma buprenorphine concentrations. After a 4-week washout period, the same birds received the same formulation at a higher dose (1.8 mg/kg, SC), and blood samples were collected at 13 time points over 96 hours. Hawks were monitored for adverse effects and assigned agitation-sedation scores at each sample collection time. Plasma buprenorphine concentrations were quantified by liquid chromatography-tandem mass spectrometry. RESULTS Mean time to maximum plasma buprenorphine concentration was 7.2 minutes and 26.1 minutes after administration of the 0.3-mg/kg and 1.8-mg/kg doses, respectively. Plasma buprenorphine concentrations were > 1 ng/mL for mean durations of 24 and 48 hours after low- and high-dose administration, respectively. Mean elimination half-life was 6.23 hours for the low dose and 7.84 hours for the high dose. Mean agitation-sedation scores were higher (indicating some degree of sedation) than the baseline values for 24 hours at both doses. No clinically important adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Concentrated buprenorphine was rapidly absorbed, and plasma drug concentrations considered to have analgesic effects in other raptor species were maintained for extended periods. Most birds had mild to moderate sedation. Additional studies are needed to evaluate the pharmacodynamics of these doses of concentrated buprenorphine in red-tailed hawks.

A revision of the gamma-evaluation concept for the comparison of dose distributions.

PubMed

Bakai, Annemarie; Alber, Markus; Nüsslin, Fridtjof

2003-11-07

A method for the quantitative four-dimensional (4D) evaluation of discrete dose data based on gradient-dependent local acceptance thresholds is presented. The method takes into account the local dose gradients of a reference distribution for critical appraisal of misalignment and collimation errors. These contribute to the maximum tolerable dose error at each evaluation point to which the local dose differences between comparison and reference data are compared. As shown, the presented concept is analogous to the gamma-concept of Low et al (1998a Med. Phys. 25 656-61) if extended to (3+1) dimensions. The pointwise dose comparisons of the reformulated concept are easier to perform and speed up the evaluation process considerably, especially for fine-grid evaluations of 3D dose distributions. The occurrences of false negative indications due to the discrete nature of the data are reduced with the method. The presented method was applied to film-measured, clinical data and compared with gamma-evaluations. 4D and 3D evaluations were performed. Comparisons prove that 4D evaluations have to be given priority, especially if complex treatment situations are verified, e.g., non-coplanar beam configurations.

Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.

PubMed

Aryankalayil, Molykutty J; Chopra, Sunita; Makinde, Adeola; Eke, Iris; Levin, Joel; Shankavaram, Uma; MacMillan, Laurel; Vanpouille-Box, Claire; Demaria, Sandra; Coleman, C Norman

2018-06-19

Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals. To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice. Mice were whole body irradiated with X-rays (2 Gy-15 Gy); blood was collected at various time-points post-exposure; total RNA was isolated; miRNA microarrays were performed; miRNAs differentially expressed in irradiated vs. unirradiated controls were identified; feature extraction and classification models were applied to predict dose-differentiating miRNA signature. We observed a time and dose responsive alteration in the expression levels of miRNAs. Maximum number of miRNAs were altered at 24-h and 48-h time-points post-irradiation. A 23-miRNA signature was identified using feature selection algorithms and classifier models. An inverse correlation in the expression level changes of miR-17 members, and their targets were observed in whole body irradiated mice and non-human primates. Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.

Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: A retrospective analysis of seventy-three patients

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

Alterio, Daniela; Jereczek-Fossa, Barbara Alicja; University of Milan, Milan

2007-01-01

Purpose: To evaluate the incidence of thyroid disorders and dose distribution to the thyroid in patients treated with radiotherapy for head-and-neck carcinomas. Methods and Materials: A retrospective evaluation of data from 73 patients treated for head-and-neck cancers in our department was performed. Thyroid function was evaluated mainly by the measurement of thyrotropin (thyroid stimulating hormone [TSH]). A retrospective analysis of treatment plans was performed for 57 patients. Percentages of thyroid glandular volume absorbing 10, 30, and 50 Gy (V10, V30, and V50 respectively) were considered for statistical analysis. Results: A majority of patients (61%) had a normal thyroid function whereasmore » 19 patients (26%) had hypothyroidism. Mean thyroid volume was 30.39 cc. Point 3 (located at isthmus) absorbed lower doses compared with other points (p < 0.0001). Median values of V10, V30, and V50 were 92% (range, 57-100%), 75% (range, 28.5-100%), and 35% (range, 3-83%) respectively. Gender was associated with toxicity (presence of any kind of thyroid disorders) (p < 0.05), with females displaying higher levels of TSHr (relative TSH = patient's value/maximum value of the laboratory range) (p = 0.0005) and smaller thyroid volume (p 0.0012) compared with male population. TSHr values were associated with thyroid volume, and the presence of midline shielding block in the anterior field was associated with relative free thyroxine (FT4r = patient's value/maximum value of the laboratory range) values. Conclusions: Gender and thyroid volume seem to play an important role in the occurrence of thyroid toxicity, but further studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are needed.« less

Applying Emax model and bivariate thin plate splines to assess drug interactions

PubMed Central

Kong, Maiying; Lee, J. Jack

2014-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95% point-wise confidence interval as well as its 95% simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies. PMID:20036878

Applying Emax model and bivariate thin plate splines to assess drug interactions.

PubMed

Kong, Maiying; Lee, J Jack

2010-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95 per cent point-wise confidence interval as well as its 95 per cent simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies.

A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut allergic patients

PubMed Central

Schneider, Lynda C.; Rachid, Rima; LeBovidge, Jennifer; Blood, Emily; Mittal, Mudita; Umetsu, Dale T.

2015-01-01

Background Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. Objective To examine the safety and efficacy of oraldesensitization in peanut allergic children in combination with a brief course of anti-IgE monoclonal antibody (omalizumab, Xolair). Methods We performed oral peanut desensitization in peanut allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered prior to and during oral peanut desensitization. Results We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE of 229 kUA/L and a median total serum IgE of 621 kU/L, who failed an initial double-blind placebo controlled food challenge at doses 100 mg peanut flour. After pre-treatment with omalizumab, all subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. 12 subjects then reached the maximum maintenance dose of 4,000 mg peanut flour/day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4,000 mg peanut flour/day and subsequently tolerated a challenge with 8,000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions; 6 subjects had Grade 2, and 2 subjects Grade 3 reactions, all of which responded rapidly to treatment. Conclusions Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization, and qualitativelyimprove the desensitization process. PMID:24176117

Factors associated with higher oxytocin requirements in labor.

PubMed

Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

2015-09-01

To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PubMed Central

Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

2012-01-01

Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. PMID:22915658

Volumetric modulated arc therapy versus step-and-shoot intensity modulated radiation therapy in the treatment of large nerve perineural spread to the skull base: a comparative dosimetric planning study

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

Gorayski, Peter; Fitzgerald, Rhys; Barry, Tamara

Cutaneous squamous cell carcinoma with large nerve perineural (LNPN) infiltration of the base of skull is a radiotherapeutic challenge given the complex target volumes to nearby organs at risk (OAR). A comparative planning study was undertaken to evaluate dosimetric differences between volumetric modulated arc therapy (VMAT) versus intensity modulated radiation therapy (IMRT) in the treatment of LNPN. Five consecutive patients previously treated with IMRT for LNPN were selected. VMAT plans were generated for each case using the same planning target volumes (PTV), dose prescriptions and OAR constraints as IMRT. Comparative parameters used to assess target volume coverage, conformity and homogeneitymore » included V95 of the PTV (volume encompassed by the 95% isodose), conformity index (CI) and homogeneity index (HI). In addition, OAR maximum point doses, V20, V30, non-target tissue (NTT) point max doses, NTT volume above reference dose, monitor units (MU) were compared. IMRT and VMAT plans generated were comparable for CI (P = 0.12) and HI (P = 0.89). VMAT plans achieved better V95 (P = < 0.001) and reduced V20 and V30 by 652 cubic centimetres (cc) (28.5%) and 425.7 cc (29.1%), respectively. VMAT increased MU delivered by 18% without a corresponding increase in NTT dose. Compared with IMRT plans for LNPN, VMAT achieved comparable HI and CI.« 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

Optimization of pre-sowing magnetic field doses through RSM in pea

NASA Astrophysics Data System (ADS)

Iqbal, M.; Ahmad, I.; Hussain, S. M.; Khera, R. A.; Bokhari, T. H.; Shehzad, M. A.

2013-09-01

Seed pre-sowing magnetic field treatment was reported to induce biochemical and physiological changes. In the present study, response surface methodology was used for deduction of optimal magnetic field doses. Improved growth and yield responses in the pea cultivar were achieved using a rotatable central composite design and multivariate data analysis. The growth parameters such as root and shoot fresh masses and lengths as well as yield were enhanced at a certain magnetic field level. The chlorophyll contents were also enhanced significantly vs. the control. The low magnetic field strength for longer duration of exposure/ high strength for shorter exposure were found to be optimal points for maximum responses in root fresh mass, chlorophyll `a' contents, and green pod yield/plant, respectively and a similar trend was observed for other measured parameters. The results indicate that the magnetic field pre-sowing seed treatment can be used practically to enhance the growth and yield in pea cultivar and response surface methodology was found an efficient experimental tool for optimization of the treatment level to obtain maximum response of interest.

High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.

PubMed

Timmermand, Oskar V; Nilsson, Jenny; Strand, Sven-Erik; Elgqvist, Jörgen

2016-12-01

The first main aim of this study was to illustrate the absorbed dose rate distribution from 177 Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90 Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177 Lu-h11B6, directed against the human kallikrein 2 antigen. Male immunodeficient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10 7 LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A″-DTPA after which conjugated h11B6 was mixed with 177 LuCl 3 . The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purified on a NAP-5 column. About 20 MBq 177 Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrificed and one tumor was collected from each of the five animals and cryosectioned into 10 μm thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code gate v7.0. The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15 ± 0.15, 0.20 ± 0.18, 0.12 ± 0.17, 0.15 ± 0.16, and 0.23 ± 0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177 Lu at the time of dissection 10 hpi showed a maximum value of 2.9 ± 0.4 Gy/h (mean ± SD), compared to 6.0 ± 0.9 and 159 ± 25 Gy/h for the hypothetical 90 Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for 177 Lu, 90 Y, and alpha-particles, respectively. The initial uptake of 177 Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90 Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to 177 Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.

SU-E-J-113: The Influence of Optimizing Pediatric CT Simulator Protocols On the Treatment Dose Calculation in Radiotherapy

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

Zhang, Y; Zhang, J; Hu, Q

2014-06-01

Purpose: To investigate the possibility of applying optimized scanning protocols for pediatric CT simulation by quantifying the dosimetric inaccuracy introduced by using a fixed HU to density conversion. Methods: The images of a CIRS electron density reference phantom (Model 062) were acquired by a Siemens CT simulator (Sensation Open) using the following settings of tube voltage and beam current: 120 kV/190mA (the reference protocol used to calibrate CT for our treatment planning system (TPS)); Fixed 190mA combined with all available kV: 80, 100, and 140; fixed 120 kV and various current from 37 to 444 mA (scanner extremes) with intervalmore » of 30 mA. To avoid the HU uncertainty of point sampling in the various inserts of known electron densities, the mean CT numbers of the central cylindrical volume were calculated using DICOMan software. The doses per 100 MU to the reference point (SAD=100cm, Depth=10cm, Field=10X10cm, 6MV photon beam) in a virtual cubic phantom (30X30X30cm) were calculated using Eclipse TPS (calculation model: AcurosXB-11031) by assigning the CT numbers to HU of typical materials acquired by various protocols. Results: For the inserts of densities less than muscle, CT number fluctuations of all protocols were within the tolerance of 10 HU as accepted by AAPM-TG66. For more condensed materials, fixed kV yielded stable HU with any mA combination where largest disparities were found in 1750mg/cc insert: HU{sub reference}=1801(106.6cGy), HU{sub minimum}=1799 (106.6cGy, error{sub dose}=0.00%), HU{sub maximum}=1815 (106.8cGy, error{sub dose}=0.19%). Yet greater disagreements were observed with increasing density when kV was modified: HU{sub minimum}=1646 (104.5cGy, error{sub dose}=- 1.97%), HU{sub maximum}=2487 (116.4cGy, error{sub dose}=9.19%) in 1750mg/cc insert. Conclusion: Without affecting treatment dose calculation, personalized mA optimization of CT simulator can be conducted by fixing kV for a better cost-effectiveness of imaging dose and quality especially for children. Unless recalibrated, kV should be constant for all anatomical sites if diagnostic CT scanner is used as a simulator. This work was partially supported by Capital Medical Development Scientific Research Fund of China.« less

NAIRAS aircraft radiation model development, dose climatology, and initial validation.

PubMed

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-10-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

NASA Astrophysics Data System (ADS)

Mertens, Christopher J.; Meier, Matthias M.; Brown, Steven; Norman, Ryan B.; Xu, Xiaojing

2013-10-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

PubMed Central

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-01-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway. PMID:26213513

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

NASA Astrophysics Data System (ADS)

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

Maximum tolerated dose of nalmefene in patients receiving epidural fentanyl and dilute bupivacaine for postoperative analgesia.

PubMed

Dougherty, T B; Porche, V H; Thall, P F

2000-04-01

This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

TU-AB-BRC-11: Moving a GPU-OpenCL-Based Monte Carlo (MC) Dose Engine Towards Routine Clinical Use: Automatic Beam Commissioning and Efficient Source Sampling

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

Tian, Z; Folkerts, M; Jiang, S

Purpose: We have previously developed a GPU-OpenCL-based MC dose engine named goMC with built-in analytical linac beam model. To move goMC towards routine clinical use, we have developed an automatic beam-commissioning method, and an efficient source sampling strategy to facilitate dose calculations for real treatment plans. Methods: Our commissioning method is to automatically adjust the relative weights among the sub-sources, through an optimization process minimizing the discrepancies between calculated dose and measurements. Six models built for Varian Truebeam linac photon beams (6MV, 10MV, 15MV, 18MV, 6MVFFF, 10MVFFF) were commissioned using measurement data acquired at our institution. To facilitate dose calculationsmore » for real treatment plans, we employed inverse sampling method to efficiently incorporate MLC leaf-sequencing into source sampling. Specifically, instead of sampling source particles control-point by control-point and rejecting the particles blocked by MLC, we assigned a control-point index to each sampled source particle, according to MLC leaf-open duration of each control-point at the pixel where the particle intersects the iso-center plane. Results: Our auto-commissioning method decreased distance-to-agreement (DTA) of depth dose at build-up regions by 36.2% averagely, making it within 1mm. Lateral profiles were better matched for all beams, with biggest improvement found at 15MV for which root-mean-square difference was reduced from 1.44% to 0.50%. Maximum differences of output factors were reduced to less than 0.7% for all beams, with largest decrease being from1.70% to 0.37% found at 10FFF. Our new sampling strategy was tested on a Head&Neck VMAT patient case. Achieving clinically acceptable accuracy, the new strategy could reduce the required history number by a factor of ∼2.8 given a statistical uncertainty level and hence achieve a similar speed-up factor. Conclusion: Our studies have demonstrated the feasibility and effectiveness of our auto-commissioning approach and new efficient source sampling strategy, implying the potential of our GPU-based MC dose engine goMC for routine clinical use.« less

Georgia fishery study: implications for dose calculations. Revision 1

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

Turcotte, M.D.S.

Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

ALL-PATHWAYS DOSE ANALYSIS FOR THE PORTSMOUTH ON-SITE WASTE DISPOSAL FACILITY

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

Smith, F.; Phifer, M.

A Portsmouth On-Site Waste Disposal Facility (OSWDF) All-Pathways analysis has been conducted that considers the radiological impacts to a resident farmer. It is assumed that the resident farmer utilizes a farm pond contaminated by the OSWDF to irrigate a garden and pasture and water livestock from which food for the resident farmer is obtained, and that the farmer utilizes groundwater from the Berea sandstone aquifer for domestic purposes (i.e. drinking water and showering). As described by FBP 2014b the Hydrologic Evaluation of Landfill Performance (HELP) model (Schroeder et al. 1994) and the Surface Transport Over Multiple Phases (STOMP) model (Whitemore » and Oostrom 2000, 2006) were used to model the flow and transport from the OSWDF to the Points of Assessment (POAs) associated with the 680-ft elevation sandstone layer (680 SSL) and the Berea sandstone aquifer. From this modeling the activity concentrations radionuclides were projected over time at the POAs. The activity concentrations were utilized as input to a GoldSimTM (GTG 2010) dose model, described herein, in order to project the dose to a resident farmer over time. A base case and five sensitivity cases were analyzed. The sensitivity cases included an evaluation of the impacts of using a conservative inventory, an uncased well to the Berea sandstone aquifer, a low waste zone uranium distribution coefficient (Kd), different transfer factors, and reference person exposure parameters (i.e. at 95 percentile). The maximum base case dose within the 1,000 year assessment period was projected to be 1.5E-14 mrem/yr, and the maximum base case dose at any time less than 10,000 years was projected to be 0.002 mrem/yr. The maximum projected dose of any sensitivity case was approximately 2.6 mrem/yr associated with the use of an uncased well to the Berea sandstone aquifer. This sensitivity case is considered very unlikely because it assumes leakage from the location of greatest concentration in the 680 SSL in to the Berea sandstone aquiver over time and does not conform to standard private water well construction practices. The bottom-line is that all predicted doses from the base case and five sensitivity cases fall well below the DOE all-pathways 25 mrem/yr Performance Objective.« less

Predicting procedural pain after ureteroscopy: does hydrodistention play a role?

PubMed Central

Gul, Zeynep; Alazem, Kareem; Li, Ina; Monga, Manoj

2016-01-01

ABSTRACT Purpose: To identify perioperative predictors of immediate pain after ureteroscopy, specifically evaluating the impact of hydrodistention from irrigation on pain. Materials and Methods: We retrospectively identified patients who underwent ureteroscopy for the treatment of calculi. Data recorded for these patients included their maximum pain score in the post-anesthesia care unit (PACU), average flow rate of irrigant used during the procedure, patient and stone characteristics, operative procedure, and details of patients' immediate, post-operative course. Spearman's rho was used to determine the relationship between non-parametric, continuous variables. Then, a linear regression was performed to assess which variables could predict the peak pain score. Results: A total of 131 patients were included in the study. A non-parametric correlation analysis revealed that maximum pain score was negatively correlated with being male (r = −0.18, p=0.04), age (r = −0.34, p<0.001), and post-op foley placement (r = −0.20, p=0.02) but positively correlated with the preoperative pain score (r = 0.41, p<0.001), time in the PACU (r = 0.19, p = 0.03), and the morphine equivalent dose (MED) of narcotics administered in the PACU (r = 0.67, p<0.001). On linear regression, the significant variables were age, preoperative pain score, and stent placement. For every ten-year increase in age post-operative pain score decreased by 4/10 of a point (p = 0.03). For every 1 point increase in preoperative pain score there was a 3/10 of a point increase in the maximum pain score (p = 0.01), and leaving a stent in place post-operatively was associated with a 1.6 point increase in the maximum pain score. Conclusions: Hydrodistention does not play a role in post-ureteroscopy pain. Patients who are younger, have higher preoperative pain scores, or who are stented will experience more post-operative pain after ureteroscopy. PMID:27564284

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

Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Foster, Ryan D.; Kogel, Albert J. van der

2011-01-01

Purpose: To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. Methods and Materials: A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eightmore » dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 {+-} 0.1, 18.9 {+-} 0.1, 21.0 {+-} 0.1, 23.0 {+-} 0.2, and 25.3 {+-} 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 43% {+-} 3%, 48% {+-} 4%, 51% {+-} 2%, 57% {+-} 2%, and 59% {+-} 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. Results: A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. Conclusions: Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.« less

Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Jiang, Runqing

Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent uniform dose per fraction (EUDf) and NTCP. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Integration of the convolution of the static dose and derivative of the PDF can also be used to determine the dose including geometric uncertainties although this method was not investigated in detail. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. Minimum SD (SDmin) is used when geometric uncertainty is corrected with verification imaging. Maximum SD (SDmax) is used when the geometric uncertainty is known to be large and difficult to manage. SDmax was 4.38 mm in anterior-posterior (AP) direction, 2.70 mm in left-right (LR) direction and 4.35 mm in superior-inferior (SI) direction; SDmin was 1.1 mm in all three directions if less than 2 mm threshold was used for uncorrected fractions in every direction. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUD f has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques (e.g. dose prescription, DVH, number of beams, bean angles). Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

Numerical study and ex vivo assessment of HIFU treatment time reduction through optimization of focal point trajectory

NASA Astrophysics Data System (ADS)

Grisey, A.; Yon, S.; Pechoux, T.; Letort, V.; Lafitte, P.

2017-03-01

Treatment time reduction is a key issue to expand the use of high intensity focused ultrasound (HIFU) surgery, especially for benign pathologies. This study aims at quantitatively assessing the potential reduction of the treatment time arising from moving the focal point during long pulses. In this context, the optimization of the focal point trajectory is crucial to achieve a uniform thermal dose repartition and avoid boiling. At first, a numerical optimization algorithm was used to generate efficient trajectories. Thermal conduction was simulated in 3D with a finite difference code and damages to the tissue were modeled using the thermal dose formula. Given an initial trajectory, the thermal dose field was first computed, then, making use of Pontryagin's maximum principle, the trajectory was iteratively refined. Several initial trajectories were tested. Then, an ex vivo study was conducted in order to validate the efficicency of the resulting optimized strategies. Single pulses were performed at 3MHz on fresh veal liver samples with an Echopulse and the size of each unitary lesion was assessed by cutting each sample along three orthogonal planes and measuring the dimension of the whitened area based on photographs. We propose a promising approach to significantly shorten HIFU treatment time: the numerical optimization algorithm was shown to provide a reliable insight on trajectories that can improve treatment strategies. The model must now be improved in order to take in vivo conditions into account and extensively validated.

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

SU-F-J-223: Patterns of Failure for Laryngeal Cancer Patients Treated with Definitive IMRT: Comparing Two Different Methods for Determining the Origin of Recurrence From Follow-Up PET/CT Scans

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

Brodin, P; Guha, C; Tome, W

Purpose: To determine patterns of failure in laryngeal cancer treated with definitive IMRT by comparing two different methods for identifying the recurrence epicenter on follow-up PET/CT. Methods: We identified 20 patients treated for laryngeal squamous cell carcinoma with definitive IMRT who had loco-regional recurrence diagnosed on PET/CT. Recurrence PET/CT scans were co-registered with the original treatment planning CT using deformable image registration with the VoxAlign deformation engine in MIM Software. Recurrence volumes were delineated on co-registered follow-up scans using a semi-automatic PETedge tool and two separate methods were used to identify the recurrence point of origin: a) Finding the pointmore » within the recurrence volume for which the maximum distance to the surface of the surrounding recurrence volume is smaller than for any other point. b) Finding the point within the recurrence volume with the maximum standardized uptake value (SUVmax), without geometric restrictions.For each method the failure pattern was determined as whether the recurrence origin fell within the original high-dose target volumes GTV70, CTV70, PTV70 (receiving 70Gy), intermediate-risk PTV59 (receiving 59.4Gy) or low-risk PTV54 (receiving 54.1Gy), in the original treatment planning CT. Results: 23 primary/nodal recurrences from the 20 patients were analyzed. The three-dimensional distance between the two different origins was on average 10.5mm (std.dev. 10mm). Most recurrences originated in the high-dose target volumes for both methods with 13 (57%) and 11 (48%) in the GTV70 and 20 (87%) and 20 (87%) in the PTV70 for method a) and b), respectively. There was good agreement between the two methods in classifying the origin target volumes with 69% concordance for GTV70, 89% for CTV70 and 100% for PTV70. Conclusion: With strong agreement in patterns of failure between two separate methods for determining recurrence origin, we conclude that most recurrences occurred within the high-dose treatment region, which influences potential risk-adaptive treatment strategies.« less

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

2018-06-01

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

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

The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

PubMed

Kishimoto, Yuka; Kanahori, Sumiko; Sakano, Katsuhisa; Ebihara, Shukuko

2013-01-01

The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.

Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom.

PubMed

Tobin, Claire L; Dobbin, Malcolm; McAvoy, Brian

2013-10-01

Analysis of the policy response by Australia's National Drugs and Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert advisory committees in New Zealand and the United Kingdom. Analysis of public policy documents of relevant regulatory authorities was conducted. Data were extracted regarding changes to over-the-counter (OTC) codeine analgesic scheduling, indications, maximum unit dose, maximum daily dose, maximum pack size, warning labels, consumer medicine information and advertising. Where available, public submissions and other issues considered by the committees and rationale for their recommendations were recorded and thematically analysed. Expert advisory committees in Australia, NZ and the UK defined the policy problem of OTC codeine misuse and harm as small relative to total use and responded by restricting availability. Pharmacist supervision was required at the point-of-sale and pack sizes were reduced to short-term use. Comparison with recommendations by expert advisory committees in NZ and the UK suggests the NDPSC's actions in response to OTC codeine misuse were appropriate given the available evidence of misuse and harm, but highlights opportunities to utilise additional regulatory levers. Framing policy problems as matters of public health in the context of limited evidence may support decision makers to implement cautionary incremental policy change. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

Mars' surface radiation environment measured with the Mars Science Laboratory's Curiosity rover.

PubMed

Hassler, Donald M; Zeitlin, Cary; Wimmer-Schweingruber, Robert F; Ehresmann, Bent; Rafkin, Scot; Eigenbrode, Jennifer L; Brinza, David E; Weigle, Gerald; Böttcher, Stephan; Böhm, Eckart; Burmeister, Soenke; Guo, Jingnan; Köhler, Jan; Martin, Cesar; Reitz, Guenther; Cucinotta, Francis A; Kim, Myung-Hee; Grinspoon, David; Bullock, Mark A; Posner, Arik; Gómez-Elvira, Javier; Vasavada, Ashwin; Grotzinger, John P

2014-01-24

The Radiation Assessment Detector (RAD) on the Mars Science Laboratory's Curiosity rover began making detailed measurements of the cosmic ray and energetic particle radiation environment on the surface of Mars on 7 August 2012. We report and discuss measurements of the absorbed dose and dose equivalent from galactic cosmic rays and solar energetic particles on the martian surface for ~300 days of observations during the current solar maximum. These measurements provide insight into the radiation hazards associated with a human mission to the surface of Mars and provide an anchor point with which to model the subsurface radiation environment, with implications for microbial survival times of any possible extant or past life, as well as for the preservation of potential organic biosignatures of the ancient martian environment.

Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

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

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

2009-04-01

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

Estimation of eye lens doses received by pediatric interventional cardiologists.

PubMed

Alejo, L; Koren, C; Ferrer, C; Corredoira, E; Serrada, A

2015-09-01

Maximum Hp(0.07) dose to the eye lens received in a year by the pediatric interventional cardiologists has been estimated. Optically stimulated luminescence dosimeters were placed on the eyes of an anthropomorphic phantom, whose position in the room simulates the most common irradiation conditions. Maximum workload was considered with data collected from procedures performed in the Hospital. None of the maximum values obtained exceed the dose limit of 20 mSv recommended by ICRP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Knowledge of appropriate acetaminophen doses and potential toxicities in an adult clinic population.

PubMed

Stumpf, Janice L; Skyles, Amy J; Alaniz, Cesar; Erickson, Steven R

2007-01-01

To evaluate the knowledge of appropriate doses and potential toxicities of acetaminophen and assess the ability to recognize products containing acetaminophen in an adult outpatient setting. Cross-sectional, prospective study. University adult general internal medicine (AGIM) clinic. 104 adult patients presenting to the clinic over consecutive weekdays in December 2003. Three-page, written questionnaire. Ability of patients to identify maximum daily doses and potential toxicities of acetaminophen and recognize products that contain acetaminophen. A large percentage of participants (68.3%) reported pain on a daily or weekly basis, and 78.9% reported use of acetaminophen in the past 6 months. Only 2 patients correctly identified the maximum daily dose of regular acetaminophen, and just 3 correctly identified the maximum dose of extra-strength acetaminophen. Furthermore, 28 patients were unsure of the maximum dose of either product. Approximately 63% of participants either had not received or were unsure whether information on the possible danger of high doses of acetaminophen had been previously provided to them. When asked to identify potential problems associated with high doses of acetaminophen, 43.3% of patients noted the liver would be affected. The majority of the patients (71.2%) recognized Tylenol as containing acetaminophen, but fewer than 15% correctly identified Vicodin, Darvocet, Tylox, Percocet, and Lorcet as containing acetaminophen. Although nearly 80% of this AGIM population reported recent acetaminophen use, their knowledge of the maximum daily acetaminophen doses and potential toxicities associated with higher doses was poor and appeared to be independent of education level, age, and race. This indicates a need for educational efforts to all patients receiving acetaminophen-containing products, especially since the ability to recognize multi-ingredient products containing acetaminophen was likewise poor.

Surface dose measurements for highly oblique electron beams.

PubMed

Ostwald, P M; Kron, T

1996-08-01

Clinical applications of electrons may involve oblique incidence of beams, and although dose variations for angles up to 60 degrees from normal incidence are well documented, no results are available for highly oblique beams. Surface dose measurements in highly oblique beams were made using parallel-plate ion chambers and both standard LiF:Mg, Ti and carbon-loaded LiF Thermoluminescent Dosimeters (TLD). Obliquity factors (OBF) or surface dose at an oblique angle divided by the surface dose at perpendicular incidence, were obtained for electron energies between 4 and 20 MeV. Measurements were performed on a flat solid water phantom without a collimator at 100 cm SSD. Comparisons were also made to collimated beams. The OBFs of surface doses plotted against the angle of incidence increased to a maximum dose followed by a rapid dropoff in dose. The increase in OBF was more rapid for higher energies. The maximum OBF occurred at larger angles for higher-energy beams and ranged from 73 degrees for 4 MeV to 84 degrees for 20 MeV. At the dose maximum, OBFs were between 130% and 160% of direct beam doses, yielding surface doses of up to 150% of Dmax for the 20 MeV beam. At 2 mm depth the dose ratio was found to increase initially with angle and then decrease as Dmax moved closer to the surface. A higher maximum dose was measured at 2 mm depth than at the surface. A comparison of ion chamber types showed that a chamber with a small electrode spacing and large guard ring is required for oblique dose measurement. A semiempirical equation was used to model the dose increase at the surface with different energy electron beams.

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

Acoustic hemostasis of porcine superficial femoral artery: Simulation and in-vivo experimental studies

NASA Astrophysics Data System (ADS)

Zeng, Xiaozheng; Mitchell, Stuart; Miller, Matthew; Barnes, Stephen; Hopple, Jerry; Kook, John; Moreau-Gobard, Romain; Hsu, Stephen; Ahiekpor-Dravi, Alexis; Crum, Lawrence A.; Eaton, John; Wong, Keith; Sekins, K. Michael

2012-10-01

In-vivo focused ultrasound studies were computationally simulated and conducted experimentally with the aim of occluding porcine superficial femoral arteries (SFA) via thermal coagulation. A multi-array HIFU applicator was used which electronically scanned multiple beam foci around the target point. The spatio-temporally averaged acoustic and temperature fields were simulated in a fluid dynamics and acousto-thermal finite element model with representative tissue fields, including muscle, vessel and blood. Simulations showed that with an acoustic power of 200W and a dose time of 60s, perivascular tissue reached 91°C; and yet blood reached a maximum 59°C, below the coagulation objective for this dose regime (75°C). Per simulations, acoustic-streaming induced velocity in blood reached 6.1cm/s. In in-vivo experiments, several arteries were treated. As simulated, thermal lesions were observed in muscle surrounding SFA in all cases. In dosing limited to 30 to 60 seconds, it required 257W to provide occlusion (one complete and one partial occlusion). Angiography and histology showed evidence of thrombogenesis and collagen shrinkage-based vessel constriction at these doses.

Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

PubMed

Biberoglu, Ebru H; Tanrıkulu, Filiz; Erdem, Mehmet; Erdem, Ahmet; Biberoglu, Kutay Omer

2016-01-01

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles.

SU-G-BRC-16: Theory and Clinical Implications of the Constant Dosimetric Leaf Gap (DLG) Approximation

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

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: Commercial dose calculation algorithms incorporate a single DLG value for a given beam energy that is applied across an entire treatment field. However, the physical processes associated with beam generation and dose delivery suggest that the DLG is not constant. The aim of this study is to evaluate the variation of DLG among all leaf pairs, to quantify how this variation impacts delivered dose, and to establish a novel method to correct dose distributions calculated using the approximation of constant DLG. Methods: A 2D diode array was used to measure the DLG for all 60 leaf pairs at severalmore » points along each leaf pair travel direction. This approach was validated by comparison to DLG values measured at select points using a 0.6 cc ion chamber with the standard formalism. In-house software was developed to enable incorporation of position dependent DLG values into dose distribution optimization and calculation. The accuracy of beam delivery of both the corrected and uncorrected treatment plans was studied through gamma pass rate evaluation. A comparison of DVH statistics in corrected and uncorrected treatment plans was made. Results: The outer 20 MLC leaf pairs (1.0 cm width) have DLG values that are 0.32 mm (mean) to 0.65 mm (maximum) lower than the central leaf-pair. VMAT plans using a large number of 1 cm wide leaves were more accurately delivered (gamma pass rate increased by 5%) and dose coverage was higher (D100 increased by 3%) when the 2D DLG was modeled. Conclusion: Using a constant DLG value for a given beam energy will result in dose optimization, dose calculation and treatment delivery inaccuracies that become significant for treatment plans with high modulation complexity scores delivered with 1 cm wide leaves.« less

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

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

Uehara, K; Ogata, T; Nakayama, M

2015-06-15

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

SU-F-BRE-04: Construction of 3D Printed Patient Specific Phantoms for Dosimetric Verification Measurements

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

Ehler, E; Higgins, P; Dusenbery, K

2014-06-15

Purpose: To validate a method to create per patient phantoms for dosimetric verification measurements. Methods: Using a RANDO phantom as a substitute for an actual patient, a model of the external features of the head and neck region of the phantom was created. A phantom was used instead of a human for two reasons: to allow for dosimetric measurements that would not be possible in-vivo and to avoid patient privacy issues. Using acrylonitrile butadiene styrene thermoplastic as the building material, a hollow replica was created using the 3D printer filled with a custom tissue equivalent mixture of paraffin wax, magnesiummore » oxide, and calcium carbonate. A traditional parallel-opposed head and neck plan was constructed. Measurements were performed with thermoluminescent dosimeters in both the RANDO phantom and in the 3D printed phantom. Calculated and measured dose was compared at 17 points phantoms including regions in high and low dose regions and at the field edges. On-board cone beam CT was used to localize both phantoms within 1mm and 1° prior to radiation. Results: The maximum difference in calculated dose between phantoms was 1.8% of the planned dose (180 cGy). The mean difference between calculated and measured dose in the anthropomorphic phantom and the 3D printed phantom was 1.9% ± 2.8% and −0.1% ± 4.9%, respectively. The difference between measured and calculated dose was determined in the RANDO and 3D printed phantoms. The differences between measured and calculated dose in each respective phantom was within 2% for 12 of 17 points. The overlap of the RANDO and 3D printed phantom was 0.956 (Jaccard Index). Conclusion: A custom phantom was created using a 3D printer. Dosimetric calculations and measurements showed good agreement between the dose in the RANDO phantom (patient substitute) and the 3D printed phantom.« less

Estimation of the radiation dose from radiotherapy for skin haemangiomas in childhood: the ICTA software for epidemiology

NASA Astrophysics Data System (ADS)

Shamsaldin, A.; Lundell, M.; Diallo, I.; Ligot, L.; Chavaudra, J.; de Vathaire, F.

2000-12-01

Radium applicators and pure beta emitters have been widely used in the past to treat skin haemangioma in early childhood. A well defined relationship between the low doses received from these applicators and radiation-induced cancers requires accurate dosimetry. A human-based CT scan phantom has been used to simulate every patient and treatment condition and then to calculate the source-target distance when radium and pure beta applicators were used. The effective transmission factor ϕ(r) for the gamma spectrum emitted by the radium sources applied on the skin surface was modelled using Monte Carlo simulations. The well-known quantization approach was used to calculate gamma doses delivered from radium applicators to various anatomical points. For 32P, 90Sr/90Y applicators and 90Y needles we have used the apparent exponential attenuation equation. The dose calculation algorithm was integrated into the ICTA software (standing for a model that constructs an Individualized phantom based on CT slices and Auxological data), which has been developed for epidemiological studies of cohorts of patients who received radium and beta-treatments for skin haemangioma. The ϕ(r) values obtained for radium skin applicators are in good agreement with the available values in the first 10 cm but higher at greater distances. Gamma doses can be calculated with this algorithm at 165 anatomical points throughout the body of patients treated with radium applicators. Lung heterogeneity and air crossed by the gamma rays are considered. Comparison of absorbed doses in water from a 10 mg equivalent radium source simulated by ICTA with those measured at the Radiumhemmet, Karolinska Hospital (RAH) showed good agreement, but ICTA estimation of organ doses did not always correspond those estimated at the RAH. Beta doses from 32P, 90Sr/90Y applicators and 90Y needles are calculated up to the maximum beta range (11 mm).

Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy.

PubMed

Lorenzen, Ebbe L; Brink, Carsten; Taylor, Carolyn W; Darby, Sarah C; Ewertz, Marianne

2016-04-01

We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982-2002. Three tangential radiotherapy regimens were reconstructed using CT-based planning scans for 40 patients with left-sided and 10 with right-sided breast cancer. Setup errors and organ motion were simulated using estimated uncertainties. For left-sided patients, mean heart dose was related to maximum heart distance in the medial field. For left-sided breast cancer, mean heart dose estimated from individual CT-scans varied from <1Gy to >8Gy, and maximum dose from 5 to 50Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always <1Gy and maximum dose always <5Gy for all three regimens. The use of stored individual simulator films provides a method for estimating heart doses in left-tangential radiotherapy for breast cancer that is almost as accurate as estimates based on individual CT-scans. Copyright © 2016. Published by Elsevier Ireland Ltd.

Use of computer code for dose distribution studies in A 60CO industrial irradiator

NASA Astrophysics Data System (ADS)

Piña-Villalpando, G.; Sloan, D. P.

1995-09-01

This paper presents a benchmark comparison between calculated and experimental absorbed dose values tor a typical product, in a 60Co industrial irradiator, located at ININ, México. The irradiator is a two levels, two layers system with overlapping product configuration with activity around 300kCi. Experimental values were obtanied from routine dosimetry, using red acrylic pellets. Typical product was Petri dishes packages, apparent density 0.13 g/cm3; that product was chosen because uniform size, large quantity and low density. Minimum dose was fixed in 15 kGy. Calculated values were obtained from QAD-CGGP code. This code uses a point kernel technique, build-up factors fitting was done by geometrical progression and combinatorial geometry is used for system description. Main modifications for the code were related with source sumilation, using punctual sources instead of pencils and an energy and anisotropic emission spectrums were included. Results were, for maximum dose, calculated value (18.2 kGy) was 8% higher than experimental average value (16.8 kGy); for minimum dose, calculated value (13.8 kGy) was 3% higher than experimental average value (14.3 kGy).

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.

40 CFR 1065.710 - Gasoline.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: Initial boiling point °C 24-35 2 24-36 10% point °C 49-57 37-48 ASTM D86-07a. 50% point °C 93-110 82-101... m3/m3 Maximum, 0.10 Maximum, 0.175 ASTM D1319-03. Aromatics Maximum, 0.35 Maximum, 0.304 Saturates.../liter Maximum, 0.0013 Maximum, 0.005 ASTM D3231-07. Total sulfur mg/kg Maximum, 80 Maximum, 80 ASTM...

HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

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

Strenge, D.L.; Peloquin, R.A.

The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure modemore » are also printed if requested.« less

[Influence of sterilization treatments on continuous carbon-fiber reinforced polyolefin composite].

PubMed

Guan, Shi-bing; Hou, Chun-lin; Chen, Ai-min; Zhang, Wei; Wang, Ji-e

2007-08-21

To evaluate the influence of sterilization treatment on continuous carbon-fiber reinforced polyolefin composite (CFRP) so as to provide experimental reference for selection of sterilization method for CFRP. Seventy bars of CFRP were divided into 7 equal groups to undergo sterilization by autoclave, 2% glutaraldehyde soaking, 75% alcohol soaking, ethylene oxide sterilization, and Co-60 gamma ray irradiation of the dosages 11 kGy, 25 kGy, and 18 kGy respectively, and another 10 bars were used as blank controls. Then the bars underwent three-point bending test and longitudinal compression test so as to measure the biomechanical changes after sterilization treatment, including the maximum load, ultimate strength, and elastic modulus. Three-point bending test showed that the levels of maximum load of the all experimental groups were lower than that of the control group, however, only those of the 3 Co-60 irradiation groups were significantly lower than that of the control group and that Co-60 radiation lowered the level of maximum load dose-dependently; and that the levels of ultimate strength of all the all experimental groups were lower than that of the control group, however, only those of the 3 Co-60 groups were significantly lower than that of the control group and that the higher the dosage of Co-60 radiation the lower the level of ultimate strength, however, not dose-dependently. The elastic modulus of the Co-60 25 KGy group was significantly higher than that of the control group, and there was no significant difference in the level of ultimate strength among the other groups. Longitudinal compression test showed that the levels of maximum load and ultimate strength of the 3 Co-60 irradiation groups, autoclave group, and circular ethylene groups were significantly lower than that of the control group, and there was no significant difference in elastic modulus among different groups. During sterilized package of CFRP products produced in quantity autoclave sterilization and Co-60 gamma ray irradiation sterilization should be avoided. Ethylene oxide is proposed as the best sterilization method. If gamma ray irradiation is to be used further technology improvement is necessary.

Dose perturbations by two carbon fiber treatment couches and the ability of a commercial treatment planning system to predict these effects.

PubMed

Gerig, L H; Niedbala, M; Nyiri, B J

2010-01-01

To measure the effect of the treatment couch on dose distributions and to investigate the ability of a modern planning system to accurately model these effects. This work measured the dose perturbation at depth and in the dose buildup region when one of two treatment couches, CIVCO (formerly MED-TEC) or Medical Intelligence, was placed between a photon beam source (6, 10, and 18 MV) and the phantom. Beam attenuation was measured in the center of a cylindrical acrylic phantom with a Farmer type ion chamber at multiple gantry angles. Dose buildup was measured in Solid Water with plane parallel ion chambers (NACP-02 and PTW Markus) with the beam normal to both the phantom and couch surfaces. The effective point of measurement method as described [M. R. McEwen et al. "The effective point of measurement of ionization chambers and the build-up anomaly in MV x-ray beams," Med. Phys. 35(3), 950-958 (2008)] was employed to calculate dose in the buildup region. Both experiments were modeled in XiO. Images of the treatment couches were merged with images of the phantoms such that they were included as part of the "patient" image. Dose distributions calculated with superposition and fast superposition algorithms were compared to measurement. The two treatment couches have different radiological signatures and dissimilar water equivalent thicknesses (4.2 vs 6.3 mm.) Maximum attenuation was 7%. Both couches caused significant loss of skin sparing, the worst case showing an increase in surface dose from 17% (no couch) to 88% (with couch). The TPS accurately predicted the surface dose (+/-3%) and the attenuation at depth when the phantom was in contact with the couch. For the open beam the TPS was less successful in the buildup region. The treatment couch is not radio-transparent. Its presence between the patient and beam source significantly alters dose in the patient. For the most part, a modern treatment planning system can adequately predict the altered dose distribution.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.

Influence of intravenous opioid dose on postoperative ileus.

PubMed

Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Role of pre-existing point defects on primary damage production and amorphization in silicon carbide (β-SiC)

NASA Astrophysics Data System (ADS)

Sahoo, Deepak Ranjan; Szlufarska, Izabela; Morgan, Dane; Swaminathan, Narasimhan

2018-01-01

Molecular dynamics simulations of displacement cascades were conducted to study the effect of point defects on the primary damage production in β-SiC. Although all types of point defects and Frenkel pairs were considered, Si interstitials and Si Frenkel pairs were unstable and hence excluded from the cascade studies. Si (C) vacancies had the maximum influence, enhancing C (Si) antisites and suppressing C interstitial production, when compared to the sample without any defects. The intracascade recombination mechanisms, in the presence of pre-existing defects, is explored by examining the evolution of point defects during the cascade. To ascertain the role of the unstable Si defects on amorphization, simulations involving explicit displacements of Si atoms were conducted. The dose to amorphization with only Si displacements was much lower than what was observed with only C displacements. The release of elastic energy accumulated due to Si defects, is found to be the amorphizing mechanism.

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

2018-01-01

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

PubMed

Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

2018-04-01

The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

SU-E-T-466: Implementation of An Extension Module for Dose Response Models in the TOPAS Monte Carlo Toolkit

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

Ramos-Mendez, J; Faddegon, B; Perl, J

2015-06-15

Purpose: To develop and verify an extension to TOPAS for calculation of dose response models (TCP/NTCP). TOPAS wraps and extends Geant4. Methods: The TOPAS DICOM interface was extended to include structure contours, for subsequent calculation of DVH’s and TCP/NTCP. The following dose response models were implemented: Lyman-Kutcher-Burman (LKB), critical element (CE), population based critical volume (CV), parallel-serials, a sigmoid-based model of Niemierko for NTCP and TCP, and a Poisson-based model for TCP. For verification, results for the parallel-serial and Poisson models, with 6 MV x-ray dose distributions calculated with TOPAS and Pinnacle v9.2, were compared to data from the benchmarkmore » configuration of the AAPM Task Group 166 (TG166). We provide a benchmark configuration suitable for proton therapy along with results for the implementation of the Niemierko, CV and CE models. Results: The maximum difference in DVH calculated with Pinnacle and TOPAS was 2%. Differences between TG166 data and Monte Carlo calculations of up to 4.2%±6.1% were found for the parallel-serial model and up to 1.0%±0.7% for the Poisson model (including the uncertainty due to lack of knowledge of the point spacing in TG166). For CE, CV and Niemierko models, the discrepancies between the Pinnacle and TOPAS results are 74.5%, 34.8% and 52.1% when using 29.7 cGy point spacing, the differences being highly sensitive to dose spacing. On the other hand, with our proposed benchmark configuration, the largest differences were 12.05%±0.38%, 3.74%±1.6%, 1.57%±4.9% and 1.97%±4.6% for the CE, CV, Niemierko and LKB models, respectively. Conclusion: Several dose response models were successfully implemented with the extension module. Reference data was calculated for future benchmarking. Dose response calculated for the different models varied much more widely for the TG166 benchmark than for the proposed benchmark, which had much lower sensitivity to the choice of DVH dose points. This work was supported by National Cancer Institute Grant R01CA140735.« less

Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

PubMed

Dickie, Colleen I; Parent, Amy L; Griffin, Anthony M; Fung, Sharon; Chung, Peter W M; Catton, Charles N; Ferguson, Peter C; Wunder, Jay S; Bell, Robert S; Sharpe, Michael B; O'Sullivan, Brian

2009-11-15

To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies.

PubMed

Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K

2017-01-01

Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.

A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients.

PubMed

Schneider, Lynda C; Rachid, Rima; LeBovidge, Jennifer; Blood, Emily; Mittal, Mudita; Umetsu, Dale T

2013-12-01

Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. To examine the safety and efficacy of oral desensitization in peanut-allergic children in combination with a brief course of anti-IgE mAb (omalizumab [Xolair]). We performed oral peanut desensitization in peanut-allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered before and during oral peanut desensitization. We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE level of 229 kU(A)/L and a median total serum IgE level of 621 kU/L, who failed an initial double-blind placebo-controlled food challenge at peanut flour doses of 100 mg or less. After pretreatment with omalizumab, all 13 subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. Twelve subjects then reached the maximum maintenance dose of 4000 mg peanut flour per day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4000 mg peanut flour per day and subsequently tolerated a challenge with 8000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions, 5 subjects had grade 2 reactions, and 2 subjects had grade 3 reactions, all of which responded rapidly to treatment. Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization and qualitatively improve the desensitization process. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

The Impact of the Grid Size on TomoTherapy for Prostate Cancer

PubMed Central

Kawashima, Motohiro; Kawamura, Hidemasa; Onishi, Masahiro; Takakusagi, Yosuke; Okonogi, Noriyuki; Okazaki, Atsushi; Sekihara, Tetsuo; Ando, Yoshitaka; Nakano, Takashi

2017-01-01

Discretization errors due to the digitization of computed tomography images and the calculation grid are a significant issue in radiation therapy. Such errors have been quantitatively reported for a fixed multifield intensity-modulated radiation therapy using traditional linear accelerators. The aim of this study is to quantify the influence of the calculation grid size on the dose distribution in TomoTherapy. This study used ten treatment plans for prostate cancer. The final dose calculation was performed with “fine” (2.73 mm) and “normal” (5.46 mm) grid sizes. The dose distributions were compared from different points of view: the dose-volume histogram (DVH) parameters for planning target volume (PTV) and organ at risk (OAR), the various indices, and dose differences. The DVH parameters were used Dmax, D2%, D2cc, Dmean, D95%, D98%, and Dmin for PTV and Dmax, D2%, and D2cc for OARs. The various indices used were homogeneity index and equivalent uniform dose for plan evaluation. Almost all of DVH parameters for the “fine” calculations tended to be higher than those for the “normal” calculations. The largest difference of DVH parameters for PTV was Dmax and that for OARs was rectal D2cc. The mean difference of Dmax was 3.5%, and the rectal D2cc was increased up to 6% at the maximum and 2.9% on average. The mean difference of D95% for PTV was the smallest among the differences of the other DVH parameters. For each index, whether there was a significant difference between the two grid sizes was determined through a paired t-test. There were significant differences for most of the indices. The dose difference between the “fine” and “normal” calculations was evaluated. Some points around high-dose regions had differences exceeding 5% of the prescription dose. The influence of the calculation grid size in TomoTherapy is smaller than traditional linear accelerators. However, there was a significant difference. We recommend calculating the final dose using the “fine” grid size. PMID:28974860

Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose.

PubMed

Wang, Qiong; Tan, Yonghong; Zhang, Na; Xu, Yingyi; Wei, Wei; She, Yingjun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiangcai

2017-07-01

The developing brains of pediatric patients are highly vulnerable to anesthetic regimen (e.g., lidocaine), potentially causing neurological impairment. Recently, dexmedetomidine (DEX) has been used as an adjunct for sedation, and was shown to exert dose-dependent neuroprotective effects during brain injury. However, the maximum safe dose of DEX is unclear, and its protective effects against lidocaine-related neurotoxicity need to be confirmed. In this study, PC12 and NG108-15 cells were used to estimate safe, non-cytotoxic doses of DEX. We found that 100 and 60μM are the maximum safe dose of DEX for PC12 and NG108-15 cells, respectively, with no significant cytotoxicity. Lidocaine was found to remarkably inhibit cell vitality, but could be reversed by different doses of DEX, especially its maximum safe dose. Furthermore, the apoptosis induced by lidocaine was also assessed, and 100 and 60μM DEX showed optimal protective effects in PC12 and NG108-15 cells, respectively. Mechanistically, DEX activated the mitogen-activated protein kinase (MAPK) pathway, impaired caspase-3 expression, and enhanced anti-apoptotic factor Bcl-2 to resist lidocaine-induced apoptosis, indicating that the optimal dose of DEX alleviates lidocaine-induced cytotoxicity and should be considered in clinical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor®-medicated feed therapy

USGS Publications Warehouse

Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.

2015-01-01

Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.

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

Loupot, S; Han, T; Salehpour, M

Purpose: To quantify the difference in dose to PTV-EVAL and OARs (skin and rib) as calculated by (TG43) and heterogeneous calculations (CCC). Methods: 25 patient plans (5 Contura and 20 SAVI) were selected for analysis. Clinical dose distributions were computed with a commercially available treatment planning algorithm (TG43-D-(w,w)) and then recomputed with a pre-clinical collapsed cone convolution algorithm (CCCD-( m,m)). PTV-EVAL coverage (V90%, V95%), and rib and skin maximum dose were compared via percent difference. Differences in dose to normal tissue (V150cc, V200cc of PTV-EVAL) were also compared. Changes in coverage and maximum dose to organs at risk are reportedmore » in percent change, (100*(TG43 − CCC) / TG43)), and changes in maximum dose to normal tissue are absolute change in cc (TG43 − CCC). Results: Mean differences in V90, V95, V150, and V200 for the SAVI cases were −0.2%, −0.4%, −0.03cc, and −0.14cc, respectively, with maximum differences of −0.78%, −1.7%, 1.28cc, and 1.01cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −1.4% and −0.22%, respectively, with maximum differences of −4.5% and 16%, respectively. Mean differences in V90, V95, V150, and V200 for the Contura cases were −1.2%, −2.1%, −1.8cc, and −0.59cc, respectively, with maximum differences of −2.0%, −3.16%, −2.9cc, and −0.76cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −2.6% and −3.9%, respectively, with maximum differences of −3.2% and −5.7%, respectively. Conclusion: The effects of translating clinical knowledge based on D-(w,w) to plans reported in D-(m,m) are minimal (2% or less) on average, but vary based on the type and placement of the device, source, and heterogeneity information.« less

A dosimetric study of cardiac dose sparing using the reverse semi-decubitus technique for left breast and internal mammary chain irradiation.

PubMed

Niglas, Mark; McCann, Claire; Keller, Brian M; Makhani, Nadiya; Presutti, Joseph; Vesprini, Danny; Rakovitch, Eileen; Elzibak, Alyaa; Mashouf, Shahram; Lee, Justin

2016-01-01

Breath-hold techniques can reduce cardiac dose in breast radiotherapy. The reverse semi-decubitus (RSD) technique is an alternative free-breathing method used at our centre. This study compares the dosimetry of free-breathing supine, RSD and moderate deep inspiration breath-hold (mDIBH) techniques. Twelve patients with left-sided breast cancer who were simulated using standard supine, RSD and mDIBH techniques were identified retrospectively. New plans using standard breast tangents and techniques for internal mammary chain (IMC) nodal coverage were assessed. Using standard tangents, mean heart dose, heart V25Gy and mean left anterior descending artery (LAD) dose were found to be significantly lower for RSD and mDIBH when compared to free-breathing supine (p ⩽ 0.03). Using wide-tangents, the maximum LAD point dose was also lower for RSD and mDIBH (p ⩽ 0.02). There were no statistically significant dosimetric differences found between the RSD and mDIBH simulation techniques for standard breast-tangent plans, though organ-at-risk doses were lower for mDIBH in wide-tangent plans. There was no improvement in cardiac dosimetry between RSD and free-breathing supine when using an electron field IMC plan. For patients unable to tolerate breath-hold, the RSD technique is an alternative approach that can reduce cardiac dose. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

First-in-Human Phase I Study of PRS-050 (Angiocal), an Anticalin Targeting and Antagonizing VEGF-A, in Patients with Advanced Solid Tumors

PubMed Central

Fischer, Richard; Scharr, Dirk; Büchert, Martin; Stern, Angelika; Gille, Hendrik; Audoly, Laurent P.; Scheulen, Max E.

2013-01-01

Background To report the nonrandomized first-in-human phase I trial of PRS-050, a novel, rationally engineered Anticalin based on human tear lipocalin that targets and antagonizes vascular endothelial growth factor A (VEGF-A). Methods Patients with advanced solid tumors received PRS-050 at 0.1 mg/kg to 10 mg/kg by IV in successive dosing cohorts according to the 3+3 escalation scheme. The primary end point was safety. Results Twenty-six patients were enrolled; 25 were evaluable. Two patients experienced dose-limiting toxicity, comprising grade (G) 3 hypertension and G3 pyrexia, respectively. The maximum tolerated dose was not reached. Most commonly reported treatment-emergent adverse events (AEs) included chills (52%; G3, 4%), fatigue (52%; G3, 4%), hypertension (44%; G3, 16%), and nausea (40%, all G1/2). No anti–PRS-050 antibodies following multiple administration of the drug were detected. PRS-050 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately 6 days. Free VEGF-A was detectable at baseline in 9/25 patients, becoming rapidly undetectable after PRS-050 infusion for up to 3 weeks. VEGF-A/PRS-050 complex was detectable for up to 3 weeks at all dose levels, including in patients without detectable baseline-free VEGF-A. We also detected a significant reduction in circulating matrix metalloproteinase 2, suggesting this end point could be a pharmacodynamic (PD) marker of the drug’s activity. Conclusions PRS-050, a novel Anticalin with high affinity for VEGF-A, was well-tolerated when administered at the highest dose tested, 10 mg/kg. Based on target engagement and PK/PD data, the recommended phase II dose is 5 mg/kg every 2 weeks administered as a 120-minute infusion. Trial Registration ClinicalTrials.gov NCT01141257 http://clinicaltrials.gov/ct2/show/NCT01141257 PMID:24349470

A chronic oral reference dose for hexavalent chromium-induced intestinal cancer†

PubMed Central

Thompson, Chad M; Kirman, Christopher R; Proctor, Deborah M; Haws, Laurie C; Suh, Mina; Hays, Sean M; Hixon, J Gregory; Harris, Mark A

2014-01-01

High concentrations of hexavalent chromium [Cr(VI)] in drinking water induce villous cytotoxicity and compensatory crypt hyperplasia in the small intestines of mice (but not rats). Lifetime exposure to such cytotoxic concentrations increases intestinal neoplasms in mice, suggesting that the mode of action for Cr(VI)-induced intestinal tumors involves chronic wounding and compensatory cell proliferation of the intestine. Therefore, we developed a chronic oral reference dose (RfD) designed to be protective of intestinal damage and thus intestinal cancer. A physiologically based pharmacokinetic model for chromium in mice was used to estimate the amount of Cr(VI) entering each intestinal tissue section (duodenum, jejunum and ileum) from the lumen per day (normalized to intestinal tissue weight). These internal dose metrics, together with corresponding incidences for diffuse hyperplasia, were used to derive points of departure using benchmark dose modeling and constrained nonlinear regression. Both modeling techniques resulted in similar points of departure, which were subsequently converted to human equivalent doses using a human physiologically based pharmacokinetic model. Applying appropriate uncertainty factors, an RfD of 0.006 mg kg–1 day–1 was derived for diffuse hyperplasia—an effect that precedes tumor formation. This RfD is protective of both noncancer and cancer effects in the small intestine and corresponds to a safe drinking water equivalent level of 210 µg l–1. This concentration is higher than the current federal maximum contaminant level for total Cr (100 µg l–1) and well above levels of Cr(VI) in US drinking water supplies (typically ≤ 5 µg l–1). © 2013 The Authors. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. PMID:23943231

Gamma-index method sensitivity for gauging plan delivery accuracy of volumetric modulated arc therapy.

PubMed

Park, Jong In; Park, Jong Min; Kim, Jung-In; Park, So-Yeon; Ye, Sung-Joon

2015-12-01

The aim of this study was to investigate the sensitivity of the gamma-index method according to various gamma criteria for volumetric modulated arc therapy (VMAT). Twenty head and neck (HN) and twenty prostate VMAT plans were retrospectively selected for this study. Both global and local 2D gamma evaluations were performed with criteria of 3%/3 mm, 2%/2 mm, 1%/2 mm and 2%/1 mm. In this study, the global and local gamma-index calculated the differences in doses relative to the maximum dose and the dose at the current measurement point, respectively. Using log files acquired during delivery, the differences in parameters at every control point between the VMAT plans and the log files were acquired. The differences in dose-volumetric parameters between reconstructed VMAT plans using the log files and the original VMAT plans were calculated. The Spearman's rank correlation coefficients (rs) were calculated between the passing rates and those differences. Considerable correlations with statistical significances were observed between global 1%/2 mm, local 1%/2 mm and local 2%/1 mm and the MLC position differences (rs = -0.712, -0.628 and -0.581). The numbers of rs values with statistical significance between the passing rates and the changes in dose-volumetric parameters were largest in global 2%/2 mm (n = 16), global 2%/1 mm (n = 15) and local 2%/1 mm (n = 13) criteria. Local gamma-index method with 2%/1 mm generally showed higher sensitivity to detect deviations between a VMAT plan and the delivery of the VMAT plan. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Cosmic radiation exposure of biological test systems during the EXPOSE-E mission.

PubMed

Berger, Thomas; Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-05-01

In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5-12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples.

Dosimetric intercomparison of permanent Ho-166 seed's implants and HDR Ir-192 brachytherapy in breast cancer.

PubMed

de Campos, Tarcisio Passos Ribeiro; Nogueira, Luciana Batista; Trindade, Bruno; Cuperschmid, Ethel Mizrahy

2016-01-01

To provide a comparative dosimetric analysis of permanent implants of Ho(166)-seeds and temporary HDR Ir(192)-brachytherapy through computational simulation. Brachytherapy with Ir(192)-HDR or LDR based on temporary wires or permanent radioactive seed implants can be used as dose reinforcement for breast radiation therapy. Permanent breast implants have not been a practical clinical routine; although, I(125) and Pd(103)-seeds have already been reported. Biodegradable Ho(166)-ceramic-seeds have been addressed recently. Simulations of implants of nine Ho(166)-seeds and equivalent with HDR Ir(192)-brachytherapy were elaborated in MCNP5, shaped in a computational multivoxel simulator which reproduced a female thorax phantom. Spatial dose rate distributions and dose-volume histograms were generated. Protocol's analysis involving exposure time, seed's activities and dose were performed. Permanent Ho(166)-seed implants presented a maximum dose rate per unit of contained activity (MDR) of 1.1601 μGy h(-1) Bq(-1); and, a normalized MDR in standard points (8 mm, equidistant to 03-seeds - SP1, 10 mm - SP2) of 1.0% (SP1) and 0.5% (SP2), respectively. Ir(192)-brachytherapy presented MDR of 4.3945 × 10(-3) μGy h(-1) Bq(-1); and, 30% (SP1), and 20% (SP2). Therefore, seed's implant activities of 333 MBq (Ho(166)) and 259 GBq (Ir(192)) produced prescribed doses of 58 Gy (SP1; 5d) and 56 Gy (SP1, 5 fractions, 6 min), respectively. Breast Ho(166)-implants of 37-111 MBq are attractive due to the high dose rate near 6-10 mm from seeds, equivalent to Ir(192)-brachytherapy of 259 GBq (3 fractions, 6 min) providing similar dose in standard points at a week; however, with spatial dose distribution better confined. The seed positioning can be adjusted for controlling the breast tumor, in stages I and II, in flat and deep tumors, without any breast volumetric limitation.

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

Ma, C; Lin, M; Chen, L

Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategiesmore » were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.« less

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans.

PubMed

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q; Otrakji, Alexi; Kalra, Mannudeep K; Xu, X George; Liu, Bob

2014-09-01

To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8%-25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2±3.3 and 16.5±2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.

Randomized study of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.

PubMed

Wang, Weiqing; Bu, Ruifang; Su, Qing; Liu, Jianying; Ning, Guang

2011-12-01

The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy. A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents. The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups. Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.

Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

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

Bakker, Akke, E-mail: akke.bakker@amc.uva.nl; Kolff, M. Willemijn; Holman, Rebecca

Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79more » sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.« less

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI.

PubMed

Papagiannis, P; Karaiskos, P; Kozicki, M; Rosiak, J M; Sakelliou, L; Sandilos, P; Seimenis, I; Torrens, M

2005-05-07

This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.

Electron fluence correction factors for various materials in clinical electron beams.

PubMed

Olivares, M; DeBlois, F; Podgorsak, E B; Seuntjens, J P

2001-08-01

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at dmax in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than +/- 1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83+/-0.01 and 1.55+/-0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1sigma level. Excluding the data for Cu, electron fluence correction factors for open electron beams are approximately proportional to the electron density of the phantom material and only weakly dependent on electron beam energy.

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

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

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

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

2015-08-15

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

Air Pathway Dose Modeling for the E-Area Low-Level Waste Facility

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

Dixon, K. L.; Minter, K. M.

2017-09-06

Dose-release factors (DRFs) were calculated for potential atmospheric releases of several radionuclides from the E-Area Low-Level Waste Facility (ELLWF). The ELLWF receives solid low-level radioactive waste from across the Savannah River Site (SRS) and offsite for disposal. These factors represent the maximum dose a receptor would receive if standing at either 100 m or 11,410 m (Site Boundary) from the edge of an ELLWF disposal unit which are points of assessment (POA) for Department of Energy (DOE) Order 435.1 performance assessments (PA). The DRFs were calculated for 1 Ci of the specified radionuclide being released from the ground surface tomore » the atmosphere (mrem per curie released). The calculation conservatively represented the ELLWF as a point source, and conservatively assumed the receptor was positioned at the center of the contaminant plume and continuously exposed for a period of one year. These DRFs can be refined to take into consideration disposal unit size, proximity and timing of peak dose to establish less conservative radionuclide specific disposal limits. DRFs were calculated for H-3 and C-14 in Revision 0 of this report. H-3 as HTO and C-14 as CO 2 were identified as volatile radionuclides of potential concern in earlier radionuclide screening studies. In Revision 1, DRFs were calculated for eight additional radionuclides identified by an updated screening analysis as potentially important volatile radionuclides. These include Ar-37, Ar-39, Ar-42, Hg-194, Hg- 203, Kr-81, Kr-85, and Xe-127.« less

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

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

Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

2016-11-01

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

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

Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael

A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy inmore » 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.« less

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.edu; Foster, Ryan D.; Kogel, Albert J. van der

2012-07-01

Purpose: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. Methods and Materials: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10%more » isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 {+-} 0.1 Gy (n = 2), 17.1 {+-} 0.3 Gy (n = 3), 19.0 {+-} 0.1 Gy (n = 5), 21.2 {+-} 0.1 Gy (n = 5), 23.4 {+-} 0.2 Gy (n = 5), and 25.4 {+-} 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 34% {+-} 1%, 40% {+-} 1%, 46% {+-} 3%, 52% {+-} 1%, 56 {+-} 3%, and 57% {+-} 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. Results: A steep dose-response curve was observed with a 50% incidence of paralysis (ED{sub 50}) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. Conclusion: Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.« less

Radio Frequency Transistors Using Aligned Semiconducting Carbon Nanotubes with Current-Gain Cutoff Frequency and Maximum Oscillation Frequency Simultaneously Greater than 70 GHz.

PubMed

Cao, Yu; Brady, Gerald J; Gui, Hui; Rutherglen, Chris; Arnold, Michael S; Zhou, Chongwu

2016-07-26

In this paper, we report record radio frequency (RF) performance of carbon nanotube transistors based on combined use of a self-aligned T-shape gate structure, and well-aligned, high-semiconducting-purity, high-density polyfluorene-sorted semiconducting carbon nanotubes, which were deposited using dose-controlled, floating evaporative self-assembly method. These transistors show outstanding direct current (DC) performance with on-current density of 350 μA/μm, transconductance as high as 310 μS/μm, and superior current saturation with normalized output resistance greater than 100 kΩ·μm. These transistors create a record as carbon nanotube RF transistors that demonstrate both the current-gain cutoff frequency (ft) and the maximum oscillation frequency (fmax) greater than 70 GHz. Furthermore, these transistors exhibit good linearity performance with 1 dB gain compression point (P1dB) of 14 dBm and input third-order intercept point (IIP3) of 22 dBm. Our study advances state-of-the-art of carbon nanotube RF electronics, which have the potential to be made flexible and may find broad applications for signal amplification, wireless communication, and wearable/flexible electronics.

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse event needs to be considered in the clinical use of cannabis. PMID:29682608

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

PubMed

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

2016-04-01

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

Dose optimization of contrast-enhanced carotid MR angiography.

PubMed

Unterweger, M; Froehlich, J M; Kubik-Huch, R A; Seifert, B; Birrer, M; Huber, T; Otto, R

2005-09-01

The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.

Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

PubMed

Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Cuttino, Laurie W; Mukhopadhyay, Nitai D

2013-06-01

Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals. Copyright © 2013 Elsevier Inc. All rights reserved.

Contura Multi-Lumen Balloon Breast Brachytherapy Catheter: Comparative Dosimetric Findings of a Phase 4 Trial

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

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.edu; Vicini, Frank A.; Todor, Dorin A.

2013-06-01

Purpose: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Methods and Materials: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥95% of the prescribed dose (PD) covering ≥95% of the target volume (TV); maximum skin dose ≤125%more » of the PD; maximum rib dose ≤145% of the PD; and V150 ≤50 cc and V200 ≤10 cc. Results: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Conclusions: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.« less

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

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

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Survey of patient dosimetry for head and neck cancer patients undergoing external radiotherapy treatment: a study from northeastern hospitals of India.

PubMed

Sharma, Arunkumar B; Singh, Tomcha Th; Singh, Khelendra N; Gartia, R K

2009-01-01

To study dosimetry of patients during the external radiotherapy of head and neck cancers from different hospitals of the northeastern region (NER) of India. 35 confirmed cases of head and neck cancers reporting to three different hospitals in the NER of India who underwent radiation treatment were the materials for the study. Dosimetry was carried out at 8(eight) anatomical points to these patients, namely, target (entrance and exit points), forehead, chest, abdomen, gonad, arm, and leg respectively by thermoluminescence (TL) as well as optically stimulated luminescence (OSL) dosimeters. Unlike conventional appliances, we used common iodized salt as TL/OSL phosphor. Patient dosimetry was found to vary with an average of 1.17 +/- 0.39 Sv at forehead, 1.24 +/- 0.39 Sv at chest, 0.52 +/- 0.13 Sv at gonad to a minimum of 0.26 +/- 0.07 Sv at leg areas when exposed to a cumulative dose of 65 Sv at the target. Maximum dose received from a stray radiation is about 1.5 Sv at forehead/chest and dosimetry of patient among the three centers is not significantly different at the 5% level of probability.

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

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

Smyth, G; Bamber, JC; Bedford, JL

2015-06-15

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

A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function

PubMed Central

Ermer, James; Corcoran, Mary; Lasseter, Kenneth; Marbury, Thomas; Yan, Brian

2016-01-01

Background: Lisdexamfetamine (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined. Methods: Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7–14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0–∞) or to last assessment (AUClast). Results: Mean LDX Cmax, AUClast, and AUC0–∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. d-amphetamine exposure (AUClast and AUC0–∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little d-amphetamine were recovered in the dialyzate. Conclusions: There seems to be prolonged d-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min−1·1.73 m−2), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min−1·1.73 m−2), the maximum LDX dose is 30 mg/d. Neither LDX nor d-amphetamine is dialyzable. PMID:26926668

Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers.

PubMed

Krishnan, Suma M; Pennick, Michael; Stark, Jeffrey G

2008-01-01

Attention-deficit/hyperactivity disorder (ADHD) in children often persists into adulthood and is potentially associated with significant social and occupational impairments. It is important to understand the effects of pharmacological treatments of ADHD in adults. This study aimed to assess the absorption, metabolism and elimination of lisdexamfetamine dimesylate in normal, healthy adult subjects following a single oral dose. A secondary objective was to assess the safety and tolerability of treatment. In an open-label, single-centre study, six healthy adult volunteers aged 22-52 years received a single oral 70 mg dose of (14)C-radiolabelled lisdexamfetamine dimesylate in solution following a 10-hour fast. Blood samples drawn pre-dose and at time points up to 120 hours post-dose were used for plasma pharmacokinetic analysis of the active d-amphetamine and the intact parent compound lisdexamfetamine dimesylate. Recovery of radioactivity was determined by liquid scintillation counting of blood samples (whole blood and plasma), urine samples and faecal samples collected pre-dose and at designated time points up to 120 hours post-dose. Urine samples were also analysed for the presence of amphetamine-derived metabolites. Safety was assessed by adverse event reporting, changes in physical findings, vital sign measurements, ECG measurements, and clinical laboratory test results. For intact lisdexamfetamine dimesylate, the median time to reach maximum plasma drug concentration (t(max)) was 1.00 hour, and the mean maximum plasma drug concentration (C(max)) was 58.2 +/- 28.1 ng/mL. Intact lisdexamfetamine dimesylate exhibited modest systemic exposure (area under the drug concentration-time curve from time 0 to infinity [AUC(infinity)] 67.04 +/- 18.94 ng . h/mL), and rapid elimination (mean apparent terminal elimination half-life [t((1/2)beta)] 0.47 hours). For d-amphetamine, the median t(max) was 3.00 hours, and the mean C(max) was 80.3 +/- 11.8 ng/mL. The AUC(infinity) of d-amphetamine was 1342 +/- 216.9 ng . h/mL, and elimination occurred as a first-order process. The t((1/2)beta) of d-amphetamine was 10.39 hours. Peaks consistent with amphetamine and hippuric acid were identified in urine samples by high-performance liquid chromatography radioactive profiling. Relative to dose administered, 41.5% was recovered in urine as d-amphetamine, 24.8% as hippuric acid and 2.2% as intact lisdexamfetamine dimesylate. Less than 0.3% of the administered dose was recovered in the faeces. During the 0- to 48-hour urine samples, no unexpected adverse events or clinically significant laboratory, ECG or physical examination findings related to the study medication were observed. Following a single 70 mg oral dose, lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated. Systemic exposure to d-amphetamine was approximately 20-fold higher than systemic exposure to intact lisdexamfetamine dimesylate in healthy adults. Lisdexamfetamine dimesylate, administered as a single 70 mg dose, was generally well tolerated in this study.

The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses

PubMed Central

Ring, Arne; Port, Andreas; Graefe-Mody, E Ulrike; Revollo, Ivette; Iovino, Mario; Dugi, Klaus A

2011-01-01

AIM To evaluate the potential effects of therapeutic and supratherapeutic doses of linagliptin (BI 1356) on the QT/QTc interval in healthy subjects. METHODS The study was a randomized, double-blind, placebo-controlled, four-period crossover study using single oral doses of linagliptin (5 mg and 100 mg), moxifloxacin (400 mg) and placebo. Electrocardiogram (ECG) profiles using triplicates of 12-lead 10-s ECGs were digitally recorded pre-dose and after drug administration. The mean change from baseline (MCfB) of the individually heart rate corrected QT interval (QTcI) between 1 and 4 h postdrug administration was the primary end point. Blood samples to measure plasma concentrations of linagliptin and its main metabolite were also obtained. RESULTS Forty-four Caucasian subjects (26 male) entered the study and 43 subjects completed the study as planned in the protocol. Linagliptin was not associated with an increase in the baseline-adjusted mean QTcI, at any time point. The placebo-corrected MCfB of QTcI was −1.1 (90% CI −2.7, 0.5) ms and −2.5 (–4.1, –0.9) ms for linagliptin 5 mg and 100 mg, respectively, thus within the non-inferiority margin of 10 ms according to ICH E14. Linagliptin was well tolerated; the assessment of ECGs and other safety parameters gave no clinically relevant findings at either dose tested. Maximum plasma concentrations after administration of 100-mg linagliptin were ∼24-fold higher than those observed previously for chronic treatment with the therapeutic 5-mg dose. Assay sensitivity was confirmed by a placebo-corrected MCfB of QTcI with moxifloxacin of 6.9 (90% CI 5.4, 8.5) ms. CONCLUSIONS Therapeutic and significantly supratherapeutic exposure to linagliptin is not associated with QT interval prolongation. PMID:21306414

NESHAP Area-Specific Dose-Release Factors for Potential Onsite Member-of-the-Public Locations at SRS using CAP88-PC Version 4.0

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

Trimor, P.

The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclidemore » being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). In this report, the DRFs were calculated for potential radionuclide atmospheric releases from 13 SRS release points. The three potential onsite MEI locations to be evaluated are B-Area, Three Rivers Landfill (TRL), and Savannah River Ecology Lab Conference Center (SRELCC) with TRL’s onsite workers considered as members-of-the-public, and the potential future constructions of dormitories at SRELCC and Barracks at B-Area. Each MEI location was evaluated at a specified compass sector with different area to receptor distances and was conducted for both ground-level and elevated release points. The analysis makes use of area-specific meteorological data (Viner 2014). The resulting DRFs are compared to the 2014 NESHAP offsite MEI DRFs for three operational areas; A-Area, H-Area, and COS for a release rate of 1 Ci of tritium oxide at 0 ft. elevation. CAP88 was executed again using the 2016 NESHAP MEI release rates for 0 and 61 m stack heights to determine the radionuclide dose at TRL from the center-of-site (COS).« less

A comparison of TPS and different measurement techniques in small-field electron beams

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

Donmez Kesen, Nazmiye, E-mail: nazo94@gmail.com; Cakir, Aydin; Okutan, Murat

In recent years, small-field electron beams have been used for the treatment of superficial lesions, which requires small circular fields. However, when using very small electron fields, some significant dosimetric problems may occur. In this study, dose distributions and outputs of circular fields with dimensions of 5 cm and smaller, for nominal energies of 6, 9, and 15 MeV from the Siemens ONCOR Linac, were measured and compared with data from a treatment planning system using the pencil-beam algorithm in electron beam calculations. All dose distribution measurements were performed using the Gafchromic EBT film; these measurements were compared with datamore » that were obtained from the Computerized Medical Systems (CMS) XiO treatment planning system (TPS), using the gamma-index method in the PTW VeriSoft software program. Output measurements were performed using the Gafchromic EBT film, an Advanced Markus ion chamber, and thermoluminescent dosimetry (TLD). Although the pencil-beam algorithm is used to model electron beams in many clinics, there is no substantial amount of detailed information in the literature about its use. As the field size decreased, the point of maximum dose moved closer to the surface. Output factors were consistent; differences from the values obtained from the TPS were, at maximum, 42% for 6 and 15 MeV and 32% for 9 MeV. When the dose distributions from the TPS were compared with the measurements from the Gafchromic EBT films, it was observed that the results were consistent for 2-cm diameter and larger fields, but the outputs for fields of 1-cm diameter and smaller were not consistent. In CMS XiO TPS, calculated using the pencil-beam algorithm, the dose distributions of electron treatment fields that were created with circular cutout of a 1-cm diameter were not appropriate for patient treatment and the pencil-beam algorithm is not convenient for monitor unit (MU) calculations in electron dosimetry.« less

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom.

PubMed

Lye, Jessica; Kenny, John; Lehmann, Joerg; Dunn, Leon; Kron, Tomas; Alves, Andrew; Cole, Andrew; Williams, Ivan

2014-10-01

The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantoms are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%-8%. The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

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

Ding, Xuanfeng, E-mail: Xuanfeng.ding@beaumont.org; Li, Xiaoqiang; Zhang, J. Michele

Purpose: To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials: A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arc{sub multi-field}) and the standard robust optimized intensity modulatedmore » proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results: The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arc{sub multi-field} plans. Conclusion: The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.« less

Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

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

Holmes, W.G.

2001-08-16

The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

SU-E-J-32: Dosimetric Evaluation Based On Pre-Treatment Cone Beam CT for Spine Stereotactic Body Radiotherapy: Does Region of Interest Focus Matter?

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

Magnelli, A; Xia, P

2015-06-15

Purpose: Spine stereotactic body radiotherapy requires very conformal dose distributions and precise delivery. Prior to treatment, a KV cone-beam CT (KV-CBCT) is registered to the planning CT to provide image-guided positional corrections, which depend on selection of the region of interest (ROI) because of imperfect patient positioning and anatomical deformation. Our objective is to determine the dosimetric impact of ROI selections. Methods: Twelve patients were selected for this study with the treatment regions varied from C-spine to T-spine. For each patient, the KV-CBCT was registered to the planning CT three times using distinct ROIs: one encompassing the entire patient, amore » large ROI containing large bony anatomy, and a small target-focused ROI. Each registered CBCT volume, saved as an aligned dataset, was then sent to the planning system. The treated plan was applied to each dataset and dose was recalculated. The tumor dose coverage (percentage of target volume receiving prescription dose), maximum point dose to 0.03 cc of the spinal cord, and dose to 10% of the spinal cord volume (V10) for each alignment were compared to the original plan. Results: The average magnitude of tumor coverage deviation was 3.9%±5.8% with external contour, 1.5%±1.1% with large ROI, 1.3%±1.1% with small ROI. Spinal cord V10 deviation from plan was 6.6%±6.6% with external contour, 3.5%±3.1% with large ROI, and 1.2%±1.0% with small ROI. Spinal cord max point dose deviation from plan was: 12.2%±13.3% with external contour, 8.5%±8.4% with large ROI, and 3.7%±2.8% with small ROI. Conclusion: A small ROI focused on the target results in the smallest deviation from planned dose to target and cord although rotations at large distances from the targets were observed. It is recommended that image fusion during CBCT focus narrowly on the target volume to minimize dosimetric error. Improvement in patient setups may further reduce residual errors.« less

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

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

Karlsson, Kristin, E-mail: kristin.karlsson@karolinska.se; Department of Oncology-Pathology, Karolinska Institute, Stockholm; Nyman, Jan

2013-11-01

Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm{sup 3} up to 2.0 cm{sup 3}]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showedmore » a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm{sup 3} (D{sub 0.1cm3}) was used for further analysis. The median value of D{sub 0.1cm3} (α/β = 3 Gy) was EQD{sub 2,LQ} = 147 Gy{sub 3} (range, 20-293 Gy{sub 3}). For patients who developed atelectasis the median value was EQD{sub 2,LQ} = 210 Gy{sub 3}, and for patients who did not develop atelectasis, EQD{sub 2,LQ} = 105 Gy{sub 3}. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.« less

Technical Note: Evaluation of plastic scintillator detector for small field stereotactic patient-specific quality assurance.

PubMed

Qin, Yujiao; Gardner, Stephen J; Kim, Joshua; Huang, Yimei; Wen, Ning; Doemer, Anthony; Chetty, Indrin J

2017-10-01

To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance (QA) measurements using flattening-filter-free beam. A total of 10 spherical targets [volume range: (0.03 cc-2 cc)] were planned with two techniques: (a) dynamic conformal arc (DCA-10 plans) and (b) volumetric modulated arc therapy (VMAT-10 plans). All plans were generated using Varian Eclipse treatment planning system, and AcurosXB v.13 algorithm in 1.0 mm grid size. Additionally, 14 previously treated cranial and spine SRS plans were evaluated [6 DCA, 8 VMAT, volume range: (0.04 cc-119.02 cc)]. Plan modulation was quantified via two metrics: MU per prescription dose (MU/Rx) and Average Leaf Pair Opening (ALPO). QA was performed on the Varian Edge linear accelerator equipped with HDMLC. Three detectors were used: (a) PinPoint ion chamber (PTW; active volume 0.015 cc), (b) Exradin W1 PSD (Standard Imaging; active volume 0.002 cc), and (c) Gafchromic EBT3 film (Ashland). PinPoint chamber and PSD were positioned perpendicular to beam axis in a Lucy phantom (Standard Imaging); films were placed horizontally capturing the coronal plane. PSD, film, and PinPoint chamber measured average differences of 1.00 ± 1.54%, 1.30 ± 1.69%, and -0.66 ± 2.36%, respectively, compared to AcurosXB dose calculation. As the target volume decreased, PinPoint chamber measured lower doses (maximum -5.07% at 0.07 cc target), while PSD and film measured higher doses (2.87% and 2.54% at 0.03 cc target) than AcurosXB. Film agreed with the benchmark detector PSD by an average difference of 0.31 ± 1.20%, but suffered from larger uncertainty; PinPoint chamber underestimated dose by more than 4% for targets smaller than 0.2 cc. Taking PSD as the measurement standard, DCA plans achieved good QA results across all volumes studied, with an average of -0.07 ± 0.89%; for VMAT plans, PSD measured consistently higher dose (1.95 ± 1.36%) than AcurosXB. Correlation study revealed that plan modulation quantified by both MU/Rx and ALPO correlated significantly with QA results. Among all three detectors, PSD demonstrated superior performances in plans with small fields and heavy modulation. High consistency and low uncertainty made PSD a suitable detector for clinical routine SRS QA. PinPoint chamber should be avoided for targets smaller than 0.2 cc; film dosimetry can be utilized with careful evaluation of its uncertainty bracket. Compared to PSD measurements, AcurosXB calculation demonstrated high accuracy for nonmodulated small fields. The positive correlation between plan modulation and QA discrepancy calls for our attention for clinical SRS plans with high modulation. © 2017 American Association of Physicists in Medicine.

Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia.

PubMed

Ricotta, Daniel N; Frishman, William

2012-01-01

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.

Doses to organs and tissues from concomitant imaging in radiotherapy: a suggested framework for clinical justification.

PubMed

Harrison, R M

2008-12-01

The increasing use of imaging for localization and verification in radiotherapy has raised issues concerning the justifiable doses to critical organs and tissues from concomitant exposures, particularly when extensive image-guided radiotherapy is indicated. Doses at positions remote from the target volume include components from high-energy leakage and scatter, as well as from concomitant imaging. In this paper, simulated prostate, breast and larynx treatments are used to compare doses from both high-energy and concomitant exposures as a function of distance from the target volume. It is suggested that the fraction, R, of the total dose at any point within the patient that is attributable to concomitant exposures may be a useful aid in their justification. R is small within the target volume and at large distances from it. However, there is a critical region immediately adjacent to the planning target volume where the dose from concomitant imaging combines with leakage and scatter to give values of R that approach 0.5 in the examples given here. This is noteworthy because the regions just outside the target volume will receive total doses in the order of 1 Gy, where commensurately high risk factors may not be substantially reduced because of cell kill. Other studies have identified these regions as sites of second cancers. The justification of an imaging regimen might therefore usefully take into account the maximum value of R encountered from the combination of imaging and radiotherapy for particular treatment sites.

Relative dosimetry with an MR-linac: Response of ion chambers, diamond, and diode detectors for off-axis, depth dose, and output factor measurements.

PubMed

O'Brien, Daniel J; Dolan, James; Pencea, Stefan; Schupp, Nicholas; Sawakuchi, Gabriel O

2018-02-01

The purpose of this study was to acquire beam data for an MR-linac, with and without a 1.5 T magnetic field, by using a variety of commercially available detectors to assess their relative response in the magnetic field. The impact of the magnetic field on the measured dose distribution was also assessed. An MR-safe 3D scanning water phantom was used to measure output factors, depth dose curves, and off-axis profiles for various depths and for field sizes between 2 × 2 cm 2 and 22 × 22 cm 2 for an Elekta MR-linac beam with the orthogonal 1.5 T magnetic field on or off. An on-board MV portal imaging system was used to ensure that the reproducibility of the detector position, both with and without the magnetic field, was within 0.1 mm. The detectors used included ionization chambers with large, medium, and small sensitive volumes; a diamond detector; a shielded diode; and an unshielded diode. The offset of the effective point of measurement of the ionization chambers was found to be reduced by at least half for each chamber in the direction parallel with the beam. A lateral shift of similar magnitude was also introduced to the chambers' effective point of measurement toward the average direction of the Lorentz force. A similar lateral shift (but in the opposite direction) was also observed for the diamond and diode detectors. The measured lateral shift in the dose distribution was independent of depth and field size for each detector for fields between 2 × 2 cm 2 and 10 × 10 cm 2 . The shielded diode significantly misrepresented the dose distribution in the lateral direction perpendicular to the magnetic field, making it seem more symmetric. The percentage depth dose was generally found to be lower with the magnetic field than without, but this difference was reduced as field size increased. The depth of maximum dose showed little dependence on field size in the presence of the magnetic field, with values from 1.2 cm to 1.3 cm between the 2 × 2 cm 2 and 22 × 22 cm 2 fields. Output factors measured in the magnetic field at the center of the beam profile produced a larger spread of values between detectors for fields smaller than 10 × 10 cm 2 (with a spread of 2% at 3 × 3 cm 2 ). The spread of values was more consistent when the output factors were measured at the point of peak intensity of the lateral dose distribution instead (except for the shielded diode which differed by up to 2% depending on field size). The magnetic field of the MR-linac alters the effective point of measurement of ionization chambers, shifting it both downstream and laterally. Shielded diodes produce incorrect and misleading dose profiles. The output factor measured at the point of peak intensity in the lateral dose distribution is more robust than the conventional output factor (measured at central axis). Diodes are not recommended for output factor measurements in the magnetic field. © 2017 American Association of Physicists in Medicine.

Developability assessment of clinical drug products with maximum absorbable doses.

PubMed

Ding, Xuan; Rose, John P; Van Gelder, Jan

2012-05-10

Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application. Three methods for calculating D(abs) were compared by assessing how well the methods predicted the absorption limit for a set of real clinical candidates. D(abs) was calculated for these clinical candidates by means of a simple equation and two computer simulation programs, GastroPlus and an program developed at Eli Lilly and Company. Results from single dose escalation studies in Phase I clinical trials were analyzed to identify the maximum absorbable doses for these compounds. Compared to the clinical results, the equation and both simulation programs provide conservative estimates of D(abs), but in general D(abs) from the computer simulations are more accurate, which may find obvious advantage for the simulations in developability assessment. Computer simulations also revealed the complex behavior associated with absorption saturation and suggested in most cases that the D(abs) limit is not likely to be achieved in a typical clinical dose range. On the basis of the validation findings, an approach is proposed for assessing absorption potential, and best practices are discussed for the use of D(abs) estimates to inform clinical formulation development strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PubMed

Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

2017-08-01

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Population pharmacokinetics and maximum a posteriori probability Bayesian estimator of abacavir: application of individualized therapy in HIV-infected infants and toddlers.

PubMed

Zhao, Wei; Cella, Massimo; Della Pasqua, Oscar; Burger, David; Jacqz-Aigrain, Evelyne

2012-04-01

Abacavir is used to treat HIV infection in both adults and children. The recommended paediatric dose is 8 mg kg(-1) twice daily up to a maximum of 300 mg twice daily. Weight was identified as the central covariate influencing pharmacokinetics of abacavir in children. A population pharmacokinetic model was developed to describe both once and twice daily pharmacokinetic profiles of abacavir in infants and toddlers. Standard dosage regimen is associated with large interindividual variability in abacavir concentrations. A maximum a posteriori probability Bayesian estimator of AUC(0-) (t) based on three time points (0, 1 or 2, and 3 h) is proposed to support area under the concentration-time curve (AUC) targeted individualized therapy in infants and toddlers. To develop a population pharmacokinetic model for abacavir in HIV-infected infants and toddlers, which will be used to describe both once and twice daily pharmacokinetic profiles, identify covariates that explain variability and propose optimal time points to optimize the area under the concentration-time curve (AUC) targeted dosage and individualize therapy. The pharmacokinetics of abacavir was described with plasma concentrations from 23 patients using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with first-order absorption and elimination was developed. The final model was validated using bootstrap, visual predictive check and normalized prediction distribution errors. The Bayesian estimator was validated using the cross-validation and simulation-estimation method. The typical population pharmacokinetic parameters and relative standard errors (RSE) were apparent systemic clearance (CL) 13.4 () h−1 (RSE 6.3%), apparent central volume of distribution 4.94 () (RSE 28.7%), apparent peripheral volume of distribution 8.12 () (RSE14.2%), apparent intercompartment clearance 1.25 () h−1 (RSE 16.9%) and absorption rate constant 0.758 h−1 (RSE 5.8%). The covariate analysis identified weight as the individual factor influencing the apparent oral clearance: CL = 13.4 × (weight/12)1.14. The maximum a posteriori probability Bayesian estimator, based on three concentrations measured at 0, 1 or 2, and 3 h after drug intake allowed predicting individual AUC0–t. The population pharmacokinetic model developed for abacavir in HIV-infected infants and toddlers accurately described both once and twice daily pharmacokinetic profiles. The maximum a posteriori probability Bayesian estimator of AUC(0-) (t) was developed from the final model and can be used routinely to optimize individual dosing. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Multileaf collimator tongue-and-groove effect on depth and off-axis doses: A comparison of treatment planning data with measurements and Monte Carlo calculations

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

Kim, Hee Jung; Department of Biomedical Engineering, Seoul National University, Seoul; Department of Radiation Oncology, Soonchunhyang University Hospital, Seoul

2015-01-01

To investigate how accurately treatment planning systems (TPSs) account for the tongue-and-groove (TG) effect, Monte Carlo (MC) simulations and radiochromic film (RCF) measurements were performed for comparison with TPS results. Two commercial TPSs computed the TG effect for Varian Millennium 120 multileaf collimator (MLC). The TG effect on off-axis dose profile at 3 depths of solid water was estimated as the maximum depth and the full width at half maximum (FWHM) of the dose dip at an interleaf position. When compared with the off-axis dose of open field, the maximum depth of the dose dip for MC and RCF rangedmore » from 10.1% to 20.6%; the maximum depth of the dose dip gradually decreased by up to 8.7% with increasing depths of 1.5 to 10 cm and also by up to 4.1% with increasing off-axis distances of 0 to 13 cm. However, TPS results showed at most a 2.7% decrease for the same depth range and a negligible variation for the same off-axis distances. The FWHM of the dose dip was approximately 0.19 cm for MC and 0.17 cm for RCF, but 0.30 cm for Eclipse TPS and 0.45 cm for Pinnacle TPS. Accordingly, the integrated value of TG dose dip for TPS was larger than that for MC and RCF and almost invariant along the depths and off-axis distances. We concluded that the TG dependence on depth and off-axis doses shown in the MC and RCF results could not be appropriately modeled by the TPS versions in this study.« less

Confusion: acetaminophen dosing changes based on NO evidence in adults.

PubMed

Krenzelok, Edward P; Royal, Mike A

2012-06-01

Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?

The use of rotation to fentanyl in cancer-related pain

PubMed Central

Dima, Delia; Tomuleasa, Ciprian; Frinc, Ioana; Pasca, Sergiu; Magdo, Lorand; Berindan-Neagoe, Ioana; Muresan, Mihai; Lisencu, Cosmin; Irimie, Alexandru; Zdrenghea, Mihnea

2017-01-01

Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. PMID:28223843

Whole-breast irradiation: a subgroup analysis of criteria to stratify for prone position treatment

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

Ramella, Sara, E-mail: s.ramella@unicampus.it; Trodella, Lucio; Ippolito, Edy

2012-07-01

To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small ({<=}400 mL), medium (400-700 mL), and large ({>=}700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volumemore » of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V{sub 5Gy} did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V{sub 5Gy}, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size.« less

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

A comparison of skin and chest wall dose delivered with multicatheter, Contura multilumen balloon, and MammoSite breast brachytherapy.

PubMed

Cuttino, Laurie W; Todor, Dorin; Rosu, Mihaela; Arthur, Douglas W

2011-01-01

Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS. Copyright © 2011 Elsevier Inc. All rights reserved.

A Comparison of Skin and Chest Wall Dose Delivered With Multicatheter, Contura Multilumen Balloon, and MammoSite Breast Brachytherapy

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

Cuttino, Laurie W., E-mail: lcuttino@mcvh-vcu.ed; Todor, Dorin; Rosu, Mihaela

2011-01-01

Purpose: Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. Methods and Materials: 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. Results: The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67%more » of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). Conclusion: The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS.« less

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

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PubMed

Ohri, Nisha; Cordeiro, Peter G; Keam, Jennifer; Ballangrud, Ase; Shi, Weiji; Zhang, Zhigang; Nerbun, Claire T; Woch, Katherine M; Stein, Nicholas F; Zhou, Ying; McCormick, Beryl; Powell, Simon N; Ho, Alice Y

2012-10-01

To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses. Published by Elsevier Inc.

Cosmic Radiation Exposure of Biological Test Systems During the EXPOSE-E Mission

PubMed Central

Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-01-01

Abstract In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5–12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples. Key Words: Space radiation—Dosimetry—Passive radiation detectors—Thermoluminescence—EXPOSE-E. Astrobiology 12, 387–392. PMID:22680685

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

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

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

Calculation of organ doses from breast cancer radiotherapy: a Monte Carlo study

PubMed Central

Berris, T.; Mazonakis, M.; Stratakis, J.; Tzedakis, A.; Fasoulaki, A.

2013-01-01

The current study aimed to: a) utilize Monte Carlo simulation methods for the assessment of radiation doses imparted to all organs at risk to develop secondary radiation induced cancer, for patients undergoing radiotherapy for breast cancer; and b) evaluate the effect of breast size on dose to organs outside the irradiation field. A simulated linear accelerator model was generated. The in‐field accuracy of the simulated photon beam properties was verified against percentage depth dose (PDD) and dose profile measurements on an actual water phantom. Off‐axis dose calculations were verified with thermoluminescent dosimetry (TLD) measurements on a humanoid physical phantom. An anthropomorphic mathematical phantom was used to simulate breast cancer radiotherapy with medial and lateral fields. The effect of breast size on the calculated organ dose was investigated. Local differences between measured and calculated PDDs and dose profiles did not exceed 2% for the points at depths beyond the depth of maximum dose and the plateau region of the profile, respectively. For the penumbral regions of the dose profiles, the distance to agreement (DTA) did not exceed 2 mm. The mean difference between calculated out‐of‐field doses and TLD measurements was 11.4%±5.9%. The calculated doses to peripheral organs ranged from 2.32 cGy up to 161.41 cGy depending on breast size and thus the field dimensions applied, as well as the proximity of the organs to the primary beam. An increase to the therapeutic field area by 50% to account for the large breast led to a mean organ dose elevation by up to 85.2% for lateral exposure. The contralateral breast dose ranged between 1.4% and 1.6% of the prescribed dose to the tumor. Breast size affects dose deposition substantially. PACS numbers: 87.10.rt, 87.56.bd, 87.53.Bn, 87.55.K‐, 87.55.ne, 87.56.jf, 87.56.J‐ PMID:23318389

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

Carotid-Sparing Intensity-Modulated Radiotherapy for Early-Stage Squamous Cell Carcinoma of the True Vocal Cord

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

Chera, Bhishamjit S.; Amdur, Robert J., E-mail: amdurr@shands.ufl.ed; Morris, Christopher G.

2010-08-01

Purpose: To compare radiation doses to carotid arteries among various radiotherapy techniques for treatment of early-stage squamous cell carcinoma (SCC) of the true vocal cords. Methods and Materials: Five patients were simulated using computed tomography (CT). Clinical and planning target volumes (PTV) were created for bilateral and unilateral stage T1 vocal cord cancers. Planning risk volumes for the carotid arteries and spinal cord were delineated. For each patient, three treatment plans were designed for bilateral and unilateral target volumes: opposed laterals (LATS), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT), for a total of 30 plans. More than 95% ofmore » the PTV received the prescription dose (63Gy at 2.25 Gy per treatment). Results: Carotid dose was lowest with IMRT. With a bilateral vocal cord target, the median carotid dose was 10Gy with IMRT vs. 25 Gy with 3DCRT and 38 Gy with LATS (p < 0.05); with a unilateral target, the median carotid dose was 4 Gy with IMRT vs. 19 Gy with 3DCRT and 39 Gy with LATS (p < 0.05). The dosimetric tradeoff with IMRT is a small area of high dose in the PTV. The worst heterogeneity results were at a maximum point dose of 80 Gy (127%) in a unilateral target that was close to the carotid. Conclusions: There is no question that IMRT can reduce the dose to the carotid arteries in patients with early-stage vocal cord cancer. The question is whether the potential advantage of reducing the carotid dose outweighs the risk of tumor recurrence due to contouring errors and organ motion and the risk of complications from dose heterogeneity.« less

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

Gong, J; Sarwan, R; Pavord, D

Purpose: To quantitatively compare low dose spillage outside of PTV edge in arc therapy modalities Methods: The machines used in the study are Tomotherapy Hi-Arc and Varian 21EX with millennium120 MLC. TPS are TomoPlaning and RayStation for VMAT, respectively. The phantom is a 30cm diameter cylindrical solid water (TOMOTHERAPY, TOMOPHANTOM ASSY). The PTV is 4cm length with ellipsoidal sectional shape with major axis=5cm, minor axis=3cm in the axial plane and reversed in the coronal plane. The PTV volume is created with interpolation. It is located at the center of the phantom. The prescribed dose is 1000x5 cGy to 95% themore » PTV. The isocenter is set co-centered with the PTV. EBT-3 film was used to measure iso-dose lines at the center plane. Film dosimetry is performed with the RIT, v6.2. Results: the study shows: (1) dose falloff gradient is usually uneven, depending on the PTV shape in the gantry rotation plane. For an elliptical shape, the low dose spillage is wider in the minor axis direction than that in the major axis direction. The more a shape is closer to circular, the more even gradient is all directions; (2)for a circular shape (CAX plane in this study), the maximum dose in % of Rx dose at 2cm from PTV is 55% for Tomo, vs. 70% for VMAT (3) the most rapid dose falloff rang is between 95%–80% IDL for both modalities. Conclusion: Tomo has more rapid dose falloff outside of PTV. In some areas, the gradient is double for Tomo helical than that for LINAC VMAT at same points. Future work will examine the differences between optimization of doses and inherent delivery limitations.« less

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

PubMed

Koffarnus, Mikhail N; Winger, Gail

2015-07-01

The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

PubMed Central

Li, Zijian; Jennings, Aaron A.

2017-01-01

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

Lung motion estimation using dynamic point shifting: An innovative model based on a robust point matching algorithm

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

Yi, Jianbing, E-mail: yijianbing8@163.com; Yang, Xuan, E-mail: xyang0520@263.net; Li, Yan-Ran, E-mail: lyran@szu.edu.cn

2015-10-15

Purpose: Image-guided radiotherapy is an advanced 4D radiotherapy technique that has been developed in recent years. However, respiratory motion causes significant uncertainties in image-guided radiotherapy procedures. To address these issues, an innovative lung motion estimation model based on a robust point matching is proposed in this paper. Methods: An innovative robust point matching algorithm using dynamic point shifting is proposed to estimate patient-specific lung motion during free breathing from 4D computed tomography data. The correspondence of the landmark points is determined from the Euclidean distance between the landmark points and the similarity between the local images that are centered atmore » points at the same time. To ensure that the points in the source image correspond to the points in the target image during other phases, the virtual target points are first created and shifted based on the similarity between the local image centered at the source point and the local image centered at the virtual target point. Second, the target points are shifted by the constrained inverse function mapping the target points to the virtual target points. The source point set and shifted target point set are used to estimate the transformation function between the source image and target image. Results: The performances of the authors’ method are evaluated on two publicly available DIR-lab and POPI-model lung datasets. For computing target registration errors on 750 landmark points in six phases of the DIR-lab dataset and 37 landmark points in ten phases of the POPI-model dataset, the mean and standard deviation by the authors’ method are 1.11 and 1.11 mm, but they are 2.33 and 2.32 mm without considering image intensity, and 1.17 and 1.19 mm with sliding conditions. For the two phases of maximum inhalation and maximum exhalation in the DIR-lab dataset with 300 landmark points of each case, the mean and standard deviation of target registration errors on the 3000 landmark points of ten cases by the authors’ method are 1.21 and 1.04 mm. In the EMPIRE10 lung registration challenge, the authors’ method ranks 24 of 39. According to the index of the maximum shear stretch, the authors’ method is also efficient to describe the discontinuous motion at the lung boundaries. Conclusions: By establishing the correspondence of the landmark points in the source phase and the other target phases combining shape matching and image intensity matching together, the mismatching issue in the robust point matching algorithm is adequately addressed. The target registration errors are statistically reduced by shifting the virtual target points and target points. The authors’ method with consideration of sliding conditions can effectively estimate the discontinuous motion, and the estimated motion is natural. The primary limitation of the proposed method is that the temporal constraints of the trajectories of voxels are not introduced into the motion model. However, the proposed method provides satisfactory motion information, which results in precise tumor coverage by the radiation dose during radiotherapy.« less

Lung motion estimation using dynamic point shifting: An innovative model based on a robust point matching algorithm.

PubMed

Yi, Jianbing; Yang, Xuan; Chen, Guoliang; Li, Yan-Ran

2015-10-01

Image-guided radiotherapy is an advanced 4D radiotherapy technique that has been developed in recent years. However, respiratory motion causes significant uncertainties in image-guided radiotherapy procedures. To address these issues, an innovative lung motion estimation model based on a robust point matching is proposed in this paper. An innovative robust point matching algorithm using dynamic point shifting is proposed to estimate patient-specific lung motion during free breathing from 4D computed tomography data. The correspondence of the landmark points is determined from the Euclidean distance between the landmark points and the similarity between the local images that are centered at points at the same time. To ensure that the points in the source image correspond to the points in the target image during other phases, the virtual target points are first created and shifted based on the similarity between the local image centered at the source point and the local image centered at the virtual target point. Second, the target points are shifted by the constrained inverse function mapping the target points to the virtual target points. The source point set and shifted target point set are used to estimate the transformation function between the source image and target image. The performances of the authors' method are evaluated on two publicly available DIR-lab and POPI-model lung datasets. For computing target registration errors on 750 landmark points in six phases of the DIR-lab dataset and 37 landmark points in ten phases of the POPI-model dataset, the mean and standard deviation by the authors' method are 1.11 and 1.11 mm, but they are 2.33 and 2.32 mm without considering image intensity, and 1.17 and 1.19 mm with sliding conditions. For the two phases of maximum inhalation and maximum exhalation in the DIR-lab dataset with 300 landmark points of each case, the mean and standard deviation of target registration errors on the 3000 landmark points of ten cases by the authors' method are 1.21 and 1.04 mm. In the EMPIRE10 lung registration challenge, the authors' method ranks 24 of 39. According to the index of the maximum shear stretch, the authors' method is also efficient to describe the discontinuous motion at the lung boundaries. By establishing the correspondence of the landmark points in the source phase and the other target phases combining shape matching and image intensity matching together, the mismatching issue in the robust point matching algorithm is adequately addressed. The target registration errors are statistically reduced by shifting the virtual target points and target points. The authors' method with consideration of sliding conditions can effectively estimate the discontinuous motion, and the estimated motion is natural. The primary limitation of the proposed method is that the temporal constraints of the trajectories of voxels are not introduced into the motion model. However, the proposed method provides satisfactory motion information, which results in precise tumor coverage by the radiation dose during radiotherapy.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans

PubMed Central

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q.; Otrakji, Alexi; Kalra, Mannudeep K.; Xu, X. George; Liu, Bob

2014-01-01

Purpose: To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Methods: Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. Results: The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8% − 25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2 ± 3.3 and 16.5 ± 2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. Conclusions: This study revealed the complexity of CT dose fluctuation and variation with a human cadaver. PMID:25186398

Sci—Sat AM: Stereo — 02: Implementation of a VMAT class solution for kidney SBRT

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

Sonier, M; Lalani, N; Korol, R

An emerging treatment option for inoperable primary renal cell carcinoma and oligometastatic adrenal lesions is stereotactic body radiation therapy (SBRT). At our center, kidney SBRT treatments were originally planned with IMRT. The goal was to plan future patients using VMAT to improve treatment delivery efficiency. The purpose of this work was twofold: 1) to develop a VMAT class solution for the treatment of kidney SBRT; and, 2) to assess VMAT plan quality when compared to IMRT plans. Five patients treated with IMRT for kidney SBRT were reviewed and replanned in Pinnacle using a single VMAT arc with a 15° collimatormore » rotation, constrained leaf motion and 4° gantry spacing. In comparison, IMRT plans utilized 7–9 6MV beams, with various collimator rotations and up to 2 non-coplanar beams for maximum organ-at-risk (OAR) sparing. Comparisons were made concerning target volume conformity, homogeneity, dose to OARs, treatment time and monitor units (MUs). There was no difference in MUs; however, VMAT reduced the treatment time from 13.0±2.6min, for IMRT, to 4.0±0.9min. The collection of target and OAR constraints and SmartArc parameters, produced a class solution that generated VMAT plans with increased target homogeneity and improved 95% conformity index calculated at < 1.2. In general, the VMAT plans displayed a reduced maximum point dose to nearby OARs with increased intermediate dose to distant OARs. Overall, the introduction of a VMAT class solution for kidney SBRT improves efficiency by reducing treatment planning and delivery time.« less

SU-E-T-01: 2-D Characterization of DLG Among All MLC Leaf Pairs

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

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: The aim of this study is to evaluate the variation of dosimetric leaf-gap (DLG) along the travel path of each MLC leaf pair. This study evaluates whether the spatial variations in DLG could cause dose differences between TPS-calculated and measured dose. Methods: The 6MV DLG values were measured for all leaf pairs in the direction of leaf motion using a 2-D diode array and 0.6cc ion chamber. These measurements were performed on two Varian Linacs, employing the Millennium 120-leaf MLC and a 2-D-DLG variation map was created via in-house software. Several test plans were created with sweeping MLC fieldsmore » using constant gaps from 2mm to 10mm and corrected for 2-D variation utilizing in-house software. Measurements were performed utilizing the MapCHECK at 5.0cm depth for plans with and without the 2-D DLG correction and compared to the TPS calculated dose via gamma analysis (3%/3mm). Results: The measured DLGs for the middle 40 MLC leaf pairs (0.5cm width) were very similar along the central superior-inferior axis, with maximum variation of 0.2mm. The outer 20 MLC leaf pairs (1.0cm width) have DLG values from 0.32mm (mean) to 0.65mm (maximum) lower than the central leaf-pair, depending on off-axis distance. Gamma pass rates for the 2mm, 4mm, and 6mm sweep plans increased by 23.2%, 28.7%, and 26.0% respectively using the 2-D-DLG correction. The most improved dose points occur in areas modulated by the 1.0cm leaf-pairs. The gamma pass rate for the 10mm sweep plan increased by only 7.7%, indicating that the 2D variation becomes less significant for dynamic plans with larger MLC gaps. Conclusion: Fluences residing significantly off-axis with narrow sweeping gaps may exhibit significant variations from planned dose due to large differences between the true DLG exhibited by the 1.0cm leaf-pairs versus the constant DLG value utilized by the TPS for dose calculation.« less

PROBABILISTIC SAFETY ASSESSMENT OF OPERATIONAL ACCIDENTS AT THE WASTE ISOLATION PILOT PLANT

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

Rucker, D.F.

2000-09-01

This report presents a probabilistic safety assessment of radioactive doses as consequences from accident scenarios to complement the deterministic assessment presented in the Waste Isolation Pilot Plant (WIPP) Safety Analysis Report (SAR). The International Council of Radiation Protection (ICRP) recommends both assessments be conducted to ensure that ''an adequate level of safety has been achieved and that no major contributors to risk are overlooked'' (ICRP 1993). To that end, the probabilistic assessment for the WIPP accident scenarios addresses the wide range of assumptions, e.g. the range of values representing the radioactive source of an accident, that could possibly have beenmore » overlooked by the SAR. Routine releases of radionuclides from the WIPP repository to the environment during the waste emplacement operations are expected to be essentially zero. In contrast, potential accidental releases from postulated accident scenarios during waste handling and emplacement could be substantial, which necessitates the need for radiological air monitoring and confinement barriers (DOE 1999). The WIPP Safety Analysis Report (SAR) calculated doses from accidental releases to the on-site (at 100 m from the source) and off-site (at the Exclusive Use Boundary and Site Boundary) public by a deterministic approach. This approach, as demonstrated in the SAR, uses single-point values of key parameters to assess the 50-year, whole-body committed effective dose equivalent (CEDE). The basic assumptions used in the SAR to formulate the CEDE are retained for this report's probabilistic assessment. However, for the probabilistic assessment, single-point parameter values were replaced with probability density functions (PDF) and were sampled over an expected range. Monte Carlo simulations were run, in which 10,000 iterations were performed by randomly selecting one value for each parameter and calculating the dose. Statistical information was then derived from the 10,000 iteration batch, which included 5%, 50%, and 95% dose likelihood, and the sensitivity of each assumption to the calculated doses. As one would intuitively expect, the doses from the probabilistic assessment for most scenarios were found to be much less than the deterministic assessment. The lower dose of the probabilistic assessment can be attributed to a ''smearing'' of values from the high and low end of the PDF spectrum of the various input parameters. The analysis also found a potential weakness in the deterministic analysis used in the SAR, a detail on drum loading was not taken into consideration. Waste emplacement operations thus far have handled drums from each shipment as a single unit, i.e. drums from each shipment are kept together. Shipments typically come from a single waste stream, and therefore the curie loading of each drum can be considered nearly identical to that of its neighbor. Calculations show that if there are large numbers of drums used in the accident scenario assessment, e.g. 28 drums in the waste hoist failure scenario (CH5), then the probabilistic dose assessment calculations will diverge from the deterministically determined doses. As it is currently calculated, the deterministic dose assessment assumes one drum loaded to the maximum allowable (80 PE-Ci), and the remaining are 10% of the maximum. The effective average of drum curie content is therefore less in the deterministic assessment than the probabilistic assessment for a large number of drums. EEG recommends that the WIPP SAR calculations be revisited and updated to include a probabilistic safety assessment.« less

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

PubMed

Alistar, Angela; Morris, Bonny B; Desnoyer, Rodwige; Klepin, Heidi D; Hosseinzadeh, Keyanoosh; Clark, Clancy; Cameron, Amy; Leyendecker, John; D'Agostino, Ralph; Topaloglu, Umit; Boteju, Lakmal W; Boteju, Asela R; Shorr, Rob; Zachar, Zuzana; Bingham, Paul M; Ahmed, Tamjeed; Crane, Sandrine; Shah, Riddhishkumar; Migliano, John J; Pardee, Timothy S; Miller, Lance; Hawkins, Gregory; Jin, Guangxu; Zhang, Wei; Pasche, Boris

2017-06-01

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m 2 , leucovorin at 400 mg/m 2 , irinotecan at 140 mg/m 2 , and fluorouracil 400 mg/m 2 bolus followed by 2400 mg/m 2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m 2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m 2 . The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m 2 , and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m 2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

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

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

SU-E-T-138: Dosimetric Verification For Volumetric Modulated Arc Therapy Cranio-Spinal Irradiation Technique

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

Goksel, E; Bilge, H; Yildiz, Yarar

2014-06-01

Purpose: Dosimetric feasibility of cranio-spinal irradiation with volumetric modulated arc therapy (VMAT-CSI) technique in terms of dose distribution accuracy was investigated using a humanlike phantom. Methods: The OARs and PTV volumes for the Rando phantom were generated on supine CT images. Eclipse (version 8.6) TPS with AAA algorithm was used to create the treatment plan with VMAT-CSI technique. RapidArc plan consisted of cranial, upper spinal (US) and lower spinal (LS) regions that were optimized in the same plan. US field was overlapped by 3cm with cranial and LS fields. Three partial arcs for cranium and 1 full arc for eachmore » US and LS region were used. The VMAT-CSI dose distribution inside the Rando phantom was measured with thermoluminescent detectors (TLD) and film dosimetry, and was compared to the calculated doses of field junctions, target and OARs. TLDs were placed at 24 positions throughout the phantom. The measured TLD doses were compared to the calculated point doses. Planar doses for field junctions were verified with Gafchromic films. Films were analyzed in PTW Verisoft application software using gamma analysis method with the 4 mm distance to agreement (DTA) and 4% dose agreement criteria. Results: TLD readings demonstrated accurate dose delivery, with a median dose difference of -0.3% (range: -8% and 12%) when compared with calculated doses for the areas inside the treatment portal. The maximum dose difference was 12% higher in testicals that are outside the treatment region and 8% lower in lungs where the heterogeinity was higher. All planar dose verifications for field junctions passed the gamma analysis and measured planar dose distributions demonstrated average 97% agreement with calculated doses. Conclusion: The dosimetric data verified with TLD and film dosimetry shows that VMAT-CSI technique provides accurate dose distribution and can be delivered safely.« less

SU-E-T-795: Validations of Dose Calculation Accuracy of Acuros BV in High-Dose-Rate (HDR) Brachytherapy with a Shielded Cylinder Applicator Using Monte Carlo Simulation

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

Li, Y; Department of Engineering Physics, Tsinghua University, Beijing; Tian, Z

Purpose: Acuros BV has become available to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity considered by solving the Boltzmann transport equation. In this work, we performed validation studies regarding the dose calculation accuracy of Acuros BV in cases with a shielded cylinder applicator using Monte Carlo (MC) simulations. Methods: Fifteen cases were considered in our studies, covering five different diameters of the applicator and three different shielding degrees. For each case, a digital phantom was created in Varian BrachyVision with the cylinder applicator inserted in the middle of a large water phantom. A treatment plan withmore » eight dwell positions was generated for these fifteen cases. Dose calculations were performed with Acuros BV. We then generated a voxelized phantom of the same geometry, and the materials were modeled according to the vendor’s specifications. MC dose calculations were then performed using our in-house developed fast MC dose engine for HDR brachytherapy (gBMC) on a GPU platform, which is able to simulate both photon transport and electron transport in a voxelized geometry. A phase-space file for the Ir-192 HDR source was used as a source model for MC simulations. Results: Satisfactory agreements between the dose distributions calculated by Acuros BV and those calculated by gBMC were observed in all cases. Quantitatively, we computed point-wise dose difference within the region that receives a dose higher than 10% of the reference dose, defined to be the dose at 5mm outward away from the applicator surface. The mean dose difference was ∼0.45%–0.51% and the 95-percentile maximum difference was ∼1.24%–1.47%. Conclusion: Acuros BV is able to accurately perform dose calculations in HDR brachytherapy with a shielded cylinder applicator.« less

Dosimetric Evaluation Between Megavoltage Cone-Beam Computed Tomography and Body Mass Index for Intracranial, Thoracic, and Pelvic Localization

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

VanAntwerp, April E.; Raymond, Sarah M., E-mail: raymons9@ccf.org; Addington, Mark C.

2011-10-01

The aim of this study was to evaluate radiation dose for organs at risk (OAR) within the cranium, thorax, and pelvis from megavoltage cone-beam computed tomography (MV-CBCT). Using a clinical treatment planning system, CBCT doses were calculated from 60 patient datasets using 27.4 x 27.4 cm{sup 2} field size and 200{sup o} arc length. The body mass indices (BMIs) for these patients range from 17.2-48.4 kg/m{sup 2}. A total of 60 CBCT plans were created and calculated with heterogeneity corrections, with monitor units (MU) that varied from 8, 4, and 2 MU per plan. The isocenters of these plans weremore » placed at defined anatomical structures. The maximum dose, dose to the isocenter, and mean dose to the selected critical organs were analyzed. The study found that maximum and isocenter doses were weakly associated with BMI, but linearly associated with the total MU. Average maximum/isocenter doses in the cranium were 10.0 ({+-} 0.18)/7.0 ({+-} 0.08) cGy, 5.0 ({+-} 0.09)/3.5 ({+-} 0.05) cGy, and 2.5 ({+-} .04)/1.8 ({+-} 0.05) cGy for 8, 4, and 2 MU, respectively. Similar trends but slightly larger maximum/isocenter doses were found in the thoracic and pelvic regions. For the cranial region, the average mean doses with a total of 8 MU to the eye, lens, and brain were 9.7 ({+-} 0.12) cGy, 9.1 ({+-} 0.16) cGy, and 7.2 ({+-} 0.10) cGy, respectively. For the thoracic region, the average mean doses to the lung, heart, and spinal cord were 6.6 ({+-} 0.05) cGy, 6.9 ({+-} 1.2) cGy, and 4.7 ({+-} 0.8) cGy, respectively. For the pelvic region, the average mean dose to the femoral heads was 6.4 ({+-} 1.1) cGy. The MV-CBCT doses were linearly associated with the total MU but weakly dependent on patients' BMIs. Daily MV-CBCT has a cumulative effect on the total body dose and critical organs, which should be carefully considered for clinical impacts.« less

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

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

Emergency department patient knowledge concerning acetaminophen (paracetamol) in over-the-counter and prescription analgesics.

PubMed

Fosnocht, D; Taylor, J R; Caravati, E M

2008-04-01

This study was designed to evaluate patient knowledge of the acetaminophen (paracetamol) content of commonly used pain medications and the maximum daily recommended dose of acetaminophen. A prospective, convenience sample of emergency department patients were enrolled. Data were recorded using a standardised questionnaire over 4 months. 1009 patients were enrolled. 492 patients (49%) did not know if Tylenol contained acetaminophen (paracetamol). The majority (66-90%) of patients did not know if Lortab, Vicodin, Percocet, non-aspirin pain reliever, ibuprofen, Motrin, or Advil contained acetaminophen. 568 patients (56%) reported not knowing the maximum daily dose of acetaminophen and only 71 patients (7%) reported the correct daily dose. Patient knowledge of the acetaminophen content of commonly used analgesic medications and its maximum recommended daily dose is limited. This may contribute to unintentional repeated supratherapeutic ingestion (RSTI) of acetaminophen, or overdose.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis.

PubMed

Freise, Kevin J; Dunbar, Martin; Jones, Aksana K; Hoffman, David; Enschede, Sari L Heitner; Wong, Shekman; Salem, Ahmed Hamed

2016-10-01

Venetoclax (ABT-199/GDC-0199) is a selective first-in-class B cell lymphoma-2 inhibitor being developed for the treatment of hematological malignancies. The aim of this study was to determine the potential of venetoclax to prolong the corrected QT (QTc) interval and to evaluate the relationship between systemic venetoclax concentration and QTc interval. The study population included 176 male and female patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 105) or non-Hodgkin's lymphoma (n = 71) enrolled in a phase 1 safety, pharmacokinetic, and efficacy study. Electrocardiograms were collected in triplicate at time-matched points (2, 4, 6, and 8 h) prior to the first venetoclax administration and after repeated venetoclax administration to achieve steady state conditions. Venetoclax doses ranged from 100 to 1200 mg daily. Plasma venetoclax samples were collected after steady state electrocardiogram measurements. The mean and upper bound of the 2-sided 90 % confidence interval (CI) QTc change from baseline were <5 and <10 ms, respectively, at all time points and doses (<400, 400, and >400 mg). Three subjects had single QTc values >500 ms and/or ΔQTc > 60 ms. The effect of venetoclax concentration on both ΔQTc and QTc was not statistically significant (P > 0.05). At the mean maximum concentrations achieved with therapeutic (400 mg) and supra-therapeutic (1200 mg) venetoclax doses, the estimated drug effects on QTc were 0.137 (90 % CI [-1.01 to 1.28]) and 0.263 (90 % CI [-1.92 to 2.45]) ms, respectively. Venetoclax does not prolong QTc interval even at supra-therapeutic doses, and there is no relationship between venetoclax concentrations and QTc interval.

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing

PubMed Central

Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2017-01-01

Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing. PMID:28771571

Effect of low-power gallium-aluminum-arsenium noncoherent light (640 nm) on muscle activity: a clinical study.

PubMed

Kelencz, Carlos A; Muñoz, Ingrid S S; Amorim, César F; Nicolau, Renata A

2010-10-01

Studies have shown the significant effects of electromagnetic irradiation in the visible region, with laser as an irradiation source. However, the effect of LEDs (light-emitting diodes) irradiation in similar wavelengths is not known. The purpose of this clinical study was to verify the effects of the LED (640 nm with 40 nm full bandwidth at half maximum) on muscle activity. The study was done with 30 test subjects, of both genders, aged 23 ± 3 years, with a mean weight of 60 kg, divided into three groups (n = 10). Fatigue was induced through the maximum power of a bite, for 60 s in two overlaid occlusal platforms, coupled to a load cell and to a biologic signal-acquisition device. LED irradiation of the right masseter muscle was applied to all subjects. The left muscle received placebo treatment. Irradiation was applied in eight points on the right masseter muscle (transcutaneous), 1.044 J per point, 2.088 J per point, or 3.132 J per point, 0.116 W, 0.522 cm(2) spot size, 0.816 cm spot Ø, continuous wave, perpendicular to the skin. An increase in muscle activity was observed after irradiation with 1.044 J per point (p < 0.05). A significant increase (p < 0.01) in the time before fatigue was observed in the irradiated muscle with 2.088 J per point, without a change in the force of contraction (p > 0.05). This change was not observed with 1.044 J per point and 3.132 J per point. The results suggest a dose-dependent relation with this kind of noncoherent irradiation in the red region of the electromagnetic spectrum in the muscle-fatigue process. It was concluded that LED can be used as a clinical tool to increase muscle activity (1.044 J per point) and to prevent fatigue (2.088 J per point), without change in the muscle force.

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer

NASA Astrophysics Data System (ADS)

Yang, J.; Li, J.; Chen, L.; Price, R.; McNeeley, S.; Qin, L.; Wang, L.; Xiong, W.; Ma, C.-M.

2005-03-01

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (Dmin), the dose received by 98% of the target volume (D98), dose at the isocentre (Diso), mean target dose (Dmean) and the maximum critical structure dose (Dmax) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

A maximum power point tracking algorithm for buoy-rope-drum wave energy converters

NASA Astrophysics Data System (ADS)

Wang, J. Q.; Zhang, X. C.; Zhou, Y.; Cui, Z. C.; Zhu, L. S.

2016-08-01

The maximum power point tracking control is the key link to improve the energy conversion efficiency of wave energy converters (WEC). This paper presents a novel variable step size Perturb and Observe maximum power point tracking algorithm with a power classification standard for control of a buoy-rope-drum WEC. The algorithm and simulation model of the buoy-rope-drum WEC are presented in details, as well as simulation experiment results. The results show that the algorithm tracks the maximum power point of the WEC fast and accurately.

Impact of knee support and shape of tabletop on rectum and prostate position

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

Steenbakkers, Roel; Duppen, Joop C.; Betgen, Anja

2004-12-01

Purpose: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. Methods and materials: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differencesmore » of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. Results: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 deg (SEM 0.8 deg ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. Conclusions: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.« less

Utilizing Maximum Power Point Trackers in Parallel to Maximize the Power Output of a Solar (Photovoltaic) Array

DTIC Science & Technology

2012-12-01

photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase... photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase the power output of the solar array. Currently, most military... MPPT ) is an optimizing circuit that is used in conjunction with photovoltaic (PV) arrays to achieve the maximum delivery of power from the array

Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

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

Lobb, Eric, E-mail: eclobb2@gmail.com

2014-04-01

The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

PubMed

Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; de Crevoisier, Renaud

2015-01-09

Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p<0.001). During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans

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

Zhang, Da; Padole, Atul; Li, Xinhua

2014-09-15

Purpose: To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Methods: Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin dosesmore » were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. Results: The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8% − 25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2 ± 3.3 and 16.5 ± 2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. Conclusions: This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.« less

Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer

PubMed Central

Torkelson, Carolyn J.; Sweet, Erin; Martzen, Mark R.; Sasagawa, Masa; Wenner, Cynthia A.; Gay, Juliette; Putiri, Amy; Standish, Leanna J.

2012-01-01

Introduction. Orally administered preparations from the Trametes versicolor (Tv) mushroom have been hypothesized to improve immune response in women with breast cancer after standard chemotherapy and radiotherapy. Methods. A phase I, two-center, dose escalation study was done to determine the maximum tolerated dose of a Tv preparation when taken daily in divided doses for 6 weeks after recent completion of radiotherapy. Eleven participants were recruited and nine women completed the study. Each cohort was comprised of three participants given one of three doses of Tv (3, 6, or 9 grams). Immune data was collected pre- and postradiation, at 3 on-treatment time points and after a 3-week washout. Results. Nine adverse events were reported (7 mild, 1 moderate, and 1 severe), suggesting that Tv was well tolerated. Immunological results indicated trends in (1) increased lymphocyte counts at 6 and 9 grams/day; (2) increased natural killer cell functional activity at 6 grams/day; (3) dose-related increases in CD8+ T cells and CD19+ B cells , but not CD4+ T cells or CD16+56+ NK cells. Conclusion. These findings show that up to 9 grams/day of a Tv preparation is safe and tolerable in women with breast cancer in the postprimary treatment setting. This Tv preparation may improve immune status in immunocompromised breast cancer patients following standard primary oncologic treatment. PMID:22701186

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

PubMed

Robinson, Jennifer G; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S; Langslet, Gisle; Raal, Frederick J; El Shahawy, Mahfouz; Koren, Michael J; Lepor, Norman E; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J P

2015-04-16

Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02). Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor(R)-medicated feed therapy (20 mg/kg BW/d for 10 days)

USGS Publications Warehouse

Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.

2013-01-01

Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor®-medicated feed therapy

USGS Publications Warehouse

Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.

2013-01-01

Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PubMed

Anagnostopoulos, G; Baltas, D; Geretschlaeger, A; Martin, T; Papagiannis, P; Tselis, N; Zamboglou, N

2003-11-15

To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

PubMed

Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

PubMed

Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

2015-01-01

To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

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

PubMed

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

2017-12-01

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

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

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

Bhandare, N.

2014-06-01

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

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer

PubMed Central

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang

2016-01-01

Lessons Learned This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity. These findings provide clinicians with evidence for application of higher-dose icotinib. Background. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100–200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Methods. Twenty-six patients with advanced NSCLC were treated at doses of 250–625 mg three times daily The EGFR mutation test was not mandatory in this study. Results. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (Tmax) ranged from 1 to 3 hours (1.5–4 hours) after multiple doses. The t1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. Conclusion. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. PMID:27789778

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.

PubMed

Woo, Young Sup; Shim, In Hee; Lee, Sang-Yeol; Lee, Dae-Bo; Kim, Moon-Doo; Jung, Young-Eun; Lee, Jonghun; Won, Seunghee; Jon, Duk-In; Bahk, Won-Myong

2017-05-31

Although aripiprazole has been widely used to treat various psychiatric disorders, little is known about the adequate dosage for Asian patients in clinical practice. Hence, we evaluated the initial and maximum doses of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean psychiatric inpatients in clinical practice. In this retrospective study, we reviewed the medical records of patients who were hospitalized in five university hospitals in Korea from March 2004 to December 2014. The psychiatric diagnosis according to the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition during index hospitalization and the initial and maximum doses of aripiprazole were evaluated. There were 74 patients in Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave 3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole in each diagnostic group were not significantly different among Waves 1, 2, and 3. The relatively low initial doses of aripiprazole documented in our study may reflect a strategy by clinicians to minimize the side effects associated with aripiprazole use, such as akathisia.

[Doses to organs at risk in conformational and stereotactic body radiation therapy: Liver].

PubMed

Debbi, K; Janoray, G; Scher, N; Deutsch, É; Mornex, F

2017-10-01

The liver is an essential organ that ensures many vital functions such as metabolism of bilirubin, glucose, lipids, synthesis of coagulation factors, destruction of many toxins, etc. The hepatic parenchyma can be irradiated during the management of digestive tumors, right basithoracic, esophagus, abdomen in toto or TBI. In addition, radiotherapy of the hepatic area, which is mainly stereotactic, now occupies a central place in the management of primary or secondary hepatic tumors. Irradiation of the whole liver, or part of it, may be complicated by radiation-induced hepatitis. It is therefore necessary to respect strict dosimetric constraints both in stereotactic and in conformational irradiation in order to limit the undesired irradiation of the hepatic parenchyma which may vary according to the treatment techniques, the basic hepatic function or the lesion size. The liver is an organ with a parallel architecture, so the average tolerable dose in the whole liver should be considered rather than the maximum tolerable dose at one point. The purpose of this article is to propose a development of dose recommendations during conformation or stereotactic radiotherapy of the liver. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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

PubMed

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

2017-08-01

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

Three-dimensional dosimetric considerations from different point A definitions in cervical cancer low-dose-rate brachytherapy

PubMed Central

Chen, Ting; Kim, Leonard H.; Nelson, Carl; Gabel, Molly; Narra, Venkat; Haffty, Bruce; Yue, Ning J.

2013-01-01

Purpose To investigate the dosimetric difference due to the different point A definitions in cervical cancer low-dose-rate (LDR) intracavitary brachytherapy. Material and methods Twenty CT-based LDR brachytherapy plans of 11 cervical patients were retrospectively reviewed. Two plans with point As following the modified Manchester system which defines point A being 2 cm superior to the cervical os along the tandem and 2 cm lateral (Aos), and the American Brachytherapy Society (ABS) guideline definition in which the point A is 2 cm superior to the vaginal fornices instead of os (Aovoid) were generated. Using the same source strength, two plans prescribed the same dose to Aos and Aovoid. Dosimetric differences between plans including point A dose rate, treatment volume encompassed by the prescription isodose line (TV), and dose rate of 2 cc of the rectum and bladder to the prescription dose were measured. Results On average Aovoid was 8.9 mm superior to Aos along the tandem direction with a standard deviation of 5.4 mm. With the same source strength and arrangement, Aos dose rate was 19% higher than Aovoid dose rate. The average TV(Aovoid) was 118.0 cc, which was 30% more than the average TV(Aos) of 93.0 cc. D2cc/D(Aprescribe) increased from 51% to 60% for rectum, and increased from 89% and 106% for bladder, if the prescription point changed from Aos to Aovoid. Conclusions Different point A definitions lead to significant dose differences. Careful consideration should be given when changing practice from one point A definition to another, to ensure dosimetric and clinical equivalency from the previous clinical experiences. PMID:24474971

Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

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

Shwetha, Bondel; Ravikumar, Manickam, E-mail: drravikumarm@gmail.com; Supe, Sanjay S.

2012-04-01

Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder,more » and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.« less

SU-E-T-169: Characterization of Pacemaker/ICD Dose in SAVI HDR Brachytherapy

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

Kalavagunta, C; Lasio, G; Yi, B

2015-06-15

Purpose: It is important to estimate dose to pacemaker (PM)/Implantable Cardioverter Defibrillator (ICD) before undertaking Accelerated Partial Breast Treatment using High Dose Rate (HDR) brachytherapy. Kim et al. have reported HDR PM/ICD dose using a single-source balloon applicator. To the authors knowledge, there have so far not been any published PM/ICD dosimetry literature for the Strut Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA). This study aims to fill this gap by generating a dose look up table (LUT) to predict maximum dose to the PM/ICD in SAVI HDR brachytherapy. Methods: CT scans for 3D dosimetric planning were acquiredmore » for four SAVI applicators (6−1-mini, 6−1, 8−1 and 10−1) expanded to their maximum diameter in air. The CT datasets were imported into the Elekta Oncentra TPS for planning and each applicator was digitized in a multiplanar reconstruction window. A dose of 340 cGy was prescribed to the surface of a 1 cm expansion of the SAVI applicator cavity. Cartesian coordinates of the digitized applicator were determined in the treatment leading to the generation of a dose distribution and corresponding distance-dose prediction look up table (LUT) for distances from 2 to 15 cm (6-mini) and 2 to 20 cm (10–1).The deviation between the LUT doses and the dose to the cardiac device in a clinical case was evaluated. Results: Distance-dose look up table were compared to clinical SAVI plan and the discrepancy between the max dose predicted by the LUT and the clinical plan was found to be in the range (−0.44%, 0.74%) of the prescription dose. Conclusion: The distance-dose look up tables for SAVI applicators can be used to estimate the maximum dose to the ICD/PM, with a potential usefulness for quick assessment of dose to the cardiac device prior to applicator placement.« less

A new concept of pencil beam dose calculation for 40-200 keV photons using analytical dose kernels.

PubMed

Bartzsch, Stefan; Oelfke, Uwe

2013-11-01

The advent of widespread kV-cone beam computer tomography in image guided radiation therapy and special therapeutic application of keV photons, e.g., in microbeam radiation therapy (MRT) require accurate and fast dose calculations for photon beams with energies between 40 and 200 keV. Multiple photon scattering originating from Compton scattering and the strong dependence of the photoelectric cross section on the atomic number of the interacting tissue render these dose calculations by far more challenging than the ones established for corresponding MeV beams. That is why so far developed analytical models of kV photon dose calculations fail to provide the required accuracy and one has to rely on time consuming Monte Carlo simulation techniques. In this paper, the authors introduce a novel analytical approach for kV photon dose calculations with an accuracy that is almost comparable to the one of Monte Carlo simulations. First, analytical point dose and pencil beam kernels are derived for homogeneous media and compared to Monte Carlo simulations performed with the Geant4 toolkit. The dose contributions are systematically separated into contributions from the relevant orders of multiple photon scattering. Moreover, approximate scaling laws for the extension of the algorithm to inhomogeneous media are derived. The comparison of the analytically derived dose kernels in water showed an excellent agreement with the Monte Carlo method. Calculated values deviate less than 5% from Monte Carlo derived dose values, for doses above 1% of the maximum dose. The analytical structure of the kernels allows adaption to arbitrary materials and photon spectra in the given energy range of 40-200 keV. The presented analytical methods can be employed in a fast treatment planning system for MRT. In convolution based algorithms dose calculation times can be reduced to a few minutes.

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application.

PubMed

Banjade, D P; Shrestha, S L; Shukri, A; Tajuddin, A A; Bhat, M

2002-09-01

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.

LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors.

PubMed

Aparicio, Ana; North, Brittany; Barske, Lindsey; Wang, Xuemei; Bollati, Valentina; Weisenberger, Daniel; Yoo, Christine; Tannir, Nizar; Horne, Erin; Groshen, Susan; Jones, Peter; Yang, Allen; Issa, Jean-Pierre

2009-04-01

Multiple clinical trials are investigating the use of the DNA methylation inhibitors azacitidine and decitabine for the treatment of solid tumors. Clinical trials in hematological malignancies have shown that optimal activity does not occur at their maximum tolerated doses but selection of an optimal biological dose and schedule for use in solid tumor patients is hampered by the difficulty of obtaining tumor tissue to measure their activity. Here we investigate the feasibility of using plasma DNA to measure the demethylating activity of the DNA methylation inhibitors in patients with solid tumors. We compared four methods to measure LINE-1 and MAGE-A1 promoter methylation in T24 and HCT116 cancer cells treated with decitabine treatment and selected Pyrosequencing for its greater reproducibility and higher signal to noise ratio. We then obtained DNA from plasma, peripheral blood mononuclear cells, buccal mucosa cells and saliva from ten patients with metastatic solid tumors at two different time points, without any intervening treatment. DNA methylation measurements were not significantly different between time point 1 and time point 2 in patient samples. We conclude that measurement of LINE-1 methylation in DNA extracted from the plasma of patients with advanced solid tumors, using Pyrosequencing, is feasible and has low within patient variability. Ongoing studies will determine whether changes in LINE-1 methylation in plasma DNA occur as a result of treatment with DNA methylation inhibitors and parallel changes in tumor tissue DNA.

An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

2015-10-01

Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

SU-E-T-378: Limits and Possibilities of a Simplistic Approach to Whole Breast Radiation Therapy Planning

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

Hipp, E; Osa, E; No, H

2014-06-01

Purpose: Challenges for radiation therapy in developing countries include unreliable infrastructure and high patient load. We propose a system to treat whole breast in the prone position without computed tomography and/or planning software. Methods: Six parameters are measured using calipers and levels with the patient prone in the treatment position. (1) The largest separation; (2) the angle that separation makes with the horizontal; (3) the separation 2 cm posterior to the nipple; (4) the vertical distance between these two separations; (5) the sup/inf length and (6) angle of the desired posterior field edge. The data in (5) (6) and (2)more » provide field length, collimator and gantry angles. Isocenter is set to the midpoint of (1), anterior jaw setting is 20cm (half-beam setup), and the dose is prescribed to a point 1.5 cm anterior to isocenter. MUs and wedge angles are calculated using an MU calculator and by requiring 100% dose at that point and 100-105% at the midpoint of (3). Measurements on 30 CT scans were taken to obtain the data 1-6. To test the resulting MU/wedge combinations, they were entered into Eclipse (Varian) and dose distributions were calculated. The MU/wedge combinations were recorded and tabulated. Results: Performing a dose volume histogram analysis, the contoured breast V95 was 90.5%, and the average V90 was 94.1%. The maximum dose never exceeded 114.5%, (average 108%). The lung V20 was <5% for 96.7%, and the heart V5 was <10% for 93.3% of our sample. Conclusion: A method to provide prone whole breast treatment without CT-planning was developed. The method provides reasonable coverage and normal tissue sparing. This approach is not recommended if imaging and planning capabilities are available; it was designed to specifically avoid the need for CT planning and should be reserved to clinics that need to avoid that step.« less

Screening-Level Risk Assessment for Styrene-Acrylonitrile (SAN) Trimer Detected in Soil and Groundwater

PubMed Central

Kirman, C. R.; Gargas, M. L.; Collins, J. J.; Rowlands, J. C.

2012-01-01

A screening-level risk assessment was conducted for styrene-acrylonitrile (SAN) Trimer detected at the Reich Farm Superfund site in Toms River, NJ. Consistent with a screening-level approach, on-site and off-site exposure scenarios were evaluated using assumptions that are expected to overestimate actual exposures and hazards at the site. Environmental sampling data collected for soil and groundwater were used to estimate exposure point concentrations. Several exposure scenarios were evaluated to assess potential on-site and off-site exposures, using parameter values for exposures to soil (oral, inhalation of particulates, and dermal contact) and groundwater (oral, dermal contact) to reflect central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. Three reference dose (RfD) values were derived for SAN Trimer for short-term, subchronic, and chronic exposures, based upon its effects on the liver in exposed rats. Benchmark (BMD) methods were used to assess the relationship between exposure and response, and to characterize appropriate points of departure (POD) for each RfD. An uncertainty factor of 300 was applied to each POD to yield RfD values of 0.1, 0.04, and 0.03 mg/kg-d for short-term, subchronic, and chronic exposures, respectively. Because a chronic cancer bioassay for SAN Trimer in rats (NTP 2011a) does not provide evidence of carcinogenicity, a cancer risk assessment is not appropriate for this chemical. Potential health hazards to human health were assessed using a hazard index (HI) approach, which considers the ratio of exposure dose (i.e., average daily dose, mg/kg-d) to toxicity dose (RfD, mg/kg-d) for each scenario. All CTE and RME HI values are well below 1 (where the average daily dose is equivalent to the RfD), indicating that there is no concern for potential noncancer effects in exposed populations even under the conservative assumptions of this screening-level assessment. PMID:23030654

Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

PubMed

Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

2016-01-01

The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments.

An approach for the regularization of a power flow solution around the maximum loading point

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

Kataoka, Y.

1992-08-01

In the conventional power flow solution, the boundary conditions are directly specified by active power and reactive power at each node, so that the singular point coincided with the maximum loading point. For this reason, the computations are often disturbed by ill-condition. This paper proposes a new method for getting the wide-range regularity by giving some modifications to the conventional power flow solution method, thereby eliminating the singular point or shifting it to the region with the voltage lower than that of the maximum loading point. Then, the continuous execution of V-P curves including maximum loading point is realized. Themore » efficiency and effectiveness of the method are tested in practical 598-nodes system in comparison with the conventional method.« less

Monte Carlo and Phantom Study of the Radiation Dose to the Body from Dedicated Computed Tomography of the Breast

PubMed Central

Sechopoulos, Ioannis; Vedantham, Srinivasan; Suryanarayanan, Sankararaman; D’Orsi, Carl J.; Karellas, Andrew

2008-01-01

Purpose To prospectively determine the radiation dose absorbed by the organs and tissues of the body during a dedicated computed tomography of the breast (DBCT) study using Monte Carlo methods and a phantom. Materials and Methods Using the Geant4 Monte Carlo toolkit, the Cristy anthropomorphic phantom and the geometry of a prototype DBCT was simulated. The simulation was used to track x-rays emitted from the source until their complete absorption or exit from the simulation limits. The interactions of the x-rays with the 65 different volumes representing organs, bones and other tissues of the anthropomorphic phantom that resulted in energy deposition were recorded. These data were used to compute the radiation dose to the organs and tissues during a complete DBCT acquisition relative to the average glandular dose to the imaged breast (ROD, relative organ dose), using the x-ray spectra proposed for DBCT imaging. The effectiveness of a lead shield for reducing the dose to the organs was investigated. Results The maximum ROD among the organs was for the ipsilateral lung with a maximum of 3.25%, followed by the heart and the thymus. Of the skeletal tissues, the sternum received the highest dose with a maximum ROD to the bone marrow of 2.24%, and to the bone surface of 7.74%. The maximum ROD to the uterus, representative of that of an early-stage fetus, was 0.026%. These maxima occurred for the highest energy x-ray spectrum (80 kVp) analyzed. A lead shield does not protect substantially the organs that receive the highest dose from DBCT. Discussion Although the dose to the organs from DBCT is substantially higher than that from planar mammography, they are comparable or considerably lower than those reached by other radiographic procedures and much lower than other CT examinations. PMID:18292479

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

PubMed

Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

2018-05-15

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

Progress report on hot particle studies

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

Baum, J.W.; Kaurin, D.G.; Waligorski, M.

1992-02-01

NCRP Report 106 on the effects of hot particles on the skin of pigs, monkeys, and humans was critically reviewed and reassessed. The analysis of the data of Forbes and Mikhail on the effects from activated UC{sub 2} particles, ranging in diameter from 144 {mu}m to 328 {mu}m, led to the formulation of a new model to predict both the threshold for acute ulceration and for ulcer diameter. In this model, a point dose of 27 Gy at a depth of 1.33 mm in tissue will cause an ulcer with a diameter determined by the radius to which this dosemore » extends. Application of the model to the Forbes and Mikhail data obtained with mixed fission product beta particles yielded a threshold'' (5% probability) of 6 {times} 10{sup 9} beta particles from a point source of high energy (2.25 MeV maximum) beta particles on skin. The above model was used to predict that approximately 1.2 {times} 10{sup 10} beta particles from Sr-Y-90 would produce similar effects, since few Sr-90 beta particles reach 1.33 mm depth. These emissions correspond to doses at 70-{mu}m depth in tissue of approximately 5.3 to 5.5 Gy averaged over 1 cm{sup 2}, respectively.« less

Progress report on hot particle studies

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

Baum, J.W.; Kaurin, D.G.; Waligorski, M.

1992-02-01

NCRP Report 106 on the effects of hot particles on the skin of pigs, monkeys, and humans was critically reviewed and reassessed. The analysis of the data of Forbes and Mikhail on the effects from activated UC{sub 2} particles, ranging in diameter from 144 {mu}m to 328 {mu}m, led to the formulation of a new model to predict both the threshold for acute ulceration and for ulcer diameter. In this model, a point dose of 27 Gy at a depth of 1.33 mm in tissue will cause an ulcer with a diameter determined by the radius to which this dosemore » extends. Application of the model to the Forbes and Mikhail data obtained with mixed fission product beta particles yielded a ``threshold`` (5% probability) of 6 {times} 10{sup 9} beta particles from a point source of high energy (2.25 MeV maximum) beta particles on skin. The above model was used to predict that approximately 1.2 {times} 10{sup 10} beta particles from Sr-Y-90 would produce similar effects, since few Sr-90 beta particles reach 1.33 mm depth. These emissions correspond to doses at 70-{mu}m depth in tissue of approximately 5.3 to 5.5 Gy averaged over 1 cm{sup 2}, respectively.« less

Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

PubMed Central

Backer, H; Hollowell, J

2000-01-01

Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

A method for photon beam Monte Carlo multileaf collimator particle transport

NASA Astrophysics Data System (ADS)

Siebers, Jeffrey V.; Keall, Paul J.; Kim, Jong Oh; Mohan, Radhe

2002-09-01

Monte Carlo (MC) algorithms are recognized as the most accurate methodology for patient dose assessment. For intensity-modulated radiation therapy (IMRT) delivered with dynamic multileaf collimators (DMLCs), accurate dose calculation, even with MC, is challenging. Accurate IMRT MC dose calculations require inclusion of the moving MLC in the MC simulation. Due to its complex geometry, full transport through the MLC can be time consuming. The aim of this work was to develop an MLC model for photon beam MC IMRT dose computations. The basis of the MC MLC model is that the complex MLC geometry can be separated into simple geometric regions, each of which readily lends itself to simplified radiation transport. For photons, only attenuation and first Compton scatter interactions are considered. The amount of attenuation material an individual particle encounters while traversing the entire MLC is determined by adding the individual amounts from each of the simplified geometric regions. Compton scatter is sampled based upon the total thickness traversed. Pair production and electron interactions (scattering and bremsstrahlung) within the MLC are ignored. The MLC model was tested for 6 MV and 18 MV photon beams by comparing it with measurements and MC simulations that incorporate the full physics and geometry for fields blocked by the MLC and with measurements for fields with the maximum possible tongue-and-groove and tongue-or-groove effects, for static test cases and for sliding windows of various widths. The MLC model predicts the field size dependence of the MLC leakage radiation within 0.1% of the open-field dose. The entrance dose and beam hardening behind a closed MLC are predicted within +/-1% or 1 mm. Dose undulations due to differences in inter- and intra-leaf leakage are also correctly predicted. The MC MLC model predicts leaf-edge tongue-and-groove dose effect within +/-1% or 1 mm for 95% of the points compared at 6 MV and 88% of the points compared at 18 MV. The dose through a static leaf tip is also predicted generally within +/-1% or 1 mm. Tests with sliding windows of various widths confirm the accuracy of the MLC model for dynamic delivery and indicate that accounting for a slight leaf position error (0.008 cm for our MLC) will improve the accuracy of the model. The MLC model developed is applicable to both dynamic MLC and segmental MLC IMRT beam delivery and will be useful for patient IMRT dose calculations, pre-treatment verification of IMRT delivery and IMRT portal dose transmission dosimetry.

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

Shin, D; Kang, S; Kim, D

Purpose: The dose difference between three-dimensional dose (3D dose) and 4D dose which considers motion due to respiratory can be varied according to geometrical relationship between planning target volume (PTV) and organ at risk (OAR). The purpose of the study is to investigate the dose difference between 3D and 4D dose using overlap volume histogram (OVH) which is an indicator that quantify geometrical relationship between a PTV and an OAR. Methods: Five liver cancer patients who previously treated stereotactic body radiotherapy (SBRT) were investigated. Four-dimensional computed tomography (4DCT) images were acquired for all patients. ITV-based treatment planning was performed. 3Dmore » dose was calculated on the end-exhale phase image as a reference phase image. 4D dose accumulation was implemented from all phase images using dose warping technique used deformable image registration (DIR) algorithm (Horn and Schunck optical flow) in DIRART. In this study OVH was used to quantify geometrical relationship between a PTV and an OAR. OVH between a PTV and a selected OAR was generated for each patient case and compared for all cases. The dose difference between 3D and 4D dose for normal organ was calculated and compared for all cases according to OVH. Results: The 3D and 4D dose difference for OAR was analyzed using dose-volume histogram (DVH). On the basis of a specific point which corresponds to 10% of OAR volume overlapped with expanded PTV, mean dose difference was 34.56% in minimum OVH distance case and 13.36% in maximum OVH distance case. As the OVH distance increased, mean dose difference between 4D and 3D dose was decreased. Conclusion: The tendency of dose difference variation was verified according to OVH. OVH is seems to be indicator that has a potential to predict the dose difference between 4D and 3D dose. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning.« less

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

PubMed

Marek, Josef; Jezková, Jana; Hána, Václav; Krsek, Michal; Bandúrová, L'ubomíra; Pecen, Ladislav; Vladyka, Vilibald; Liscák, Roman

2011-02-01

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

Detection of DNA damage induced in vivo by a cross-linking agent with a circular channel crucible oscillating viscometer.

PubMed

Balbi, C; Abelmoschi, M L; Roner, R; Giaretti, W; Parodi, S; Santi, L

1985-11-01

DNA damage induced in vivo by the cross-linking agent mitomycin C (MMC) was investigated with a new oscillating crucible viscometer. Viscosity was measured by lysing rat liver nuclei in an alkaline lysing solution (pH 12.5; 25 degrees C). In control samples the viscosity increased very slowly with time, reaching a plateau only after 10-12 h. The process was accelerated and the maximum viscosity was decreased by alkaline single-stranded breaks arising from methylation and subsequent depurination of DNA in vitro with dimethylsulphate (DMS). MMC, when given alone, had no evident effect on the time needed for reaching plateau viscosity but it induced a small increase in maximum viscosity. When MMC was given in association with DMS, the time of disentanglement remained unchanged (accelerated) but maximum viscosity was increased in a dose dependent way. We conclude that these data clearly confirm that the slow steady increase of the viscosity of control DNA with time reflects mainly the process of unwinding of the two strands. The speed of this process seems to depend only from the number of unwinding points in DNA (breaks).

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

PubMed

Yoshikawa, Hiroto; Roback, Donald M; Larue, Susan M; Nolan, Michael W

2015-01-01

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning. © 2015 American College of Veterinary Radiology.

Life-stage-, sex-, and dose-dependent dietary toxicokinetics and relationship to toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats: implications for toxicity test dose selection, design, and interpretation.

PubMed

Saghir, Shakil A; Marty, Mary S; Zablotny, Carol L; Passage, Julie K; Perala, Adam W; Neal, Barbara H; Hammond, Larry; Bus, James S

2013-12-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥ 1200 ppm (63 mg/kg/day) for P1 males and between 200 and 400 ppm (14-27 mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21-35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies.

Life-Stage-, Sex-, and Dose-Dependent Dietary Toxicokinetics and Relationship to Toxicity of 2,4-Dichlorophenoxyacetic Acid (2,4-D) in Rats: Implications for Toxicity Test Dose Selection, Design, and Interpretation

PubMed Central

Marty, Mary S.

2013-01-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥1200 ppm (63mg/kg/day) for P1 males and between 200 and 400 ppm (14–27mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21–35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies. PMID:24105888

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams

NASA Astrophysics Data System (ADS)

Lang, Stephanie; Hrbacek, Jan; Leong, Aidan; Klöck, Stephan

2012-05-01

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min-1 (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min-1. For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min-1. All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts.

Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949.

PubMed

Stalder, Anna K; Lott, Dominik; Strasser, Daniel S; Cruz, Hans G; Krause, Andreas; Groenen, Peter M A; Dingemanse, Jasper

2017-03-01

The main objectives of these two phase I studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective formyl peptide receptor type 2 (FPR2)/Lipoxin A 4 receptor (ALX) agonist ACT-389949. A challenge model was used to assess the drug's anti-inflammatory potential, with the aim of selecting a dosing regimen for future patient studies. Two double-blind, randomized phase I studies investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of ACT-389949 at different doses and dosing regimens. Drug exposure was correlated with target engagement markers such as receptor internalization and cytokine measurements. The effect of FPR2/ALX agonism on neutrophil migration was studied in a lipopolysaccharide (LPS) inhalation model. ACT-389949 was well tolerated. Maximum concentrations were reached around 2 h after dosing, with a mean terminal half-life of 29.3 h [95% confidence interval (CI) 25.5, 33.7]. After multiple-dose administration, exposure increased by 111% (95% CI 89, 136), indicating drug accumulation. Administration of ACT-389949 resulted in a dose-dependent, long-lasting internalization of FPR2/ALX into leukocytes. Pro- and anti-inflammatory cytokines were dose-dependently but transiently upregulated only after the first dose. No pharmacological effect on neutrophil count was observed in the LPS challenge test performed at steady state. FPR2/ALX agonism with ACT-389949 was shown to be safe and well tolerated in healthy subjects. Receptor internalization and downstream mediators pointed towards a desensitization of the system, which may explain the lack of effect on neutrophil recruitment in the LPS challenge model. © 2016 The British Pharmacological Society.

Visible photoluminescence of color centers in LiF crystals for absorbed dose evaluation in clinical dosimetry

NASA Astrophysics Data System (ADS)

Villarreal-Barajas, J. E.; Piccinini, M.; Vincenti, M. A.; Bonfigli, F.; Khan, R. F.; Montereali, R. M.

2015-04-01

Among insulating materials, lithium fluoride (LiF) has been successfully used as ionizing radiation dosemeter for more than 60 years. Thermoluminescence (TL) has been the most commonly used reading technique to evaluate the absorbed dose. Lately, optically stimulated luminescence (OSL) of visible emitting color centers (CCs) has also been explored in pure and doped LiF. This work focuses on the experimental behaviour of nominally pure LiF crystals dosemeters for 6 MV x rays at low doses based on photoluminescence (PL) of radiation induced CCs. Polished LiF crystals were irradiated using 6 MV x rays produced by a clinical linear accelerator. The doses (absorbed dose to water) covered the 1-100 Gy range. Optical absorption spectra show stable formation of primary F defects up to a maximum concentration of 2×1016 cm-3, while no significant M absorption band at around 450 nm was detected. On the other hand, under Argon laser excitation at 458 nm, PL spectra of the irradiated LiF crystals clearly exhibited the characteristic F2 and F+3 visible broad emission bands. Their sum intensity is linearly proportional to the absorbed dose in the investigated range. PL integrated intensity was also measured using a conventional fluorescence optical microscope under blue lamp illumination. The relationship between the absorbed dose and the integrated F2 and F+3 PL intensities, represented by the net average pixel number in the optical fluorescence images, is also fairly linear. Even at the low point defect densities obtained at the investigated doses, these preliminary experimental results are encouraging for further investigation of CCs PL in LiF crystals for clinical dosimetry.

Microprocessor-controlled step-down maximum-power-point tracker for photovoltaic systems

NASA Astrophysics Data System (ADS)

Mazmuder, R. K.; Haidar, S.

1992-12-01

An efficient maximum power point tracker (MPPT) has been developed and can be used with a photovoltaic (PV) array and a load which requires lower voltage than the PV array voltage to be operated. The MPPT makes the PV array to operate at maximum power point (MPP) under all insolation and temperature, which ensures the maximum amount of available PV power to be delivered to the load. The performance of the MPPT has been studied under different insolation levels.

High dose rate brachytherapy source measurement intercomparison.

PubMed

Poder, Joel; Smith, Ryan L; Shelton, Nikki; Whitaker, May; Butler, Duncan; Haworth, Annette

2017-06-01

This work presents a comparison of air kerma rate (AKR) measurements performed by multiple radiotherapy centres for a single HDR 192 Ir source. Two separate groups (consisting of 15 centres) performed AKR measurements at one of two host centres in Australia. Each group travelled to one of the host centres and measured the AKR of a single 192 Ir source using their own equipment and local protocols. Results were compared to the 192 Ir source calibration certificate provided by the manufacturer by means of a ratio of measured to certified AKR. The comparisons showed remarkably consistent results with the maximum deviation in measurement from the decay-corrected source certificate value being 1.1%. The maximum percentage difference between any two measurements was less than 2%. The comparisons demonstrated the consistency of well-chambers used for 192 Ir AKR measurements in Australia, despite the lack of a local calibration service, and served as a valuable focal point for the exchange of ideas and dosimetry methods.

Volumetric modulated arc therapy planning for primary prostate cancer with selective intraprostatic boost determined by 18F-choline PET/CT.

PubMed

Kuang, Yu; Wu, Lili; Hirata, Emily; Miyazaki, Kyle; Sato, Miles; Kwee, Sandi A

2015-04-01

This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by (18)F-choline positron emission tomography/computed tomography (PET/CT). Thirty patients with localized prostate cancer underwent (18)F-choline PET/CT before treatment. Two VMAT plans, plan79 Gy and plan100-105 Gy, were compared for each patient. The whole-prostate planning target volume (PTVprostate) prescription was 79 Gy in both plans, but plan100-105 Gy added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, defined by 60% and 70% of maximum prostatic uptake on (18)F-choline PET (IDLsuv60% and IDLsuv70%, respectively, with IDLsuv70% nested inside IDLsuv60% to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDLsuv60% adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan100-105 Gy had significantly higher TCP than plan79 Gy across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan100-105 Gy. VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a (18)F-choline PET-defined IDL. Copyright © 2015 Elsevier Inc. All rights reserved.

Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model

PubMed Central

Au, Adrian; Stuyt, John Gerka; Chen, Daniel; Alagramam, Kumar

2013-01-01

Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans. PMID:24244454

Ups and downs of Viagra: revisiting ototoxicity in the mouse model.

PubMed

Au, Adrian; Stuyt, John Gerka; Chen, Daniel; Alagramam, Kumar

2013-01-01

Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans.

Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients.

PubMed

Kaska, Milan; Havel, Eduard; Selke-Krulichova, Iva; Safranek, Petr; Bezouska, Jan; Martinkova, Jirina

2018-03-27

Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Cl cr ) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry. The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Cl cr ≥130 mL/min/1.73m 2 . Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vd me =70.3 L (41.9-101.5), Vd pip = 46.8 L (39.7-60.0). 100%fT me >MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFB pip with Vd pip (P=0.021). Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vd pip across subjects at each and every time point.

Volumetric tumor burden and its effect on brachial plexus dosimetry in head and neck intensity-modulated radiotherapy

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

Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

2014-07-01

To determine the effect of gross tumor volume of the primary (GTV-P) and nodal (GTV-N) disease on planned radiation dose to the brachial plexus (BP) in head and neck intensity-modulated radiotherapy (IMRT). Overall, 75 patients underwent definitive IMRT to a median total dose of 69.96 Gy in 33 fractions. The right BP and left BP were prospectively contoured as separate organs at risk. The GTV was related to BP dose using the unpaired t-test. Receiver operating characteristics curves were constructed to determine optimized volumetric thresholds of GTV-P and GTV-N corresponding to a maximum BP dose cutoff of > 66 Gy.more » Multivariate analyses were performed to account for factors associated with a higher maximal BP dose. A higher maximum BP dose (> 66 vs ≤ 66 Gy) correlated with a greater mean GTV-P (79.5 vs 30.8 cc; p = 0.001) and ipsilateral GTV-N (60.6 vs 19.8 cc; p = 0.014). When dichotomized by the optimized nodal volume, patients with an ipsilateral GTV-N ≥ 4.9 vs < 4.9 cc had a significant difference in maximum BP dose (64.2 vs 59.4 Gy; p = 0.001). Multivariate analysis confirmed that an ipsilateral GTV-N ≥ 4.9 cc was an independent predictor for the BP to receive a maximal dose of > 66 Gy when adjusted individually for BP volume, GTV-P, the use of a low anterior neck field technique, total planned radiation dose, and tumor category. Although both the primary and the nodal tumor volumes affected the BP maximal dose, the ipsilateral nodal tumor volume (GTV-N ≥ 4.9 cc) was an independent predictor for high maximal BP dose constraints in head and neck IMRT.« less

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

PubMed

Sandborn, W J; Bhandari, B R; Fogel, R; Onken, J; Yen, E; Zhao, X; Jiang, Z; Ge, D; Xin, Y; Ye, Z; French, D; Silverman, J A; Kanwar, B; Subramanian, G M; McHutchison, J G; Lee, S D; Shackelton, L M; Pai, R K; Levesque, B G; Feagan, B G

2016-07-01

Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

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

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H

2011-06-01

To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.

Effect of gamma irradiation on the structural, mechanical and optical properties of polytetrafluoroethylene sheet

NASA Astrophysics Data System (ADS)

Mohammadian-Kohol, M.; Asgari, M.; Shakur, H. R.

2018-04-01

In this study, the effects of gamma radiation on the chemical structure, mechanical and optical properties of polytetrafluoroethylene (PTFE) sheet were investigated with various doses up to 12 kGy. The chemical changes in the structure were studied by FTIR spectroscopy. Also, effects of radiation on the different mechanical parameters such as Young's modulus, toughness, strain, and stress were studied at the maximum tolerable force and the fracture points. Furthermore, changing the various optical parameters such as absorption coefficient, Urbach energy, optical band gaps, refractive index, optical dispersion parameters and plasma resonance frequency were studied by UV-visible spectroscopy. Formation of a band at 1594 cm-1, which was belonged to double carbon bonds, indicated that chain-scission was occurred at 12 kGy gamma irradiation dose. As well, the mechanical results showed an increase in the elastic behavior of PTFE sheets and a decrease in the plastic behavior of it with absorbed dose increasing. Moreover, the results showed that gamma irradiation can effectively change the various optical properties of PTFE sheets due to different phenomena such as degradation of the main chains, occurring chain-scission, formation of free radicals and cross-linking in the polymer structure.

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

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

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« 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.

CT Fluoroscopy Shielding: Decreases in Scattered Radiation for the Patient and Operator

PubMed Central

Neeman, Ziv; Dromi, Sergio A.; Sarin, Shawn; Wood, Bradford J.

2008-01-01

PURPOSE High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator’s torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. PMID:17185699

Maximum dose angle for oblique incidence on primary beam protective barriers in the design of medical radiation therapy facilities.

PubMed

Fondevila, Damián; Arbiser, Silvio; Sansogne, Rosana; Brunetto, Mónica; Dosoretz, Bernardo

2008-05-01

Primary barrier determinations for the shielding of medical radiation therapy facilities are generally made assuming normal beam incidence on the barrier, since this is geometrically the most unfavorable condition for that shielding barrier whenever the occupation line is allowed to run along the barrier. However, when the occupation line (for example, the wall of an adjacent building) runs perpendicular to the barrier (especially roof barrier), then two opposing factors come in to play: increasing obliquity angle with respect to the barrier increases the attenuation, while the distance to the calculation point decreases, hence, increasing the dose. As a result, there exists an angle (alpha(max)) for which the equivalent dose results in a maximum, constituting the most unfavorable geometric condition for that shielding barrier. Based on the usual NCRP Report No. 151 model, this article presents a simple formula for obtaining alpha(max), which is a function of the thickness of the barrier (t(E)) and the equilibrium tenth-value layer (TVL(e)) of the shielding material for the nominal energy of the beam. It can be seen that alpha(max) increases for increasing TVL(e) (hence, beam energy) and decreases for increasing t(E), with a range of variation that goes from 13 to 40 deg for concrete barriers thicknesses in the range of 50-300 cm and most commercially available teletherapy machines. This parameter has not been calculated in the existing literature for radiotherapy facilities design and has practical applications, as in calculating the required unoccupied roof shielding for the protection of a nearby building located in the plane of the primary beam rotation.

SU-F-T-08: Brachytherapy Film Dosimetry in a Water Phantom for a Ring and Tandem HDR Applicator

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

Lee, B; Grelewicz, Z; Kang, Z

2016-06-15

Purpose: The feasibility of dose measurement using new generation EBT3 film was explored in a water phantom for a ring and tandem HDR applicator for measurements tracking mucosal dose during cervical brachytherapy. Methods: An experimental fixture was assembled to position the applicator in a water phantom. Prior to measurement, calibration curves for EBT3 film in water and in solidwater were verified. EBT3 film was placed at different known locations around the applicator in the water tank. A CT scan of the phantom with applicator was performed using clinical protocol. A typical cervical cancer treatment plan was then generated by Oncentramore » brachytherapy planning system. A dose of 500 cGy was prescribed to point A (2 cm, 2 cm). Locations measured by film included the outer surface of the ring, measurement point A-m (2.2 cm, 2.2 cm), and profiles extending from point A-m parallel to the tandem. Three independent measurements were conducted. The doses recorded by film were carefully analyzed and compared with values calculated by the treatment planning system. Results: Assessment of the EBT3 films indicate that the dose at point A matches the values predicted by the planning system. Dose to the point A-m was 411.5 cGy, and the outer circumferential surface dose of the ring was between 500 and 1150 cGy. It was found that from the point A-m, the dose drops 60% within 4.5 cm on the line parallel to the tandem. The measurement doses agree with the treatment planning system. Conclusion: Use of EBT3 film is feasible for in-water measurements for brachytherapy. A carefully machined apparatus will likely improve measurement accuracy. In a typical plan, our study found that the ring surface dose can be 2.5 times larger than the point A prescription dose. EBT3 film can be used to monitor mucosal dose in brachytherapy treatments.« less

A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

PubMed

Yannovits, N; Zintzaras, E; Pouli, A; Koukoulis, G; Lyberi, S; Savari, E; Potamianos, S; Triposkiadis, F; Stefanidis, I; Zartaloudis, E; Benakis, A

2006-01-01

Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic parameters AUC(last) and Cmax lie within the acceptance limits for bioequivalence (0.80, 1.25), for both T3 and T4.

Measurement and properties of the dose-area product ratio in external small-beam radiotherapy.

PubMed

Niemelä, Jarkko; Partanen, Mari; Ojala, Jarkko; Sipilä, Petri; Björkqvist, Mikko; Kapanen, Mika; Keyriläinen, Jani

2017-06-21

In small-beam radiation therapy (RT) the measurement of the beam quality parameter, i.e. the tissue-phantom ratio or TPR 20,10 , using a conventional point detector is a challenge. To obtain reliable results, one has to consider potential sources of error, including volume averaging and adjustment of the point detector into the narrow beam. To overcome these challenges, a different type of beam quality parameter in small beams was studied, namely the dose-area product ratio, or DAPR 20,10 . With this method, the measurement of a dose-area product (DAP) using a large-area plane-parallel chamber (LAC) eliminates the uncertainties in detector positioning and volume averaging that are present when using a point detector. In this study, the properties of the DAPR 20,10 of a cone-collimated 6 MV photon beam were investigated using Monte Carlo (MC) calculations and the obtained values were compared to measurements obtained using two LAC detectors, PTW Type 34073 and PTW Type 34070. In addition, the possibility of determining the DAP using EBT3 film and a Razor diode detector was studied. The determination of the DAPR 20,10 value was found to be feasible in external small-beam radiotherapy using cone-collimated beams with diameters from 4-40 mm, based on the results of the two LACs, the MC calculations and the Razor diode. The measurements indicated a constant DAPR 20,10 value for fields 20-40 mm in diameter, with a maximum relative change of 0.6%, but an increase of 7.0% for fields from 20-4 mm in diameter for the PTW Type 34070 chamber. Simulations and measurements showed an increase of DAPR 20,10 with increasing LAC size or dose integral area for the studied 4-40 mm cone-collimated 6 MV photon beams. This has the consequence that there should be a reference to the size of the used LAC active area or the DAP integration area with the reported DAPR 20,10 value.

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

PubMed Central

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

2016-01-01

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

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

PubMed

Mangold, C A; Rijnders, A; Georg, D; Van Limbergen, E; Pötter, R; Huyskens, D

2001-01-01

In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer

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

Liu, Alan J.; Vora, Nayana; Suh, Steve

2015-04-01

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 secondsmore » after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V{sub 45} {sub Gy}, V{sub 30} {sub Gy}, and V{sub 20} {sub Gy} organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.« less

Reconstruction of organ dose for external radiotherapy patients in retrospective epidemiologic studies

NASA Astrophysics Data System (ADS)

Lee, Choonik; Jung, Jae Won; Pelletier, Christopher; Pyakuryal, Anil; Lamart, Stephanie; Kim, Jong Oh; Lee, Choonsik

2015-03-01

Organ dose estimation for retrospective epidemiological studies of late effects in radiotherapy patients involves two challenges: radiological images to represent patient anatomy are not usually available for patient cohorts who were treated years ago, and efficient dose reconstruction methods for large-scale patient cohorts are not well established. In the current study, we developed methods to reconstruct organ doses for radiotherapy patients by using a series of computational human phantoms coupled with a commercial treatment planning system (TPS) and a radiotherapy-dedicated Monte Carlo transport code, and performed illustrative dose calculations. First, we developed methods to convert the anatomy and organ contours of the pediatric and adult hybrid computational phantom series to Digital Imaging and Communications in Medicine (DICOM)-image and DICOM-structure files, respectively. The resulting DICOM files were imported to a commercial TPS for simulating radiotherapy and dose calculation for in-field organs. The conversion process was validated by comparing electron densities relative to water and organ volumes between the hybrid phantoms and the DICOM files imported in TPS, which showed agreements within 0.1 and 2%, respectively. Second, we developed a procedure to transfer DICOM-RT files generated from the TPS directly to a Monte Carlo transport code, x-ray Voxel Monte Carlo (XVMC) for more accurate dose calculations. Third, to illustrate the performance of the established methods, we simulated a whole brain treatment for the 10 year-old male phantom and a prostate treatment for the adult male phantom. Radiation doses to selected organs were calculated using the TPS and XVMC, and compared to each other. Organ average doses from the two methods matched within 7%, whereas maximum and minimum point doses differed up to 45%. The dosimetry methods and procedures established in this study will be useful for the reconstruction of organ dose to support retrospective epidemiological studies of late effects in radiotherapy patients.

Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

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

Amini, Arya; Westerly, David C.; Waxweiler, Timothy V.

Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involvedmore » lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V{sub 70} (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V{sub 70} was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.« less

SU-G-201-08: Energy Response of Thermoluminescent Microcube Dosimeters in Water for Kilovoltage X-Ray Beams

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

Di Maso, L; Lawless, M; Culberson, W

Purpose: To characterize the energy dependence for TLD-100 microcubes in water at kilovoltage energies. Methods: TLD-100 microcubes with dimensions of (1 × 1 × 1) mm{sup 3} were irradiated with kilovoltage x-rays in a custom-built thin-window liquid water phantom. The TLD-100 microcubes were held in Virtual Water™ probes and aligned at a 2 cm depth in water. Irradiations were performed using the M-series x-ray beams of energies ranging from 50-250 kVp and normalized to a {sup 60}Co beam located at the UWADCL. Simulations using the EGSnrc Monte Carlo Code System were performed to model the x-ray beams, the {sup 60}Comore » beam, the water phantom and the dosimeters in the phantom. The egs-chamber user code was used to tally the dose to the TLDs and the dose to water. The measurements and calculations were used to determine the intrinsic energy dependence, absorbed-dose energy dependence, and absorbed-dose sensitivity. These values were compared to TLD-100 chips with dimensions of (3.2 × 0.9 × 0.9) mm{sup 3}. Results: The measured TLD-100 microcube response per dose to water among all investigated x-ray energies had a maximum percent difference of 61% relative to {sup 60}Co. The simulated ratio of dose to water to the dose to TLD had a maximum percent difference of 29% relative to {sup 60}Co. The ratio of dose to TLD to the TLD output had a maximum percent difference of 13% relative to {sup 60}Co. The maximum percent difference for the absorbed-dose sensitivity was 15% more than the used value of 1.41. Conclusion: These results confirm that differences in beam quality have a significant effect on TLD response when irradiated in water. These results also indicated a difference in TLD-100 response between microcube and chip geometries. The intrinsic energy dependence and the absorbed-dose energy dependence deviated up to 10% between TLD-100 microcubes and chips.« less

A comparison of TPS and different measurement techniques in small-field electron beams.

PubMed

Donmez Kesen, Nazmiye; Cakir, Aydin; Okutan, Murat; Bilge, Hatice

2015-01-01

In recent years, small-field electron beams have been used for the treatment of superficial lesions, which requires small circular fields. However, when using very small electron fields, some significant dosimetric problems may occur. In this study, dose distributions and outputs of circular fields with dimensions of 5cm and smaller, for nominal energies of 6, 9, and 15MeV from the Siemens ONCOR Linac, were measured and compared with data from a treatment planning system using the pencil-beam algorithm in electron beam calculations. All dose distribution measurements were performed using the Gafchromic EBT film; these measurements were compared with data that were obtained from the Computerized Medical Systems (CMS) XiO treatment planning system (TPS), using the gamma-index method in the PTW VeriSoft software program. Output measurements were performed using the Gafchromic EBT film, an Advanced Markus ion chamber, and thermoluminescent dosimetry (TLD). Although the pencil-beam algorithm is used to model electron beams in many clinics, there is no substantial amount of detailed information in the literature about its use. As the field size decreased, the point of maximum dose moved closer to the surface. Output factors were consistent; differences from the values obtained from the TPS were, at maximum, 42% for 6 and 15MeV and 32% for 9MeV. When the dose distributions from the TPS were compared with the measurements from the Gafchromic EBT films, it was observed that the results were consistent for 2-cm diameter and larger fields, but the outputs for fields of 1-cm diameter and smaller were not consistent. In CMS XiO TPS, calculated using the pencil-beam algorithm, the dose distributions of electron treatment fields that were created with circular cutout of a 1-cm diameter were not appropriate for patient treatment and the pencil-beam algorithm is not convenient for monitor unit (MU) calculations in electron dosimetry. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-229: Craniospinal Radiotherapy Planning with VMAT, Two First Years Experience

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

Lliso, F; Carmona, V; Gimeno, J

2015-06-15

Purpose: To describe how we moved to VMAT in the craniospinal radiotherapy planning process, the actual procedure details, and the results for the patients treated. Methods: Twelve patients underwent craniospinal irradiation with the new procedure, based on the paper by Lee et al. (IJROBP 82, 2012), with some additional modifications. Patients were treated in supine position in Varian Clinac iX linacs with 6 MV RapidArc; prescription doses ranged from 23.4 to 40 Gy (13 to 20 fractions); depending on the PTV length, 2 or 3 isocenters were used, all coordinates being equal except the longitudinal one, setting a few centimeter-longmore » overlapping region; 2 arcs (RA) sharing isocentre for the cranial region, RA1 encompassing cranium and superior spinal region, and RA2 intended to improve conformity, only for cranium; for spine, 1 or 2 isocenters were employed; optimization was performed with Eclipse (V 13.0) using AAA algorithm, establishing sets of optimization parameters to give high conformity while sparing OAR. In pediatric patients, homogeneous irradiation of the vertebrae was also required.Conformity (CI) and heterogeneity (HI) indices (same as Lee et al.), and mean and maximum doses for OAR were calculated. Several pre-treatment verification methods were used: Octavius4D (PTW) for each isocentre, point dose at the junction region, Portal Dosimetry (when possible), and independent MU verification software (Diamond, PTW). Results: CI median value was 1.02 (0.99–1.07) and HI, 1.07 (1.06–1.09); a great reduction was observed for CI and OAR mean doses with respect to Lee et al. data; median maximum eye lens dose was 7.3 Gy (4.0–12.0); mean LungV20Gy was 1.9%; in children, vertebrae were homogeneously irradiated (D95%=20.8 Gy, Dmean= 23.2 Gy).All pre-treatment verifications were found within our action levels except for Portal Dosimetry. Conclusion: A RapidArc planning process for craniospinal axis irradiation has been implemented with significant advantages on conformity, homogeneity, feasibility and efficiency. and increase brain tissue sparing. Variations in volume decrease may be related to shape or location of the tumor.« less

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom

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

Lye, Jessica; Dunn, Leon, E-mail: leon.dunn@arpansa.gov.au; Alves, Andrew

Purpose: The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. Methods: The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantomsmore » are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. Results: At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%–8%. Conclusions: The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.« less

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

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

Bosarge, Christina L., E-mail: cbosarge@umail.iu.edu; Ewing, Marvene M.; DesRosiers, Colleen M.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PA{sub AAA}), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PA{sub AAA} using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PA{sub NONE} without heterogeneitymore » corrections, (5) S-AP/PA{sub PB} using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PA{sub AAA[FM]} using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PA{sub AAA} technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PA{sub AAA} approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.« less

Phototherapy for Improvement of Performance and Exercise Recovery: Comparison of 3 Commercially Available Devices.

PubMed

De Marchi, Thiago; Schmitt, Vinicius Mazzochi; Danúbia da Silva Fabro, Carla; da Silva, Larissa Lopes; Sene, Juliane; Tairova, Olga; Salvador, Mirian

2017-05-01

  Recent studies suggest the prophylactic use of low-powered laser/light has ergogenic effects on athletic performance and postactivity recovery. Manufacturers of high-powered lasers/light devices claim that these can produce the same clinical benefits with increased power and decreased irradiation time; however, research with high-powered lasers is lacking.   To evaluate the magnitude of observed phototherapeutic effects with 3 commercially available devices.   Randomized double-blind placebo-controlled study.   Laboratory.   Forty healthy untrained male participants.   Participants were randomized into 4 groups: placebo, high-powered continuous laser/light, low-powered continuous laser/light, or low-powered pulsed laser/light (comprising both lasers and light-emitting diodes). A single dose of 180 J or placebo was applied to the quadriceps.   Maximum voluntary contraction, delayed-onset muscle soreness (DOMS), and creatine kinase (CK) activity from baseline to 96 hours after the eccentric exercise protocol.   Maximum voluntary contraction was maintained in the low-powered pulsed laser/light group compared with placebo and high-powered continuous laser/light groups in all time points (P < .05). Low-powered pulsed laser/light demonstrated less DOMS than all groups at all time points (P < .05). High-powered continuous laser/light did not demonstrate any positive effects on maximum voluntary contraction, CK activity, or DOMS compared with any group at any time point. Creatine kinase activity was decreased in low-powered pulsed laser/light compared with placebo (P < .05) and high-powered continuous laser/light (P < .05) at all time points. High-powered continuous laser/light resulted in increased CK activity compared with placebo from 1 to 24 hours (P < .05).   Low-powered pulsed laser/light demonstrated better results than either low-powered continuous laser/light or high-powered continuous laser/light in all outcome measures when compared with placebo. The increase in CK activity using the high-powered continuous laser/light compared with placebo warrants further research to investigate its effect on other factors related to muscle damage.

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

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

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

2015-01-15

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

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.

PubMed

Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J

2013-11-01

Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of <24 hours. A liposomal bupivacaine formulation (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration but not peripheral nerve blocks. Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n = 14). For each block, liposomal bupivacaine (0-80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received 2 different doses, 1 on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI, 43%-93%), block duration usually lasted much longer: for bupivacaine doses >40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.

Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study

PubMed Central

Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.

2013-01-01

Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with bupivacaine dose (0.06 h/mg, SE = 0.14, 95% CI −0.27 to 0.39, p = 0.707). Conclusions The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of more than 24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a Phase 3 study with a far larger sample size, and these results should be viewed as suggestive, requiring confirmation in a future trial. PMID:24108252

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

PubMed

Al-Jundi, J; Ulanovsky, A; Pröhl, G

2009-10-01

The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

A Study of a Two Stage Maximum Power Point Tracking Control of a Photovoltaic System under Partially Shaded Insolation Conditions

NASA Astrophysics Data System (ADS)

Kobayashi, Kenji; Takano, Ichiro; Sawada, Yoshio

A photovoltaic array shows relatively low output power density, and has a greatly drooping Current-Voltage (I-V) characteristic. Therefore, Maximum Power Point Tracking (MPPT) control is used to maximize the output power of the array. Many papers have been reported in relation to MPPT. However, the Current-Power (I-P) curve sometimes shows multi-local maximum points mode under non-uniform insolation conditions. The operating point of the PV system tends to converge to a local maximum output point which is not the real maximal output point on the I-P curve. Some papers have been also reported, trying to avoid this difficulty. However most of those control systems become rather complicated. Then, the two stage MPPT control method is proposed in this paper to realize a relatively simple control system which can track the real maximum power point even under non-uniform insolation conditions. The feasibility of this control concept is confirmed for steady insolation as well as for rapidly changing insolation by simulation study using software PSIM and LabVIEW. In addition, simulated experiment confirms fundament al operation of the two stage MPPT control.

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

SU-E-T-607: Performance Quantification of the Nine Detectors Used for Dosimetry Measurements in Advanced Radiation Therapy Treatments

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

Markovic, M; Stathakis, S; Jurkovic, I

2015-06-15

Purpose: The purpose of this study was to quantify performance of the nine detectors used for dosimetry measurements in advanced radiation therapy treatments. Methods: The 6 MV beam was utilized for measurements of the field sizes with the lack of lateral charge particle equilibrium. For dose fidelity aspect, energy dependence was studied by measuring PDD and profiles at different depths. The volume effect and its influence on the measured dose profiles have been observed by measuring detector’s response function. Output factor measurements with respect to change in energy spectrum have been performed and collected data has been analyzed. The linearitymore » of the measurements with the dose delivered has been evaluated and relevant comparisons were done. Results: The measured values of the output factors with respect to change in energy spectrum indicated presence of the energy dependence. The detectors with active volume size ≤ 0.3 mm3 maximum deviation from the mean is 5.6% for the field size 0.5 x 0.5 cm2 while detectors with active volume size > 0.3 mm3 have maximum deviation from the mean 7.1%. Linearity with dose at highest dose rate examined for diode detectors showed maximum deviation of 4% while ion chambers showed maximum deviation of 2.2%. Dose profiles showed energy dependence at shallow depths (surface to dmax) influenced by low energy particles with 12 % maximum deviation from the mean for 5 mm2 field size. In relation to Monte Carlo calculation, the detector’s response function σ values were between (0.42±0.25) mm and (1.2±0.25) mm. Conclusion: All the detectors are appropriate for the dosimetry measurements in advanced radiation therapy treatments. The choice of the detectors has to be determined by the application and the scope of the measurements in respect to energy dependence and ability to accurately resolve dose profiles as well as to it’s intrinsic characteristics.« less

Toxicological studies on palytoxin and ostreocin-D administered to mice by three different routes.

PubMed

Ito, Emiko; Yasumoto, Takeshi

2009-09-01

Palytoxin (PLT) first isolated from zoanthids is extremely lethal to animals by intraperitoneal or intravenous administration but shows little toxicity by gavage dosing in contradiction to the occurrence of fatal poisoning due to PLT-containing seafood. In order to fully elucidate its potential risks to human we evaluated the toxicological effects via three ways of dosing: gavage, intra-tracheal administration (IT) and sublingual administration. A new analog, 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin isolated from the dinoflagellate Ostreopsis siamensis and named ostreocin-D (OSD), was also used for comparison, additionally conducted by i.p. By gavage dosing, both toxins did not produce death in mice at the maximum dosage of 200 microg/kg of PLT and 300 microg/kg of OSD. Addition of dietary lipid components to PLT solutions for gavage or use of ulcerated mice did not alter the results, indicating no enhancement of PLT absorption. The two toxins were most toxic by the IT route, causing bleeding and alveolar destruction in the lung and resultant death at 2 microg/kg of PLT, and 11 microg/kg of OSD. Both toxins also induced organ injuries after 24h when dosed by sublingual administration at about 200 microg/kg. The injuries became fatal when PLT was dosed 2 or 3 times. The results pointed to the necessity of taking multiple approaches to assess the potential health risks due to PLT and its analogs in food and environments.

Independent calculation of monitor units for VMAT and SPORT

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

Chen, Xin; Bush, Karl; Ding, Aiping

Purpose: Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulatedmore » arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). Methods: The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. Results: For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours, dose profiles, gamma index, and dose volume histogram (DVH) for these cases. For the lung cases, the MC-calculated MUs differ significantly from that of the treatment plan computed using AAA. However, the discrepancies are reduced to within 3% when the TPS dose calculation algorithm is switched to a transport equation-based technique (Acuros™). Comparison in the dose domain between the MC and Eclipse AAA/Acuros calculation yields conclusion consistent with the MU calculation. Conclusions: A computational framework relating the MU and dose domains has been established. The framework does not only enable them to verify the MU values of the involved station points of a VMAT plan directly in the MU domain but also provide a much needed mechanism to adaptively modify the MU values of the station points in accordance to a specific change in the dose domain.« less

SU-F-T-117: A Pilot Study of Organ Dose Reconstruction for Wilms Tumor Patients Treated with Radiation Therapy

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

Makkia, R; Pelletier, C; Jung, J

Purpose: To reconstruct major organ doses for the Wilms tumor pediatric patients treated with radiation therapy using pediatric computational phantoms, treatment planning system (TPS), and Monte Carlo (MC) dose calculation methods. Methods: A total of ten female and male pediatric patients (15–88 months old) were selected from the National Wilms Tumor Study cohort and ten pediatric computational phantoms corresponding to the patient’s height and weight were selected for the organ dose reconstruction. Treatment plans were reconstructed on the computational phantoms in a Pinnacle TPS (v9.10) referring to treatment records and exported into DICOM-RT files, which were then used to generatemore » the input files for XVMC MC code. The mean doses to major organs and the dose received by 50% of the heart were calculated and compared between TPS and MC calculations. The same calculations were conducted by replacing the computational human phantoms with a series of diagnostic patient CT images selected by matching the height and weight of the patients to validate the anatomical accuracy of the computational phantoms. Results: Dose to organs located within the treatment fields from the computational phantoms and the diagnostic patient CT images agreed within 2% for all cases for both TPS and MC calculations. The maximum difference of organ doses was 55.9 % (thyroid), but the absolute dose difference in this case was 0.33 Gy which was 0.96% of the prescription dose. The doses to ovaries and testes from MC in out-of-field provided more discrepancy (the maximum difference of 13.2% and 50.8%, respectively). The maximum difference of the 50% heart volume dose between the phantoms and the patient CT images was 40.0%. Conclusion: This study showed the pediatric computational phantoms are applicable to organ doses reconstruction for the radiotherapy patients whose three-dimensional radiological images are not available.« less

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

SU-F-P-61: Does It Matter Not to Use Optimization Points at the Apex for Vaginal Cylinder HDR Brachytherapy Planning?

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

Kim, Y

2016-06-15

Purpose: To test the impact of the use of apex optimization points for new vaginal cylinder (VC) applicators. Methods: New “ClickFit” single channel VC applicators (Varian) that have a different top thicknesses but the same diameters as the old VC applicators (2.3 cm diameter, 2.6 cm, 3.0 cm, and 3.5 cm) were compared using phantom studies. Old VC applicator plans without apex optimization points were also compared to the plans with the optimization points. The apex doses were monitored at 5 mm depth doses (8 points) where a prescription dose (Rx) of 6Gy was prescribed. VC surface doses (8 points)more » were also analyzed. Results: The new VC applicator plans without apex optimization points presented significantly lower 5mm depth doses than Rx (on average −31 ± 7%, p <0.00001) due to their thicker VC tops (3.4 ± 1.1 mm thicker with the range of 1.2 to 4.4 mm) than the old VC applicators. Old VC applicator plans also showed a statistically significant reduction (p <0.00001) due to Ir-192 source anisotropic effect at the apex region but the % reduction over Rx was only −7 ± 9%. However, by adding apex optimization points to the new VC applicator plans, the plans improved 5 mm depth doses (−7 ± 9% over Rx) that were not statistically different from old VC plans (p = 0.923), along with apex VC surface doses (−22 ± 10% over old VC versus −46 ± 7% without using apex optimization points). Conclusion: The use of apex optimization points are important in order to avoid significant additional cold doses (−24 ± 2%) at the prescription depth (5 mm) of apex, especially for the new VC applicators that have thicker tops.« less

Environmental consequences of postulated plutonium releases from General Electric Company Vallecitos Nuclear Center, Vallecitos, California, as a result of severe natural phenomena

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

Jamison, J.D.; Watson, E.C.

1980-11-01

Potential environmental consequences in terms of radiation dose to people are presented for postulated plutonium releases caused by severe natural phenomena at the General Electric Company Vallecitos Nuclear Center, Vallecitos, California. The severe natural phenomena considered are earthquakes, tornadoes, and high straight-line winds. Maximum plutonium deposition values are given for significant locations around the site. All important potential exposure pathways are examined. The most likely 50-year committed dose equivalents are given for the maximum-exposed individual and the population within a 50-mile radius of the plant. The maximum plutonium deposition values likely to occur offsite are also given. The most likelymore » calculated 50-year collective committed dose equivalents are all much lower than the collective dose equivalent expected from 50 years of exposure to natural background radiation and medical x-rays. The most likely maximum residual plutonium contamination estimated to be deposited offsite following the earthquakes, and the 180-mph and 230-mph tornadoes are above the Environmental Protection Agency's (EPA) proposed guideline for plutonium in the general environment of 0.2 ..mu..Ci/m/sup 2/. The deposition values following the 135-mph tornado are below the EPA proposed guidelines.« less

Control strategy of grid-connected photovoltaic generation system based on GMPPT method

NASA Astrophysics Data System (ADS)

Wang, Zhongfeng; Zhang, Xuyang; Hu, Bo; Liu, Jun; Li, Ligang; Gu, Yongqiang; Zhou, Bowen

2018-02-01

There are multiple local maximum power points when photovoltaic (PV) array runs under partial shading condition (PSC).However, the traditional maximum power point tracking (MPPT) algorithm might be easily trapped in local maximum power points (MPPs) and cannot find the global maximum power point (GMPP). To solve such problem, a global maximum power point tracking method (GMPPT) is improved, combined with traditional MPPT method and particle swarm optimization (PSO) algorithm. Under different operating conditions of PV cells, different tracking algorithms are used. When the environment changes, the improved PSO algorithm is adopted to realize the global optimal search, and the variable step incremental conductance (INC) method is adopted to achieve MPPT in optimal local location. Based on the simulation model of the PV grid system built in Matlab/Simulink, comparative analysis of the tracking effect of MPPT by the proposed control algorithm and the traditional MPPT method under the uniform solar condition and PSC, validate the correctness, feasibility and effectiveness of the proposed control strategy.

Evaluation of the Potential for Drug Interactions With Patiromer in Healthy Volunteers

PubMed Central

Offman, Elliot; Brew, Christine Taylor; Garza, Dahlia; Benton, Wade; Mayo, Martha R.; Romero, Alain; Du Mond, Charles; Weir, Matthew R.

2017-01-01

Introduction: Patiromer is a potassium-binding polymer that is not systemically absorbed; however, it may bind coadministered oral drugs in the gastrointestinal tract, potentially reducing their absorption. Methods: Twelve randomized, open-label, 3-period, 3-sequence crossover studies were conducted in healthy volunteers to evaluate the effect of patiromer (perpetrator drug) on absorption and single-dose pharmacokinetics (PK) of drugs (victims) that might be commonly used with patiromer. Subjects received victim drug alone, victim drug administered together with patiromer 25.2 g (highest approved dose), and victim drug administered 3 hours before patiromer 25.2 g. The primary PK endpoints were area under the curve (AUC), extrapolated to infinity (AUC0-∞), and maximum concentration (C max). Results were reported as 90% confidence intervals (CIs) about the geometric mean AUC0-∞ and C max ratios with prespecified equivalence limits of 80% to 125%. Results: Overall, 370 subjects were enrolled, with 365 receiving ≥1 dose of patiromer; 351 subjects completed the studies and all required treatments. When coadministered with patiromer, the 90% CIs for AUC0-∞ remained within 80% to 125% for 9 drugs (amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, and warfarin). The AUC0-∞ point estimate ratios for levothyroxine and metformin with patiromer coadministration were ≥80%, with the lower bounds of the 90% CIs at 76.8% and 72.8%, respectively. For ciprofloxacin, the point estimate for AUC0-∞ was 71.5% (90% CI: 65.3-78.4). For 8 of 12 drugs, point estimates for C max were ≥80% with patiromer coadministration; for ciprofloxacin, clopidogrel, metformin, and metoprolol, the point estimates were <80%. When patiromer was administered 3 hours after each victim drug, the 90% CIs for AUC0-∞ and C max for each drug were within the prespecified 80% to 125% limits. Conclusion: For 9 of the 12 drugs coadministered with patiromer, there were no clinically significant drug–drug interactions. For 3 drugs (ciprofloxacin, levothyroxine, and metformin), a 3-hour separation between patiromer and their administration resulted in no clinically significant drug–drug interactions. PMID:28585859

Ultrafast 3D balanced steady-state free precession MRI of the lung: Assessment of anatomic details in comparison to low-dose CT.

PubMed

Heye, Tobias; Sommer, Gregor; Miedinger, David; Bremerich, Jens; Bieri, Oliver

2015-09-01

To evaluate the anatomical details offered by a new single breath-hold ultrafast 3D balanced steady-state free precession (uf-bSSFP) sequence in comparison to low-dose chest computed tomography (CT). This was an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant prospective study. A total of 20 consecutive patients enrolled in a lung cancer screening trial underwent same-day low-dose chest CT and 1.5T MRI. The presence of pulmonary nodules and anatomical details on 1.9 mm isotropic uf-bSSFP images was compared to 2 mm lung window reconstructions by two readers. The number of branching points on six predefined pulmonary arteries and the distance between the most peripheral visible vessel segment to the pleural surface on thin slices and 50 mm maximum intensity projections (MIP) were assessed. Image quality and sharpness of the pulmonary vasculature were rated on a 5-point scale. The uf-bSSFP detection rate of pulmonary nodules (32 nodules visible on CT and MRI, median diameter 3.9 mm) was 45.5% with 21 false-positive findings (pooled data of both readers). Uf-bSSFP detected 71.2% of branching points visible on CT data. The mean distance between peripheral vasculature and pleural surface was 13.0 ± 4.2 mm (MRI) versus 8.5 ± 3.3 mm (CT) on thin slices and 8.6 ± 3.9 mm (MRI) versus 4.6 ± 2.5 mm (CT) on MIPs. Median image quality and sharpness were rated 4 each. Although CT is superior to MRI, uf-bSSFP imaging provides good anatomical details with sufficient image quality and sharpness obtainable in a single breath-hold covering the entire chest. © 2014 Wiley Periodicals, Inc.

Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats.

PubMed

Fukano, Y; Kawazu, K

2009-08-01

The disposition and metabolism of tafluprost, an ester prodrug of the 15,15-difluoro-prostaglandin F(2alpha) antiglaucoma agent, have been studied in rats after ocular administration. Radioactivity was absorbed very rapidly into the eye and systemic circulation after a single ocular dose of 0.005% [(3)H]tafluprost ophthalmic solution, with maximum levels in plasma and most eye tissues occurring within 15 min. The absorption ratio of radioactivity was approximately 75%, suggesting the high availability of ocular administration of tafluprost. Approximately 10% of the dose was present in cornea at this time, and radioactivity concentrations in this tissue exceeded those in aqueous humor and iris/ciliary body throughout the 24-h study period. After repeated daily ocular doses, radioactivity levels remained greatest in cornea, followed by iris/ciliary body that replaced aqueous humor as the eye tissue containing the second highest radioactivity concentration. In female rats, radioactivity was excreted equally between urine and feces after a single ocular dose, whereas in male rats more was excreted in feces, reflecting the greater biliary excretion in males rats (50% dose) compared with females rats (33% dose). Tafluprost was extensively metabolized in the rat, such that intact prodrug was not detected in plasma, tissues, or excreta by radio-high-performance liquid chromatography. On the other hand, the active moiety, tafluprost acid, was the only noteworthy radioactive component in cornea, aqueous humor, and iris/ciliary body for at least 8 h after the ocular dose, and it was also a major plasma metabolite in early time points. The gender differences in conjugation reactions resulted in the differences in the excretion.

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

Risk analysis: divergent models and convergent interpretations

NASA Technical Reports Server (NTRS)

Carnes, B. A.; Gavrilova, N.

2001-01-01

Material presented at a NASA-sponsored workshop on risk models for exposure conditions relevant to prolonged space flight are described in this paper. Analyses used mortality data from experiments conducted at Argonne National Laboratory on the long-term effects of external whole-body irradiation on B6CF1 mice by 60Co gamma rays and fission neutrons delivered as a single exposure or protracted over either 24 or 60 once-weekly exposures. The maximum dose considered was restricted to 1 Gy for neutrons and 10 Gy for gamma rays. Proportional hazard models were used to investigate the shape of the dose response at these lower doses for deaths caused by solid-tissue tumors and tumors of either connective or epithelial tissue origin. For protracted exposures, a significant mortality effect was detected at a neutron dose of 14 cGy and a gamma-ray dose of 3 Gy. For single exposures, radiation-induced mortality for neutrons also occurred within the range of 10-20 cGy, but dropped to 86 cGy for gamma rays. Plots of risk relative to control estimated for each observed dose gave a visual impression of nonlinearity for both neutrons and gamma rays. At least for solid-tissue tumors, male and female mortality was nearly identical for gamma-ray exposures, but mortality risks for females were higher than for males for neutron exposures. As expected, protracting the gamma-ray dose reduced mortality risks. Although curvature consistent with that observed visually could be detected by a model parameterized to detect curvature, a relative risk term containing only a simple term for total dose was usually sufficient to describe the dose response. Although detectable mortality for the three pathology end points considered typically occurred at the same level of dose, the highest risks were almost always associated with deaths caused by tumors of epithelial tissue origin.

Vedolizumab Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability Following Administration of a Single, Ascending, Intravenous Dose to Healthy Volunteers.

PubMed

Rosario, Maria; Wyant, Timothy; Leach, Timothy; Sankoh, Serap; Scholz, Catherine; Parikh, Asit; Fox, Irving; Feagan, Brian G

2016-11-01

Vedolizumab, a humanized monoclonal antibody against the α 4 β 7 integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn's disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab were evaluated in healthy volunteers. Forty-nine participants (in five cohorts) were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of either vedolizumab (0.2, 0.5, 2.0, 6.0, or 10.0 mg/kg) or placebo. Blood samples were collected for measurement of vedolizumab serum concentrations and α 4 β 7 saturation on peripheral blood lymphocytes by vedolizumab. Pharmacokinetic parameters were computed using a non-compartmental approach. Adverse events were monitored. Vedolizumab maximum observed serum concentration (C max ) demonstrated dose proportionality over the dose range tested. Greater than dose-proportional increases in area under the serum concentration-time curve from time 0 to infinity (AUC 0-inf ) and shorter terminal elimination half-life (t 1/2 ) were observed from 0.2 to 2.0 mg/kg, suggestive of nonlinear pharmacokinetics at lower doses. At doses higher than 2.0 mg/kg, these parameters increased dose proportionally. Saturation of α 4 β 7 was at or near maximal levels (>90 %) at all doses and time points when vedolizumab was measurable in serum. A total of 21 of 39 (54 %) vedolizumab-treated participants were anti-drug antibody (ADA) positive, and 11 (28 %) were persistently ADA positive. Overall, no adverse event signals, including serious infections or malignancies, were apparent. Vedolizumab exhibited target-mediated disposition, characterized by a rapid, saturable, nonlinear elimination process at low concentrations and a slower linear elimination process at higher concentrations. Nearly complete α 4 β 7 saturation was observed at all doses. A single intravenous infusion of vedolizumab was well tolerated by healthy volunteers.

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

Li, Y; Liu, B; Liang, B

Purpose: Current CyberKnife treatment planning system (TPS) provided two dose calculation algorithms: Ray-tracing and Monte Carlo. Ray-tracing algorithm is fast, but less accurate, and also can’t handle irregular fields since a multi-leaf collimator system was recently introduced to CyberKnife M6 system. Monte Carlo method has well-known accuracy, but the current version still takes a long time to finish dose calculations. The purpose of this paper is to develop a GPU-based fast C/S dose engine for CyberKnife system to achieve both accuracy and efficiency. Methods: The TERMA distribution from a poly-energetic source was calculated based on beam’s eye view coordinate system,more » which is GPU friendly and has linear complexity. The dose distribution was then computed by inversely collecting the energy depositions from all TERMA points along 192 collapsed-cone directions. EGSnrc user code was used to pre-calculate energy deposition kernels (EDKs) for a series of mono-energy photons The energy spectrum was reconstructed based on measured tissue maximum ratio (TMR) curve, the TERMA averaged cumulative kernels was then calculated. Beam hardening parameters and intensity profiles were optimized based on measurement data from CyberKnife system. Results: The difference between measured and calculated TMR are less than 1% for all collimators except in the build-up regions. The calculated profiles also showed good agreements with the measured doses within 1% except in the penumbra regions. The developed C/S dose engine was also used to evaluate four clinical CyberKnife treatment plans, the results showed a better dose calculation accuracy than Ray-tracing algorithm compared with Monte Carlo method for heterogeneous cases. For the dose calculation time, it takes about several seconds for one beam depends on collimator size and dose calculation grids. Conclusion: A GPU-based C/S dose engine has been developed for CyberKnife system, which was proven to be efficient and accurate for clinical purpose, and can be easily implemented in TPS.« less

Pharmacokinetics of Lopinavir in HIV-Infected Adults Receiving Rifampin with Adjusted Doses of Lopinavir-Ritonavir Tablets▿

PubMed Central

Decloedt, Eric H.; McIlleron, Helen; Smith, Peter; Merry, Concepta; Orrell, Catherine; Maartens, Gary

2011-01-01

Rifampin coadministration dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of a lopinavir-ritonavir (LPV/r) capsule formulation overcame this interaction, but a subsequent study of double doses of the tablet formulation was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-infected adults. We evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled. The median [interquartile range (IQR)] predose LPV concentrations (C0) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), C0, C12, maximum concentration of drug in serum (Cmax), or half-life (t1/2) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies. PMID:21537021

Pediatric dosimetry for intrapleural lung injections of 32P chromic phosphate

NASA Astrophysics Data System (ADS)

Konijnenberg, Mark W.; Olch, Arthur

2010-10-01

Intracavitary injections of 32P chromic phosphate are used in the therapy of pleuropulmonary blastoma and pulmonary sarcomas in children. The lung dose, however, has never been calculated despite the potential risk of lung toxicity from treatment. In this work the dosimetry has been calculated in target tissue and lung for pediatric phantoms. Pleural cavities were modeled in the Monte Carlo code MCNP within the pediatric MIRD phantoms. Both the depth-dose curves in the pleural lining and into the lung as well as 3D dose distributions were calculated for either homogeneous or inhomogeneous 32P activity distributions. Dose-volume histograms for the lung tissue and isodose graphs were generated. The results for the 2D depth-dose curve to the pleural lining and tumor around the pleural cavity correspond well with the point kernel model-based recommendations. With a 2 mm thick pleural lining, one-third of the lung parenchyma volume gets a dose more than 30 Gy (V30) for 340 MBq 32P in a 10 year old. This is close to lung tolerance. Younger children will receive a larger dose to the lung when the lung density remains equal to the adult value; the V30 relative lung volume for a 5 year old is 35% at an activity of 256 MBq and for a 1 year old 165 MBq yields a V30 of 43%. At higher densities of the lung tissue V30 stays below 32%. All activities yield a therapeutic dose of at least 225 Gy in the pleural lining. With a more normal pleural lining thickness (0.5 mm instead of 2 mm) the injected activities will have to be reduced by a factor 5 to obtain tolerable lung doses in pediatric patients. Previous dosimetry recommendations for the adult apply well down to lung surface areas of 400 cm2. Monte Carlo dosimetry quantitates the three-dimensional dose distribution, providing a better insight into the maximum tolerable activity for this therapy.

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

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

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

Modeling the truebeam linac using a CAD to Geant4 geometry implementation: dose and IAEA-compliant phase space calculations.

PubMed

Constantin, Magdalena; Perl, Joseph; LoSasso, Tom; Salop, Arthur; Whittum, David; Narula, Anisha; Svatos, Michelle; Keall, Paul J

2011-07-01

To create an accurate 6 MV Monte Carlo simulation phase space for the Varian TrueBeam treatment head geometry imported from CAD (computer aided design) without adjusting the input electron phase space parameters. GEANT4 v4.9.2.p01 was employed to simulate the 6 MV beam treatment head geometry of the Varian TrueBeam linac. The electron tracks in the linear accelerator were simulated with Parmela, and the obtained electron phase space was used as an input to the Monte Carlo beam transport and dose calculations. The geometry components are tessellated solids included in GEANT4 as GDML (generalized dynamic markup language) files obtained via STEP (standard for the exchange of product) export from Pro/Engineering, followed by STEP import in Fastrad, a STEP-GDML converter. The linac has a compact treatment head and the small space between the shielding collimator and the divergent are of the upper jaws forbids the implementation of a plane for storing the phase space. Instead, an IAEA (International Atomic Energy Agency) compliant phase space writer was implemented on a cylindrical surface. The simulation was run in parallel on a 1200 node Linux cluster. The 6 MV dose calculations were performed for field sizes varying from 4 x 4 to 40 x 40 cm2. The voxel size for the 60 x 60 x 40 cm3 water phantom was 4 x 4 x 4 mm3. For the 10 x 10 cm2 field, surface buildup calculations were performed using 4 x 4 x 2 mm3 voxels within 20 mm of the surface. For the depth dose curves, 98% of the calculated data points agree within 2% with the experimental measurements for depths between 2 and 40 cm. For depths between 5 and 30 cm, agreement within 1% is obtained for 99% (4 x 4), 95% (10 x 10), 94% (20 x 20 and 30 x 30), and 89% (40 x 40) of the data points, respectively. In the buildup region, the agreement is within 2%, except at 1 mm depth where the deviation is 5% for the 10 x 10 cm2 open field. For the lateral dose profiles, within the field size for fields up to 30 x 30 cm2, the agreement is within 2% for depths up to 10 cm. At 20 cm depth, the in-field maximum dose difference for the 30 x 30 cm2 open field is within 4%, while the smaller field sizes agree within 2%. Outside the field size, agreement within 1% of the maximum dose difference is obtained for all fields. The calculated output factors varied from 0.938 +/- 0.015 for the 4 x 4 cm2 field to 1.088 +/- 0.024 for the 40 x 40 cm2 field. Their agreement with the experimental output factors is within 1%. The authors have validated a GEANT4 simulated IAEA-compliant phase space of the TrueBeam linac for the 6 MV beam obtained using a high accuracy geometry implementation from CAD. These files are publicly available and can be used for further research.

Final Aperture Superposition Technique applied to fast calculation of electron output factors and depth dose curves

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

Faddegon, B.A.; Villarreal-Barajas, J.E.; Mt. Diablo Regional Cancer Center, 2450 East Street, Concord, California

2005-11-15

The Final Aperture Superposition Technique (FAST) is described and applied to accurate, near instantaneous calculation of the relative output factor (ROF) and central axis percentage depth dose curve (PDD) for clinical electron beams used in radiotherapy. FAST is based on precalculation of dose at select points for the two extreme situations of a fully open final aperture and a final aperture with no opening (fully shielded). This technique is different than conventional superposition of dose deposition kernels: The precalculated dose is differential in position of the electron or photon at the downstream surface of the insert. The calculation for amore » particular aperture (x-ray jaws or MLC, insert in electron applicator) is done with superposition of the precalculated dose data, using the open field data over the open part of the aperture and the fully shielded data over the remainder. The calculation takes explicit account of all interactions in the shielded region of the aperture except the collimator effect: Particles that pass from the open part into the shielded part, or visa versa. For the clinical demonstration, FAST was compared to full Monte Carlo simulation of 10x10,2.5x2.5, and 2x8 cm{sup 2} inserts. Dose was calculated to 0.5% precision in 0.4x0.4x0.2 cm{sup 3} voxels, spaced at 0.2 cm depth intervals along the central axis, using detailed Monte Carlo simulation of the treatment head of a commercial linear accelerator for six different electron beams with energies of 6-21 MeV. Each simulation took several hours on a personal computer with a 1.7 Mhz processor. The calculation for the individual inserts, done with superposition, was completed in under a second on the same PC. Since simulations for the pre calculation are only performed once, higher precision and resolution can be obtained without increasing the calculation time for individual inserts. Fully shielded contributions were largest for small fields and high beam energy, at the surface, reaching a maximum of 5.6% at 21 MeV. Contributions from the collimator effect were largest for the large field size, high beam energy, and shallow depths, reaching a maximum of 4.7% at 21 MeV. Both shielding contributions and the collimator effect need to be taken into account to achieve an accuracy of 2%. FAST takes explicit account of the shielding contributions. With the collimator effect set to that of the largest field in the FAST calculation, the difference in dose on the central axis (product of ROF and PDD) between FAST and full simulation was generally under 2%. The maximum difference of 2.5% exceeded the statistical precision of the calculation by four standard deviations. This occurred at 18 MeV for the 2.5x2.5 cm{sup 2} field. The differences are due to the method used to account for the collimator effect.« less

SU-E-T-613: Dosimetric Consequences of Systematic MLC Leaf Positioning Errors

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

Kathuria, K; Siebers, J

2014-06-01

Purpose: The purpose of this study is to determine the dosimetric consequences of systematic MLC leaf positioning errors for clinical IMRT patient plans so as to establish detection tolerances for quality assurance programs. Materials and Methods: Dosimetric consequences were simulated by extracting mlc delivery instructions from the TPS, altering the file by the specified error, reloading the delivery instructions into the TPS, recomputing dose, and extracting dose-volume metrics for one head-andneck and one prostate patient. Machine error was simulated by offsetting MLC leaves in Pinnacle in a systematic way. Three different algorithms were followed for these systematic offsets, and aremore » as follows: a systematic sequential one-leaf offset (one leaf offset in one segment per beam), a systematic uniform one-leaf offset (same one leaf offset per segment per beam) and a systematic offset of a given number of leaves picked uniformly at random from a given number of segments (5 out of 10 total). Dose to the PTV and normal tissue was simulated. Results: A systematic 5 mm offset of 1 leaf for all delivery segments of all beams resulted in a maximum PTV D98 deviation of 1%. Results showed very low dose error in all reasonably possible machine configurations, rare or otherwise, which could be simulated. Very low error in dose to PTV and OARs was shown in all possible cases of one leaf per beam per segment being offset (<1%), or that of only one leaf per beam being offset (<.2%). The errors resulting from a high number of adjacent leaves (maximum of 5 out of 60 total leaf-pairs) being simultaneously offset in many (5) of the control points (total 10–18 in all beams) per beam, in both the PTV and the OARs analyzed, were similarly low (<2–3%). Conclusions: The above results show that patient shifts and anatomical changes are the main source of errors in dose delivered, not machine delivery. These two sources of error are “visually complementary” and uncorrelated (albeit not additive in the final error) and one can easily incorporate error resulting from machine delivery in an error model based purely on tumor motion.« less

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

Ma, R; Zhu, X; Li, S

Purpose: High Dose Rate (HDR) brachytherapy forward planning is principally an iterative process; hence, plan quality is affected by planners’ experiences and limited planning time. Thus, this may lead to sporadic errors and inconsistencies in planning. A statistical tool based on previous approved clinical treatment plans would help to maintain the consistency of planning quality and improve the efficiency of second checking. Methods: An independent dose calculation tool was developed from commercial software. Thirty-three previously approved cervical HDR plans with the same prescription dose (550cGy), applicator type, and treatment protocol were examined, and ICRU defined reference point doses (bladder, vaginalmore » mucosa, rectum, and points A/B) along with dwell times were collected. Dose calculation tool then calculated appropriate range with a 95% confidence interval for each parameter obtained, which would be used as the benchmark for evaluation of those parameters in future HDR treatment plans. Model quality was verified using five randomly selected approved plans from the same dataset. Results: Dose variations appears to be larger at the reference point of bladder and mucosa as compared with rectum. Most reference point doses from verification plans fell between the predicted range, except the doses of two points of rectum and two points of reference position A (owing to rectal anatomical variations & clinical adjustment in prescription points, respectively). Similar results were obtained for tandem and ring dwell times despite relatively larger uncertainties. Conclusion: This statistical tool provides an insight into clinically acceptable range of cervical HDR plans, which could be useful in plan checking and identifying potential planning errors, thus improving the consistency of plan quality.« less

Wake Flow About the Mars Pathfinder Entry Vehicle

NASA Technical Reports Server (NTRS)

Mitcheltree, R. A.; Gnoffo, P. A.

1995-01-01

A computational approach is used to describe the aerothermodynamics of the Mars Pathfinder vehicle entering the Mars atmosphere at the maximum heating and maximum deceleration points in its trajectory. Ablating and nonablating boundary conditions are developed which produce maximum recombination of CO2 on the surface. For the maximum heating trajectory point, an axisymmetric, nonablating calculation predicts a stagnation-point value for the convective heating of 115 W/cm(exp 2). Radiative heating estimates predict an additional 5-12 W/cm(exp 2) at the stagnation point. Peak convective heating on the afterbody occurs on the vehicle's flat stern with a value of 5.9% of the stagnation value. The forebody flow exhibits chemical nonequilibrium behavior, and the flow is frozen in the near wake. Including ablation injection on the forebody lowers the stagnation-point convective heating 18%.

Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

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

McGregor, J.F.

1979-04-01

Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Althoughmore » the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.« less

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PubMed

Ciulla, Thomas A; Criswell, Mark H; Danis, Ronald P; Snyder, Wendy J; Small, Ward

2004-08-01

To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

SU-E-T-270: Optimized Shielding Calculations for Medical Linear Accelerators (LINACs).

PubMed

Muhammad, W; Lee, S; Hussain, A

2012-06-01

The purpose of radiation shielding is to reduce the effective equivalent dose from a medical linear accelerator (LINAC) to a point outside the room to a level determined by individual state/international regulations. The study was performed to design LINAC's room for newly planned radiotherapy centers. Optimized shielding calculations were performed for LINACs having maximum photon energy of 20 MV based on NCRP 151. The maximum permissible dose limits were kept 0.04 mSv/week and 0.002 mSv/week for controlled and uncontrolled areas respectively by following ALARA principle. The planned LINAC's room was compared to the already constructed (non-optimized) LINAC's room to evaluate the shielding costs and the other facilities those are directly related to the room design. In the evaluation process it was noted that the non-optimized room size (i.e., 610 × 610 cm 2 or 20 feet × 20 feet) is not suitable for total body irradiation (TBI) although the machine installed inside was having not only the facility of TBI but the license was acquired. By keeping this point in view, the optimized INAC's room size was kept 762 × 762 cm 2. Although, the area of the optimized rooms was greater than the non-planned room (i.e., 762 × 762 cm 2 instead of 610 × 610 cm 2), the shielding cost for the optimized LINAC's rooms was reduced by 15%. When optimized shielding calculations were re-performed for non-optimized shielding room (i.e., keeping room size, occupancy factors, workload etc. same), it was found that the shielding cost may be lower to 41 %. In conclusion, non- optimized LINAC's room can not only put extra financial burden on the hospital but also can cause of some serious issues related to providing health care facilities for patients. © 2012 American Association of Physicists in Medicine.

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

PubMed

Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for brain penetration. This indicates that variables influencing brain penetration may not be limiting factors for use of piracetam in ischemic stroke.

Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects

PubMed Central

Upreti, Vijay V; Boulton, David W; Li, Li; Ching, Agatha; Su, Hong; LaCreta, Frank P; Patel, Chirag G

2011-01-01

AIM To investigate the effect of co-administration of rifampicin, a potent inducer of cytochrome P450 (CYP) 3A4 enzymes, on the pharmacokinetics (PK) and pharmacodynamics (PD) of saxagliptin and 5-hydroxy saxagliptin in healthy subjects. Saxagliptin is metabolized by CYP3A4/3A5 to 5-hydroxy saxagliptin, its major pharmacologically active metabolite. METHODS In a non-randomized, open label, single sequence design, 14 healthy subjects received single oral doses of saxagliptin 5 mg with and without steady-state rifampicin (600 mg once daily for 6 days). PK (saxagliptin and 5-hydroxy saxagliptin) and PD (plasma DPP-4 activity) were measured for up to 24 h on days 1 and 7. RESULTS Concomitant administration with rifampicin resulted in 53% (point estimate 0.47, 90% CI 0.38, 0.57) and 76% (point estimate 0.24, 90% CI 0.21, 0.27) decreases in the geometric mean Cmax and AUC values of saxagliptin, respectively, with a 39% (point estimate 1.39, 90% CI 1.23, 1.56) increase in the geometric mean Cmax and no change (point estimate 1.03, 90% CI 0.97, 1.09) in the AUC of 5-hydroxy saxagliptin. Similar maximum % inhibition and area under the % inhibition−time effect curve over 24 h for DPP-4 activity were observed when saxagliptin was administered alone or with rifampicin. The saxagliptin total active moieties exposure (AUC) decreased by 27% (point estimate 0.73, 90% CI 0.66, 0.81). Saxagliptin with or without rifampicin in this study was generally well tolerated. CONCLUSIONS Lack of change of PD effect of saxagliptin is consistent with the observed 27% reduction in systemic exposure to the total active moieties, which is not considered clinically meaningful. Based on these findings, it is not necessary to adjust the saxagliptin dose when co-administered with rifampicin. PMID:21651615

Efficacy and safety of Privigen(®) in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study).

PubMed

Léger, Jean-Marc; De Bleecker, Jan L; Sommer, Claudia; Robberecht, Wim; Saarela, Mika; Kamienowski, Jerzy; Stelmasiak, Zbigniew; Mielke, Orell; Tackenberg, Björn; Shebl, Amgad; Bauhofer, Artur; Zenker, Othmar; Merkies, Ingemar S J

2013-06-01

This prospective, multicenter, single-arm, open-label Phase III study aimed to evaluate the efficacy and safety of Privigen(®) (10% liquid human intravenous immunoglobulin [IVIG], stabilized with L-proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3-week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being ≥35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG-pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%-76.43%). IVIG-pretreated patients demonstrated a higher responder rate than IVIG-naïve patients (76.9% vs. 46.7%). The median (25%-75% quantile) INCAT score improved from 3.5 (3.0-4.5) points at baseline to 2.5 (1.0-3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5-72.0] points vs. 75.5 [71.5-79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well-tolerated induction and maintenance treatment in patients with CIDP. © 2013 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

An evaluation of several different classification schemes - Their parameters and performance. [maximum likelihood decision for crop identification

NASA Technical Reports Server (NTRS)

Scholz, D.; Fuhs, N.; Hixson, M.

1979-01-01

The overall objective of this study was to apply and evaluate several of the currently available classification schemes for crop identification. The approaches examined were: (1) a per point Gaussian maximum likelihood classifier, (2) a per point sum of normal densities classifier, (3) a per point linear classifier, (4) a per point Gaussian maximum likelihood decision tree classifier, and (5) a texture sensitive per field Gaussian maximum likelihood classifier. Three agricultural data sets were used in the study: areas from Fayette County, Illinois, and Pottawattamie and Shelby Counties in Iowa. The segments were located in two distinct regions of the Corn Belt to sample variability in soils, climate, and agricultural practices.

Sci—Thur AM: YIS - 11: Estimation of Bladder-Wall Cumulative Dose in Multi-Fraction Image-Based Gynaecological Brachytherapy Using Deformable Point Set Registration

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

Zakariaee, R; Brown, C J; Hamarneh, G

2014-08-15

Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions ofmore » 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.« less

Leaf position optimization for step-and-shoot IMRT.

PubMed

De Gersem, W; Claus, F; De Wagter, C; Van Duyse, B; De Neve, W

2001-12-01

To describe the theoretical basis, the algorithm, and implementation of a tool that optimizes segment shapes and weights for step-and-shoot intensity-modulated radiation therapy delivered by multileaf collimators. The tool, called SOWAT (Segment Outline and Weight Adapting Tool) is applied to a set of segments, segment weights, and corresponding dose distribution, computed by an external dose computation engine. SOWAT evaluates the effects of changing the position of each collimating leaf of each segment on an objective function, as follows. Changing a leaf position causes a change in the segment-specific dose matrix, which is calculated by a fast dose computation algorithm. A weighted sum of all segment-specific dose matrices provides the dose distribution and allows computation of the value of the objective function. Only leaf position changes that comply with the multileaf collimator constraints are evaluated. Leaf position changes that tend to decrease the value of the objective function are retained. After several possible positions have been evaluated for all collimating leaves of all segments, an external dose engine recomputes the dose distribution, based on the adapted leaf positions and weights. The plan is evaluated. If the plan is accepted, a segment sequencer is used to make the prescription files for the treatment machine. Otherwise, the user can restart SOWAT using the new set of segments, segment weights, and corresponding dose distribution. The implementation was illustrated using two example cases. The first example is a T1N0M0 supraglottic cancer case that was distributed as a multicenter planning exercise by investigators from Rotterdam, The Netherlands. The exercise involved a two-phase plan. Phase 1 involved the delivery of 46 Gy to a concave-shaped planning target volume (PTV) consisting of the primary tumor volume and the elective lymph nodal regions II-IV on both sides of the neck. Phase 2 involved a boost of 24 Gy to the primary tumor region only. SOWAT was applied to the Phase 1 plan. Parotid sparing was a planning goal. The second implementation example is an ethmoid sinus cancer case, planned with the intent of bilateral visus sparing. The median PTV prescription dose was 70 Gy with a maximum dose constraint to the optic pathway structures of 60 Gy. The initial set of segments, segment weights, and corresponding dose distribution were obtained, respectively, by an anatomy-based segmentation tool, a segment weight optimization tool, and a differential scatter-air ratio dose computation algorithm as external dose engine. For the supraglottic case, this resulted in a plan that proved to be comparable to the plans obtained at the other institutes by forward or inverse planning techniques. After using SOWAT, the minimum PTV dose and PTV dose homogeneity increased; the maximum dose to the spinal cord decreased from 38 Gy to 32 Gy. The left parotid mean dose decreased from 22 Gy to 19 Gy and the right parotid mean dose from 20 to 18 Gy. For the ethmoid sinus case, the target homogeneity increased by leaf position optimization, together with a better sparing of the optical tracts. By using SOWAT, the plans improved with respect to all plan evaluation end points. Compliance with the multileaf collimator constraints is guaranteed. The treatment delivery time remains almost unchanged, because no additional segments are created.

SU-E-T-614: Derivation of Equations to Define Inflection Points and Its Analysis in Flattening Filter Free Photon Beams Based On the Principle of Polynomial function

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

Muralidhar, K Raja; Komanduri, K

2014-06-01

Purpose: The objective of this work is to present a mechanism for calculating inflection points on profiles at various depths and field sizes and also a significant study on the percentage of doses at the inflection points for various field sizes and depths for 6XFFF and 10XFFF energy profiles. Methods: Graphical representation was done on Percentage of dose versus Inflection points. Also using the polynomial function, the authors formulated equations for calculating spot-on inflection point on the profiles for 6X FFF and 10X FFF energies for all field sizes and at various depths. Results: In a flattening filter free radiationmore » beam which is not like in Flattened beams, the dose at inflection point of the profile decreases as field size increases for 10XFFF. Whereas in 6XFFF, the dose at the inflection point initially increases up to 10x10cm2 and then decreases. The polynomial function was fitted for both FFF beams for all field sizes and depths. For small fields less than 5x5 cm2 the inflection point and FWHM are almost same and hence analysis can be done just like in FF beams. A change in 10% of dose can change the field width by 1mm. Conclusion: The present study, Derivative of equations based on the polynomial equation to define inflection point concept is precise and accurate way to derive the inflection point dose on any FFF beam profile at any depth with less than 1% accuracy. Corrections can be done in future studies based on the multiple number of machine data. Also a brief study was done to evaluate the inflection point positions with respect to dose in FFF energies for various field sizes and depths for 6XFFF and 10XFFF energy profiles.« less

Mars surface radiation exposure for solar maximum conditions and 1989 solar proton events

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.

1992-01-01

The Langley heavy-ion/nucleon transport code, HZETRN, and the high-energy nucleon transport code, BRYNTRN, are used to predict the propagation of galactic cosmic rays (GCR's) and solar flare protons through the carbon dioxide atmosphere of Mars. Particle fluences and the resulting doses are estimated on the surface of Mars for GCR's during solar maximum conditions and the Aug., Sep., and Oct. 1989 solar proton events. These results extend previously calculated surface estimates for GCR's at solar minimum conditions and the Feb. 1956, Nov. 1960, and Aug. 1972 solar proton events. Surface doses are estimated with both a low-density and a high-density carbon dioxide model of the atmosphere for altitudes of 0, 4, 8, and 12 km above the surface. A solar modulation function is incorporated to estimate the GCR dose variation between solar minimum and maximum conditions over the 11-year solar cycle. By using current Mars mission scenarios, doses to the skin, eye, and blood-forming organs are predicted for short- and long-duration stay times on the Martian surface throughout the solar cycle.

The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test.

PubMed

Perry, Paul J; Fredriksen, Kristian; Chew, Stephanie; Ip, Eric J; Lopes, Ingrid; Doroudgar, Shadi; Thomas, Kelan

2015-09-01

Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was assessed by their performance in a driving simulator (STISIM® Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1-h postdrug administration. The one-time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM® Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior. © 2015 American Academy of Forensic Sciences.

Pharmacology of 13-cis-retinoic acid in humans.

PubMed

Kerr, I G; Lippman, M E; Jenkins, J; Myers, C E

1982-05-01

Vitamin A and its analogs (retinoids) have shown great promise for the chemoprevention of cancer as well as being a possible new class of chemotherapeutic agents. A Phase I and II trial of 13-cis-retinoic acid in advanced cancers was initiated, and the clinical pharmacology of the drug was studied. All patients received p.o. 13-cis-retinoic acid starting at 0.5 mg/kg/day, escalating over 4 weeks to a maximum dose of 8 mg/kg/day in divided doses. Although there was a linear correlation of plasma concentration with dose escalation, large inter-individual variations in peak plasma concentrations were noted. At the maximum drug dose, the mean peak plasma concentration was 4 X 10(-6) M. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 X 10(-6) M. The drug was metabolized extensively to a metabolite, the concentrations of which exceeding parent 13-cis-retinoic acid concentrations with chronic dosing. Retinol concentrations were below the normal range.

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

PubMed

Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-06

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

An analysis of collegiate band directors' exposure to sound pressure levels

NASA Astrophysics Data System (ADS)

Roebuck, Nikole Moore

Noise-induced hearing loss (NIHL) is a significant but unfortunate common occupational hazard. The purpose of the current study was to measure the magnitude of sound pressure levels generated within a collegiate band room and determine if those sound pressure levels are of a magnitude that exceeds the policy standards and recommendations of the Occupational Safety and Health Administration (OSHA), and the National Institute of Occupational Safety and Health (NIOSH). In addition, reverberation times were measured and analyzed in order to determine the appropriateness of acoustical conditions for the band rehearsal environment. Sound pressure measurements were taken from the rehearsal of seven collegiate marching bands. Single sample t test were conducted to compare the sound pressure levels of all bands to the noise exposure standards of OSHA and NIOSH. Multiple regression analysis were conducted and analyzed in order to determine the effect of the band room's conditions on the sound pressure levels and reverberation times. Time weighted averages (TWA), noise percentage doses, and peak levels were also collected. The mean Leq for all band directors was 90.5 dBA. The total accumulated noise percentage dose for all band directors was 77.6% of the maximum allowable daily noise dose under the OSHA standard. The total calculated TWA for all band directors was 88.2% of the maximum allowable daily noise dose under the OSHA standard. The total accumulated noise percentage dose for all band directors was 152.1% of the maximum allowable daily noise dose under the NIOSH standards, and the total calculated TWA for all band directors was 93dBA of the maximum allowable daily noise dose under the NIOSH standard. Multiple regression analysis revealed that the room volume, the level of acoustical treatment and the mean room reverberation time predicted 80% of the variance in sound pressure levels in this study.

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

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

Cunliffe, A; Contee, C; White, B

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

Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging.

PubMed

Burghelea, Manuela; Verellen, Dirk; Poels, Kenneth; Gevaert, Thierry; Depuydt, Tom; Tournel, Koen; Hung, Cecilia; Simon, Viorica; Hiraoka, Masahiro; de Ridder, Mark

2015-07-15

The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°. Copyright © 2015 Elsevier Inc. All rights reserved.

Organ dose measurement using Optically Stimulated Luminescence Detector (OSLD) during CT examination

NASA Astrophysics Data System (ADS)

Yusuf, Muhammad; Alothmany, Nazeeh; Abdulrahman Kinsara, Abdulraheem

2017-10-01

This study provides detailed information regarding the imaging doses to patient radiosensitive organs from a kilovoltage computed tomography (CT) scan procedure using OSLD. The study reports discrepancies between the measured dose and the calculated dose from the ImPACT scan, as well as a comparison with the dose from a chest X-ray radiography procedure. OSLDs were inserted in several organs, including the brain, eyes, thyroid, lung, heart, spinal cord, breast, spleen, stomach, liver and ovaries, of the RANDO phantom. Standard clinical scanning protocols were used for each individual site, including the brain, thyroid, lung, breast, stomach, liver and ovaries. The measured absorbed doses were then compared with the simulated dose obtained from the ImPACT scan. Additionally, the equivalent doses for each organ were calculated and compared with the dose from a chest X-ray radiography procedure. Absorbed organ doses measured by OSLD in the RANDO phantom of up to 17 mGy depend on the organ scanned and the scanning protocols used. A maximum 9.82% difference was observed between the target organ dose measured by OSLD and the results from the ImPACT scan. The maximum equivalent organ dose measured during this experiment was equal to 99.899 times the equivalent dose from a chest X-ray radiography procedure. The discrepancies between the measured dose with the OSLD and the calculated dose from the ImPACT scan were within 10%. This report recommends the use of OSLD for measuring the absorbed organ dose during CT examination.

Identifying a maximum tolerated contour in two-dimensional dose-finding

PubMed Central

Wages, Nolan A.

2016-01-01

The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

A Hybrid Maximum Power Point Tracking Method for Automobile Exhaust Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Quan, Rui; Zhou, Wei; Yang, Guangyou; Quan, Shuhai

2017-05-01

To make full use of the maximum output power of automobile exhaust thermoelectric generator (AETEG) based on Bi2Te3 thermoelectric modules (TEMs), taking into account the advantages and disadvantages of existing maximum power point tracking methods, and according to the output characteristics of TEMs, a hybrid maximum power point tracking method combining perturb and observe (P&O) algorithm, quadratic interpolation and constant voltage tracking method was put forward in this paper. Firstly, it searched the maximum power point with P&O algorithms and a quadratic interpolation method, then, it forced the AETEG to work at its maximum power point with constant voltage tracking. A synchronous buck converter and controller were implemented in the electric bus of the AETEG applied in a military sports utility vehicle, and the whole system was modeled and simulated with a MATLAB/Simulink environment. Simulation results demonstrate that the maximum output power of the AETEG based on the proposed hybrid method is increased by about 3.0% and 3.7% compared with that using only the P&O algorithm and the quadratic interpolation method, respectively. The shorter tracking time is only 1.4 s, which is reduced by half compared with that of the P&O algorithm and quadratic interpolation method, respectively. The experimental results demonstrate that the tracked maximum power is approximately equal to the real value using the proposed hybrid method,and it can preferentially deal with the voltage fluctuation of the AETEG with only P&O algorithm, and resolve the issue that its working point can barely be adjusted only with constant voltage tracking when the operation conditions change.

SU-E-T-450: How Important Is a Reproducible Breath Hold for DIBH Breast Radiotherapy?

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

Liu, H; Wentworth, S; Sintay, B

Purpose: Deep inspiration breath hold (DIBH) for left-sided breast cancer has been shown to reduce heart dose. Surface imaging helps to ensure accurate breast positioning, but does not guarantee a reproducible breath hold (BH) at DIBH treatments. We examine the effects of variable BH positions for DIBH treatments. Methods: Twenty-Five patients with free breathing (FB) and DIBH scans were reviewed. Four plans were created for each patient: 1) FB, 2) DIBH, 3) FB-DIBH – the DIBH plans were copied to the FB images and recalculated (image registration was based on breast tissue), and 4) P-DIBH – a partial BH withmore » the heart shifted midway between the FB and DIBH positions. The FB-DIBH plans give “worst case” scenarios for surface imaging DIBH, where the breast is aligned by surface imaging but the patient is not holding their breath. Students t-tests were used to compare dose metrics. Results: The DIBH plans gave lower heart dose and comparable breast coverage versus FB in all cases. The FB-DIBH plans showed no significant difference versus FB plans for breast coverage, mean heart dose, or maximum heart dose (p >= 0.10). The mean heart dose differed between FB-DIBH and FB by < 2 Gy for all cases, the maximum heart dose differed by < 2 Gy for 21 cases. The P-DIBH plans showed significantly lower mean heart dose than FB (p = 0.01). The mean heart doses for the P-DIBH plans were < FB for 22 cases, the maximum dose < FB for 18 cases. Conclusions: A DIBH plan delivered to a FB patient set-up with surface imaging will yield similar dosimetry to a plan created and delivered FB. A DIBH plan delivered with even a partial BH can give reduced heart dose compared to FB techniques when the breast tissue is well aligned.« less

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

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

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

SU-F-T-403: Impact of Dose Reduction for Simulation CT On Radiation Therapy Treatment Planning

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

Liang, Q; Shah, P; Li, S

Purpose: To investigate the feasibility of applying ALARA principles to current treatment planning CT scans. The study aims to quantitatively verify lower dose scans does not alter treatment planning. Method: Gammex 467 tissue characterization phantom with inserts of 14 different materials was scanned at seven different mA levels (30∼300 mA). CT numbers of different inserts were measured. Auto contouring for bone and lung in treatment planning system (Pinnacle) was used to evaluate the effect of CT number accuracy from treatment planning aspect, on the 30 and 300 mA-scanned images. A head CT scan intended for a 3D whole brain radiationmore » treatment was evaluated. Dose calculations were performed on normal scanned images using clinical protocol (120 kVP, Smart mA, maximum 291 mA), and the images with added simulating noise mimicking a 70 mA scan. Plan parameters including isocenter, beam arrangements, block shapes, dose grid size and resolution, and prescriptions were kept the same for these two plans. The calculated monitor units (MUs) for these two plans were compared. Results: No significant degradation of CT number accuracy was found at lower dose levels from both the phantom scans, and the patient images with added noise. The CT numbers kept consistent when mA is higher than 60 mA. The auto contoured volumes for lung and cortical bone show 0.3% and 0.12% of differences between 30 mA and 300 mA respectively. The two forward plans created on regular and low dose images gave the same calculated MU, and 98.3% of points having <1% of dose difference. Conclusion: Both phantom and patient studies quantitatively verified low dose CT provides similar quality for treatment planning at 20–25% of regular scan dose. Therefore, there is the potential to optimize simulation CT scan protocol to fulfil the ALARA principle and limit unnecessary radiation exposure to non-targeted tissues.« less

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.

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

PubMed

Haslett, Kate; Franks, Kevin; Hanna, Gerard G; Harden, Susan; Hatton, Matthew; Harrow, Stephen; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil; Faivre-Finn, Corinne

2016-04-15

The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. NCT01836692; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

SU-E-T-276: Dose Calculation Accuracy with a Standard Beam Model for Extended SSD Treatments

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

Kisling, K; Court, L; Kirsner, S

2015-06-15

Purpose: While most photon treatments are delivered near 100cm SSD or less, a subset of patients may benefit from treatment at SSDs greater than 100cm. A proposed rotating chair for upright treatments would enable isocentric treatments at extended SSDs. The purpose of this study was to assess the accuracy of the Pinnacle{sup 3} treatment planning system dose calculation for standard beam geometries delivered at extended SSDs with a beam model commissioned at 100cm SSD. Methods: Dose to a water phantom at 100, 110, and 120cm SSD was calculated with the Pinnacle {sup 3} CC convolve algorithm for 6x beams formore » 5×5, 10×10, 20×20, and 30×30cm{sup 2} field sizes (defined at the water surface for each SSD). PDDs and profiles (depths of 1.5, 12.5, and 22cm) were compared to measurements in water with an ionization chamber. Point-by-point agreement was analyzed, as well as agreement in field size defined by the 50% isodose. Results: The deviations of the calculated PDDs from measurement, analyzed from depth of maximum dose to 23cm, were all within 1.3% for all beam geometries. In particular, the calculated PDDs at 10cm depth were all within 0.7% of measurement. For profiles, the deviations within the central 80% of the field were within 2.2% for all geometries. The field sizes all agreed within 2mm. Conclusion: The agreement of the PDDs and profiles calculated by Pinnacle3 for extended SSD geometries were within the acceptability criteria defined by Van Dyk (±2% for PDDs and ±3% for profiles). The accuracy of the calculation of more complex beam geometries at extended SSDs will be investigated to further assess the feasibility of using a standard beam model commissioned at 100cm SSD in Pinnacle3 for extended SSD treatments.« less

In Vivo Pharmacokinetics of Bromfenac Ophthalmic Solution 0.075%, Bromfenac Ophthalmic Solution 0.07%, and Nepafenac/Amfenac Ophthalmic Suspension 0.3% in Rabbits.

PubMed

Sheppard, John D; Cockrum, Paul C; Justice, Angela; Jasek, Mark C

2018-05-14

Little is known of the ocular distribution characteristics of currently branded non-steroidal anti-inflammatory drugs (NSAIDs) in the United States. This study was designed to predict the ocular bioavailability characteristics in humans using Dutch Belted rabbits as a surrogate. Commercially available, topically-applied NSAIDs containing bromfenac or nepafenac/amfenac were evaluated. 126 healthy adult Dutch Belted rabbits were randomly assigned to three treatment cohorts (BromSite ® twice daily [BID] in the right eye, BromSite ® once daily [QD] in the right eye, Prolensa ® QD in the right eye and Ilevro™ QD in the left eye) and 7 post-dosing time points (0.5, 1, 2, 4, 8, 12, 24 h after final instillation). The study eyes received 40 µL of the assigned drug for a consecutive 9 days. Samples of aqueous humor, iris-ciliary body, choroid, sclera, and retina were harvested from the study eyes at the assigned time point after the last dose on the 9th day. NSAID content in ocular tissues was analyzed using high-performance liquid chromatography (HPLC), and area under the curve (AUC 0.5-24h ), maximum concentration (C max ), and time to maximum concentration (T max ) were determined. Peak NSAID concentrations were reached within 1-3 h in the anterior segment and within 1-3 h in the posterior segment after last dose. Throughout the ocular tissues, both AUC and C max for BromSite ® (BID and QD) were consistently higher than respective NSAID concentrations of Prolensa ® QD and Ilevro ® QD. When comparing BromSite ® BID to QD, the BID regimen produced generally higher but statistically similar bromfenac concentrations throughout the ocular tissues except in the aqueous humor and iris-ciliary body, where the AUC BID was statistically significantly higher with BromSite ® BID. As a surrogate to human ocular bioavailability, BromSite ® demonstrated significantly greater NSAID compared to Prolensa ® QD and Ilevro ® QD. The DuraSite ® component of BromSite ® appears to enhance ocular penetration throughout both anterior and posterior tissues. Sun Pharmaceutical Industries Ltd.

Development of a novel low-radiation-absorbent lok-bar to reduce X-ray scattering and absorption in RapidArc® treatment planning and dose delivery.

PubMed

Monzen, Hajime; Kubo, Kazuki; Tamura, Mikoto; Hayakawa, Masaru; Nishimura, Yasumasa

2017-05-01

We developed a novel low-radiation-absorbent lok-bar (HM-bar) that is used to secure the immobilizers to the couch. The aim of this study was to investigate the X-ray scattering and absorption properties of the HM-bar in computed tomography (CT) simulation and radiotherapy dose delivery using the Varian Exact™ lok-bar (VL-bar) as a benchmark. CT images were obtained with or without lok-bar, and then each image was visually evaluated for artifacts. The attenuation rates for each lok-bar were measured using a farmer-type ionization chamber (PTW30013) and the I'mRT phantom (IBA Dosimetry GmbH). Measurement points were between gantry angles of 110 and 180°. The treatment apparatus was a NovalisTx (Brainlab AG); X-ray energies were set at 6 MV and 10 MV. In the presence of each lok-bar, the radiation dose was measured in accordance with 10 volumetric modulated arc therapy-stereotactic body radiation therapy (VMAT-SBRT) plans for lung cancer. Artifacts were seldom observed in the CT scans of the HM-bar. The attenuation rate of each lok-bar was higher when the X-ray energy was set at 6 MV than at 10 MV. The highest attenuation rate in the VL-bar was observed at a gantry angle of 112°; the rates were 22.4% at 6 MV and 19.3% at 10 MV. Similarly, the highest attenuation rate for the HM-bar was also observed at a gantry angle of 112°; the rates were 12.2% and 10.1% at 6 MV and 10 MV, respectively. When the VL-bar was evaluated, the isocenter dose of the VMAT-SBRT plans was attenuated by 2.6% as a maximum case. In the case of the HM-bar, the maximum attenuation was 1.4%. In the measurements of each VMAT-SBRT plan, the difference of the dose attenuation rate between the VL-bar and HM-bar was approximately 1%. The HM-bar could be used to minimize the occurrence of artifacts and provide good images in CT scans regarding radiotherapy planning and dose calculation. It can be used for patient therapy at hospitals to provide accurate dose delivery because of its low X-ray scattering and absorption characteristics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with I-131 radiation dose and other characteristics

PubMed Central

Leeman-Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.

2012-01-01

Background Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Methods We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were <18 y.o. in 1986 and received 0.008-8.6 Gy of I-131 to the thyroid and explored associations between mutation types and I-131 dose and other characteristics. Results RET/PTC rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ rearrangement were identified. We found a significant negative association with I-131 dose for BRAF and RAS point mutations and a significant concave association with I-131 dose, with an inflection point at 1.6 Gy and odds ratio 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared to point mutations, rearrangements were associated with residence in the relatively iodine deficient Zhytomyr region, younger age at exposure or surgery, and male gender. Conclusions Our results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. PMID:23436219

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

2016-03-01

Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

Commissioning and comprehensive quality assurance of commercial 3D treatment planning system using IAEA Technical Report Series-430.

PubMed

Jamema, S V; Upreti, R R; Sharma, S; Deshpande, D D

2008-09-01

The purpose of this work is to report the results of commissioning and to establish a quality assurance (QA) program for commercial 3D treatment planning system (TPS) based on IAEA Technical Report Series 430. Eclipse v 7.3.10, (Varian Medical Systems, Palo Alto, CA, U.S.A.) TPS was commissioned for a Clinac 6EX (Varian Medical Systems, Palo Alto, CA, USA) linear accelerator. CT images of a phantom with various known in-homogeneities were acquired. The images were transferred to TPS and tested for various parameters related to patient data acquisition, anatomical modeling, plan evaluation and dose calculation. Dosimetric parameters including open, asymmetric and wedged shaped fields, oblique incidence, buildup region behavior and SSD dependence were evaluated. Representative clinical cases were tested for MU calculation and point doses. The maximum variation between the measured and the known CT numbers was 20 +/- 11.7 HU (1 SD). The results of all non-dosimetric tests were found within tolerance, however expansion at the sharp corners was found distorted. The accuracy of the DVH calculations depends on the grid size. TPS calculations of all the dosimetric parameters were in good agreement with the measured values, however for asymmetric open and wedged fields, few points were found out of tolerance. Smaller grid size calculation showed better agreement of dose calculation in the build-up region. Independent tests for MU calculation showed a variation within +/-2% (relative to planning system), meanwhile variation of 3.0% was observed when the central axis was blocked. The test results were in agreement with the tolerance specified by IAEA TRS 430. A subset of the commissioning tests has been identified as a baseline data for an ongoing QA program.

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D

2009-01-01

AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066

Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.

PubMed

Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

2004-01-01

A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably.

Octanoic acid in alcohol-responsive essential tremor

PubMed Central

McCrossin, Gayle; Lungu, Codrin; Considine, Elaine; Toro, Camilo; Nahab, Fatta B.; Auh, Sungyoung; Buchwald, Peter; Grimes, George J.; Starling, Judith; Potti, Gopal; Scheider, Linda; Kalowitz, Daniel; Bowen, Daniel; Carnie, Andrea; Hallett, Mark

2013-01-01

Objective: To assess safety and efficacy of an oral, single, low dose of octanoic acid (OA) in subjects with alcohol-responsive essential tremor (ET). Methods: We conducted a double-blind, placebo-controlled, crossover, phase I/II clinical trial evaluating the effect of 4 mg/kg OA in 19 subjects with ET. The primary outcome was accelerometric postural tremor power of the dominant hand 80 minutes after administration. Secondary outcomes included digital spiral analysis, pharmacokinetic sampling, as well as safety measures. Results: OA was safe and well tolerated. Nonserious adverse events were mild (Common Terminology Criteria for Adverse Events grade 1) and equally present after OA and placebo. At the primary outcome, OA effects were not different from placebo. Secondary outcome analyses of digital spiral analysis, comparison across the entire time course in weighted and nonweighted accelerometry, as well as nondominant hand tremor power did not show a benefit of OA over placebo. The analysis of individual time points showed that OA improved tremor at 300 minutes (dominant hand, F1,16 = 5.49, p = 0.032 vs placebo), with a maximum benefit at 180 minutes after OA (both hands, F1,16 = 6.1, p = 0.025). Conclusions: Although the effects of OA and placebo at the primary outcome were not different, secondary outcome measures suggest superiority of OA in reducing tremor at later time points, warranting further trials at higher dose levels. Classification of evidence: This study provides Class I evidence that a single 4-mg/kg dose of OA is not effective in reducing postural tremor in patients with ET at a primary outcome of 80 minutes, but is effective for a secondary outcome after 180 minutes. PMID:23408867

SU-E-T-62: Cardiac Toxicity in Dynamic Conformal Arc Therapy, Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy of Lung Cancers

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

Ming, X; Zhang, Y; Yale University, New Haven, CT, US

2014-06-01

Purpose: The cardiac toxicity for lung cancer patients, each treated with dynamic conformal arc therapy (DAT), intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) is investigated. Methods: 120 lung patients were selected for this study: 25 treated with DAT, 50 with IMRT and 45 with VMAT. For comparison, all plans were generated in the same treatment planning system, normalized such that the 100% isodose lines encompassed 95% of planning target volume. The plan quality was evaluated in terms of homogeneity index (HI) and 95% conformity index (%95 CI) for target dose coverage and mean dose, maximum dose, V{submore » 30} Gy as well as V{sub 5} Gy for cardiac toxicity analysis. Results: When all the plans were analyzed, the VMAT plans offered the best target coverage with 95% CI = 0.992 and HI = 1.23. The DAT plans provided the best heart sparing with mean heart dose = 2.3Gy and maximum dose = 11.6Gy, as compared to 5.7 Gy and 31.1 Gy by IMRT as well as 4.6 Gy and 30.9 Gy by VMAT. The mean V30Gy and V5Gy of the heart in the DAT plans were up to 11.7% lower in comparison to the IMRT and VMAT plans. When the tumor volume was considered, the VMAT plans spared up to 70.9% more doses to the heart when the equivalent diameter of the tumor was larger than 4cm. Yet the maximum dose to the heart was reduced the most in the DAT plans with up to 139.8% less than that of the other two plans. Conclusion: Overall, the VMAT plans achieved the best target coverage among the three treatment modalities, and would spare the heart the most for the larger tumors. The DAT plans appeared advantageous in delivering the least maximum dose to the heart as compared to the IMRT and VMAT plans.« less

The effect of tandem-ovoid titanium applicator on points A, B, bladder, and rectum doses in gynecological brachytherapy using 192Ir.

PubMed

Sadeghi, Mohammad Hosein; Sina, Sedigheh; Mehdizadeh, Amir; Faghihi, Reza; Moharramzadeh, Vahed; Meigooni, Ali Soleimani

2018-02-01

The dosimetry procedure by simple superposition accounts only for the self-shielding of the source and does not take into account the attenuation of photons by the applicators. The purpose of this investigation is an estimation of the effects of the tandem and ovoid applicator on dose distribution inside the phantom by MCNP5 Monte Carlo simulations. In this study, the superposition method is used for obtaining the dose distribution in the phantom without using the applicator for a typical gynecological brachytherapy (superposition-1). Then, the sources are simulated inside the tandem and ovoid applicator to identify the effect of applicator attenuation (superposition-2), and the dose at points A, B, bladder, and rectum were compared with the results of superposition. The exact dwell positions, times of the source, and positions of the dosimetry points were determined in images of a patient and treatment data of an adult woman patient from a cancer center. The MCNP5 Monte Carlo (MC) code was used for simulation of the phantoms, applicators, and the sources. The results of this study showed no significant differences between the results of superposition method and the MC simulations for different dosimetry points. The difference in all important dosimetry points was found to be less than 5%. According to the results, applicator attenuation has no significant effect on the calculated points dose, the superposition method, adding the dose of each source obtained by the MC simulation, can estimate the dose to points A, B, bladder, and rectum with good accuracy.

The Advantages of Collimator Optimization for Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Doozan, Brian

The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA 0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam's eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same control of the PTV.

Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity.

PubMed

Hornsby, Lori B; Whitley, Heather P; Hester, E Kelly; Thompson, Melissa; Donaldson, Amy

2010-01-01

To assess patient knowledge regarding acetaminophen dosing, toxicity, and recognition of acetaminophen-containing products. Descriptive, nonexperimental, cross-sectional study. Alabama, January 2007 to February 2008. 284 patients at four outpatient medical facilities. 12-item investigator-administered questionnaire. Degree of patient knowledge regarding acetaminophen safety, dosing recommendations, toxicity, alternative names and abbreviations, and products. Two-thirds of the 284 patients completing the survey reported current or recent use of pain, cold, or allergy medication. Of these, 25% reported knowing the active ingredient. Of patients, 46% and 13% knew that "acetaminophen" and "APAP," respectively, were synonymous with "Tylenol." Several patients (12%) believed that ingesting a harmful amount of acetaminophen was difficult or impossible. One-third of patients correctly identified the maximum daily dose, 10% reported a dose greater than 4 g, 25% were unsure of the dose, and 7% were unsure whether a maximum dose existed. One-half recognized liver damage as the primary toxicity. Results were similar between acetaminophen users and nonusers. Deficiencies were found in patient knowledge regarding acetaminophen recognition, dosing, and potential for toxicity. The development of effective educational initiatives is warranted to ensure patient awareness and limit the potential for acetaminophen overdose.

SU-F-T-585: A Novel Phantom for Dosimetric Validation of SBRT for Spinal Lesions

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

Papanikolaou, KN; Ha, C; Kirby, N

2016-06-15

Purpose: SBRT is proving to be a very efficacious treatment modality for an increasing number of indications, including spine lesions. We have developed a novel phantom to serve as an end-to-end QA tool for either patient specific QA or commissioning QA of SBRT for spine lesions. Methods: In this feasibility study, we have selected a patient with a single metastatic lesion in the L5 vertebral body. The patient’s CT simulation scan was used to develop a VMAT treatment plan delivering 18Gy to at least 90% of the target volume, following the guidelines of RTOG 0631. The treatment plan was developedmore » with the Pinnacle planning system using the adaptive convolution superposition calculation mode. The approved plan was re-calculated using the Monaco planning system. We performed a pseudo-in-vivo study whereby we manufactured two copies of a phantom to the exact shape and anatomy of the patient. The phantom was made from the CT images of the patient using a 3D printer with sub-millimeter accuracy. One phantom was filled with a gel dosimeter and the other was made with two ion chamber inserts to allow us to obtain point dose measurements in the target’s center and the spinal cord. Results: The prescribed dose of 18Gy was planned for the target while keeping the maximum spinal cord dose to less than 14Gy in 0.03cc of the cord. The VMAT plan was delivered to both the gel dosimeter filed phantom and the phantom with the ion chambers. The 3D gel dosimetry revealed a very good agreement between the monte carlo and measured point and volumetric dose. Conclusion: A patient like phantom was developed and validated for use as an end-to-end tool of dose verification for SBRT of spine lesions. We found that gel dosimetry is ideally suited to assess positional and dosimetric accuracy in 3D. RTsafe provided the phantoms and the gel dosimeter used for this study.« less

Comparison of depth-dose distributions of proton therapeutic beams calculated by means of logical detectors and ionization chamber modeled in Monte Carlo codes

NASA Astrophysics Data System (ADS)

Pietrzak, Robert; Konefał, Adam; Sokół, Maria; Orlef, Andrzej

2016-08-01

The success of proton therapy depends strongly on the precision of treatment planning. Dose distribution in biological tissue may be obtained from Monte Carlo simulations using various scientific codes making it possible to perform very accurate calculations. However, there are many factors affecting the accuracy of modeling. One of them is a structure of objects called bins registering a dose. In this work the influence of bin structure on the dose distributions was examined. The MCNPX code calculations of Bragg curve for the 60 MeV proton beam were done in two ways: using simple logical detectors being the volumes determined in water, and using a precise model of ionization chamber used in clinical dosimetry. The results of the simulations were verified experimentally in the water phantom with Marcus ionization chamber. The average local dose difference between the measured relative doses in the water phantom and those calculated by means of the logical detectors was 1.4% at first 25 mm, whereas in the full depth range this difference was 1.6% for the maximum uncertainty in the calculations less than 2.4% and for the maximum measuring error of 1%. In case of the relative doses calculated with the use of the ionization chamber model this average difference was somewhat greater, being 2.3% at depths up to 25 mm and 2.4% in the full range of depths for the maximum uncertainty in the calculations of 3%. In the dose calculations the ionization chamber model does not offer any additional advantages over the logical detectors. The results provided by both models are similar and in good agreement with the measurements, however, the logical detector approach is a more time-effective method.

Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

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

Fouchardiere, Christelle de la, E-mail: delafo@lyon.fnclcc.f; Negrier, Sylvie; Labrosse, Hugues

2010-06-01

Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m{sup 2} per day and then escalated by increments of 2 mg/m{sup 2} every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperabilitymore » was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m{sup 2} to 20 mg/m{sup 2} per day). The maximum tolerated dose was determined to be 18 mg/m{sup 2} per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m{sup 2} per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.« less

SU-F-T-409: Modelling of the Magnetic Port in Temporary Breast Tissue Expanders for a Treatment Planning System

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

Yoon, J; Heins, D; Zhang, R

Purpose: To model the magnetic port in the temporary breast tissue expanders and to improve accuracy of dose calculation in Pinnacle, a commercial treatment planning system (TPS). Methods: A magnetic port in the tissue expander was modeled with a radiological measurement-basis; we have determined the dimension and the density of the model by film images and ion chamber measurement under the magnetic port, respectively. The model was then evaluated for various field sizes and photon energies by comparing depth dose values calculated by TPS (using our new model) and ion chamber measurement in a water tank. Also, the model wasmore » further evaluated by using a simplified anthropomorphic phantom with realistic geometry by placing thermoluminescent dosimeters (TLD)s around the magnetic port. Dose perturbations in a real patient’s treatment plan from the new model and a current clinical model, which is based on the subjective contouring created by the dosimetrist, were also compared. Results: Dose calculations based on our model showed less than 1% difference from ion chamber measurements for various field sizes and energies under the magnetic port when the magnetic port was placed parallel to the phantom surface. When it was placed perpendicular to the phantom surface, the maximum difference was 3.5%, while average differences were less than 3.1% for all cases. For the simplified anthropomorphic phantom, the calculated point doses agreed with TLD measurements within 5.2%. By comparing with the current model which is being used in clinic by TPS, it was found that current clinical model overestimates the effect from the magnetic port. Conclusion: Our new model showed good agreement with measurement for all cases. It could potentially improve the accuracy of dose delivery to the breast cancer patients.« less

Outpatient radioiodine therapy for thyroid cancer: a safe nuclear medicine procedure.

PubMed

Willegaignon, José; Sapienza, Marcelo; Ono, Carla; Watanabe, Tomoco; Guimarães, Maria Inês; Gutterres, Ricardo; Marechal, Maria Helena; Buchpiguel, Carlos

2011-06-01

To evaluate the dosimetric effect of outpatient radioiodine therapy for thyroid cancer in members of a patient's family and their living environment, when using iodine-131 doses reaching 7.4 GBq. The following parameters were thus defined: (a) whole-body radiation doses to caregivers, (b) the production of contaminated solid waste, and (c) radiation potential and surface contamination within patients' living quarters. In total, 100 patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation safety guidelines. Both the caregivers and the radiation dose potentiality inside patients' residences were monitored by using thermoluminescent dosimeters. Surface contamination and contaminated solid wastes were identified and measured with a Geiger-Müller detector. A total of 90 monitored individuals received a mean dose of 0.27 (±0.28) mSv, and the maximum dose registered was 1.6 mSv. The mean value for the potential dose within all living quarters was 0.31 (±0.34) mSv, and the mean value per monitored surface was 5.58 Bq/cm(2) for all the 1659 points measured. The overall production of contaminated solid wastes was at a low level, being about 3 times less than the exemption level indicated by the International Atomic Energy Agency. This study indicates that the treatment of thyroid cancer by applying radioiodine activities up to 7.4 GBq, on an outpatient basis, is a safe procedure, especially when supervised by qualified professionals. This alternative therapy should be a topic for careful discussion considering the high potential for reducing costs in healthcare and improving patient acceptance.

Phase I and Pharmacokinetic Study of Cetuximab and Irinotecan in Children With Refractory Solid Tumors: A Study of the Pediatric Oncology Experimental Therapeutic Investigators' Consortium

PubMed Central

Trippett, Tanya M.; Herzog, Cynthia; Whitlock, James A.; Wolff, Johannes; Kuttesch, John; Bagatell, Rochelle; Hunger, Stephen P.; Boklan, Jessica; Smith, Amy A.; Arceci, Robert J.; Katzenstein, Howard M.; Harbison, Christopher; Zhou, Xiaofei; Lu, Haolan; Langer, Christiane; Weber, Martin; Gore, Lia

2009-01-01

Purpose To determine the dose of cetuximab that can be safely combined with irinotecan for treatment of pediatric and adolescent patients with refractory solid tumors. Patients and Methods This open-label, phase I study enrolled patients ages 1 to 18 years with advanced refractory solid tumors, including tumors of the CNS. Patient cohorts by age group (children, ages 1 to 12 years; adolescents, ages 13 to 18 years) received escalating weekly doses of cetuximab (75, 150, 250 mg/m2) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m2/d) for 5 days for 2 consecutive weeks every 21 days. The primary end points were establishing the maximum-tolerated dose (MTD), recommended phase II dose (RPIID), and pharmacokinetics of the combination. Preliminary safety and efficacy data were also collected. Results Twenty-seven children and 19 adolescents received a median of 7.1 and 6.0 weeks of cetuximab therapy, respectively. Cetuximab 250 mg/m2 weekly plus irinotecan 16 mg/m2/d (pediatric) or 20 mg/m2/d (adolescent) have been established as the MTD/RPIID. Dose-limiting toxicities included diarrhea and neutropenia. Mild to moderate (grade 1 to 2) acneiform rash occurred in a majority of patients; no grade 3 to 4 rashes were observed. Cetuximab demonstrated dose-dependent clearance in both children and adolescents, similar to that in adults. There were two confirmed partial responses, both in patients with CNS tumors. Stable disease was achieved in 18 patients overall, including 10 patients with CNS tumors (38.5%). Conclusion The cetuximab/irinotecan combination can be given safely to children and adolescents with cancer. Promising activity, particularly in CNS tumors, warrants phase II evaluation of this regimen. PMID:19770383

Annual committed effective dose from olive oil (due to 238U, 232Th, and 222Rn) estimated for members of the Moroccan public from ingestion and skin application.

PubMed

Misdaq, M A; Touti, R

2012-03-01

Olive oil is traditionally refined and widely consumed by Moroccan rural populations. Uranium (238U), thorium (232Th), radon (222Rn), and thoron (220Rn) contents were measured in various locally produced olive oil samples collected in rural areas of Morocco. These radionuclides were also measured inside various bottled virgin olive oils consumed by the Moroccan populations. CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs) were used. Annual committed effective doses due to 238U, 232Th, and 222Rn from the ingestion of olive oil by the members of the general public were determined. The maximum total committed effective dose due to 238U, 232Th, and 222Rn from the ingestion of olive oil by adult members of Moroccan rural populations was found equal to 5.9 µSv y-1. The influence of pollution due to building material dusts and phosphates on the radiation dose to workers from the ingestion of olive oil was investigated, and it was found that the maximum total committed effective dose due to 238U, 232Th, and 222Rn was on the order of 0.22 mSy y-1. Committed effective doses to skin due to 238U, 232Th, and 222Rn from the application of olive oil masks by rural women were evaluated. The maximum total committed effective dose to skin due to 238U, 232Th, and 222Rn was found equal to 0.07 mSy y-1 cm-2.

Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

PubMed

Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

2017-05-01

Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

Methylphenidate bioavailability in adults when an extended-release multiparticulate formulation is administered sprinkled on food or as an intact capsule.

PubMed

Pentikis, Helen S; Simmons, Roy D; Benedict, Michael F; Hatch, Simon J

2002-04-01

To determine the single-dose bioavailability of 20-mg Metadate CD (methylphenidate HCI, USP) Extended-Release Capsules sprinkled onto 1 level tablespoon (15 mL) of applesauce relative to an intact capsule under fasted conditions in healthy adults. This was a single-center, open-label, single-dose, randomized, two-way crossover study with a 6-day washout period between doses, in healthy male and female subjects (N= 26), aged 21-40 years. Plasma concentration-time data for methylphenidate were used to calculate the pharmacokinetic parameters for each treatment. The pharmacokinetic profile for Metadate CD exhibited biphasic release characteristics with a sharp initial slope and a second rising portion. For Cmax (maximum observed concentration), AUC(0-infinity) (area under the plasma concentration curve from time 0 to infinity) and AUC(0-infinity) (area under the plasma concentration curve from time 0 to the last measurable time point), the geometric least squares mean ratios and 90% confidence intervals were within the 80% to 125% confidence interval for bioequivalence. Adverse events were similar to those reported for methylphenidate. The bioavailability of methylphenidate was not altered when Metadate CD capsules were administered by sprinkling their contents onto a small amount of applesauce.

Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

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

Leavitt, Jacqueline A., E-mail: leavitt.jacqueline@mayo.edu; Stafford, Scott L.; Link, Michael J.

2013-11-01

Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0more » Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.« less

Modeling, control, and simulation of grid connected intelligent hybrid battery/photovoltaic system using new hybrid fuzzy-neural method.

PubMed

Rezvani, Alireza; Khalili, Abbas; Mazareie, Alireza; Gandomkar, Majid

2016-07-01

Nowadays, photovoltaic (PV) generation is growing increasingly fast as a renewable energy source. Nevertheless, the drawback of the PV system is its dependence on weather conditions. Therefore, battery energy storage (BES) can be considered to assist for a stable and reliable output from PV generation system for loads and improve the dynamic performance of the whole generation system in grid connected mode. In this paper, a novel topology of intelligent hybrid generation systems with PV and BES in a DC-coupled structure is presented. Each photovoltaic cell has a specific point named maximum power point on its operational curve (i.e. current-voltage or power-voltage curve) in which it can generate maximum power. Irradiance and temperature changes affect these operational curves. Therefore, the nonlinear characteristic of maximum power point to environment has caused to development of different maximum power point tracking techniques. In order to capture the maximum power point (MPP), a hybrid fuzzy-neural maximum power point tracking (MPPT) method is applied in the PV system. Obtained results represent the effectiveness and superiority of the proposed method, and the average tracking efficiency of the hybrid fuzzy-neural is incremented by approximately two percentage points in comparison to the conventional methods. It has the advantages of robustness, fast response and good performance. A detailed mathematical model and a control approach of a three-phase grid-connected intelligent hybrid system have been proposed using Matlab/Simulink. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Soft-tissue allografts terminally sterilized with an electron beam are biomechanically equivalent to aseptic, nonsterilized tendons.

PubMed

Elenes, Egleide Y; Hunter, Shawn A

2014-08-20

Allograft safety is contingent on effective sterilization. However, current sterilization methods have been associated with decreased biomechanical strength and higher failure rates of soft-tissue allografts. In this study, electron beam (e-beam) sterilization was explored as an alternative sterilization method to preserve biomechanical integrity. We hypothesized that e-beam sterilization would not significantly alter the biomechanical properties of tendon allograft compared with aseptic, nonsterilized controls and gamma-irradiated grafts. Separate sets of forty fresh-frozen tibialis tendon allografts (four from each of ten donors) and forty bisected bone-patellar tendon-bone (BTB) allografts (four from each of ten donors) were randomly assigned to four study groups. One group received a 17.1 to 21.0-kGy gamma radiation dose; two other groups were sterilized with an e-beam at either a high (17.1 to 21.0-kGy) or low (9.2 to 12.2-kGy) dose. A fourth group served as nonsterilized controls. Each graft was cyclically loaded to 200 N of tension for 2000 cycles at a frequency of 2 Hz, allowed to relax for five minutes, and then tested in tension until failure at a 100%/sec strain rate. One-way analysis of variance testing was used to identify significant differences. Tibialis tendons sterilized with both e-beam treatments and with gamma irradiation exhibited values for cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus that were not significantly different from those of nonsterilized controls. BTB allografts sterilized with the high e-beam dose and with gamma irradiation were not significantly different in cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus from nonsterilized controls. BTB allografts sterilized with the e-beam at the lower dose were significantly less stiff than nonsterilized controls (p = 0.014) but did not differ from controls in any other properties. The difference in stiffness likely resulted from variations in tendon size rather than the treatments, as the elastic moduli of the groups were similar. The biomechanical properties of tibialis and BTB allografts sterilized with use of an e-beam at a dose range of 17.1 to 21.0 kGy were not different from those of aseptic, nonsterilized controls or gamma-irradiated allografts. E-beam sterilization can be a viable method to produce safe and biomechanically uncompromised soft-tissue allografts. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

A survival model for fractionated radiotherapy with an application to prostate cancer

NASA Astrophysics Data System (ADS)

Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

2001-10-01

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

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

Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel

Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, definedmore » as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.« less

Is eye lens dosimetry needed in nuclear medicine?

PubMed

Wrzesień, M; Królicki, L; Albiniak, Ł; Olszewski, J

2018-06-01

The exact level of exposure experienced by nuclear medicine personnel, whose work often requires performing manual procedures involving radioactive isotopes, is associated with the form of radiation source used. The variety of radionuclides and medical procedures, and the yearly increase in the number of patients, as well as the change of the individual dose limit for the lens of the eye from a value of 150 mSv yr -1 to 20 mSv yr -1 , mean that issues of eye lens routine dosimetry become interesting from the radiation protection point of view. This paper presents an analysis of the exposure of the eye lenses of nuclear medicine department personnel, as well as those of personnel in the facilities that produce radiopharmaceuticals for the purpose of diagnosis by positron emission tomography, from the viewpoint of the advisability of routine eye lens exposure monitoring, taking into account changes in the dose limit for the lens of the eye. The paper considers the two most commonly used radionuclides for diagnostic purposes 99m Tc, 18 F, and-for therapeutic purposes- 131 I. Dose measurements were made using thermoluminescent detectors. The estimated exposure analysis identifies the cases when the maximum annual value of the personal dose equivalent, in terms of Hp(3), exceeds threefold the new limit value (20 mSv yr -1 ). It is recommended that Hp(3) doses be routinely monitored in the group of radiopharmacists who label pharmaceuticals with the radionuclide 99m Tc and in chemists working in 18 F-FDG quality control departments in production units, where this is carried out manually.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

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

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to themore » hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.« less

SU-F-T-522: Dosimetric Study of Junction Dose in Double Isocenter Flatten and Flatten Filter Free IMRT and VMAT Plan Delivery

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

Samuvel, K; Yadav, G; Bhushan, M

2016-06-15

Purpose: To quantify the dosimetric accuracy of junction dose in double isocenter flattened and flatten filter free(FFF) intensity modulated radiation therapy(IMRT) and volumetric modulated arc therapy(VMAT) plan delivery using pelvis phantom. Methods: Five large field pelvis patients were selected for this study. Double isocenter IMRT and VMAT treatment plans were generated in Eclipse Treatment planning System (V.11.0) using 6MV FB and FFF beams. For all the plans same distance 17.0cm was kept between one isocenter to another isocenter. IMRT Plans were made with 7 coplanar fields and VMAT plans were made with full double arcs. Dose calculation was performed usingmore » AAA algorithms with dose grid size of 0.25 cm. Verification plans were calculated on Scanditronix Wellhofer pelvis slab phantom. Measurement point was selected and calculated, where two isocenter plan fields are overlapping, this measurement point was kept at distance 8.5cm from both isocenter. The plans were delivered using Varian TrueBeamTM machine on pelvis slab phantom. Point dose measurements was carried out using CC13 ion chamber volume of 0.13cm3. Results: The measured junction point dose are compared with TPS calculated dose. The mean difference observed was 4.5%, 6.0%, 4.0% and 7.0% for IMRT-FB,IMRT-FFF, VMAT-FB and VMAT-FFF respectively. The measured dose results shows closer agreement with calculated dose in Flatten beam planning in both IMRT and VMAT, whereas in FFF beam plan dose difference are more compared with flatten beam plan. Conclusion: Dosimetry accuracy of Large Field junction dose difference was found less in Flatten beam compared with FFF beam plan delivery. Even though more dosimetric studies are required to analyse junction dose for FFF beam planning using multiple point dose measurements and fluence map verification in field junction area.« less

A rule of unity for human intestinal absorption 3: Application to pharmaceuticals.

PubMed

Patel, Raj B; Yalkowsky, Samuel H

2018-02-01

The rule of unity is based on a simple absorption parameter, Π, that can accurately predict whether or not an orally administered drug will be well absorbed or poorly absorbed. The intrinsic aqueous solubility and octanol-water partition coefficient, along with the drug dose are used to calculate Π. We show that a single delineator value for Π exist that can distinguish whether a drug is likely to be well absorbed (FA ≥ 0.5) or poorly absorbed (FA < 0.5) at any specified dose. The model is shown to give 82.5% correct predictions for over 938 pharmaceuticals. The maximum well-absorbed dose (i.e. the maximum dose that will be more than 50% absorbed) calculated using this model can be utilized as a guideline for drug design and synthesis. Copyright © 2017 John Wiley & Sons, Ltd.

Commissioning dosimetry and in situ dose mapping of a semi-industrial Cobalt-60 gamma-irradiation facility using Fricke and Ceric-cerous dosimetry system and comparison with Monte Carlo simulation data

NASA Astrophysics Data System (ADS)

Mortuza, Md Firoz; Lepore, Luigi; Khedkar, Kalpana; Thangam, Saravanan; Nahar, Arifatun; Jamil, Hossen Mohammad; Bandi, Laxminarayan; Alam, Md Khorshed

2018-03-01

Characterization of a 90 kCi (3330 TBq), semi-industrial, cobalt-60 gamma irradiator was performed by commissioning dosimetry and in-situ dose mapping experiments with Ceric-cerous and Fricke dosimetry systems. Commissioning dosimetry was carried out to determine dose distribution pattern of absorbed dose in the irradiation cell and products. To determine maximum and minimum absorbed dose, overdose ratio and dwell time of the tote boxes, homogeneous dummy product (rice husk) with a bulk density of 0.13 g/cm3 were used in the box positions of irradiation chamber. The regions of minimum absorbed dose of the tote boxes were observed in the lower zones of middle plane and maximum absorbed doses were found in the middle position of front plane. Moreover, as a part of dose mapping, dose rates in the wall positions and some selective strategic positions were also measured to carry out multiple irradiation program simultaneously, especially for low dose research irradiation program. In most of the cases, Monte Carlo simulation data, using Monte Carlo N-Particle eXtended code version MCNPX 2.7., were found to be in congruence with experimental values obtained from Ceric-cerous and Fricke dosimetry; however, in close proximity positions from the source, the dose rate variation between chemical dosimetry and MCNP was higher than distant positions.

Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy.

PubMed

Fogliata, Antonella; Scorsetti, Marta; Navarria, Piera; Catalano, Maddalena; Clivio, Alessandro; Cozzi, Luca; Lobefalo, Francesca; Nicolini, Giorgia; Palumbo, Valentina; Pellegrini, Chiara; Reggiori, Giacomo; Roggio, Antonella; Vanetti, Eugenio; Alongi, Filippo; Pentimalli, Sara; Mancosu, Pietro

2013-04-01

To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to-maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma.

Relation of gastric acid and pepsin secretion to serum gastrin levels in dogs given bombesin and gastrin-17.

PubMed

Hirschowitz, B I; Molina, E

1983-05-01

To quantitate bombesin stimulation of gastric acid and pepsin via release of gastrin, five gastric fistula dogs were given graded doses (60-1,250 pmol X kg-1 X h-1) of bombesin tetradecapeptide and 40-2,000 pmol X kg-1 X h-1 of synthetic gastrin-17 (G-17). Acid and pepsin output and serum gastrin were proportional to the dose of stimulant. The half-maximal dose of bombesin for gastrin release was 200 pmol X kg-1 X h-1. Bombesin-stimulated acid secretion related to serum gastrin concentrations was congruent with the G-17 curve, but with a maximum of only 62% of the G-17 maximum before declining by 27% despite higher serum gastrin levels. This suggested that bombesin stimulates acid secretion only via gastrin release and inhibits at higher doses by releasing another inhibitory peptide, most likely somatostatin, which is also released by bombesin. The same mechanism could apply to supramaximal inhibition of acid and pepsin seen with high doses of G-17. Because the pepsin curve related to serum gastrin was to the left of the G-17 curve, we concluded that another secretagogue released by bombesin acts synergistically with gastrin on pepsin secretion. Therefore, bombesin stimulates gastric secretion through gastrin release, but its effects are modified by peptides coreleased to a) increase pepsin output at low doses and b) limit the output of acid and pepsin to 50-60% of the G-17 maximum.

Research of PV Power Generation MPPT based on GABP Neural Network

NASA Astrophysics Data System (ADS)

Su, Yu; Lin, Xianfu

2018-05-01

Photovoltaic power generation has become the main research direction of new energy power generation. But high investment and low efficiency of photovoltaic industry arouse concern in some extent. So maximum power point tracking of photovoltaic power generation has been a popular study point. Due to slow response, oscillation at maximum power point and low precision, the algorithm based on genetic algorithm combined with BP neural network are designed detailedly in this paper. And the modeling and simulation are completed by use of MATLAB/SIMULINK. The results show that the algorithm is effective and the maximum power point can be tracked accurately and quickly.

Tracing Personalized Health Curves during Infections

PubMed Central

Schneider, David S.

2011-01-01

It is difficult to describe host–microbe interactions in a manner that deals well with both pathogens and mutualists. Perhaps a way can be found using an ecological definition of tolerance, where tolerance is defined as the dose response curve of health versus parasite load. To plot tolerance, individual infections are summarized by reporting the maximum parasite load and the minimum health for a population of infected individuals and the slope of the resulting curve defines the tolerance of the population. We can borrow this method of plotting health versus microbe load in a population and make it apply to individuals; instead of plotting just one point that summarizes an infection in an individual, we can plot the values at many time points over the course of an infection for one individual. This produces curves that trace the course of an infection through phase space rather than over a more typical timeline. These curves highlight relationships like recovery and point out bifurcations that are difficult to visualize with standard plotting techniques. Only nine archetypical curves are needed to describe most pathogenic and mutualistic host–microbe interactions. The technique holds promise as both a qualitative and quantitative approach to dissect host–microbe interactions of all kinds. PMID:21957398

Proposed patient motion monitoring system using feature point tracking with a web camera.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Matsuura, Takaaki; Yamada, Kiyoshi; Nagata, Yasushi

2017-12-01

Patient motion monitoring systems play an important role in providing accurate treatment dose delivery. We propose a system that utilizes a web camera (frame rate up to 30 fps, maximum resolution of 640 × 480 pixels) and an in-house image processing software (developed using Microsoft Visual C++ and OpenCV). This system is simple to use and convenient to set up. The pyramidal Lucas-Kanade method was applied to calculate motions for each feature point by analysing two consecutive frames. The image processing software employs a color scheme where the defined feature points are blue under stable (no movement) conditions and turn red along with a warning message and an audio signal (beeping alarm) for large patient movements. The initial position of the marker was used by the program to determine the marker positions in all the frames. The software generates a text file that contains the calculated motion for each frame and saves it as a compressed audio video interleave (AVI) file. We proposed a patient motion monitoring system using a web camera, which is simple and convenient to set up, to increase the safety of treatment delivery.

A segmentation and point-matching enhanced efficient deformable image registration method for dose accumulation between HDR CT images

NASA Astrophysics Data System (ADS)

Zhen, Xin; Chen, Haibin; Yan, Hao; Zhou, Linghong; Mell, Loren K.; Yashar, Catheryn M.; Jiang, Steve; Jia, Xun; Gu, Xuejun; Cervino, Laura

2015-04-01

Deformable image registration (DIR) of fractional high-dose-rate (HDR) CT images is challenging due to the presence of applicators in the brachytherapy image. Point-to-point correspondence fails because of the undesired deformation vector fields (DVF) propagated from the applicator region (AR) to the surrounding tissues, which can potentially introduce significant DIR errors in dose mapping. This paper proposes a novel segmentation and point-matching enhanced efficient DIR (named SPEED) scheme to facilitate dose accumulation among HDR treatment fractions. In SPEED, a semi-automatic seed point generation approach is developed to obtain the incremented fore/background point sets to feed the random walks algorithm, which is used to segment and remove the AR, leaving empty AR cavities in the HDR CT images. A feature-based ‘thin-plate-spline robust point matching’ algorithm is then employed for AR cavity surface points matching. With the resulting mapping, a DVF defining on each voxel is estimated by B-spline approximation, which serves as the initial DVF for the subsequent Demons-based DIR between the AR-free HDR CT images. The calculated DVF via Demons combined with the initial one serve as the final DVF to map doses between HDR fractions. The segmentation and registration accuracy are quantitatively assessed by nine clinical HDR cases from three gynecological cancer patients. The quantitative analysis and visual inspection of the DIR results indicate that SPEED can suppress the impact of applicator on DIR, and accurately register HDR CT images as well as deform and add interfractional HDR doses.

A segmentation and point-matching enhanced efficient deformable image registration method for dose accumulation between HDR CT images.

PubMed

Zhen, Xin; Chen, Haibin; Yan, Hao; Zhou, Linghong; Mell, Loren K; Yashar, Catheryn M; Jiang, Steve; Jia, Xun; Gu, Xuejun; Cervino, Laura

2015-04-07

Deformable image registration (DIR) of fractional high-dose-rate (HDR) CT images is challenging due to the presence of applicators in the brachytherapy image. Point-to-point correspondence fails because of the undesired deformation vector fields (DVF) propagated from the applicator region (AR) to the surrounding tissues, which can potentially introduce significant DIR errors in dose mapping. This paper proposes a novel segmentation and point-matching enhanced efficient DIR (named SPEED) scheme to facilitate dose accumulation among HDR treatment fractions. In SPEED, a semi-automatic seed point generation approach is developed to obtain the incremented fore/background point sets to feed the random walks algorithm, which is used to segment and remove the AR, leaving empty AR cavities in the HDR CT images. A feature-based 'thin-plate-spline robust point matching' algorithm is then employed for AR cavity surface points matching. With the resulting mapping, a DVF defining on each voxel is estimated by B-spline approximation, which serves as the initial DVF for the subsequent Demons-based DIR between the AR-free HDR CT images. The calculated DVF via Demons combined with the initial one serve as the final DVF to map doses between HDR fractions. The segmentation and registration accuracy are quantitatively assessed by nine clinical HDR cases from three gynecological cancer patients. The quantitative analysis and visual inspection of the DIR results indicate that SPEED can suppress the impact of applicator on DIR, and accurately register HDR CT images as well as deform and add interfractional HDR doses.

US Transuranium and Uranium Registries case study on accidental exposure to uranium hexafluoride.

PubMed

Avtandilashvili, Maia; Puncher, Matthew; McComish, Stacey L; Tolmachev, Sergei Y

2015-03-01

The United States Transuranium and Uranium Registries' (USTUR) whole-body donor (Case 1031) was exposed to an acute inhalation of uranium hexafluoride (UF6) produced from an explosion at a uranium processing plant 65 years prior to his death. The USTUR measurements of tissue samples collected at the autopsy indicated long-term retention of inhaled slightly enriched uranium material (0.85% (235)U) in the deep lungs and thoracic lymph nodes. In the present study, the authors combined the tissue measurement results with historical bioassay data, and analysed them with International Commission on Radiological Protection (ICRP) respiratory tract models and the ICRP Publication 69 systemic model for uranium using maximum likelihood and Bayesian statistical methods. The purpose of the analysis was to estimate intakes and model parameter values that best describe the data, and evaluate their effect on dose assessment. The maximum likelihood analysis, which used the ICRP Publication 66 human respiratory tract model, resulted in a point estimate of 79 mg of uranium for the occupational intake composed of 86% soluble, type F material and 14% insoluble, type S material. For the Bayesian approach, the authors applied the Markov Chain Monte Carlo method, but this time used the revised human respiratory tract model, which is currently being used by ICRP to calculate new dose coefficients for workers. The Bayesian analysis estimated that the mean uranium intake was 160 mg, and calculated the case-specific lung dissolution parameters with their associated uncertainties. The parameters were consistent with the inhaled uranium material being predominantly soluble with a small but significant insoluble component. The 95% posterior range of the rapid dissolution fraction (the fraction of deposited material that is absorbed to blood rapidly) was 0.12 to 0.91 with a median of 0.37. The remaining fraction was absorbed slowly, with a 95% range of 0.000 22 d(-1) to 0.000 36 d(-1) and a median of 0.000 31 d(-1). The effective dose per unit intake calculated using the dissolution parameters derived from the maximum likelihood and the Bayesian analyses was higher than the current ICRP dose coefficient for type F uranium by a factor of 2 or 7, respectively; the higher value of the latter was due to use of the revised respiratory tract model. The dissolution parameter values obtained here may be more appropriate to use for radiation protection purposes when individuals are exposed to a UF6 mixture that contains an insoluble uranium component.

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

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

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

Bakalyar, D; McKenney, S; Feng, W

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

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

Demirag, N

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 andmore » 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.« less

47 CFR 90.1215 - Power limits.

Code of Federal Regulations, 2011 CFR

2011-10-01

...Bm/MHz. If transmitting antennas of directional gain greater than 9 dBi are used, both the maximum... the directional gain of the antenna exceeds 9 dBi. However, high power point-to-point and point-to... directional gain up to 26 dBi without any corresponding reduction in the maximum conducted output power or...

47 CFR 90.1215 - Power limits.

Code of Federal Regulations, 2014 CFR

2014-10-01

...Bm/MHz. If transmitting antennas of directional gain greater than 9 dBi are used, both the maximum... the directional gain of the antenna exceeds 9 dBi. However, high power point-to-point and point-to... directional gain up to 26 dBi without any corresponding reduction in the maximum conducted output power or...

47 CFR 90.1215 - Power limits.

Code of Federal Regulations, 2013 CFR

2013-10-01

...Bm/MHz. If transmitting antennas of directional gain greater than 9 dBi are used, both the maximum... the directional gain of the antenna exceeds 9 dBi. However, high power point-to-point and point-to... directional gain up to 26 dBi without any corresponding reduction in the maximum conducted output power or...

47 CFR 90.1215 - Power limits.

Code of Federal Regulations, 2012 CFR

2012-10-01

...Bm/MHz. If transmitting antennas of directional gain greater than 9 dBi are used, both the maximum... the directional gain of the antenna exceeds 9 dBi. However, high power point-to-point and point-to... directional gain up to 26 dBi without any corresponding reduction in the maximum conducted output power or...

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

On the interplay effects with proton scanning beams in stage III lung cancer.

PubMed

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-02-01

To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

PubMed Central

Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

2013-01-01

Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

PubMed

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Monte Carlo simulated corrections for beam commissioning measurements with circular and MLC shaped fields on the CyberKnife M6 System: a study including diode, microchamber, point scintillator, and synthetic microdiamond detectors.

PubMed

Francescon, P; Kilby, W; Noll, J M; Masi, L; Satariano, N; Russo, S

2017-02-07

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between  -6.1% and  -3.5% for the diode models evaluated, while in a 7.6 mm  ×  7.7 mm MLC field these are  -4.5% to  -1.8%. The corresponding microchamber corrections are  +9.9% to  +10.7% and  +3.5% to  +4.0%. The microdiamond corrections have a maximum of  -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are  <1% in all beams. Measured OF showed uncorrected inter-detector differences  >15%, reducing to  <3% after correction. PDD corrections at d  >  d max were  <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were  <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

Monte Carlo simulated corrections for beam commissioning measurements with circular and MLC shaped fields on the CyberKnife M6 System: a study including diode, microchamber, point scintillator, and synthetic microdiamond detectors

NASA Astrophysics Data System (ADS)

Francescon, P.; Kilby, W.; Noll, J. M.; Masi, L.; Satariano, N.; Russo, S.

2017-02-01

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between  -6.1% and  -3.5% for the diode models evaluated, while in a 7.6 mm  ×  7.7 mm MLC field these are  -4.5% to  -1.8%. The corresponding microchamber corrections are  +9.9% to  +10.7% and  +3.5% to  +4.0%. The microdiamond corrections have a maximum of  -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are  <1% in all beams. Measured OF showed uncorrected inter-detector differences  >15%, reducing to  <3% after correction. PDD corrections at d  >  d max were  <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were  <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

The effect of tandem-ovoid titanium applicator on points A, B, bladder, and rectum doses in gynecological brachytherapy using 192Ir

PubMed Central

Sadeghi, Mohammad Hosein; Mehdizadeh, Amir; Faghihi, Reza; Moharramzadeh, Vahed; Meigooni, Ali Soleimani

2018-01-01

Purpose The dosimetry procedure by simple superposition accounts only for the self-shielding of the source and does not take into account the attenuation of photons by the applicators. The purpose of this investigation is an estimation of the effects of the tandem and ovoid applicator on dose distribution inside the phantom by MCNP5 Monte Carlo simulations. Material and methods In this study, the superposition method is used for obtaining the dose distribution in the phantom without using the applicator for a typical gynecological brachytherapy (superposition-1). Then, the sources are simulated inside the tandem and ovoid applicator to identify the effect of applicator attenuation (superposition-2), and the dose at points A, B, bladder, and rectum were compared with the results of superposition. The exact dwell positions, times of the source, and positions of the dosimetry points were determined in images of a patient and treatment data of an adult woman patient from a cancer center. The MCNP5 Monte Carlo (MC) code was used for simulation of the phantoms, applicators, and the sources. Results The results of this study showed no significant differences between the results of superposition method and the MC simulations for different dosimetry points. The difference in all important dosimetry points was found to be less than 5%. Conclusions According to the results, applicator attenuation has no significant effect on the calculated points dose, the superposition method, adding the dose of each source obtained by the MC simulation, can estimate the dose to points A, B, bladder, and rectum with good accuracy. PMID:29619061

Comparative evaluation of two-dimensional radiography and three dimensional computed tomography based dose-volume parameters for high-dose-rate intracavitary brachytherapy of cervical cancer: a prospective study.

PubMed

Madan, Renu; Pathy, Sushmita; Subramani, Vellaiyan; Sharma, Seema; Mohanti, Bidhu Kalyan; Chander, Subhash; Thulkar, Sanjay; Kumar, Lalit; Dadhwal, Vatsla

2014-01-01

Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

PubMed

Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

2018-05-08

Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P <0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

Improving IMRT delivery efficiency using intensity limits during inverse planning.

PubMed

Coselmon, Martha M; Moran, Jean M; Radawski, Jeffrey D; Fraass, Benedick A

2005-05-01

Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly modulated due to the large number of degrees of freedom involved in the inverse planning process. Additional modulation typically results in a more optimal plan, although the clinical rewards may be small or offset by additional delivery complexity and/or increased dose from transmission and leakage. Increasing modulation decreases delivery efficiency, and may lead to plans that are more sensitive to geometrical uncertainties. The purpose of this work is to assess the use of maximum intensity limits in inverse IMRT planning as a simple way to increase delivery efficiency without significantly affecting plan quality. Nine clinical cases (three each for brain, prostate, and head/neck) were used to evaluate advantages and disadvantages of limiting maximum intensity to increase delivery efficiency. IMRT plans were generated using in-house protocol-based constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume objectives in the prostate. Each case was optimized at a series of maximum intensity ratios (the product of the maximum intensity and the number of beams divided by the prescribed dose to the target volume), and evaluated in terms of clinical metrics, dose-volume histograms, monitor units (MU) required per fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the beam modulation). In each site tested, it was possible to reduce total monitor units by constraining the maximum allowed intensity without compromising the clinical acceptability of the plan. Monitor unit reductions up to 38% were observed for SMLC delivery, while reductions up to 29% were achieved for DMLC delivery. In general, complicated geometries saw a smaller reduction in monitor units for both delivery types, although DMLC delivery required significantly more monitor units in all cases. Constraining the maximum intensity in an inverse IMRT plan is a simple way to improve delivery efficiency without compromising plan objectives.

Structural properties of H-implanted InP crystals

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

Bocchi, C.; Franzosi, P.; Lazzarini, L.

1993-07-01

H has been implanted in InP crystals at the energy E [equals] 100 keV and at different doses ranging from [sigma] [equals] 1 x 10[sup 13] to [sigma] [equals] 5 x 10[sup 16] cm[sup [minus]2]. The depth dependence of the elastic lattice strain has been investigated by high resolution X-ray diffractometry. The implantation produces a lattice dilation. The strain increases with increasing depth, reaches the maximum at about 0.75 [mu]m, and then decreases rapidly; moreover the maximum strain is proportional to the dose. No extended crystal defects have been detected by transmission electron microscopy up to [sigma] <1 x 10[supmore » 16] cm[sup [minus]2] a buried amorphous layer 28 nm in thickness has been observed at the same depth where the strain is maximum. The thickness of the amorphous layer increases by further increasing the dose and reaches a value of about 0.18 [mu]m for [sigma] [equals] 5 x 10[sup 16] cm[sup [minus]2].« less

Calculated and measured brachytherapy dosimetry parameters in water for the Xoft Axxent X-Ray Source: an electronic brachytherapy source.

PubMed

Rivard, Mark J; Davis, Stephen D; DeWerd, Larry A; Rusch, Thomas W; Axelrod, Steve

2006-11-01

A new x-ray source, the model S700 Axxent X-Ray Source (Source), has been developed by Xoft Inc. for electronic brachytherapy. Unlike brachytherapy sources containing radionuclides, this Source may be turned on and off at will and may be operated at variable currents and voltages to change the dose rate and penetration properties. The in-water dosimetry parameters for this electronic brachytherapy source have been determined from measurements and calculations at 40, 45, and 50 kV settings. Monte Carlo simulations of radiation transport utilized the MCNP5 code and the EPDL97-based mcplib04 cross-section library. Inter-tube consistency was assessed for 20 different Sources, measured with a PTW 34013 ionization chamber. As the Source is intended to be used for a maximum of ten treatment fractions, tube stability was also assessed. Photon spectra were measured using a high-purity germanium (HPGe) detector, and calculated using MCNP. Parameters used in the two-dimensional (2D) brachytherapy dosimetry formalism were determined. While the Source was characterized as a point due to the small anode size, < 1 mm, use of the one-dimensional (1D) brachytherapy dosimetry formalism is not recommended due to polar anisotropy. Consequently, 1D brachytherapy dosimetry parameters were not sought. Calculated point-source model radial dose functions at gP(5) were 0.20, 0.24, and 0.29 for the 40, 45, and 50 kV voltage settings, respectively. For 1

Flu Vaccine and People with Egg Allergies

MedlinePlus

... 12 through 2014–15 reported maximum amounts of ≤1 µg/0.5 mL dose for flu shots and 0.24 µg/0.2 mL dose ... reactions, including anaphylaxis. In a Vaccine Safety Datalink study, there were ... other vaccines, (rate of 1.35 per one million doses). Most of these ...

Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to man.

PubMed

Colburn, W A; Vane, F M; Shorter, H J

1983-01-01

A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

PubMed Central

Parikh, Megha A.; Aaron, Carrie P.; Hoffman, Eric A.; Schwartz, Joseph E.; Madrigano, Jaime; Austin, John H. M.; Lovasi, Gina; Watson, Karol; Stukovsky, Karen Hinckley

2017-01-01

Rationale: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. Objectives: To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. Methods: The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45–84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than −950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. Results: Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. Conclusions: In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema. PMID:28207279

SU-F-T-68: Characterizes of Microdetectors in Electron Beam Dosimetry

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

Das, I; Andersen, A; Akino, Y

Purpose: Electron beam dosimetry requires high resolution data due to finite range that can be accomplished with small volume detectors. The small-field used in advance technologies in photon beam has created a market for microdetectors, however characteristics are significantly variable in photon beams and relatively unknown in electron beam that is investigated in this study. Methods: Among nearly 2 dozen microdetectors that have been investigated in small fields of photon beam, two popular detectors (microDiamond 60019 (PTW)) and W1 plastic scintillator detector (Standard Imaging)) that are tissue equivalent and have very small sensitive volume are selected. Electron beams from Varianmore » linear accelerators were used to investigate dose linearity dose rate dependence, energy dependence, depth dose and profiles in a reference condition in a water phantom. For W1 that has its own Supermax electrometer point by point measurements were performed. For microDiamond, a PTW-scanning tank was used for both scanning and point dose measurements. Results: W1 detector showed excellent dose linearity (r{sup 2} =1.0) from 5–500 MU either with variation of dose rate or beam energy. Similar findings were also observed for microdiamond with r{sup 2}=1.0. Percent variations in dose/MU for W1 and microDiamond were 0.2–1.1% and 0.4–1.2%, respectively among dose rate and beam energy. This variation was random for microDiamond, whereas it decreased with beam energy and dose rate for W1. The depth dose and profiles were within ±1 mm for both detectors. Both detectors did not show any energy dependence in electron beams. Conclusion: Both microDiamond and W1 detectors provided superior characteristics of beam parameters in electron beam including dose, dose rate linearity and energy independence. Both can be used in electron beam except W1 require point by point measurements and microdiamond requires 1500 MU for initial quenching.« less

SU-E-T-184: Clinical VMAT QA Practice Using LINAC Delivery Log Files

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

Johnston, H; Jacobson, T; Gu, X

2015-06-15

Purpose: To evaluate the accuracy of volumetric modulated arc therapy (VMAT) treatment delivery dose clouds by comparing linac log data to doses measured using an ionization chamber and film. Methods: A commercial IMRT quality assurance (QA) process utilizing a DICOM-RT framework was tested for clinical practice using 30 prostate and 30 head and neck VMAT plans. Delivered 3D VMAT dose distributions were independently checked using a PinPoint ionization chamber and radiographic film in a solid water phantom. DICOM RT coordinates were used to extract the corresponding point and planar doses from 3D log file dose distributions. Point doses were evaluatedmore » by computing the percent error between log file and chamber measured values. A planar dose evaluation was performed for each plan using a 2D gamma analysis with 3% global dose difference and 3 mm isodose point distance criteria. The same analysis was performed to compare treatment planning system (TPS) doses to measured values to establish a baseline assessment of agreement. Results: The mean percent error between log file and ionization chamber dose was 1.0%±2.1% for prostate VMAT plans and −0.2%±1.4% for head and neck plans. The corresponding TPS calculated and measured ionization chamber values agree within 1.7%±1.6%. The average 2D gamma passing rates for the log file comparison to film are 98.8%±1.0% and 96.2%±4.2% for the prostate and head and neck plans, respectively. The corresponding passing rates for the TPS comparison to film are 99.4%±0.5% and 93.9%±5.1%. Overall, the point dose and film data indicate that log file determined doses are in excellent agreement with measured values. Conclusion: Clinical VMAT QA practice using LINAC treatment log files is a fast and reliable method for patient-specific plan evaluation.« less

Comprehensive evaluations of cone-beam CT dose in image-guided radiation therapy via GPU-based Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Montanari, Davide; Scolari, Enrica; Silvestri, Chiara; Jiang Graves, Yan; Yan, Hao; Cervino, Laura; Rice, Roger; Jiang, Steve B.; Jia, Xun

2014-03-01

Cone beam CT (CBCT) has been widely used for patient setup in image-guided radiation therapy (IGRT). Radiation dose from CBCT scans has become a clinical concern. The purposes of this study are (1) to commission a graphics processing unit (GPU)-based Monte Carlo (MC) dose calculation package gCTD for Varian On-Board Imaging (OBI) system and test the calculation accuracy, and (2) to quantitatively evaluate CBCT dose from the OBI system in typical IGRT scan protocols. We first conducted dose measurements in a water phantom. X-ray source model parameters used in gCTD are obtained through a commissioning process. gCTD accuracy is demonstrated by comparing calculations with measurements in water and in CTDI phantoms. Twenty-five brain cancer patients are used to study dose in a standard-dose head protocol, and 25 prostate cancer patients are used to study dose in pelvis protocol and pelvis spotlight protocol. Mean dose to each organ is calculated. Mean dose to 2% voxels that have the highest dose is also computed to quantify the maximum dose. It is found that the mean dose value to an organ varies largely among patients. Moreover, dose distribution is highly non-homogeneous inside an organ. The maximum dose is found to be 1-3 times higher than the mean dose depending on the organ, and is up to eight times higher for the entire body due to the very high dose region in bony structures. High computational efficiency has also been observed in our studies, such that MC dose calculation time is less than 5 min for a typical case.

An Assessment of Common Approaches to Estimating Peak Skin Dose Resulting From Fluoroscopically Guided Interventions

NASA Astrophysics Data System (ADS)

Smith, Caleb Martin

Fluoroscopy guided procedures are increasing in complexity, and with that, Peak Skin Doses (PSD) that produce cutaneous radiation injury are a growing concern. Direct measurement of PSD is possible, but the decision to do so must be made in advance. PSD estimates and correctly monitoring their possible deterministic skin injuries are important to patient care. Three methods of indirect PSD estimation are examined for nine cases at MedStar Georgetown University Hospital. The aim of the study is to determine the magnitude of variation between these three methods for estimating the PSD. Method 1 (Fluoroscopy Time and Maximum Entrance Skin Exposure) was used at MedStar Georgetown University Hospital up until 2016. Methods 2 and 3 incorporate procedure information (Reference Point Air Kerma, Source-to-Patent distance, and Backscatter Factor) from DICOM (Digital Imaging and Communications in Medicine) tags into PSD estimates. Method 1 PSD estimates are vastly different, by as much as 136%, than those from Methods 2 and 3. Method 2 and 3 PSD estimates differ very little, 7.3% or less. Governing bodies have discounted Method 1 as a reliable dose metric because of its poor correlation with PSD. The accuracy of Method 2 is suitable to determine PSD and which dose band a patient fits so their injuries can be accurately monitored. Method 3, the most time intensive approach, should only be used in the case of a sentinel event where a full investigation is warranted.

The Pharmacokinetics of Enrofloxacin in Adult African Clawed Frogs (Xenopus laevis)

PubMed Central

Howard, Antwain M; Papich, Mark G; Felt, Stephen A; Long, Charles T; McKeon, Gabriel P; Bond, Emmitt S; Torreilles, Stéphanie L; Luong, Richard H; Green, Sherril L

2010-01-01

Pharmacokinetics of enrofloxacin, a fluoroquinolone antibiotic, was determined in adult female Xenopus laevis after single-dose administration (10 mg/kg) by intramuscular or subcutaneous injection. Frogs were evaluated at various time points until 8 h after injection. Plasma was analyzed for antibiotic concentration levels by HPLC. We computed pharmacokinetic parameters by using noncompartmental analysis of the pooled concentrations (naive pooled samples). After intramuscular administration of enrofloxacin, the half-life was 5.32 h, concentration maximum was 10.85 µg/mL, distribution volume was 841.96 mL/kg, and area under the time–concentration curve was 57.59 µg×h/mL; after subcutaneous administration these parameters were 4.08 h, 9.76 µg/mL, 915.85 mL/kg, and 47.42 µg×h/mL, respectively. According to plasma pharmacokinetics, Xenopus seem to metabolize enrofloxacin in a manner similar to mammals: low levels of the enrofloxacin metabolite, ciprofloxacin, were detected in the frogs’ habitat water and plasma. At necropsy, there were no gross or histologic signs of toxicity after single-dose administration; toxicity was not evaluated for repeated dosing. The plasma concentrations reached levels considered effective against common aquatic pathogens and suggest that a single, once-daily dose would be a reasonable regimen to consider when treating sick frogs. The treatment of sick frogs should be based on specific microbiologic identification of the pathogen and on antibiotic susceptibility testing. PMID:21205443

Effect of Food on the Single-dose Pharmacokinetics and Tolerability of Subutinib and its Active Metabolite in Chinese Healthy Volunteers.

PubMed

Ding, L-K; Jia, N; Yang, L; Li, J-K; Song, W; Wang, M-H; Wang, C; Gao, X-H; Wen, A-D

2016-03-01

The aim of this study is to investigate a food effect on the single-dose pharmacokinetics and tolerability of subutinib maleate capsules in healthy Chinese volunteers. The author evaluated the effect of being under a fasting or fed state at the time of drug intake on the single-dose of subutinib maleate capsules in a randomized, balanced, single-dose, 2-treatment (fasting and fed), 2-period design with a 3-week washout period. The end points were the maximum plasma drug concentration (Cmax) and areas under the plasma-concentration curve (AUC) for 336 h exposure (AUC0-336) and total exposure (AUC0-∞). All volunteers completed the whole study without side effects being observed. For subutinib, Cmax were 6.13 and 5.04 ng·mL(-1), and AUC0-336 were 278.4 and 304.5 h·ng·mL(-1) in the fasting and the fed state, respectively. For active metabolite, Cmax were 0.90 and 0.61 ng·mL(-1), and AUC0-336 were 65.5 and 56.4 h·ng·mL(-1) in the fasting and the fed state, respectively. The authors showed that food intake was associated with a slight increase in AUC values but decrease in Cmax of subutinib, and it was associated with a decrease both in AUC and Cmax of active metabolite. © Georg Thieme Verlag KG Stuttgart · New York.

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

PubMed

Campbell, Bruce C V; Mitchell, Peter J; Churilov, Leonid; Yassi, Nawaf; Kleinig, Timothy J; Dowling, Richard J; Yan, Bernard; Bush, Steven J; Dewey, Helen M; Thijs, Vincent; Scroop, Rebecca; Simpson, Marion; Brooks, Mark; Asadi, Hamed; Wu, Teddy Y; Shah, Darshan G; Wijeratne, Tissa; Ang, Timothy; Miteff, Ferdinand; Levi, Christopher R; Rodrigues, Edrich; Zhao, Henry; Salvaris, Patrick; Garcia-Esperon, Carlos; Bailey, Peter; Rice, Henry; de Villiers, Laetitia; Brown, Helen; Redmond, Kendal; Leggett, David; Fink, John N; Collecutt, Wayne; Wong, Andrew A; Muller, Claire; Coulthard, Alan; Mitchell, Ken; Clouston, John; Mahady, Kate; Field, Deborah; Ma, Henry; Phan, Thanh G; Chong, Winston; Chandra, Ronil V; Slater, Lee-Anne; Krause, Martin; Harrington, Timothy J; Faulder, Kenneth C; Steinfort, Brendan S; Bladin, Christopher F; Sharma, Gagan; Desmond, Patricia M; Parsons, Mark W; Donnan, Geoffrey A; Davis, Stephen M

2018-04-26

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

SU-E-J-165: Dosimetric Impact of Liver Rotations in Stereotactic Body Radiation Therapy

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

Pinnaduwage, D; Paulsson, A; Sudhyadhom, A

2015-06-15

Purpose: Often in liver stereotactic body radiotherapy a single fiducial is implanted near the tumor for image-guided treatment delivery. In such cases, rotational corrections are calculated based on the spine. This study quantifies rotational differences between the spine and liver, and investigates the corresponding dosimetric impact. Methods: Seven patients with 3 intrahepatic fiducials and 4DCT scans were identified. The planning CT was separately co-registered with 4 phases of the 4DCT (0%, 50%, 100% inhale and 50% exhale) by 1) rigid registration of the spine, and 2) point-based registration of the 3 fiducials. Rotation vectors were calculated for each registration. Translationalmore » differences in fiducial positions between the 2 registrations methods were investigated. Dosimetric impact due to liver rotations and deformations was assessed using critical structures delineated on the 4DCT phases. For dose comparisons, a single fiducial was translationally aligned following spine alignment to represent what is typically done in the clinic. Results: On average, differences between spine and liver rotations during the 0%, 50%, 100% inhale, and 50% exhale phases were 3.23°, 3.27°, 2.26° and 3.11° (pitch), 3.00°, 2.24°, 3.12° and 1.73° (roll), and 1.57°, 1.98°, 2.09° and 1.36° (yaw), respectively. The maximum difference in rotations was 12°, with differences of >3° seen in 14/28 (pitch), 10/28 (roll), and 6/28 (yaw) cases. Average fiducial displacements of 2.73 (craniocaudal), 1.04 (lateral) and 1.82 mm (vertical) were seen. Evaluating percent dose differences for 5 patients at the peaks of the respiratory cycle, the maximum dose to the duodenum, stomach, bowel and esophagus differed on average by 11.4%, 5.3%, 11.2% and 49.1% between the 2 registration methods. Conclusion: Lack of accounting for liver rotation during treatment might Result in clinically significant dose differences to critical structures. Both rotational and translational deviations should be considered in planning margins when using spine alignment for liver treatments.« less

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

Kuang, Yu; Wu, Lili; Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong

Purpose: This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by {sup 18}F-choline positron emission tomography/computed tomography (PET/CT). Methods and Materials: Thirty patients with localized prostate cancer underwent {sup 18}F-choline PET/CT before treatment. Two VMAT plans, plan{sub 79} {sub Gy} and plan{sub 100-105} {sub Gy}, were compared for each patient. The whole-prostate planning target volume (PTV{sub prostate}) prescription was 79 Gy in both plans, but plan{sub 100-105} {sub Gy} added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, definedmore » by 60% and 70% of maximum prostatic uptake on {sup 18}F-choline PET (IDL{sub suv60%} and IDL{sub suv70%}, respectively, with IDL{sub suv70%} nested inside IDL{sub suv60%} to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Results: Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDL{sub suv60%} adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan{sub 100-105} {sub Gy} had significantly higher TCP than plan{sub 79} {sub Gy} across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan{sub 100-105} {sub Gy}. Conclusions: VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a {sup 18}F-choline PET-defined IDL.« less

Investigation on the Maximum Power Point in Solar Panel Characteristics Due to Irradiance Changes

NASA Astrophysics Data System (ADS)

Abdullah, M. A.; Fauziah Toha, Siti; Ahmad, Salmiah

2017-03-01

One of the disadvantages of the photovoltaic module as compared to other renewable resources is the dynamic characteristics of solar irradiance due to inconsistency weather condition and surrounding temperature. Commonly, a photovoltaic power generation systems consist of an embedded control system to maximize the power generation due to the inconsistency in irradiance. In order to improve the simplicity of the power optimization control, this paper present the characteristic of Maximum Power Point with various irradiance levels for Maximum Power Point Tracking (MPPT). The technique requires a set of data from photovoltaic simulation model to be extrapolated as a standard relationship between irradiance and maximum power. The result shows that the relationship between irradiance and maximum power can be represented by a simplified quadratic equation. The first section in your paper

SU-F-T-437: 3 Field VMAT Technique for Irradiation of Large Pelvic Tumors

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

Stakhursky, V

2016-06-15

Purpose: VMAT treatment planning for large pelvic volume irradiation could be suboptimal due to inability of Varian linac to split MLC carriage during VMAT delivery for fields larger than 14.5cm in X direction (direction of leaf motion). We compare the dosimetry between 3 VMAT planning techniques, two 2-arc field techniques and a 3-arc field technique: a) two small in X direction (less than 14.5cm) arc fields, complementing each other to cover the whole lateral extent of target during gantry rotation, b) two large arc fields, each covering the targets completely during the rotation, c) a 3 field technique with 2more » small in X direction arcs and 1 large field covering whole target. Methods: 5 GYN cancer patients were selected to evaluate the 3 VMAT planning techniques. Treatment plans were generated using Varian Eclipse (ver. 11) TPS. Dose painting technique was used to deliver 5300 cGy to primary target and 4500 cGy to pelvic/abdominal node target. All the plans were normalized so that the prescription dose of 5300 cGy covered 95% of primary target volume. PTV and critical structures DVH curves were compared to evaluate all 3 planning techniques. Results: The dosimetric differences between the two 2-arc techniques were minor. The small field 2-arc technique showed a colder hot spot (0.4% averaged), while variations in maximum doses to critical structures were statistically nonsignificant (under 1.3%). In comparison, the 3-field technique demonstrated a colder hot spot (1.1% less, 105.8% averaged), and better sparing of critical structures. The maximum doses to larger bowel, small bowel and gluteal fold were 3% less, cord/cauda sparing was 4.2% better, and bladder maximum dose was 4.6% less. The differences in maximum doses to stomach and rectum were statistically nonsignificant. Conclusion: 3-arc VMAT technique for large field irradiation of pelvis demonstrates dosimetric advantages compared to 2-arc VMAT techniques.« less

Knowledge of appropriate acetaminophen use: A survey of college-age women.

PubMed

Stumpf, Janice L; Liao, Allison C; Nguyen, Stacy; Skyles, Amy J; Alaniz, Cesar

To evaluate college-age women's knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen. In this cross-sectional prospective study, a 20-item written survey was provided to female college students at a University of Michigan fundraising event in March 2015. A total of 203 female college students, 18-24 years of age, participated in the study. Pain was experienced on a daily or weekly basis by 22% of the subjects over the previous 6 months, and 83% reported taking acetaminophen. The maximum 3-gram daily dose of extra-strength acetaminophen was correctly identified by 64 participants; an additional 51 subjects indicated the generally accepted 4 grams daily as the maximum dose. When provided with the Tylenol Drug Facts label, 68.5% correctly identified the maximum amount of regular-strength acetaminophen recommended for a healthy adult. Hepatotoxicity was associated with high acetaminophen doses by 63.6% of participants, significantly more than those who selected distracter responses (P < 0.001). Knowledge of liver damage as a potential toxicity was correlated with age 20 years and older (P < 0.001) but was independent from race and ethnicity and level of alcohol consumption. Although more than one-half of the subjects (58.6%) recognized that Tylenol contained acetaminophen, fewer than one-fourth correctly identified other acetaminophen-containing products. Despite ongoing educational campaigns, a large proportion of the college-age women who participated in our study did not know and could not interpret the maximum recommended daily dose from Drug Facts labeling, did not know that liver damage was a potential toxicity of acetaminophen, and could not recognize acetaminophen-containing products. These data suggest a continued role for pharmacists in educational efforts targeted to college-age women. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Modeling the TrueBeam linac using a CAD to Geant4 geometry implementation: Dose and IAEA-compliant phase space calculations

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

Constantin, Magdalena; Perl, Joseph; LoSasso, Tom

2011-07-15

Purpose: To create an accurate 6 MV Monte Carlo simulation phase space for the Varian TrueBeam treatment head geometry imported from cad (computer aided design) without adjusting the input electron phase space parameters. Methods: geant4 v4.9.2.p01 was employed to simulate the 6 MV beam treatment head geometry of the Varian TrueBeam linac. The electron tracks in the linear accelerator were simulated with Parmela, and the obtained electron phase space was used as an input to the Monte Carlo beam transport and dose calculations. The geometry components are tessellated solids included in geant4 as gdml (generalized dynamic markup language) files obtainedmore » via STEP (standard for the exchange of product) export from Pro/Engineering, followed by STEP import in Fastrad, a STEP-gdml converter. The linac has a compact treatment head and the small space between the shielding collimator and the divergent arc of the upper jaws forbids the implementation of a plane for storing the phase space. Instead, an IAEA (International Atomic Energy Agency) compliant phase space writer was implemented on a cylindrical surface. The simulation was run in parallel on a 1200 node Linux cluster. The 6 MV dose calculations were performed for field sizes varying from 4 x 4 to 40 x 40 cm{sup 2}. The voxel size for the 60x60x40 cm{sup 3} water phantom was 4x4x4 mm{sup 3}. For the 10x10 cm{sup 2} field, surface buildup calculations were performed using 4x4x2 mm{sup 3} voxels within 20 mm of the surface. Results: For the depth dose curves, 98% of the calculated data points agree within 2% with the experimental measurements for depths between 2 and 40 cm. For depths between 5 and 30 cm, agreement within 1% is obtained for 99% (4x4), 95% (10x10), 94% (20x20 and 30x30), and 89% (40x40) of the data points, respectively. In the buildup region, the agreement is within 2%, except at 1 mm depth where the deviation is 5% for the 10x10 cm{sup 2} open field. For the lateral dose profiles, within the field size for fields up to 30x30 cm{sup 2}, the agreement is within 2% for depths up to 10 cm. At 20 cm depth, the in-field maximum dose difference for the 30x30 cm{sup 2} open field is within 4%, while the smaller field sizes agree within 2%. Outside the field size, agreement within 1% of the maximum dose difference is obtained for all fields. The calculated output factors varied from 0.938{+-}0.015 for the 4x4 cm{sup 2} field to 1.088{+-}0.024 for the 40x40 cm{sup 2} field. Their agreement with the experimental output factors is within 1%. Conclusions: The authors have validated a geant4 simulated IAEA-compliant phase space of the TrueBeam linac for the 6 MV beam obtained using a high accuracy geometry implementation from cad. These files are publicly available and can be used for further research.« less

Maximum likelihood analysis of bioassay data from long-term follow-up of two refractory PuO2 inhalation cases.

PubMed

Avtandilashvili, Maia; Brey, Richard; James, Anthony C

2012-07-01

The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.

Collective dose estimates by the marine food pathway from liquid radioactive wastes dumped in the Sea of Japan.

PubMed

Togawa, O; Povinec, P P; Pettersson, H B

1999-09-30

IAEA-MEL has been engaged in an assessment programme related to radioactive waste dumping by the former USSR and other countries in the western North Pacific Ocean and its marginal seas. This paper focuses on the Sea of Japan and on estimation of collective doses from liquid radioactive wastes. The results from the Japanese-Korean-Russian joint expeditions are summarized, and collective doses for the Japanese population by the marine food pathway are estimated from liquid radioactive wastes dumped in the Sea of Japan and compared with those from global fallout and natural radionuclides. The collective effective dose equivalents by the annual intake of marine products caught in each year show a maximum a few years after the disposals. The total dose from all radionuclides reaches a maximum of 0.8 man Sv in 1990. Approximately 90% of the dose derives from 137Cs, most of which is due to consumption of fish. The total dose from liquid radioactive wastes is approximately 5% of that from global fallout, the contribution of which is below 0.1% of that of natural 210Po.

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

SU-G-BRC-02: A Novel Multi-Criteria Optimization Approach to Generate Deliverable Intensity-Modulated Radiation Therapy (IMRT) Treatment Plans

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

Kirlik, G; D’Souza, W; Zhang, H

2016-06-15

Purpose: To present a novel multi-criteria optimization (MCO) solution approach that generates treatment plans with deliverable apertures using column generation. Methods: We demonstrate our method with 10 locally advanced head-and-neck cancer cases retrospectively. In our MCO formulation, we defined an objective function for each structure in the treatment volume. This resulted in 9 objective functions, including 3 distinct objectives for primary target volume, high-risk and low-risk target volumes, 5 objectives for each of the organs-at-risk (OARs) (two parotid glands, spinal cord, brain stem and oral cavity), and one for the non-target non-OAR normal tissue. Conditional value-at-risk (CVaR) constraints were utilizedmore » to ensure at least certain fraction of the target volumes receiving the prescription doses. To directly generate deliverable plans, column generation algorithm was embedded within our MCO approach for aperture shape generation. Final dose distributions for all plans were generated using a Monte Carlo kernel-superposition dose calculation. We compared the MCO plans with the clinical plans, which were created by clinicians. Results: At least 95% target coverage was achieved by both MCO plans and clinical plans. However, the average conformity indices of clinical plans and the MCO plans were 1.95 and 1.35, respectively (31% reduction, p<0.01). Compared to the conventional clinical plan, the proposed MCO method achieved average reductions in left parotid mean dose of 5% (p=0.06), right parotid mean dose of 18% (p<0.01), oral cavity mean dose of 21% (p=0.03), spinal cord maximum dose of 20% (p<0.01), brain stem maximum dose of 61% (p<0.01), and normal tissue maximum dose of 5% (p<0.01), respectively. Conclusion: We demonstrated that the proposed MCO method was able to obtain deliverable IMRT treatment plans while achieving significant improvements in dosimetric plan quality.« less

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

Liu, D; Chi, Z; Yang, H

Purpose: To investigate the performances of three commercial treatment planning systems (TPS) for intensity modulated radiotherapy (IMRT) optimization regarding cervical cancer. Methods: For twenty cervical cancer patients, three IMRT plans were retrospectively re-planned: one with Pinnacle TPS,one with Oncentra TPS and on with Eclipse TPS. The total prescribed dose was 50.4 Gy delivered for PTV and 58.8 Gy for PTVnd by simultaneous integrated boost technique. The treatments were delivered using the Varian 23EX accelerator. All optimization schemes generated clinically acceptable plans. They were evaluated based on target coverage, homogeneity (HI) and conformity (CI). The organs at risk (OARs) were analyzedmore » according to the percent volume under some doses and the maximum doses. The statistical method of the collected data of variance analysis was used to compare the difference among the quality of plans. Results: IMRT with Eclipse provided significant better HI, CI and all the parameters of PTV. However, the trend was not extension to the PTVnd, it was still significant better at mean dose, D50% and D98%, but plans with Oncentra showed significant better in the hight dosage volume, such as maximum dose and D2%. For the bladder wall, there were not notable difference among three groups, although Pinnacle and Oncentra systems provided a little lower dose sparing at V50Gy of bladder and rectal wall and V40Gy of bladder wall, respectively. V40Gy of rectal wall (p=0.037), small intestine (p=0.001 for V30Gy, p=0.010 for maximum dose) and V50Gy of right-femoral head (p=0.019) from Eclipse plans showed significant better than other groups. Conclusion: All SIB-IMRT plans were clinically acceptable which were generated by three commercial TPSs. The plans with Eclipse system showed advantages over the plans with Oncentra and Pinnacle system in the overwhelming majority of the dose coverage for targets and dose sparing of OARs in cervical cancer.« less

Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident.

PubMed

Little, Mark P; Kwon, Deukwoo; Zablotska, Lydia B; Brenner, Alina V; Cahoon, Elizabeth K; Rozhko, Alexander V; Polyanskaya, Olga N; Minenko, Victor F; Golovanov, Ivan; Bouville, André; Drozdovitch, Vladimir

2015-01-01

The excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of 131I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error. We examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996-2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied. There was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy- (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy- (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy- (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy- (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053-0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2). In summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.

SU-E-J-33: Cardiac Movement in Deep Inspiration Breath-Hold for Left-Breast Cancer Radiotherapy

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

Kim, M; Lee, S; Suh, T

Purpose: The present study was designed to investigate the displacement of heart using Deep Inspiration Breath Hold (DIBH) CT data compared to free-breathing (FB) CT data and radiation exposure to heart. Methods: Treatment planning was performed on the computed tomography (CT) datasets of 20 patients who had received lumpectomy treatments. Heart, lung and both breasts were outlined. The prescribed dose was 50 Gy divided into 28 fractions. The dose distributions in all the plans were required to fulfill the International Commission on Radiation Units and Measurement specifications that include 100% coverage of the CTV with ≥ 95% of the prescribedmore » dose and that the volume inside the CTV receiving > 107% of the prescribed dose should be minimized. Displacement of heart was measured by calculating the distance between center of heart and left breast. For the evaluation of radiation dose to heart, minimum, maximum and mean dose to heart were calculated. Results: The maximum and minimum left-right (LR) displacements of heart were 8.9 mm and 3 mm, respectively. The heart moved > 4 mm in the LR direction in 17 of the 20 patients. The distances between the heart and left breast ranged from 8.02–17.68 mm (mean, 12.23 mm) and 7.85–12.98 mm (mean, 8.97 mm) with DIBH CT and FB CT, respectively. The maximum doses to the heart were 3115 cGy and 4652 cGy for the DIBH and FB CT dataset, respectively. Conclusion: The present study has demonstrated that the DIBH technique could help to reduce the risk of radiation dose-induced cardiac toxicity by using movement of cardiac; away from radiation field. The DIBH technique could be used in an actual treatment room for a few minutes and could effectively reduce the cardiac dose when used with a sub-device or image acquisition standard to maintain consistent respiratory motion.« less

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

Liang, X; Li, Z; Zheng, D

Purpose: In the context of evaluating dosimetric impacts of a variety of uncertainties involved in HDR Tandem-and-Ovoid treatment, to study the correlations between conventional point doses and 3D volumetric doses. Methods: For 5 cervical cancer patients treated with HDR T&O, 150 plans were retrospectively created to study dosimetric impacts of the following uncertainties: (1) inter-fractional applicator displacement between two treatment fractions within a single insertion by applying Fraction#1 plan to Fraction#2 CT; (2) positional dwell error simulated from −5mm to 5mm in 1mm steps; (3) simulated temporal dwell error of 0.05s, 0.1s, 0.5s, and 1s. The original plans were basedmore » on point dose prescription, from which the volume covered by the prescription dose was generated as the pseudo target volume to study the 3D target dose effect. OARs were contoured. The point and volumetric dose errors were calculated by taking the differences between original and simulated plans. The correlations between the point and volumetric dose errors were analyzed. Results: For the most clinically relevant positional dwell uncertainty of 1mm, temporal uncertainty of 0.05s, and inter-fractional applicator displacement within the same insertion, the mean target D90 and V100 deviation were within 1%. Among these uncertainties, the applicator displacement showed the largest potential target coverage impact (2.6% on D90) as well as the OAR dose impact (2.5% and 3.4% on bladder D2cc and rectum D2cc). The Spearman correlation analysis shows a correlation coefficient of 0.43 with a p-value of 0.11 between target D90 coverage and H point dose. Conclusion: With the most clinically relevant positional and temporal dwell uncertainties and patient interfractional applicator displacement within the same insertion, the dose error is within clinical acceptable range. The lack of correlation between H point and 3D volumetric dose errors is a motivator for the use of 3D treatment planning in cervical HDR brachytherapy.« less

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Singh, Anurag K; Lockett, Mary Ann; Bradley, Jeffrey D

2003-02-01

To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Maximum power point tracker for photovoltaic power plants

NASA Astrophysics Data System (ADS)

Arcidiacono, V.; Corsi, S.; Lambri, L.

The paper describes two different closed-loop control criteria for the maximum power point tracking of the voltage-current characteristic of a photovoltaic generator. The two criteria are discussed and compared, inter alia, with regard to the setting-up problems that they pose. Although a detailed analysis is not embarked upon, the paper also provides some quantitative information on the energy advantages obtained by using electronic maximum power point tracking systems, as compared with the situation in which the point of operation of the photovoltaic generator is not controlled at all. Lastly, the paper presents two high-efficiency MPPT converters for experimental photovoltaic plants of the stand-alone and the grid-interconnected type.

Correlation of Osteoradionecrosis and Dental Events With Dosimetric Parameters in Intensity-Modulated Radiation Therapy for Head-and-Neck Cancer

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Estilo, Cherry L.; Wolden, Suzanne L.

Purpose: Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated. Methods and Materials: From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845more » cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints. Results: With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT. Conclusions: ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions.« less

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Correlation of osteoradionecrosis and dental events with dosimetric parameters in intensity-modulated radiation therapy for head-and-neck cancer.

PubMed

Gomez, Daniel R; Estilo, Cherry L; Wolden, Suzanne L; Zelefsky, Michael J; Kraus, Dennis H; Wong, Richard J; Shaha, Ashok R; Shah, Jatin P; Mechalakos, James G; Lee, Nancy Y

2011-11-15

Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated. From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845 cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints. With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT. ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions. Copyright © 2011 Elsevier Inc. All rights reserved.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.

PubMed

Leeman-Neill, Rebecca J; Brenner, Alina V; Little, Mark P; Bogdanova, Tetiana I; Hatch, Maureen; Zurnadzy, Liudmyla Y; Mabuchi, Kiyohiko; Tronko, Mykola D; Nikiforov, Yuri E

2013-05-15

Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored. RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Copyright © 2013 American Cancer Society.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

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

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-Targeted Dual-Variable Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid Arthritis: Results from Three Phase I Trials.

PubMed

Khatri, Amit; Goss, Sandra; Jiang, Ping; Mansikka, Heikki; Othman, Ahmed A

2018-05-01

ABT-122 is a dual-variable domain immunoglobulin that neutralizes both tumor necrosis factor-α and interleukin-17A, with the goal of achieving greater clinical efficacy than can be achieved by blocking either cytokine alone. This work characterized the pharmacokinetics of ABT-122 in healthy subjects and in patients with rheumatoid arthritis. ABT-122 pharmacokinetics was evaluated in three phase I studies. In Study 1, single intravenous (0.1, 0.3, 1, 3, and 10 mg/kg) and subcutaneous (0.3, 1, and 3 mg/kg) doses were evaluated in healthy subjects. In Studies 2 and 3, multiple subcutaneous doses (1 mg/kg every other week or 0.5-3 mg/kg every week) were evaluated for 8 weeks in patients with rheumatoid arthritis on stable methotrexate therapy. Pharmacokinetic data were available from 48 healthy subjects and 31 patients with rheumatoid arthritis. ABT-122 showed multi-exponential disposition with more than dose-proportional exposures at the 0.1-1 mg/kg doses and approximately dose-proportional exposures at doses ≥1 mg/kg. ABT-122 absolute subcutaneous bioavailability was approximately 50% with maximum serum concentrations observed 3-4 days after dosing. Steady state was achieved by week 6 of subcutaneous dosing. ABT-122 maximum serum concentration-to-trough concentration ratio was 2.6 for every other week dosing and 1.3 for every week dosing, corresponding to an effective half-life of 10-18 days. ABT-122 median area under the serum concentration-time curve accumulation ratio was 3.8-4.8 with every week dosing. Measureable antidrug antibodies were observed in all 48 subjects in Study 1 by day 15 post-dose and 19 of 31 ABT-122-treated patients in Studies 2 and 3 [median time to appearance of antidrug antibodies of 64 days (range 15-92 days)]. No dose-limiting toxicities were observed in these studies and the maximum tolerated dose was not identified. Results from these three phase I studies supported testing ABT-122 every week and every other week regimens in phase II trials in subjects with rheumatoid and psoriatic arthritis. Study 2 (EudraCT: 2012-003448-54); Study 3 (NCT01853033).

SU-F-T-131: No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons

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

Matsuura, T; Takao, S; Matsuzaki, Y

Purpose: To reduce the lateral penumbra of low-energy proton beams, brass collimators are often used in spot-scanning proton therapy (SSPT). This study investigates the increase in biological effectiveness through collimator scattered protons in SSPT. Methods: The SSPT system of the Hokkaido University Hospital Proton Beam Therapy Center, which consists of a scanning nozzle, a 2-cm thick brass collimator, and a 4-cm thick energy absorber, was simulated with our validated Geant4 Monte Carlo code (ver. 9.3). A water phantom was irradiated with proton pencil beams of 76, 110, and 143 MeV. The tested collimator opening areas (COA) were 5×5, 10×10, andmore » 15×15 cm{sup 2}. Comparisons were made among the dose-averaged LET values of protons that hit the collimators (LETDColl), protons that did not hit the collimators (LETDNoColl), and all protons (LETDTotal). X-ray equivalent doses (Deq) were calculated using the linear-quadratic model with LETDNoColl and LETDTotal, and their maximum difference was determined over regions where the physical dose was greater than 10% of the peak dose of 2 Gy. Results: The ratio of the dose contribution of collimator scattered protons to that of all protons, defined as λ, was large at high proton energies and large COAs. The maximum λ value ranged from 3% (76 MeV, 5×5 cm{sup 2}) to 29% (143 MeV, 15×15 cm{sup 2}). Moreover, a large difference between LETDColl and LETDNoColl was only found in regions where λ was below 20% (ΔLETD > 2 keV/µm) and 8% (ΔLETD > 5 keV/µm). Consequently, the maximum difference between LETDNoColl and LETDTotal was as small as 0.8 keV/µm in all simulated voxels, and the difference of Deq reached a maximum of 1.5% that of the peak dose obtained at the water surface with a 76 MeV beam. Conclusion: Although collimator scattered protons have high LET, they only increase the physical dose, not the biological effectiveness.« less

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers

PubMed Central

Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-01

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step‐and‐shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose <45 Gy to spinal cord and <50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5±2.2 Gy and 36.7±14.0 Gy), without significant changes on the other OARs. A marked difference (−15.9±1.9 Gy and −10.1±5.7 Gy) was obtained at the expense of a small difference (−1.3%±0.9%) from initial PTV195% coverage (96.6%±0.9%). Similar difference (−15.7±2.2 Gy and −10.2±6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (−0.3%±0.3% from the initial 98.3%±0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer. PACS number: 87.55.D PMID:24423836