Monte Carlo dose calculations in homogeneous media and at interfaces: a comparison between GEPTS, EGSnrc, MCNP, and measurements.

PubMed

Chibani, Omar; Li, X Allen

2002-05-01

Three Monte Carlo photon/electron transport codes (GEPTS, EGSnrc, and MCNP) are bench-marked against dose measurements in homogeneous (both low- and high-Z) media as well as at interfaces. A brief overview on physical models used by each code for photon and electron (positron) transport is given. Absolute calorimetric dose measurements for 0.5 and 1 MeV electron beams incident on homogeneous and multilayer media are compared with the predictions of the three codes. Comparison with dose measurements in two-layer media exposed to a 60Co gamma source is also performed. In addition, comparisons between the codes (including the EGS4 code) are done for (a) 0.05 to 10 MeV electron beams and positron point sources in lead, (b) high-energy photons (10 and 20 MeV) irradiating a multilayer phantom (water/steel/air), and (c) simulation of a 90Sr/90Y brachytherapy source. A good agreement is observed between the calorimetric electron dose measurements and predictions of GEPTS and EGSnrc in both homogeneous and multilayer media. MCNP outputs are found to be dependent on the energy-indexing method (Default/ITS style). This dependence is significant in homogeneous media as well as at interfaces. MCNP(ITS) fits more closely the experimental data than MCNP(DEF), except for the case of Be. At low energy (0.05 and 0.1 MeV), MCNP(ITS) dose distributions in lead show higher maximums in comparison with GEPTS and EGSnrc. EGS4 produces too penetrating electron-dose distributions in high-Z media, especially at low energy (<0.1 MeV). For positrons, differences between GEPTS and EGSnrc are observed in lead because GEPTS distinguishes positrons from electrons for both elastic multiple scattering and bremsstrahlung emission models. For the 60Co source, a quite good agreement between calculations and measurements is observed with regards to the experimental uncertainty. For the other cases (10 and 20 MeV photon sources and the 90Sr/90Y beta source), a good agreement is found between the three

Direct ultrasensitive electrochemical biosensing of pathogenic DNA using homogeneous target-initiated transcription amplification

PubMed Central

Yan, Yurong; Ding, Shijia; Zhao, Dan; Yuan, Rui; Zhang, Yuhong; Cheng, Wei

2016-01-01

Sensitive and specific methodologies for detection of pathogenic gene at the point-of-care are still urgent demands in rapid diagnosis of infectious diseases. This work develops a simple and pragmatic electrochemical biosensing strategy for ultrasensitive and specific detection of pathogenic nucleic acids directly by integrating homogeneous target-initiated transcription amplification (HTITA) with interfacial sensing process in single analysis system. The homogeneous recognition and specific binding of target DNA with the designed hairpin probe triggered circular primer extension reaction to form DNA double-strands which contained T7 RNA polymerase promoter and served as templates for in vitro transcription amplification. The HTITA protocol resulted in numerous single-stranded RNA products which could synchronously hybridized with the detection probes and immobilized capture probes for enzyme-amplified electrochemical detection on the biosensor surface. The proposed electrochemical biosensing strategy showed very high sensitivity and selectivity for target DNA with a dynamic response range from 1 fM to 100 pM. Using salmonella as a model, the established strategy was successfully applied to directly detect invA gene from genomic DNA extract. This proposed strategy presented a simple, pragmatic platform toward ultrasensitive nucleic acids detection and would become a versatile and powerful tool for point-of-care pathogen identification. PMID:26729209

Direct ultrasensitive electrochemical biosensing of pathogenic DNA using homogeneous target-initiated transcription amplification

NASA Astrophysics Data System (ADS)

Yan, Yurong; Ding, Shijia; Zhao, Dan; Yuan, Rui; Zhang, Yuhong; Cheng, Wei

2016-01-01

Sensitive and specific methodologies for detection of pathogenic gene at the point-of-care are still urgent demands in rapid diagnosis of infectious diseases. This work develops a simple and pragmatic electrochemical biosensing strategy for ultrasensitive and specific detection of pathogenic nucleic acids directly by integrating homogeneous target-initiated transcription amplification (HTITA) with interfacial sensing process in single analysis system. The homogeneous recognition and specific binding of target DNA with the designed hairpin probe triggered circular primer extension reaction to form DNA double-strands which contained T7 RNA polymerase promoter and served as templates for in vitro transcription amplification. The HTITA protocol resulted in numerous single-stranded RNA products which could synchronously hybridized with the detection probes and immobilized capture probes for enzyme-amplified electrochemical detection on the biosensor surface. The proposed electrochemical biosensing strategy showed very high sensitivity and selectivity for target DNA with a dynamic response range from 1 fM to 100 pM. Using salmonella as a model, the established strategy was successfully applied to directly detect invA gene from genomic DNA extract. This proposed strategy presented a simple, pragmatic platform toward ultrasensitive nucleic acids detection and would become a versatile and powerful tool for point-of-care pathogen identification.

Direct ultrasensitive electrochemical biosensing of pathogenic DNA using homogeneous target-initiated transcription amplification.

PubMed

Yan, Yurong; Ding, Shijia; Zhao, Dan; Yuan, Rui; Zhang, Yuhong; Cheng, Wei

2016-01-05

Sensitive and specific methodologies for detection of pathogenic gene at the point-of-care are still urgent demands in rapid diagnosis of infectious diseases. This work develops a simple and pragmatic electrochemical biosensing strategy for ultrasensitive and specific detection of pathogenic nucleic acids directly by integrating homogeneous target-initiated transcription amplification (HTITA) with interfacial sensing process in single analysis system. The homogeneous recognition and specific binding of target DNA with the designed hairpin probe triggered circular primer extension reaction to form DNA double-strands which contained T7 RNA polymerase promoter and served as templates for in vitro transcription amplification. The HTITA protocol resulted in numerous single-stranded RNA products which could synchronously hybridized with the detection probes and immobilized capture probes for enzyme-amplified electrochemical detection on the biosensor surface. The proposed electrochemical biosensing strategy showed very high sensitivity and selectivity for target DNA with a dynamic response range from 1 fM to 100 pM. Using salmonella as a model, the established strategy was successfully applied to directly detect invA gene from genomic DNA extract. This proposed strategy presented a simple, pragmatic platform toward ultrasensitive nucleic acids detection and would become a versatile and powerful tool for point-of-care pathogen identification.

A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based linear accelerator IMRT treatment plans

PubMed Central

Saenz, Daniel L.; Paliwal, Bhudatt R.; Bayouth, John E.

2014-01-01

ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is investigated for treatment planning capabilities assessing treatment plan dose homogeneity and conformity compared with linear accelerator plans. ViewRay offers both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co-60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with multiple beams. This study investigated head and neck, lung, and prostate treatment plans to understand what is possible on ViewRay to narrow focus toward sites with optimal dosimetry. The goal is not to provide a rigorous assessment of planning capabilities, but rather a first order demonstration of ViewRay planning abilities. Images, structure sets, points, and dose from treatment plans created in Pinnacle for patients in our clinic were imported into ViewRay. The same objectives were used to assess plan quality and all critical structures were treated as similarly as possible. Homogeneity index (HI), conformity index (CI), and volume receiving <20% of prescription dose (DRx) were calculated to assess the plans. The 95% confidence intervals were recorded for all measurements and presented with the associated bars in graphs. The homogeneity index (D5/D95) had a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for prostate. CI revealed a modest conformity increase for lung. The volume receiving 20% of the prescription dose increased 2-8% for head and neck and up to 4% for lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned with its Monte Carlo treatment planning software were comparable with 6 MV plans computed with convolution superposition algorithm on Pinnacle treatment planning system. PMID:24872603

A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based linear accelerator IMRT treatment plans.

PubMed

Saenz, Daniel L; Paliwal, Bhudatt R; Bayouth, John E

2014-04-01

ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is investigated for treatment planning capabilities assessing treatment plan dose homogeneity and conformity compared with linear accelerator plans. ViewRay offers both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co-60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with multiple beams. This study investigated head and neck, lung, and prostate treatment plans to understand what is possible on ViewRay to narrow focus toward sites with optimal dosimetry. The goal is not to provide a rigorous assessment of planning capabilities, but rather a first order demonstration of ViewRay planning abilities. Images, structure sets, points, and dose from treatment plans created in Pinnacle for patients in our clinic were imported into ViewRay. The same objectives were used to assess plan quality and all critical structures were treated as similarly as possible. Homogeneity index (HI), conformity index (CI), and volume receiving <20% of prescription dose (DRx) were calculated to assess the plans. The 95% confidence intervals were recorded for all measurements and presented with the associated bars in graphs. The homogeneity index (D5/D95) had a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for prostate. CI revealed a modest conformity increase for lung. The volume receiving 20% of the prescription dose increased 2-8% for head and neck and up to 4% for lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned with its Monte Carlo treatment planning software were comparable with 6 MV plans computed with convolution superposition algorithm on Pinnacle treatment planning system.

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

PubMed

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

2018-02-01

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

Glandular radiation dose in tomosynthesis of the breast using tungsten targets.

PubMed

Sechopoulos, Ioannis; D'Orsi, Carl J

2008-10-24

With the advent of new detector technology, digital tomosynthesis imaging of the breast has, in the past few years, become a technique intensely investigated as a replacement for planar mammography. As with all other x-ray-based imaging methods, radiation dose is of utmost concern in the development of this new imaging technology. For virtually all development and optimization studies, knowledge of the radiation dose involved in an imaging protocol is necessary. A previous study characterized the normalized glandular dose in tomosynthesis imaging and its variation with various breast and imaging system parameters. This characterization was performed with x-ray spectra generated by molybdenum and rhodium targets. In the recent past, many preliminary patient studies of tomosynthesis imaging have been reported in which the x-ray spectra were generated with x-ray tubes with tungsten targets. The differences in x-ray distribution among spectra from these target materials make the computation of new normalized glandular dose values for tungsten target spectra necessary. In this study we used previously obtained monochromatic normalized glandular dose results to obtain spectral results for twelve different tungsten target x-ray spectra. For each imaging condition, two separate values were computed: the normalized glandular dose for the zero degree projection angle (DgN0), and the ratio of the glandular dose for non-zero projection angles to the glandular dose for the zero degree projection (the relative glandular dose, RGD(alpha)). It was found that DgN0 is higher for tungsten target x-ray spectra when compared with DgN0 values for molybdenum and rhodium target spectra of both equivalent tube voltage and first half value layer. Therefore, the DgN0 for the twelve tungsten target x-ray spectra and different breast compositions and compressed breast thicknesses simulated are reported. The RGD(alpha) values for the tungsten spectra vary with the parameters studied in a

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

PubMed

Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

Homogeneous assay of target molecules based on chemiluminescence resonance energy transfer (CRET) using DNAzyme-linked aptamers.

PubMed

Mun, Hyoyoung; Jo, Eun-Jung; Li, Taihua; Joung, Hyou-Arm; Hong, Dong-Gu; Shim, Won-Bo; Jung, Cheulhee; Kim, Min-Gon

2014-08-15

We have designed a single-stranded DNAzyme-aptamer sensor for homogeneous target molecular detection based on chemiluminescence resonance energy transfer (CRET). The structure of the engineered single-stranded DNA (ssDNA) includes the horseradish peroxidase (HRP)-like DNAzyme, optimum-length linker (10-mer-length DNA), and target-specific aptamer sequences. A quencher dye was modified at the 3' end of the aptamer sequence. The incorporation of hemin into the G-quadruplex structure of DNAzyme yields an active HRP-like activity that catalyzes luminol to generate a chemiluminescence (CL) signal. In the presence of target molecules, such as ochratoxin A (OTA), adenosine triphosphate (ATP), or thrombin, the aptamer sequence was folded due to the formation of the aptamer/analyte complex, which induced the quencher dye close to the DNAzyme structure. Consequently, the CRET occurred between a DNAzyme-catalyzed chemiluminescence reaction and the quencher dye. Our results showed that CRET-based DNAzyme-aptamer biosensing enabled specific OTA analysis with a limit of detection of 0.27ng/mL. The CRET platform needs no external light source and avoids autofluorescence and photobleaching, and target molecules can be detected specifically and sensitively in a homogeneous manner. Copyright © 2014 Elsevier B.V. All rights reserved.

Monte Carlo evaluation of glandular dose in cone-beam X-ray computed tomography dedicated to the breast: Homogeneous and heterogeneous breast models.

PubMed

Sarno, Antonio; Mettivier, Giovanni; Tucciariello, Raffaele M; Bliznakova, Kristina; Boone, John M; Sechopoulos, Ioannis; Di Lillo, Francesca; Russo, Paolo

2018-06-07

In cone-beam computed tomography dedicated to the breast (BCT), the mean glandular dose (MGD) is the dose metric of reference, evaluated from the measured air kerma by means of normalized glandular dose coefficients (DgN CT ). This work aimed at computing, for a simple breast model, a set of DgN CT values for monoenergetic and polyenergetic X-ray beams, and at validating the results vs. those for patient specific digital phantoms from BCT scans. We developed a Monte Carlo code for calculation of monoenergetic DgN CT coefficients (energy range 4.25-82.25 keV). The pendant breast was modelled as a cylinder of a homogeneous mixture of adipose and glandular tissue with glandular fractions by mass of 0.1%, 14.3%, 25%, 50% or 100%, enveloped by a 1.45 mm-thick skin layer. The breast diameter ranged between 8 cm and 18 cm. Then, polyenergetic DgN CT coefficients were analytically derived for 49-kVp W-anode spectra (half value layer 1.25-1.50 mm Al), as in a commercial BCT scanner. We compared the homogeneous models to 20 digital phantoms produced from classified 3D breast images. Polyenergetic DgN CT resulted 13% lower than most recent published data. The comparison vs. patient specific breast phantoms showed that the homogeneous cylindrical model leads to a DgN CT percentage difference between -15% and +27%, with an average overestimation of 8%. A dataset of monoenergetic and polyenergetic DgN CT coefficients for BCT was provided. Patient specific breast models showed a different volume distribution of glandular dose and determined a DgN CT 8% lower, on average, than homogeneous breast model. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny in the human lung.

PubMed

Nikezic, D; Lau, B M F; Stevanovic, N; Yu, K N

2006-01-01

To calculate the absorbed dose in the human lung due to inhaled radon progeny, ICRP focussed on the layers containing the target cells, i.e., the basal and secretory cells. Such an approach did not consider details of the sensitive cells in the layers. The present work uses the microdosimetric approach and determines the absorbed alpha-particle energy in non-spherical nuclei of target cells (basal and secretory cells). The absorbed energy for alpha particles emitted by radon progeny in the human respiratory tract was calculated in basal- and secretory-cell nuclei, assuming conical and ellipsoidal forms for these cells. Distributions of specific energy for different combinations of alpha-particle sources, energies and targets are calculated and shown. The dose conversion coefficient for radon progeny is reduced for about 2mSv/WLM when conical and ellipsoidal cell nuclei are considered instead of the layers. While changes in the geometry of secretory-cell nuclei do not have significant effects on their absorbed dose, changes from spherical to conical basal-cell nuclei have significantly reduced their absorbed dose from approximately 4 to approximately 3mGy/WLM. This is expected because basal cells are situated close to the end of the range of 6MeV alpha particles. This also underlines the significance of better and more precise information on targets in the T-B tree. A further change in the dose conversion coefficient can be achieved if a different weighting scheme is adopted for the doses for the cells. The results demonstrate the necessity for better information on the target cells for more accurate dosimetry for radon progeny.

Preparation and Immunoaffinity Depletion of Fresh Frozen Tissue Homogenates for Mass Spectrometry-Based Proteomics in the Context of Drug Target/Biomarker Discovery.

PubMed

Prieto, DaRue A; Chan, King C; Johann, Donald J; Ye, Xiaoying; Whitely, Gordon; Blonder, Josip

2017-01-01

The discovery of novel drug targets and biomarkers via mass spectrometry (MS)-based proteomic analysis of clinical specimens has proven to be challenging. The wide dynamic range of protein concentration in clinical specimens and the high background/noise originating from highly abundant proteins in tissue homogenates and serum/plasma encompass two major analytical obstacles. Immunoaffinity depletion of highly abundant blood-derived proteins from serum/plasma is a well-established approach adopted by numerous researchers; however, the utilization of this technique for immunodepletion of tissue homogenates obtained from fresh frozen clinical specimens is lacking. We first developed immunoaffinity depletion of highly abundant blood-derived proteins from tissue homogenates, using renal cell carcinoma as a model disease, and followed this study by applying it to different tissue types. Tissue homogenate immunoaffinity depletion of highly abundant proteins may be equally important as is the recognized need for depletion of serum/plasma, enabling more sensitive MS-based discovery of novel drug targets, and/or clinical biomarkers from complex clinical samples. Provided is a detailed protocol designed to guide the researcher through the preparation and immunoaffinity depletion of fresh frozen tissue homogenates for two-dimensional liquid chromatography, tandem mass spectrometry (2D-LC-MS/MS)-based molecular profiling of tissue specimens in the context of drug target and/or biomarker discovery.

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Low-dose fixed-target serial synchrotron crystallography.

PubMed

Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

2017-04-01

The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

Evaluation of Mean Glandular Dose and Modulation Transfer Function for Different Tube Potentials and Target-Filter Combinations in Computed Radiography Mammography

PubMed Central

Abdul Aziz,, Siti Aishah; Mohd Saparudin, Abdul Khaliq; Harun, Ahmad Zaky

2013-01-01

Background: Different target-filter combinations in computed radiography have different impacts on the dose and image quality in digital radiography. This study aims to evaluate the mean glandular dose (MGD) and modulation transfer function (MTF) of various target-filter combinations by investigating the signal intensities of X-ray beams. Methods: General Electric (GE) Senographe DMR Plus mammography unit was used for MGD and MTF evaluation. The measured MGD was compared with the dose reference level (DRL), whereas the MTF was evaluated using ImageJ 1.46o software. A modified Mammography Accreditation Phantom RMI 156 was exposed using different target-filter combinations of molybdenum-molybdenum (Mo-Mo), molybdenum-rhodium (Mo-Rh) and rhodium-rhodium (Rh-Rh) at two different tube voltages, 26 kV and 32 kV with 50 mAs. Results: In the MGD evaluations, all target-filters gave an MGD value of < 1.5 mGy. The one-way ANOVA test showed a highly significant interaction between the MGD and the kilovoltage and target-filter material used (26 kV: F (2,12) = 49,234, P = 0.001;32 kV: F (2,12) = 89,972, P = 0.001). A Tukey post-hoc test revealed that the MGD for 26 kV and 32 kV was highly affected by the target-filter combinations. The test of homogeneity of variances indicates that the MGD varies significantly for 26 kV and 32 kV images (0.045 and 0.030 (P < 0.05), respectively). However, the one-way ANOVA for the MTF shows that no significant difference exists between the target-filter combinations used with 26 kV and 32 kV images either in parallel or perpendicular to the chest wall side F (2,189) = 0.26, P > 0.05). Conclusion: Higher tube voltage and atomic number target-filter yield higher MGD values. However, the MTF is independent of the X-ray energy and the type of target-filter combinations used. PMID:23966821

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

PubMed

Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Analytical dose modeling for preclinical proton irradiation of millimetric targets.

PubMed

Vanstalle, Marie; Constanzo, Julie; Karakaya, Yusuf; Finck, Christian; Rousseau, Marc; Brasse, David

2018-01-01

Due to the considerable development of proton radiotherapy, several proton platforms have emerged to irradiate small animals in order to study the biological effectiveness of proton radiation. A dedicated analytical treatment planning tool was developed in this study to accurately calculate the delivered dose given the specific constraints imposed by the small dimensions of the irradiated areas. The treatment planning system (TPS) developed in this study is based on an analytical formulation of the Bragg peak and uses experimental range values of protons. The method was validated after comparison with experimental data from the literature and then compared to Monte Carlo simulations conducted using Geant4. Three examples of treatment planning, performed with phantoms made of water targets and bone-slab insert, were generated with the analytical formulation and Geant4. Each treatment planning was evaluated using dose-volume histograms and gamma index maps. We demonstrate the value of the analytical function for mouse irradiation, which requires a targeting accuracy of 0.1 mm. Using the appropriate database, the analytical modeling limits the errors caused by misestimating the stopping power. For example, 99% of a 1-mm tumor irradiated with a 24-MeV beam receives the prescribed dose. The analytical dose deviations from the prescribed dose remain within the dose tolerances stated by report 62 of the International Commission on Radiation Units and Measurements for all tested configurations. In addition, the gamma index maps show that the highly constrained targeting accuracy of 0.1 mm for mouse irradiation leads to a significant disagreement between Geant4 and the reference. This simulated treatment planning is nevertheless compatible with a targeting accuracy exceeding 0.2 mm, corresponding to rat and rabbit irradiations. Good dose accuracy for millimetric tumors is achieved with the analytical calculation used in this work. These volume sizes are typical in mouse

Non-targeted effects of ionizing radiation–implications for low dose risk

PubMed Central

Kadhim, Munira; Salomaa, Sisko; Wright, Eric; Hildebrandt, Guido; Belyakov, Oleg V.; Prise, Kevin M.; Little, Mark P.

2014-01-01

Non-DNA targeted effects of ionizing radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionizing radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the Non-targeted effects of ionizing radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. PMID:23262375

SU-E-T-535: Proton Dose Calculations in Homogeneous Media.

PubMed

Chapman, J; Fontenot, J; Newhauser, W; Hogstrom, K

2012-06-01

To develop a pencil beam dose calculation algorithm for scanned proton beams that improves modeling of scatter events. Our pencil beam algorithm (PBA) was developed for calculating dose from monoenergetic, parallel proton beams in homogeneous media. Fermi-Eyges theory was implemented for pencil beam transport. Elastic and nonelastic scatter effects were each modeled as a Gaussian distribution, with root mean square (RMS) widths determined from theoretical calculations and a nonlinear fit to a Monte Carlo (MC) simulated 1mm × 1mm proton beam, respectively. The PBA was commissioned using MC simulations in a flat water phantom. Resulting PBA calculations were compared with results of other models reported in the literature on the basis of differences between PBA and MC calculations of 80-20% penumbral widths. Our model was further tested by comparing PBA and MC results for oblique beams (45 degree incidence) and surface irregularities (step heights of 1 and 4 cm) for energies of 50-250 MeV and field sizes of 4cm × 4cm and 10cm × 10cm. Agreement between PBA and MC distributions was quantified by computing the percentage of points within 2% dose difference or 1mm distance to agreement. Our PBA improved agreement between calculated and simulated penumbral widths by an order of magnitude compared with previously reported values. For comparisons of oblique beams and surface irregularities, agreement between PBA and MC distributions was better than 99%. Our algorithm showed improved accuracy over other models reported in the literature in predicting the overall shape of the lateral profile through the Bragg peak. This improvement was achieved by incorporating nonelastic scatter events into our PBA. The increased modeling accuracy of our PBA, incorporated into a treatment planning system, may improve the reliability of treatment planning calculations for patient treatments. This research was supported by contract W81XWH-10-1-0005 awarded by The U.S. Army Research

Stimulus homogeneity enhances implicit learning: evidence from contextual cueing.

PubMed

Feldmann-Wüstefeld, Tobias; Schubö, Anna

2014-04-01

Visual search for a target object is faster if the target is embedded in a repeatedly presented invariant configuration of distractors ('contextual cueing'). It has also been shown that the homogeneity of a context affects the efficiency of visual search: targets receive prioritized processing when presented in a homogeneous context compared to a heterogeneous context, presumably due to grouping processes at early stages of visual processing. The present study investigated in three Experiments whether context homogeneity also affects contextual cueing. In Experiment 1, context homogeneity varied on three levels of the task-relevant dimension (orientation) and contextual cueing was most pronounced for context configurations with high orientation homogeneity. When context homogeneity varied on three levels of the task-irrelevant dimension (color) and orientation homogeneity was fixed, no modulation of contextual cueing was observed: high orientation homogeneity led to large contextual cueing effects (Experiment 2) and low orientation homogeneity led to low contextual cueing effects (Experiment 3), irrespective of color homogeneity. Enhanced contextual cueing for homogeneous context configurations suggest that grouping processes do not only affect visual search but also implicit learning. We conclude that memory representation of context configurations are more easily acquired when context configurations can be processed as larger, grouped perceptual units. However, this form of implicit perceptual learning is only improved by stimulus homogeneity when stimulus homogeneity facilitates grouping processes on a dimension that is currently relevant in the task. Copyright © 2014 Elsevier B.V. All rights reserved.

A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer

PubMed Central

Hutton, Brian; Addison, Christina L.; Campbell, Kaitryn; Fergusson, Dean; Mazarello, Sasha; Clemons, Mark

2013-01-01

Background Bone-targeted agents are usually administered to breast cancer patients with bone metastases every 3–4 weeks. Less frequent (‘de-escalated’) treatment may provide similar benefits with improved safety and reduced cost. Methods To systematically review randomised trials comparing de-escalated treatment with bone-targeted agents (i.e. every 12–16 weeks) to standard treatment (i.e. every 3–4 weeks), a formal systematic review of the literature was performed. Two individuals independently screened citations and full text articles. Random effects meta-analyses of clinically important outcomes were planned provided homogeneous studies were identified. Results Five relevant studies (n=1287 patients) were identified. Sample size ranged from 38 to 425. Information on outcomes including occurrence of SREs, bone pain, urinary N-telopeptide concentrations, serum C-telopeptide concentrations, pain medication use and safety outcomes was not consistently available. Two trials were non-inferiority studies, two dose-response evaluations and one was a pilot study. Bone-targeted agents use varied between studies, as did duration of prior therapy. Patient populations were considered heterogeneous in several ways, and thus no meta-analyses were performed. Observations from the included studies suggest there is potential that 3 month de-escalated treatment may provide similar benefits compared to 3–4 weekly treatment and that lower doses of zoledronic acid and denosumab might be equally effective. Conclusions Studies comparing standard and de-escalated treatment with bone-targeted agents in breast cancer are rare. The benefits of standard treatment compared to de-escalated therapy on important clinical outcomes remain unclear. Future pragmatic studies must be conducted to determine the merits of this approach. PMID:26909282

From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

PubMed

Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

2016-06-01

When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when

In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

PubMed

Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

2012-01-01

Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

NASA Technical Reports Server (NTRS)

Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

1999-01-01

To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

Poster - 36: Effect of Planning Target Volume Coverage on the Dose Delivered in Lung Radiotherapy

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

Dekker, Chris; Wierzbicki, Marcin

2016-08-15

Purpose: In lung radiotherapy, breathing motion may be encompassed by contouring the internal target volume (ITV). Remaining uncertainties are included in a geometrical expansion to the planning target volume (PTV). In IMRT, the treatment is then optimized until a desired PTV fraction is covered by the appropriate dose. The resulting beams often carry high fluence in the PTV margin to overcome low lung density and to generate steep dose gradients. During treatment, the high density tumour can enter the PTV margin, potentially increasing target dose. Thus, planning lung IMRT with a reduced PTV dose may still achieve the desired ITVmore » dose during treatment. Methods: A retrospective analysis was carried out with 25 IMRT plans prescribed to 63 Gy in 30 fractions. The plans were re-normalized to cover various fractions of the PTV by different isodose lines. For each case, the isocentre was moved using 125 shifts derived from all 3D combinations of 0 mm, (PTV margin - 1 mm), and PTV margin. After each shift, the dose was recomputed to approximate the delivered dose. Results and Conclusion: Our plans typically cover 95% of the PTV by 95% of the dose. Reducing the PTV covered to 94% did not significantly reduce the delivered ITV doses for (PTV margin - 1 mm) shifts. Target doses were reduced significantly for all other shifts and planning goals studied. Thus, a reduced planning goal will likely deliver the desired target dose as long as the ITV rarely enters the last mm of the PTV margin.« less

Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.

PubMed

Mok, Henry; Crane, Christopher H; Palmer, Matthew B; Briere, Tina M; Beddar, Sam; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

2011-06-08

, without incurring penalty with respect to adjacent organs-at-risk. For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

PubMed

Hou, X; Tanguay, J; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2016-01-21

In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-01-01

In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

Feasibility study on inverse four-dimensional dose reconstruction using the continuous dose-image of EPID

PubMed Central

Yeo, Inhwan Jason; Jung, Jae Won; Yi, Byong Yong; Kim, Jong Oh

2013-01-01

Purpose: When an intensity-modulated radiation beam is delivered to a moving target, the interplay effect between dynamic beam delivery and the target motion due to miss-synchronization can cause unpredictable dose delivery. The portal dose image in electronic portal imaging device (EPID) represents radiation attenuated and scattered through target media. Thus, it may possess information about delivered radiation to the target. Using a continuous scan (cine) mode of EPID, which provides temporal dose images related to target and beam movements, the authors’ goal is to perform four-dimensional (4D) dose reconstruction. Methods: To evaluate this hypothesis, first, the authors have derived and subsequently validated a fast method of dose reconstruction based on virtual beamlet calculations of dose responses using a test intensity-modulated beam. This method was necessary for processing a large number of EPID images pertinent for four-dimensional reconstruction. Second, cine mode acquisition after summation over all images was validated through comparison with integration mode acquisition on EPID (IAS3 and aS1000) for the test beam. This was to confirm the agreement of the cine mode with the integrated mode, specifically for the test beam, which is an accepted mode of image acquisition for dosimetry with EPID. Third, in-phantom film and exit EPID dosimetry was performed on a moving platform using the same beam. Heterogeneous as well as homogeneous phantoms were used. The cine images were temporally sorted at 10% interval. The authors have performed dose reconstruction to the in-phantom plane from the sorted cine images using the above validated method of dose reconstruction. The reconstructed dose from each cine image was summed to compose a total reconstructed dose from the test beam delivery, and was compared with film measurements. Results: The new method of dose reconstruction was validated showing greater than 95.3% pass rates of the gamma test with the criteria

[EEG-adjusted target-controlled infusion : Propofol target concentration with different doses of remifentanil].

PubMed

Büttner, N; Schultz, B; Grouven, U; Schultz, A

2010-02-01

The aim of this study was to examine to what extent the use of electroencephalography (EEG) monitoring leads to an adaptation of the target-controlled infusion (TCI) concentration of propofol during propofol anaesthesia with different doses of remifentanil. With ethics committee approval 60 patients (27-69 years old) with American Society of Anesthesiologists classification (ASA) I-III received anaesthestics with propofol (TCI, Diprifusor, AstraZeneca, Wedel, Deutschland) and 0.2, 0.4, or 0.6 microg/kg body weight remifentanil, respectively (groups 1-3). Anaesthesia was maintained at a level of deep hypnosis (EEG stages D(2)/E(0), EEG monitor: Narcotrend, version 2.0/5.0, manufacturer: MT MonitorTechnik, Bad Bramstedt, Germany). During the steady state the propofol concentration in groups 1-3 was 3.02+/-0.86, 1.93+/-0.53 and 1.60+/-0.55 microg/ml, respectively (p<0.001). Women had a higher propofol consumption than men (p<0.05). Dreams during anaesthesia were more often reported by women than by men (p<0.05). The need for postoperative analgesia decreased with an increasing intraoperative remifentanil dose (p<0.05). The study demonstrates that remifentanil has both analgetic and hypnotic effects. With increasing remifentanil dose the propofol requirement decreased and in this context EEG monitoring is useful to adapt the target concentrations of propofol to the patients' age and gender.

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

PubMed

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

Margin selection to compensate for loss of target dose coverage due to target motion during external‐beam radiation therapy of the lung

PubMed Central

Osei, Ernest; Barnett, Rob

2015-01-01

The aim of this study is to provide guidelines for the selection of external‐beam radiation therapy target margins to compensate for target motion in the lung during treatment planning. A convolution model was employed to predict the effect of target motion on the delivered dose distribution. The accuracy of the model was confirmed with radiochromic film measurements in both static and dynamic phantom modes. 502 unique patient breathing traces were recorded and used to simulate the effect of target motion on a dose distribution. A 1D probability density function (PDF) representing the position of the target throughout the breathing cycle was generated from each breathing trace obtained during 4D CT. Changes in the target D95 (the minimum dose received by 95% of the treatment target) due to target motion were analyzed and shown to correlate with the standard deviation of the PDF. Furthermore, the amount of target D95 recovered per millimeter of increased field width was also shown to correlate with the standard deviation of the PDF. The sensitivity of changes in dose coverage with respect to target size was also determined. Margin selection recommendations that can be used to compensate for loss of target D95 were generated based on the simulation results. These results are discussed in the context of clinical plans. We conclude that, for PDF standard deviations less than 0.4 cm with target sizes greater than 5 cm, little or no additional margins are required. Targets which are smaller than 5 cm with PDF standard deviations larger than 0.4 cm are most susceptible to loss of coverage. The largest additional required margin in this study was determined to be 8 mm. PACS numbers: 87.53.Bn, 87.53.Kn, 87.55.D‐, 87.55.Gh

A novel concept for tumour targeting with radiation: Inverse dose-painting or targeting the "Low Drug Uptake Volume".

PubMed

Yaromina, Ala; Granzier, Marlies; Biemans, Rianne; Lieuwes, Natasja; van Elmpt, Wouter; Shakirin, Georgy; Dubois, Ludwig; Lambin, Philippe

2017-09-01

We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake. 18 F-HX4 hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV with the lowest or highest 18 F-HX4 uptake, respectively. Two hours post TH-302/saline administration, animals received either single dose radiotherapy (RT) uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50% higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse treatment planning system and radiation was delivered using VMAT. Tumour response was quantified as time to reach 3 times starting tumour volume. Non-uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average 3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose escalation. The results support targeted dose escalation to non-hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs. This strategy applies on average a lower radiation dose and is as effective as uniform dose escalation to the entire tumour. It could be applied to other type of drugs provided that their distribution can be imaged. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Dosimetric feasibility of an “off-target isocenter” technique for cranial intensity-modulated radiosurgery

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

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

2015-01-01

To evaluate the dosimetric effect of placing the isocenter away from the planning target volume (PTV) on intensity-modulated radiosurgery (IMRS) plans to treat brain lesions. A total of 15 patients who received cranial IMRS at our institution were randomly selected. Each patient was treated with an IMRS plan designed with the isocenter located at the target center (plan A). A second off-target isocenter plan (plan B) was generated for each case. In all the plans,100% of the prescription dose covered 99% of the target volume. The plans A and B were compared for the target dosage (conformity index [CI] andmore » homogeneity index) and organs-at-risk (OAR) dose sparing. Peripheral dose falloff was compared by using the metrics volume of normal brain receiving more than 12-Gy dose (V12) and CI at the level of the 50% of the prescription dose (CI 50%). The values found for each metric (plan B vs plan A) were (mean ± standard deviation [SD]) as follows—CI: 1.28 ± 0.15 vs 1.28 ± 0.15, p = 0.978; homogeneity index (HI): 1.29 ± 0.14 vs 1.34 ± 0.17, p = 0.079; maximum dose to the brainstem: 2.95 ± 2.11 vs 2.89 ± 1.88 Gy, p = 0.813; maximum dose to the optical pathway: 2.65 ± 4.18 vs 2.44 ± 4.03 Gy, p = 0.195; and maximum dose to the eye lens: 0.33 ± 0.73 vs 0.33 ± 0.53 Gy, p = 0.970. The values of the peripheral dose falloff were (plan B vs plan A) as follows—V12: 5.98 ± 4.95 vs 6.06 ± 4.92 cm{sup 3}, p = 0.622, and CI 50%: 6.08 ± 2.77 vs 6.28 ± 3.01, p = 0.119. The off-target isocenter solution resulted in dosimetrically comparable plans as the center-target isocenter technique, by avoiding the risk of gantry-couch collision during the cone beam computed tomography (CBCT) acquisition.« less

Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn-177Lu is superior to 90Y-177Lu in peptide receptor radiotherapy

NASA Astrophysics Data System (ADS)

Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

2012-07-01

Clinical trials on 177Lu-90Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1-25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93Y, 90Y and 125Sn in combination with 177Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75-25% combination of 177Lu and 90Y activity. However, 125Sn-177Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125Sn is the best RN for combination with 177Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125Sn-labelled somatostatin analogues.

SU-F-T-568: QA of a Multi-Target Multi-Dose VMAT SRS

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

Roa, D; Kuo, J; Gonzales, A

2016-06-15

Purpose: To, experimentally, corroborated the prescribed doses utilizing dosimeters (e.g. films and TLDs) that can provide high spatial resolution, allow dose measurement of multiple targets at once, and provide accurate dosimetric results. Methods: A single-isocenter 6FFF SRS VMAT plan consisting of one 358° arc at 0° couch angle and four 179° arcs at 30°, 60°, 330° and 300° couch angles respectively, was generated in ECLIPSE v.11 using a Rando-Alderson anthropomorphic head phantom CT study. This plan was a reproduction of a clinical plan generated for a stage-IV melanoma patient diagnosed with 19 intracranial lesions. The phantom was loaded with axiallymore » mounted (between phantom slabs) Gafchromic EBT3 film and TLDs strategically positioned within various target volumes. Film and TLDS were calibrated according to established protocols. Target prescription doses were 16 Gy (3cc≤, 3 lesions), 18 Gy (∼1–3cc, 10 lesions) and 20 Gy (≤1cc, 6 lesions). Phantom setup was verified through CBCT imaging prior to irradiation. Gafchromic films were scanned in transmission mode and TLDs were read, respectively, ∼24 hrs after irradiation. Results: Dose calibrated Gafchromic film data were compared to the ECLIPSE calculated data using a 3% / 3mm gamma function analysis. Results for the gamma values were 96–99% in agreement with the calculated data and with 84–90% of the film pixels within the 3% dose difference. TLD data showed a dose difference of 0.4–8% while the film data for those same locations yielded a difference of 0.4–4%. It was observed that the highest dose discrepancies correlated with the location of the small volume targets. Conclusion: Overall this study corroborated that a VMAT SRS treatment, employing various treatment table rotations and arcs, to multiple intracranial lesions with multiple dose prescriptions can be delivered accurately with the existing radiotherapy technology.« less

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Online compensation for target motion with scanned particle beams: simulation environment.

PubMed

Li, Qiang; Groezinger, Sven Oliver; Haberer, Thomas; Rietzel, Eike; Kraft, Gerhard

2004-07-21

Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

Evaluation of various boluses in dose distribution for electron therapy of the chest wall with an inward defect

PubMed Central

Mahdavi, Hoda; Jabbari, Keyvan; Roayaei, Mahnaz

2016-01-01

Delivering radiotherapy to the postmastectomy chest wall can be achieved using matched electron fields. Surgical defects of the chest wall change the dose distribution of electrons. In this study, the improvement of dose homogeneity using simple, nonconformal techniques of thermoplastic bolus application on a defect is evaluated. The proposed phantom design improves the capability of film dosimetry for obtaining dose profiles of a patient's anatomical condition. A modeled electron field of a patient with a postmastectomy inward surgical defect was planned. High energy electrons were delivered to the phantom in various settings, including no bolus, a bolus that filled the inward defect (PB0), a uniform thickness bolus of 5 mm (PB1), and two 5 mm boluses (PB2). A reduction of mean doses at the base of the defect was observed by any bolus application. PB0 increased the dose at central parts of the defect, reduced hot areas at the base of steep edges, and reduced dose to the lung and heart. Thermoplastic boluses that compensate a defect (PB0) increased the homogeneity of dose in a fixed depth from the surface; adversely, PB2 increased the dose heterogeneity. This study shows that it is practical to investigate dose homogeneity profiles inside a target volume for various techniques of electron therapy. PMID:27051169

Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

PubMed

Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

2008-06-01

Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

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.

Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

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

Levegrün, Sabine, E-mail: sabine.levegruen@uni-due.de; Pöttgen, Christoph; Wittig, Andrea

2013-07-15

Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N{sub mets}) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV{sub mets}) and of the individual metastasis planning target volume (PTV{sub ind} {sub met}) were 8.7 ± 8.9 cm{sup 3} (range, 1.3-35.5more » cm{sup 3}) and 2.5 ± 4.5 cm{sup 3} (range, 0.19-24.7 cm{sup 3}), respectively. Dose distributions in PTV{sub mets} and PTV{sub ind} {sub met} were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N{sub mets} was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV{sub mets} amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV{sub ind} {sub met} were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV{sub mets} (CN = 0.737 for PTV{sub mets} ≤4.32 cm{sup 3} vs CN = 0.848 for PTV{sub mets} >4.32 cm{sup 3}, P=.006), in contrast to N{sub mets}. The

Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

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

Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael

2008-06-01

Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm{sup 3} before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapymore » with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm{sup 3} subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon {alpha}) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm{sup 3}. More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.« less

SU-E-T-278: Dose Conformity Index for the Target in a Multitarget Environment

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

Harikrishnaperumal, Sudahar

2015-06-15

Purpose: The existing conformity index formulations are failing when multiple targets present outside the target of interest with same or different dose prescriptions. In the present study a novel methodology is introduced to solve this issue. Methods: The conformity index used by Nakamura et al (Int J Radiat Oncol Biol Phys 2001; 51(5):1313–1319) is taken as the base for this methodology. In this proposal, the prescription isodose volume (PIV) which normally includes the normal tissue and other target regions is restricted as PIV in annular regions of different thickness around the target of interest. The graphical line plotted between themore » thickness of annular region and the corresponding conformity index, will increase in the beginning and will reach a flat region, then it will increase again. The second increase in the conformity index depends basically on the distance between the targets, dose prescriptions, and size of the targets. The conformity index in the flat region should be the conformity index of the target of interest. This methodology was validated on dual target environment on a skull phantom in Multiplan planning system (Accuray Inc. Sunnyvale, USA) Results: When the surrounding target’s (sphere) size is changed from 1.5cm to 6cm diameter, the conformity index of the target of interest (3cm diameter) changed from 1.09 to 1.25. When the distance between the targets changed from 7.5cm to 2.5cm, the conformity index changed from 1.10 to 1.17. Similarly, when the prescribed dose changed from 25Gy to 50Gy the conformity index changed from 1.09 to 1.42. These values were above 2.0 when Nakamura et al formula was used. Conclusion: The proposed conformity index methodology eliminates the influence of surrounding targets to a greater extend. However, the limitations of this method should be studied further. Application of this method in clinical situations is the future scope.« less

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

NASA Technical Reports Server (NTRS)

Chappelli, Lori J.; Cucinotta, Francis A.

2010-01-01

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data

Dose-finding designs for trials of molecularly targeted agents and immunotherapies

PubMed Central

Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

2017-01-01

Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs. PMID:28166468

Trends in erythemal doses at the Polish Polar Station, Hornsund, Svalbard based on the homogenized measurements (1996-2016) and reconstructed data (1983-1995)

NASA Astrophysics Data System (ADS)

Krzyścin, Janusz W.; Sobolewski, Piotr S.

2018-01-01

Erythemal daily doses measured at the Polish Polar Station, Hornsund (77°00' N, 15°33' E), for the periods 1996-2001 and 2005-2016 are homogenized using yearly calibration constants derived from the comparison of observed doses for cloudless conditions with the corresponding doses calculated by radiative transfer (RT) simulations. Modeled all-sky doses are calculated by the multiplication of cloudless RT doses by the empirical cloud modification factor dependent on the daily sunshine duration. An all-sky model is built using daily erythemal doses measured in the period 2005-2006-2007. The model is verified by comparisons with the 1996-1997-1998 and 2009-2010-2011 measured data. The daily doses since 1983 (beginning of the proxy data) are reconstructed using the all-sky model with the historical data of the column ozone from satellite measurements (SBUV merged ozone data set), the snow depth (for ground albedo estimation), and the observed daily sunshine duration at the site. Trend analyses of the monthly and yearly time series comprised of the reconstructed and observed doses do not reveal a statistically significant trend in the period 1983-2016. The trends based on the observed data only (1996-2001 and 2005-2016) show declining tendency (about -1 % per year) in the monthly mean of daily erythemal doses in May and June, and in the yearly sum of daily erythemal doses. An analysis of sources of the yearly dose variability since 1983 shows that cloud cover changes are a basic driver of the long-term UV changes at the site.

Homogeneity of GAFCHROMIC EBT2 film among different lot numbers

PubMed Central

Takahashi, Yutaka; Tanaka, Atsushi; Hirayama, Takamitsu; Yamaguchi, Tsuyoshi; Katou, Hiroaki; Takahara, Keiko; Okamoto, Yoshiaki; Teshima, Teruki

2012-01-01

EBT2 film is widely used for quality assurance in radiation therapy. The purpose of this study was to investigate the homogeneity of EBT2 film among various lots, and the dose dependence of heterogeneity. EBT2 film was positioned in the center of a flatbed scanner and scanned in transmission mode at 75 dpi. Homogeneity was investigated by evaluating gray value and net optical density (netOD) with the red color channel. The dose dependence of heterogeneity in a single sheet from five lots was investigated at 0.5, 2, and 3 Gy. Maximum coefficient of variation as evaluated by netOD in a single film was 3.0% in one lot, but no higher than 0.5% in other lots. Dose dependence of heterogeneity was observed on evaluation by gray value but not on evaluation by netOD. These results suggest that EBT2 should be examined in each lot number before clinical use, and that the dose calibration curve should be constructed using netOD. PACS number: 87 PMID:22766947

Low dose megavoltage cone beam computed tomography with an unflattened 4 MV beam from a carbon target

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

Faddegon, Bruce A.; Wu, Vincent; Pouliot, Jean

2008-12-15

Megavoltage cone beam computed tomography (MVCBCT) is routinely used for visualizing anatomical structures and implanted fiducials for patient positioning in radiotherapy. MVCBCT using a 6 MV treatment beam with high atomic number (Z) target and flattening filter in the beamline, as done conventionally, has lower image quality than can be achieved with a MV beam due to heavy filtration of the low-energy bremsstrahlung. The unflattened beam of a low Z target has an abundance of diagnostic energy photons, detected with modern flat panel detectors with much higher efficiency given the same dose to the patient. This principle guided the developmentmore » of a new megavoltage imaging beamline (IBL) for a commercial radiotherapy linear accelerator. A carbon target was placed in one of the electron primary scattering foil slots on the target-foil slide. A PROM on a function controller board was programed to put the carbon target in place for MVCBCT. A low accelerating potential of 4.2 MV was used for the IBL to restrict leakage of primary electrons through the target such that dose from x rays dominated the signal in the monitor chamber and the patient surface dose. Results from phantom and cadaver images demonstrated that the IBL had much improved image quality over the treatment beam. For similar imaging dose, the IBL improved the contrast-to-noise ratio by as much as a factor of 3 in soft tissue over that of the treatment beam. The IBL increased the spatial resolution by about a factor of 2, allowing the visualization of finer anatomical details. Images of the cadaver contained useful information with doses as low as 1 cGy. The IBL may be installed on certain models of linear accelerators without mechanical modification and results in significant improvement in the image quality with the same dose, or images of the same quality with less than one-third of the dose.« less

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

Radionuclide production and dose rate estimation during the commissioning of the W-Ta spallation target

NASA Astrophysics Data System (ADS)

Yu, Q. Z.; Liang, T. J.

2018-06-01

China Spallation Neutron Source (CSNS) is intended to begin operation in 2018. CSNS is an accelerator-base multidisciplinary user facility. The pulsed neutrons are produced by a 1.6GeV short-pulsed proton beam impinging on a W-Ta spallation target, at a beam power of100 kW and a repetition rate of 25 Hz. 20 neutron beam lines are extracted for the neutron scattering and neutron irradiation research. During the commissioning and maintenance scenarios, the gamma rays induced from the W-Ta target can cause the dose threat to the personal and the environment. In this paper, the gamma dose rate distributions for the W-Ta spallation are calculated, based on the engineering model of the target-moderator-reflector system. The shipping cask is analyzed to satisfy the dose rate limit that less than 2 mSv/h at the surface of the shipping cask. All calculations are performed by the Monte carlo code MCNPX2.5 and the activation code CINDER’90.

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2008-06-01

brachytherapy treatment planning has been demonstrated. Using the inverse planning program IPSA , dose escalation of target regions with a higher tumor...algorithm (called IPSA ) was used to generate dose distributions for five different levels of DIL- boost, at least 110%, 120%, 130%, 140% and 150...and LDR, VI Last Generation Radiotherapy Course, São Paulo, Brazil, Oct. 19, 2006. Principles and Clinical Applications of IPSA ; Nucletron

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

PubMed Central

Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł

2014-01-01

Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411

Homogeneous illusion device exhibiting transformed and shifted scattering effect

NASA Astrophysics Data System (ADS)

Mei, Jin-Shuo; Wu, Qun; Zhang, Kuang; He, Xun-Jun; Wang, Yue

2016-06-01

Based on the theory of transformation optics, a type of homogeneous illusion device exhibiting transformed and shifted scattering effect is proposed in this paper. The constitutive parameters of the proposed device are derived, and full-wave simulations are performed to validate the electromagnetic properties of transformed and shifted scattering effect. The simulation results show that the proposed device not only can visually shift the image of target in two dimensions, but also can visually transform the shape of target. It is expected that such homogeneous illusion device could possess potential applications in military camouflage and other field of electromagnetic engineering.

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.

Effect of lung and target density on small-field dose coverage and PTV definition

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

Higgins, Patrick D., E-mail: higgi010@umn.edu; Ehler, Eric D.; Cho, Lawrence C.

We have studied the effect of target and lung density on block margin for small stereotactic body radiotherapy (SBRT) targets. A phantom (50 × 50 × 50 cm{sup 3}) was created in the Pinnacle (V9.2) planning system with a 23-cm diameter lung region of interest insert. Diameter targets of 1.6, 2.0, 3.0, and 4.0 cm were placed in the lung region of interest and centered at a physical depth of 15 cm. Target densities evaluated were 0.1 to 1.0 g/cm{sup 3}, whereas the surrounding lung density was varied between 0.05 and 0.6 g/cm{sup 3}. A dose of 100 cGy wasmore » delivered to the isocenter via a single 6-MV field, and the ratio of the average dose to points defining the lateral edges of the target to the isocenter dose was recorded for each combination. Field margins were varied from none to 1.5 cm in 0.25-cm steps. Data obtained in the phantom study were used to predict planning treatment volume (PTV) margins that would match the clinical PTV and isodose prescription for a clinical set of 39 SBRT cases. The average internal target volume (ITV) density was 0.73 ± 0.17, average local lung density was 0.33 ± 0.16, and average ITV diameter was 2.16 ± 0.8 cm. The phantom results initially underpredicted PTV margins by 0.35 cm. With this offset included in the model, the ratio of predicted-to-clinical PTVs was 1.05 ± 0.32. For a given target and lung density, it was found that treatment margin was insensitive to target diameter, except for the smallest (1.6-cm diameter) target, for which the treatment margin was more sensitive to density changes than the larger targets. We have developed a graphical relationship for block margin as a function of target and lung density, which should save time in the planning phase by shortening the design of PTV margins that can satisfy Radiation Therapy Oncology Group mandated treatment volume ratios.« less

Comparison of composite prostate radiotherapy plan doses with dependent and independent boost phases.

PubMed

Narayanasamy, Ganesh; Avila, Gabrielle; Mavroidis, Panayiotis; Papanikolaou, Niko; Gutierrez, Alonso; Baacke, Diana; Shi, Zheng; Stathakis, Sotirios

2016-09-01

Prostate cases commonly consist of dual phase planning with a primary plan followed by a boost. Traditionally, the boost phase is planned independently from the primary plan with the risk of generating hot or cold spots in the composite plan. Alternatively, boost phase can be planned taking into account the primary dose. The aim of this study was to compare the composite plans from independently and dependently planned boosts using dosimetric and radiobiological metrics. Ten consecutive prostate patients previously treated at our institution were used to conduct this study on the Raystation™ 4.0 treatment planning system. For each patient, two composite plans were developed: a primary plan with an independently planned boost and a primary plan with a dependently planned boost phase. The primary plan was prescribed to 54 Gy in 30 fractions to the primary planning target volume (PTV1) which includes prostate and seminal vesicles, while the boost phases were prescribed to 24 Gy in 12 fractions to the boost planning target volume (PTV2) that targets only the prostate. PTV coverage, max dose, median dose, target conformity, dose homogeneity, dose to OARs, and probabilities of benefit, injury, and complication-free tumor control (P+) were compared. Statistical significance was tested using either a 2-tailed Student's t-test or Wilcoxon signed-rank test. Dosimetrically, the composite plan with dependent boost phase exhibited smaller hotspots, lower maximum dose to the target without any significant change to normal tissue dose. Radiobiologically, for all but one patient, the percent difference in the P+ values between the two methods was not significant. A large percent difference in P+ value could be attributed to an inferior primary plan. The benefits of considering the dose in primary plan while planning the boost is not significant unless a poor primary plan was achieved.

Use of radiation protraction to escalate biologically effective dose to the treatment target

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

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

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

Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre; Tsiamas, Panogiotis

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam,more » (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.« less

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.

PubMed

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart D mean ), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRT DIBH decreased the Heart D mean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRT FB . IMRT further lowered mean LAD dose by 18%. Heart D mean was lower with 3DCRT DIBH over IMRT DIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V 20 of ipsilateral lung were lower with 3DCRT DIBH over IMRT DIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRT DIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer

PubMed Central

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Introduction: Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. Aim: In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Materials and Methods: Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart Dmean), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Results: Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRTDIBH decreased the Heart Dmean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRTFB. IMRT further lowered mean LAD dose by 18%. Heart Dmean was lower with 3DCRTDIBH over IMRTDIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V20 of ipsilateral lung were lower with 3DCRTDIBH over IMRTDIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. Conclusions: 3DCRTDIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT. PMID:28974856

TU-H-BRC-06: Temperature Simulation of Tungsten and W25Re Targets to Deliver High Dose Rate 10 MV Photons

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

Wang, J; Trovati, S; Loo, B

Purpose: To study the impact of electron beam size, target thickness, and target temperature on the ability of the flattening filter-free mode (FFF) treatment head to deliver high-dose-rate irradiations. Methods: The dose distribution and transient temperature of the X-ray target under 10 MeV electron beam with pulse length of 5 microseconds, and repetition rate of 1000 Hz was studied. A MCNP model was built to calculate the percentage depth dose (PPD) distribution in a water phantom at a distance of 100 cm. ANSYS software was used to run heat transfer simulations. The PPD and temperature for both tungsten and W25Remore » targets for different electron beam sizes (FHWM 0.2, 0.5, 1 and 2 mm) and target thickness (0.2 to 2 mm) were studied. Results: Decreasing the target thickness from 1 mm to 0.5 mm, caused a surface dose increase about 10 percent. For both target materials, the peak temperature was about 1.6 times higher for 0.5 mm electron beam compared to the 1 mm beam after reaching their equilibrium. For increasing target thicknesses, the temperature rise caused by the first pulse is similar for all thicknesses, however the temperature difference for subsequent pulses becomes larger until a constant ratio is reached. The target peak temperature after reaching equilibrium can be calculated by adding the steady state temperature and the amplitude of the temperature oscillation. Conclusion: This work indicates the potential to obtain high dose rate irradiation by selecting target material, geometry and electron beam parameters. W25Re may not outperformed tungsten when the target is thick due to its relatively low thermal conductivity. The electron beam size only affects the target temperature but not the PPD. Thin target is preferred to obtain high dose rate and low target temperature, however, the resulting high surface dose is a major concern. NIH funding:R21 EB015957-01; DOD funding:W81XWH-13-1-0165 BL, PM, PB, and RF are founders of TibaRay, Inc. BL is also

Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity.

PubMed

Balderson, Michael J; Kirkby, Charles

2015-01-01

In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. In terms of

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

PubMed

Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

2013-01-01

The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Is high–dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

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

Zhao, Bo; Yang, Yong, E-mail: yangy2@upmc.edu; Li, Xiang

In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high–dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA planmore » with multiple noncoplanar arcs, (2) a high–dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high–dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high–dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V{sub 12} {sub Gy}) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for

Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations.

PubMed

Langrand-Escure, J; de Crevoisier, R; Llagostera, C; Créhange, G; Delaroche, G; Lafond, C; Bonin, C; Bideault, F; Sargos, P; Belhomme, S; Pasquier, D; Latorzeff, I; Supiot, S; Hennequin, C

2018-04-01

Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques. Copyright © 2018. Published by Elsevier SAS.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

PubMed

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.

PubMed

Vassal, G; Michel, G; Espérou, H; Gentet, J C; Valteau-Couanet, D; Doz, F; Mechinaud, F; Galambrun, C; Neven, B; Zouabi, H; Nguyen, L; Puozzo, C

2008-01-01

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

Versatile and Programmable DNA Logic Gates on Universal and Label-Free Homogeneous Electrochemical Platform.

PubMed

Ge, Lei; Wang, Wenxiao; Sun, Ximei; Hou, Ting; Li, Feng

2016-10-04

Herein, a novel universal and label-free homogeneous electrochemical platform is demonstrated, on which a complete set of DNA-based two-input Boolean logic gates (OR, NAND, AND, NOR, INHIBIT, IMPLICATION, XOR, and XNOR) is constructed by simply and rationally deploying the designed DNA polymerization/nicking machines without complicated sequence modulation. Single-stranded DNA is employed as the proof-of-concept target/input to initiate or prevent the DNA polymerization/nicking cyclic reactions on these DNA machines to synthesize numerous intact G-quadruplex sequences or binary G-quadruplex subunits as the output. The generated output strands then self-assemble into G-quadruplexes that render remarkable decrease to the diffusion current response of methylene blue and, thus, provide the amplified homogeneous electrochemical readout signal not only for the logic gate operations but also for the ultrasensitive detection of the target/input. This system represents the first example of homogeneous electrochemical logic operation. Importantly, the proposed homogeneous electrochemical logic gates possess the input/output homogeneity and share a constant output threshold value. Moreover, the modular design of DNA polymerization/nicking machines enables the adaptation of these homogeneous electrochemical logic gates to various input and output sequences. The results of this study demonstrate the versatility and universality of the label-free homogeneous electrochemical platform in the design of biomolecular logic gates and provide a potential platform for the further development of large-scale DNA-based biocomputing circuits and advanced biosensors for multiple molecular targets.

In vivo skin dose measurement in breast conformal radiotherapy.

PubMed

Soleymanifard, Shokouhozaman; Aledavood, Seyed Amir; Noghreiyan, Atefeh Vejdani; Ghorbani, Mahdi; Jamali, Farideh; Davenport, David

2016-01-01

Accurate skin dose assessment is necessary during breast radiotherapy to assure that the skin dose is below the tolerance level and is sufficient to prevent tumour recurrence. The aim of the current study is to measure the skin dose and to evaluate the geometrical/anatomical parameters that affect it. Forty patients were simulated by TIGRT treatment planning system and treated with two tangential fields of 6 MV photon beam. Wedge filters were used to homogenise dose distribution for 11 patients. Skin dose was measured by thermoluminescent dosimeters (TLD-100) and the effects of beam incident angle, thickness of irradiated region, and beam entry separation on the skin dose were analysed. Average skin dose in treatment course of 50 Gy to the clinical target volume (CTV) was 36.65 Gy. The corresponding dose values for patients who were treated with and without wedge filter were 35.65 and 37.20 Gy, respectively. It was determined that the beam angle affected the average skin dose while the thickness of the irradiated region and the beam entry separation did not affect dose. Since the skin dose measured in this study was lower than the amount required to prevent tumour recurrence, application of bolus material in part of the treatment course is suggested for post-mastectomy advanced breast radiotherapy. It is more important when wedge filters are applied to homogenize dose distribution.

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PubMed

Traneus, Erik; Bizzocchi, Nicola; Fellin, Francesco; Rombi, Barbara; Farace, Paolo

2018-01-01

The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer

PubMed Central

Seruga, B.; Gan, H.K.; Knox, J.J.

2009-01-01

The toxicities of new, targeted drugs may diminish their effectiveness in advanced kidney cancer if those toxicities are not recognized and properly addressed early in patient treatment. Most of the drug-related toxicities in advanced kidney cancer are manageable with supportive care, obviating a need for long interruptions, dose reductions, or permanent discontinuation of the treatment. PMID:19478903

Improving target coverage and organ-at-risk sparing in intensity-modulated radiotherapy for cervical oesophageal cancer using a simple optimisation method.

PubMed

Lu, Jia-Yang; Cheung, Michael Lok-Man; Huang, Bao-Tian; Wu, Li-Li; Xie, Wen-Jia; Chen, Zhi-Jian; Li, De-Rui; Xie, Liang-Xi

2015-01-01

To assess the performance of a simple optimisation method for improving target coverage and organ-at-risk (OAR) sparing in intensity-modulated radiotherapy (IMRT) for cervical oesophageal cancer. For 20 selected patients, clinically acceptable original IMRT plans (Original plans) were created, and two optimisation methods were adopted to improve the plans: 1) a base dose function (BDF)-based method, in which the treatment plans were re-optimised based on the original plans, and 2) a dose-controlling structure (DCS)-based method, in which the original plans were re-optimised by assigning additional constraints for hot and cold spots. The Original, BDF-based and DCS-based plans were compared with regard to target dose homogeneity, conformity, OAR sparing, planning time and monitor units (MUs). Dosimetric verifications were performed and delivery times were recorded for the BDF-based and DCS-based plans. The BDF-based plans provided significantly superior dose homogeneity and conformity compared with both the DCS-based and Original plans. The BDF-based method further reduced the doses delivered to the OARs by approximately 1-3%. The re-optimisation time was reduced by approximately 28%, but the MUs and delivery time were slightly increased. All verification tests were passed and no significant differences were found. The BDF-based method for the optimisation of IMRT for cervical oesophageal cancer can achieve significantly better dose distributions with better planning efficiency at the expense of slightly more MUs.

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

PubMed

Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

2006-09-07

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an

Homogeneity Pursuit

PubMed Central

Ke, Tracy; Fan, Jianqing; Wu, Yichao

2014-01-01

This paper explores the homogeneity of coefficients in high-dimensional regression, which extends the sparsity concept and is more general and suitable for many applications. Homogeneity arises when regression coefficients corresponding to neighboring geographical regions or a similar cluster of covariates are expected to be approximately the same. Sparsity corresponds to a special case of homogeneity with a large cluster of known atom zero. In this article, we propose a new method called clustering algorithm in regression via data-driven segmentation (CARDS) to explore homogeneity. New mathematics are provided on the gain that can be achieved by exploring homogeneity. Statistical properties of two versions of CARDS are analyzed. In particular, the asymptotic normality of our proposed CARDS estimator is established, which reveals better estimation accuracy for homogeneous parameters than that without homogeneity exploration. When our methods are combined with sparsity exploration, further efficiency can be achieved beyond the exploration of sparsity alone. This provides additional insights into the power of exploring low-dimensional structures in high-dimensional regression: homogeneity and sparsity. Our results also shed lights on the properties of the fussed Lasso. The newly developed method is further illustrated by simulation studies and applications to real data. Supplementary materials for this article are available online. PMID:26085701

Dose gradient curve: A new tool for evaluating dose gradient.

PubMed

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Dose gradient curve: A new tool for evaluating dose gradient

PubMed Central

Choi, Young Eun

2018-01-01

Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

PubMed

Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

2012-12-01

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures. © 2011 Blackwell Publishing Ltd.

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

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

Yaparpalvi, R; Mynampati, D; Kuo, H

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

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

Yao Rui; Bernard, Damian; Turian, Julius

2012-04-15

Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lungmore » dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.« less

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

PubMed

van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

2018-05-03

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells

PubMed Central

Metzler, Philipp; Pilarczyk, Götz; Bobu, Vladimir; Kriz, Wilhelm; Hosser, Hiltraud; Fleckenstein, Jens; Krufczik, Matthias; Bestvater, Felix; Wenz, Frederik; Hausmann, Michael

2018-01-01

Localization microscopy has shown to be capable of systematic investigations on the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with nanometer resolution. In this article, we show that the application of specially modified RNA targeting gold nanoparticles (“SmartFlares”) can result in ring like shaped GNP arrangements around the cell nucleus. Transmission electron microscopy revealed GNP accumulation in vicinity to the intracellular membrane structures including them of the endoplasmatic reticulum. A quantification of the radio therapeutic dose enhancement as a proof of principle was conducted with γH2AX foci analysis: The application of both—SmartFlares and unmodified GNPs—lead to a significant dose enhancement with a factor of up to 1.2 times the dose deposition compared to non-treated breast cancer cells. This enhancement effect was even more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field of 1 Tesla simultaneously applied during irradiation has no detectable influence on neither the structure nor the dose enhancement dealt by gold nanoparticles. PMID:29346397

SU-E-T-495: Influence of Reduced Target-To-Nozzle Distance On Secondary Neutron Dose Equivalent in Proton and Carbon Ion Radiotherapy

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

Sheng, Y; Shahnazi, K; Wang, W

Purpose: Ion beams have an unavoidable lateral spread due to nuclear interactions interacting with the air and monitoring systems. To minimize this spread, the distance between the nozzle and the patient should be kept as small as possible.The purpose of this work was to determine the impact of the target-to-nozzle distance reduction on the secondary neutron dose equivalent in proton and carbon ion radiotherapy. Methods: In this study, abdominal and head phantoms were scanned with our CT scanner. Cubical targets with side lengths of 3 cm to 10 cm and 1 cm to 5 cm were drawn in the abdominalmore » and head phantoms respectively. Two intensity-modulated plans were made for each phantom and ion. The first of these plans placed the target at the isocenter while the other shifted the phantom 30 cm towards the nozzle. The plans at both phantom locations were optimized to provide identical dose coverage to the PTVs.Secondary neutron dose equivalent at 50 cm lateral to the center of target. Results: The neutron dose equivalent was higher for the larger field size from 0.25µSv per Gy (RBE) to 72µSv per Gy (RBE). The neutron dose equivalent was smaller when the phantom was placed at the upstream target location versus at the isocenter location by 8.9% to 10.4% and 11.0% to 22.1% for proton plans of the abdominal and head phantoms respectively. Differences for carbon plans with different target-to-nozzle locations were less than 3% for both phantoms. Conclusion: A reduction of target-to-nozzle distance can lead to benefits for proton radiotherapy. In this study, a reduction of secondary neutron dose equivalent was found for proton plans with a smaller target-to-nozzle distance. A greater impact was found for a head phantom with a smaller field size; however, a reduction of the target-to-nozzle distance had little effect for carbon therapy.« less

SU-F-T-563: Delivered Dose Reconstruction of Moving Targets for Gated Volumetric Modulated Arc Therapy (VMAT)

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

Chung, H; Cho, S; Jeong, C

2016-06-15

Purpose: Actual delivered dose of moving tumors treated with gated volumetric arc therapy (VMAT) may significantly differ from the planned dose assuming static target. In this study, we developed a method which reconstructs actual delivered dose distribution of moving target by taking into account both tumor motion and dynamic beam delivery of gated VMAT, and applied to abdominal tumors. Methods: Fifteen dual-arc VMAT plans (Eclipse, Varian Medical Systems) for 5 lung, 5 pancreatic, and 5 liver cancer patients treated with gated VMAT stereotactic body radiotherapy (SBRT) were studied. For reconstruction of the delivered dose distribution, we divided each original arcmore » beam into control-point-wise sub-beams, and applied beam isocenter shifting to each sub-beam to reflect the tumor motion. The tumor positions as a function of beam delivery were estimated by synchronizing the beam delivery with the respiratory signal which acquired during treatment. For this purpose, an in-house program (MATLAB, Mathworks) was developed to convert the original DICOM plan data into motion-involved treatment plan. The motion-involved DICOM plan was imported into Eclipse for dose calculation. The reconstructed delivered dose was compared to the plan dose using the dose coverage of gross tumor volume (GTV) and dose distribution of organs at risk (OAR). Results: The mean GTV dose coverage difference between the reconstructed delivered dose and the plan dose was 0.2 % in lung and pancreas cases, and no difference in liver cases. Mean D1000cc of ipsilateral lungs was reduced (0.8 ± 1.4cGy). Conclusion: We successfully developed a method of delivered dose reconstruction taking into account both respiratory tumor motion and dynamic beam delivery, and applied it to abdominal tumors treated with gated VAMT. No significant deterioration of delivered dose distribution indicates that interplay effect would be minimal even in the case of gated SBRT. This work was supported by the National

Dosimetric study and in-vivo dose verification for conformal avoidance treatment of anal adenocarcinoma using helical tomotherapy

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

Han Chunhui; Chen Yijen; Liu An

2007-04-01

This study evaluated the efficacy of using helical tomotherapy for conformal avoidance treatment of anal adenocarcinoma. We retrospectively generated step-and-shoot intensity-modulated radiotherapy (sIMRT) plans and helical tomotherapy plans for two anal cancer patients, one male and one female, who were treated by the sIMRT technique. Dose parameters for the planning target volume (PTV) and the organs-at-risk (OARs) were compared between the sIMRT and the helical tomotherapy plans. The helical tomotherapy plans showed better dose homogeneity in the PTV, better dose conformity around the PTV, and, therefore, better sparing of nearby OARs compared with the sIMRT plans. In-vivo skin dose measurementsmore » were performed during conformal avoidance helical tomotherapy treatment of an anal cancer patient to verify adequate delivery of skin dose and sparing of OARs.« less

SU-E-T-133: Dosimetric Impact of Scan Orientation Relative to Target Motion During Spot Scanning Proton Therapy

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

Stoker, J; Summers, P; Li, X

2014-06-01

Purpose: This study seeks to evaluate the dosimetric effects of intra-fraction motion during spot scanning proton beam therapy as a function of beam-scan orientation and target motion amplitude. Method: Multiple 4DCT scans were collected of a dynamic anthropomorphic phantom mimicking respiration amplitudes of 0 (static), 0.5, 1.0, and 1.5 cm. A spot-scanning treatment plan was developed on the maximum intensity projection image set, using an inverse-planning approach. Dynamic phantom motion was continuous throughout treatment plan delivery.The target nodule was designed to accommodate film and thermoluminescent dosimeters (TLD). Film and TLDs were uniquely labeled by location within the target. The phantommore » was localized on the treatment table using the clinically available orthogonal kV on-board imaging device. Film inserts provided data for dose uniformity; TLDs provided a 3% precision estimate of absolute dose. An inhouse script was developed to modify the delivery order of the beam spots, to orient the scanning direction parallel or perpendicular to target motion.TLD detector characterization and analysis was performed by the Imaging and Radiation Oncology Core group (IROC)-Houston. Film inserts, exhibiting a spatial resolution of 1mm, were analyzed to determine dose homogeneity within the radiation target. Results: Parallel scanning and target motions exhibited reduced target dose heterogeneity, relative to perpendicular scanning orientation. The average percent deviation in absolute dose for the motion deliveries relative to the static delivery was 4.9±1.1% for parallel scanning, and 11.7±3.5% (p<<0.05) for perpendicularly oriented scanning. Individual delivery dose deviations were not necessarily correlated to amplitude of motion for either scan orientation. Conclusions: Results demonstrate a quantifiable difference in dose heterogeneity as a function of scan orientation, more so than target amplitude. Comparison to the analyzed planar dose of a

Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

PubMed

Gauer, Tobias; Sothmann, Thilo; Blanck, Oliver; Petersen, Cordula; Werner, René

2018-06-01

Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

Mechanical Homogenization Increases Bacterial Homogeneity in Sputum

PubMed Central

Stokell, Joshua R.; Khan, Ammad

2014-01-01

Sputum obtained from patients with cystic fibrosis (CF) is highly viscous and often heterogeneous in bacterial distribution. Adding dithiothreitol (DTT) is the standard method for liquefaction prior to processing sputum for molecular detection assays. To determine if DTT treatment homogenizes the bacterial distribution within sputum, we measured the difference in mean total bacterial abundance and abundance of Burkholderia multivorans between aliquots of DTT-treated sputum samples with and without a mechanical homogenization (MH) step using a high-speed dispersing element. Additionally, we measured the effect of MH on bacterial abundance. We found a significant difference between the mean bacterial abundances in aliquots that were subjected to only DTT treatment and those of the aliquots which included an MH step (all bacteria, P = 0.04; B. multivorans, P = 0.05). There was no significant effect of MH on bacterial abundance in sputum. Although our results are from a single CF patient, they indicate that mechanical homogenization increases the homogeneity of bacteria in sputum. PMID:24759710

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum

SU-E-T-76: Comparing Homogeneity Between Gafchromic Film EBT2 and EBT3

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

Mizuno, H; Sumida, I; Ogawa, K

2014-06-01

Purpose: We found out that homogeneity of EBT2 was different among lot numbers in previous study. Variation in local homogeneity of EBT3 among several lot numbers has not been reported. In this study, we investigated film homogeneity of Gafcrhomic EBT3 films compared with EBT2 films. Methods: All sheets from five lots were cut into 12 pieces to investigate film homogeneity, and were irradiated at 0.5, 2, and 3 Gy. To investigate intra- and inter-sheet uniformity, five sheets from five lots were exposed to 2 Gy: intra-sheet uniformity was evaluated by the coefficient of variation of homogeneity for all pieces ofmore » a single sheet, and inter-sheet uniformity was evaluated by the coefficient of variation of homogeneity among the same piece numbers in the five sheets. To investigate the difference of ADC value in various doses, a single sheet from each of five lots was irradiated at 0.5 Gy and 3 Gy in addition to 2 Gy. A scan resolution of 72 dots per inch (dpi) and color depth of 48-bit RGB were used. Films were analyzed by the inhouse software; Average of ADC value in center ROI and profile X and Y axis were measured. Results and Conclusion: Intra-sheet uniformity of non-irradiated EBT2 films were ranged from 0.1% to 0.4%, however that of irradiated EBT2 films were ranged from 0.2% to 1.5%. On the other hand, intra-sheet uniformity of irradiated and non-irradiated EBT3 films were from 0.2% to 0.6%. Inter-sheet uniformity of all films were less than 0.5%. It was interesting point that homogeneity of EBT3 between no-irradiated and irradiated films were similar value, whereas EBT2 had dose dependence of homogeneity in ADC value evaluation. These results suggested that EBT3 homogeneity was corrected by this feature.« less

Monte Carlo Estimation of Absorbed Dose Distributions Obtained from Heterogeneous 106Ru Eye Plaques.

PubMed

Zaragoza, Francisco J; Eichmann, Marion; Flühs, Dirk; Sauerwein, Wolfgang; Brualla, Lorenzo

2017-09-01

The distribution of the emitter substance in 106 Ru eye plaques is usually assumed to be homogeneous for treatment planning purposes. However, this distribution is never homogeneous, and it widely differs from plaque to plaque due to manufacturing factors. By Monte Carlo simulation of radiation transport, we study the absorbed dose distribution obtained from the specific CCA1364 and CCB1256 106 Ru plaques, whose actual emitter distributions were measured. The idealized, homogeneous CCA and CCB plaques are also simulated. The largest discrepancy in depth dose distribution observed between the heterogeneous and the homogeneous plaques was 7.9 and 23.7% for the CCA and CCB plaques, respectively. In terms of isodose lines, the line referring to 100% of the reference dose penetrates 0.2 and 1.8 mm deeper in the case of heterogeneous CCA and CCB plaques, respectively, with respect to the homogeneous counterpart. The observed differences in absorbed dose distributions obtained from heterogeneous and homogeneous plaques are clinically irrelevant if the plaques are used with a lateral safety margin of at least 2 mm. However, these differences may be relevant if the plaques are used in eccentric positioning.

Robotic path-finding in inverse treatment planning for stereotactic radiosurgery with continuous dose delivery

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

Vandewouw, Marlee M., E-mail: marleev@mie.utoronto

Purpose: Continuous dose delivery in radiation therapy treatments has been shown to decrease total treatment time while improving the dose conformity and distribution homogeneity over the conventional step-and-shoot approach. The authors develop an inverse treatment planning method for Gamma Knife® Perfexion™ that continuously delivers dose along a path in the target. Methods: The authors’ method is comprised of two steps: find a path within the target, then solve a mixed integer optimization model to find the optimal collimator configurations and durations along the selected path. Robotic path-finding techniques, specifically, simultaneous localization and mapping (SLAM) using an extended Kalman filter, aremore » used to obtain a path that travels sufficiently close to selected isocentre locations. SLAM is novelly extended to explore a 3D, discrete environment, which is the target discretized into voxels. Further novel extensions are incorporated into the steering mechanism to account for target geometry. Results: The SLAM method was tested on seven clinical cases and compared to clinical, Hamiltonian path continuous delivery, and inverse step-and-shoot treatment plans. The SLAM approach improved dose metrics compared to the clinical plans and Hamiltonian path continuous delivery plans. Beam-on times improved over clinical plans, and had mixed performance compared to Hamiltonian path continuous plans. The SLAM method is also shown to be robust to path selection inaccuracies, isocentre selection, and dose distribution. Conclusions: The SLAM method for continuous delivery provides decreased total treatment time and increased treatment quality compared to both clinical and inverse step-and-shoot plans, and outperforms existing path methods in treatment quality. It also accounts for uncertainty in treatment planning by accommodating inaccuracies.« less

WE-EF-BRA-07: High Performance Preclinical Irradiation Through Optimized Dual Focal Spot Dose Painting and Online Virtual Isocenter Radiation Field Targeting

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

Stewart, J; Princess Margaret Cancer Centre, University Health Network, Toronto, CA; Lindsay, P

Purpose: Advances in radiotherapy practice facilitated by collimation systems to shape radiation fields and image guidance to target these conformal beams have motivated proposals for more complex dose patterns to improve the therapeutic ratio. Recent progress in small animal radiotherapy platforms has provided the foundation to validate the efficacy of such interventions, but robustly delivering heterogeneous dose distributions at the scale and accuracy demanded by preclinical studies remains challenging. This work proposes a dual focal spot optimization method to paint spatially heterogeneous dose regions and an online virtual isocenter targeting method to accurately target the dose distributions. Methods: Two-dimensional dosemore » kernels were empirically measured for the 1 mm diameter circular collimator with radiochromic film in a solid water phantom for the small and large x-ray focal spots on the X-RAD 225Cx microirradiator. These kernels were used in an optimization framework which determined a set of animal stage positions, beam-on times, and focal spot settings to optimally deliver a given desired dose distribution. An online method was developed which defined a virtual treatment isocenter based on a single image projection of the collimated radiation field. The method was demonstrated by optimization of a 6 mm circular 2 Gy target adjoining a 4 mm semicircular avoidance region. Results: The dual focal spot technique improved the optimized dose distribution with the proportion of avoidance region receiving more than 0.5 Gy reduced by 40% compared to the large focal spot technique. Targeting tests performed by irradiating ball bearing targets on radiochromic film pieced revealed the online targeting method improved the three-dimensional accuracy from 0.48 mm to 0.15 mm. Conclusion: The dual focal spot optimization and online virtual isocenter targeting framework is a robust option for delivering dose at the preclinical level and provides a new

Dose Volume Histogram (DVH) Analysis in Intensity Modulation Radiation Therapy (IMRT) Treatments for Prostate Cancers

NASA Astrophysics Data System (ADS)

Pyakuryal, Anil

2009-05-01

Studies have shown that as many as 8 out of 10 men had prostate cancer by age 80.Prostate cancer begins with small changes (prostatic intraepithelial neoplasia(PIN)) in size and shape of prostate gland cells,known as prostate adenocarcinoma.With advent in technology, prostate cancer has been the most widely used application of IMRT with the longest follow-up periods.Prostate cancer fits the ideal target criteria for IMRT of adjacent sensitive dose-limiting tissue (rectal, bladder).A retrospective study was performed on 10 prostate cancer patients treated with radiation to a limited pelvic field with a standard 4 field arrangements at dose 45 Gy, and an IMRT boost field to a total isocenter dose of 75 Gy.Plans were simulated for 4 field and the supplementary IMRT treatments with proposed dose delivery at 1.5 Gy/fraction in BID basis.An automated DVH analysis software, HART (S. Jang et al., 2008,Med Phys 35,p.2812)was used to perform DVH assessments in IMRT plans.A statistical analysis of dose coverage at targets in prostate gland and neighboring critical organs,and the plan indices(homogeneity, conformality etc) evaluations were also performed using HART extracted DVH statistics.Analyzed results showed a better correlation with the proposed outcomes (TCP, NTCP) of the treatments.

COMPARISON OF THE PERIPHERAL DOSES FROM DIFFERENT IMRT TECHNIQUES FOR PEDIATRIC HEAD AND NECK RADIATION THERAPY.

PubMed

Toyota, Masahiko; Saigo, Yasumasa; Higuchi, Kenta; Fujimura, Takuya; Koriyama, Chihaya; Yoshiura, Takashi; Akiba, Suminori

2017-11-01

Intensity-modulated radiation therapy (IMRT) can deliver high and homogeneous doses to the target area while limiting doses to organs at risk. We used a pediatric phantom to simulate the treatment of a head and neck tumor in a child. The peripheral doses were examined for three different IMRT techniques [dynamic multileaf collimator (DMLC), segmental multileaf collimator (SMLC) and volumetric modulated arc therapy (VMAT)]. Peripheral doses were evaluated taking thyroid, breast, ovary and testis as the points of interest. Doses were determined using a radio-photoluminescence glass dosemeter, and the COMPASS system was used for three-dimensional dose evaluation. VMAT achieved the lowest peripheral doses because it had the highest monitor unit efficiency. However, doses in the vicinity of the irradiated field, i.e. the thyroid, could be relatively high, depending on the VMAT collimator angle. DMLC and SMLC had a large area of relatively high peripheral doses in the breast region. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dosimetric and Clinical Analysis of Spatial Distribution of the Radiation Dose in Gamma Knife Radiosurgery for Vestibular Schwannoma

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

Massager, Nicolas, E-mail: nmassage@ulb.ac.be; Neurosurgery-Department, Hospital Erasme, Brussels; Lonneville, Sarah

2011-11-15

Objectives: We investigated variations in the distribution of radiation dose inside (dose inhomogeneity) and outside (dose falloff) the target volume during Gamma Knife (GK) irradiation of vestibular schwannoma (VS). We analyzed the relationship between some parameters of dose distribution and the clinical and radiological outcome of patients. Methods and Materials: Data from dose plans of 203 patients treated for a vestibular schwannoma by GK C using same prescription dose (12 Gy at the 50% isodose) were collected. Four different dosimetric indexes were defined and calculated retrospectively in all plannings on the basis of dose-volume histograms: Paddick conformity index (PI), gradientmore » index (GI), homogeneity index (HI), and unit isocenter (UI). The different measures related to distribution of the radiation dose were compared with hearing and tumor outcome of 203 patients with clinical and radiological follow-up of minimum 2 years. Results: Mean, median, SD, and ranges of the four indexes of dose distribution analyzed were calculated; large variations were found between dose plans. We found a high correlation between the target volume and PI, GI, and UI. No significant association was found between the indexes of dose distribution calculated in this study and tumor control, tumor volume shrinkage, hearing worsening, loss of functional hearing, or complete hearing loss at last follow-up. Conclusions: Parameters of distribution of the radiation dose during GK radiosurgery for VS can be highly variable between dose plans. The tumor and hearing outcome of patients treated is not significantly related to these global indexes of dose distribution inside and around target volume. In GK radiosurgery for VS, the outcome seems more to be influenced by local radiation dose delivered to specific structures or volumes than by global dose gradients.« less

A novel approach to make homogeneous protease-stable monovalent streptavidin

DOE PAGES

Zhang, M.; Shao, J; Xiao, J.; ...

2015-06-11

The interaction between the tetramer streptavidin and biotin is recognized as one of the strongest non-covalent associations. Owing to the tight and specific binding, the streptavidin-biotin system has been used widely for bimolecular labeling, purification, immobilization, and even for targeted delivery of therapeutics drugs. Here, we report a novel approach to make homogeneous monovalent tetramer streptavidin. The purified monovalent protein showed both thermal stability and protease stability. Unexpectedly, we found that two proteases, Proteinase K (PK) and Subtilisin (SU), can efficiently remove the His8-tag from the wild-type subunit without affecting the tetramer architecture of monovalent streptavidin, thus making it moremore » homogeneous. In addition, crystallization was performed to assure the homogeneity of the monovalent protein prepared. Overall, monovalent streptavidin shows increased homogeneity and will likely be valuable for many future applications in a wide range of research areas.« less

Four-dimensional layer-stacking carbon-ion beam dose distribution by use of a lung numeric phantom.

PubMed

Mori, Shinichiro; Kumagai, Motoki; Miki, Kentaro

2015-07-01

To extend layer-stacking irradiation to accommodate intrafractional organ motion, we evaluated the carbon-ion layer-stacking dose distribution using a numeric lung phantom. We designed several types of range compensators. The planning target volume was calculated from the respective respiratory phases for consideration of intrafractional beam range variation. The accumulated dose distribution was calculated by registering of the dose distributions at respective phases to that at the reference phase. We evaluated the dose distribution based on the following six parameters: motion displacement, direction, gating window, respiratory cycle, range-shifter change time, and prescribed dose. All parameters affected the dose conformation to the moving target. By shortening of the gating window, dose metrics for superior-inferior (SI) and anterior-posterior (AP) motions were decreased from a D95 of 94 %, Dmax of 108 %, and homogeneity index (HI) of 23 % at T00-T90, to a D95 of 93 %, Dmax of 102 %, and HI of 20 % at T40-T60. In contrast, all dose metrics except the HI were independent of respiratory cycle. All dose metrics in SI motion were almost the same in respective motion displacement, with a D95 of 94 %, Dmax of 108 %, Dmin of 89 %, and HI of 23 % for the ungated phase, and D95 of 93 %, Dmax of 102 %, Dmin of 85 %, and HI of 20 % for the gated phase. The dose conformation to a moving target was improved by the gating strategy and by an increase in the prescribed dose. A combination of these approaches is a practical means of adding them to existing treatment protocols without modifications.

Gamma index evaluation of IMRT technique using gafchromic film EBT3 for homogeneous and inhomogeneous material

NASA Astrophysics Data System (ADS)

Nisauf, T. A.; Wibowo, W. E.; Pawiro, S. A.

2017-07-01

This study was done to evaluate the gamma index for registering between the planar of dose planning and the measurement of EBT film. The treatment plan was simulated for 5 patients using Fan Beam Computerized Tomography (FBCT) modality, Philips Pinnacle planning system, 6 MV photon energy, 50 segments IMRT technique, and calculation grid resolution (CGR) of 0.2 cm. Gamma Index (GI) evaluation was done with criteria of dose difference (DD) of 2 %, dose to agreement (DTA) of 2 mm and dose difference (DD) of 5 % DTA of 3 mm, SAD 100 cm, depth of 5 cm and 10 cm of the phantom. The result shows that GI for homogeneous material is greater than for inhomogeneous material with discrepancy to previous work is about 1.98 % for homogeneous material (depth 5 cm) and 2.05 % (depth 10 cm) while it was found of 2.98 % for inhomogeneous material (equivalent depth 5 cm) and 4.59 % (equivalent depth 10 cm).

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Anthropogenic disturbance homogenizes seagrass fish communities.

PubMed

Iacarella, Josephine C; Adamczyk, Emily; Bowen, Dan; Chalifour, Lia; Eger, Aaron; Heath, William; Helms, Sibylla; Hessing-Lewis, Margot; Hunt, Brian P V; MacInnis, Andrew; O'Connor, Mary I; Robinson, Clifford L K; Yakimishyn, Jennifer; Baum, Julia K

2018-05-01

Anthropogenic activities have led to the biotic homogenization of many ecological communities, yet in coastal systems this phenomenon remains understudied. In particular, activities that locally affect marine habitat-forming foundation species may perturb habitat and promote species with generalist, opportunistic traits, in turn affecting spatial patterns of biodiversity. Here, we quantified fish diversity in seagrass communities across 89 sites spanning 6° latitude along the Pacific coast of Canada, to test the hypothesis that anthropogenic disturbances homogenize (i.e., lower beta-diversity) assemblages within coastal ecosystems. We test for patterns of biotic homogenization at sites within different anthropogenic disturbance categories (low, medium, and high) at two spatial scales (within and across regions) using both abundance- and incidence-based beta-diversity metrics. Our models provide clear evidence that fish communities in high anthropogenic disturbance seagrass areas are homogenized relative to those in low disturbance areas. These results were consistent across within-region comparisons using abundance- and incidence-based measures of beta-diversity, and in across-region comparisons using incidence-based measures. Physical and biotic characteristics of seagrass meadows also influenced fish beta-diversity. Biotic habitat characteristics including seagrass biomass and shoot density were more differentiated among high disturbance sites, potentially indicative of a perturbed environment. Indicator species and trait analyses revealed fishes associated with low disturbance sites had characteristics including stenotopy, lower swimming ability, and egg guarding behavior. Our study is the first to show biotic homogenization of fishes across seagrass meadows within areas of relatively high human impact. These results support the importance of targeting conservation efforts in low anthropogenic disturbance areas across land- and seascapes, as well as managing

Corneal targeted nanoparticles for sustained natamycin delivery and their PK/PD indices: an approach to reduce dose and dosing frequency.

PubMed

Chandasana, Hardik; Prasad, Yarra Durga; Chhonker, Yashpal S; Chaitanya, Telaprolu K; Mishra, Nripendra N; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2014-12-30

Natamycin is the only approved medication for the treatment of mycotic keratitis. Current dosage regimen include one drop of natamycin suspension (5% w/v) instilled in the conjunctival sac at hourly or two hourly intervals for several days which has poor patient compliance. The purpose of the present study was to design a corneal targeted nanoformulation in order to reduce dose and dosing frequency of natamycin and evaluate its pharmacokinetic/pharmacodynamic indices in comparison with clinical marketed preparation. The nanoparticles prepared by nanoprecipitation method were in nanometer size range with high entrapment efficiency and positive surface charge. In-vitro release studies indicated prolonged release of natamycin up to 8h. In-vitro antifungal activity was comparable with marketed preparation. The performance of nanoformulations was evaluated in rabbit eyes. The concentration of natamycin in tear fluid was determined by using LC-MS/MS. The pharmacokinetic parameters such as area under the curve, t½ and mean residence time were significantly higher and clearance was significantly lower for nanoformulations with that of marketed preparation. The optimized dosing schedule to maintain natamycin concentration above tenfold of MIC90 was one instillation in every 5h. Moreover, 1/5th dose reduction of nanoformulation was also effective. Copyright © 2014 Elsevier B.V. All rights reserved.

Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

NASA Astrophysics Data System (ADS)

Yazdani, Mohammad Reza; Setayeshi, Saeed; Arabalibeik, Hossein; Akbari, Mohammad Esmaeil

2017-05-01

Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

Sperm quality and oxidative status as affected by homogenization of liquid-stored boar semen diluted in short- and long-term extenders.

PubMed

Menegat, Mariana B; Mellagi, Ana Paula G; Bortolin, Rafael C; Menezes, Tila A; Vargas, Amanda R; Bernardi, Mari Lourdes; Wentz, Ivo; Gelain, Daniel P; Moreira, José Cláudio F; Bortolozzo, Fernando P

2017-04-01

Homogenization of diluted boar semen during storage has for a long time been regarded as beneficial. Recent studies indicated an adverse effect of homogenization on sperm quality for yet unknown reasons. This study aimed to verify the effect of homogenization on sperm parameters and to elucidate the impact of oxidative stress. Twenty-one normospermic ejaculates (21 boars) were diluted with Androstar ® Plus (AND) and Beltsville Thawing Solution (BTS). Semen doses were submitted to no-homogenization (NoHom) or twice-a-day manual homogenization (2xHom) during storage at 17°C for 168h. NoHom and 2xHom were similar (P>0.05) for both short- and long-term extenders with respect to motility and kinematics parameters (CASA system), membrane viability (SYBR-14/PI), acrosome integrity, lipid peroxidation, protein oxidation, intracellular reactive oxygen species, sulfhydryl content, and total radical-trapping antioxidant potential. 2xHom reduced sperm motility and motion kinematics (VCL, VSL, VAP, BCF, and ALH) following the thermoresistance test and presented with a slight increase in pH along the storage (P=0.05) as compared to NoHom. Furthermore, 2xHom semen doses presented with a constant SOD and GSH-Px activity during storage whereas enzymatic activity increased for NoHom at the end of the storage. These findings confirm that homogenization of semen doses is detrimental to sperm quality. Moreover, it is shown that the effect of homogenization is unlikely to be primarily related to oxidative stress. Homogenization is not recommended for storage of liquid boar semen for up to 168h in both short- and long-term extenders. Copyright © 2017 Elsevier B.V. All rights reserved.

Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

PubMed

Takada, Masashi; Kosako, Kazuaki; Oishi, Koji; Nakamura, Takashi; Sato, Kouichi; Kamiyama, Takashi; Kiyanagi, Yoshiaki

2013-03-01

Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

Patient dose analysis in total body irradiation through in vivo dosimetry.

PubMed

Ganapathy, K; Kurup, P G G; Murali, V; Muthukumaran, M; Bhuvaneshwari, N; Velmurugan, J

2012-10-01

Total body irradiation (TBI) is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF) TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinum showed a similar pattern with the average measured dose from 96 to 97% of the prescription dose. Extremities and chest received a dose greater than the prescription dose in many instances (more than 20% of measurements). Homogeneous dose delivery to the whole body is checked by calculating the mean dose with standard deviation for each fraction. Reasons for the difference between prescription dose and measured dose for each site are discussed. Dose homogeneity within ±10% is achieved using our in-house TBI protocol.

Patient dose analysis in total body irradiation through in vivo dosimetry

PubMed Central

Ganapathy, K.; Kurup, P. G. G.; Murali, V.; Muthukumaran, M.; Bhuvaneshwari, N.; Velmurugan, J.

2012-01-01

Total body irradiation (TBI) is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF) TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinum showed a similar pattern with the average measured dose from 96 to 97% of the prescription dose. Extremities and chest received a dose greater than the prescription dose in many instances (more than 20% of measurements). Homogeneous dose delivery to the whole body is checked by calculating the mean dose with standard deviation for each fraction. Reasons for the difference between prescription dose and measured dose for each site are discussed. Dose homogeneity within ±10% is achieved using our in-house TBI protocol. PMID:23293453

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

Spatial fractionation of the dose in heavy ions therapy: An optimization study.

PubMed

González, W; Prezado, Y

2018-06-01

The alliance of charged particle therapy and the spatial fractionation of the dose, as in minibeam or Grid therapy, is an innovative strategy to improve the therapeutic index in the treatment of radioresistant tumors. The aim of this work was to assess the optimum irradiation configuration in heavy ion spatially fractionated radiotherapy (SFRT) in terms of ion species, beam width, center-to-center distances, and linear energy transfer (LET), information that could be used to guide the design of the future biological experiments. The nuclear fragmentation leading to peak and valley regions composed of different secondary particles, creates the need for a more complete dosimetric description that the classical one in SFRT. Monte Carlo simulations (GATE 6.2) were performed to evaluate the dose distributions for different ions, beam widths, and spacings. We have also assessed the 3D-maps of dose-averaged LET and proposed a new parameter, the peak-to-valley-LET ratio, to offer a more thorough physical evaluation of the technique. Our results show that beam widths larger than 400 μm are needed in order to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. A large ctc distance (3500 μm) would favor tissue sparing since it provides higher PVDR, it leads to a reduced contribution of the heavier nuclear fragments and a LET value in the valleys a factor 2 lower than the LET in the ctc leading to homogeneous distributions in the target. Heavy ions MBRT provide advantageous dose distributions. Thanks to the reduced lateral scattering, the use of submillimetric beams still allows to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. Large ctc distances (3500 μm) should be preferred since they lead to valley doses composed of lighter nuclear fragments resulting in a much reduced dose-averaged LET values in normal tissue, favoring its

Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model.

PubMed

Malhotra, Meenakshi; Sekar, Thillai Veerapazham; Ananta, Jeyarama S; Devulapally, Rammohan; Afjei, Rayhaneh; Babikir, Husam A; Paulmurugan, Ramasamy; Massoud, Tarik F

2018-04-20

Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

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

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we

Homogenization versus homogenization-free method to measure muscle glycogen fractions.

PubMed

Mojibi, N; Rasouli, M

2016-12-01

The glycogen is extracted from animal tissues with or without homogenization using cold perchloric acid. Three methods were compared for determination of glycogen in rat muscle at different physiological states. Two groups of five rats were kept at rest or 45 minutes muscular activity. The glycogen fractions were extracted and measured by using three methods. The data of homogenization method shows that total glycogen decreased following 45 min physical activity and the change occurred entirely in acid soluble glycogen (ASG), while AIG did not change significantly. Similar results were obtained by using "total-glycogen-fractionation methods". The findings of "homogenization-free method" indicate that the acid insoluble fraction (AIG) was the main portion of muscle glycogen and the majority of changes occurred in AIG fraction. The results of "homogenization method" are identical with "total glycogen fractionation", but differ with "homogenization-free" protocol. The ASG fraction is the major portion of muscle glycogen and is more metabolically active form.

Homogeneous and label-free electrochemiluminescence aptasensor based on the difference of electrostatic interaction and exonuclease-assisted target recycling amplification.

PubMed

Ni, Jiancong; Yang, Weiqiang; Wang, Qingxiang; Luo, Fang; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Yang, Huanghao

2018-05-15

The difference of electrostatic interaction between free Ru(phen) 3 2+ and Ru(phen) 3 2+ embedded in double strand DNA (dsDNA) to the negatively charged indium tin oxide (ITO) electrode has been applied to develop a homogeneous and label-free electrochemiluminescence (ECL) aptasensor for the first time. Ochratoxin A (OTA) has been chosen as the model target. The OTA aptamer is first hybridized with its complementary single strand DNA (ssDNA) to form dsDNA and then interacted with Ru(phen) 3 2+ via the grooves binding mode to form dsDNA-Ru(phen) 3 2+ complex, which remains negatively charged feature as well as low diffusion capacity to the negatively charged ITO electrode surface owing to the electrostatic repulsion. Meanwhile, the intercalated Ru(phen) 3 2+ in the grooves of dsDNA works as an ECL signal reporter instead of the labor-intensive labeling steps and can generate much more ECL signal than that from the labeling probe. In the presence of target, the aptamer prefers to form an aptamer-target complex in lieu of dsDNA, which induces the releasing of Ru(phen) 3 2+ from the dsDNA-Ru(phen) 3 2+ complex into the solution. With the assistance of RecJ f exonuclease (a ssDNA specific exonuclease), the released ssDNA and the aptamer in the target-complex were digested into mononucleotides. In the meantime, the target can be also liberated from OTA-aptamer complex and induce target cycling and large amount of free Ru(phen) 3 2+ present in the solution. Since Ru(phen) 3 2+ contains positive charges, which can diffuses easily to the ITO electrode surface because of electrostatic attraction, causing an obviously enhanced ECL signal detected. Under the optimal conditions, the enhanced ECL of the system has a linear relationship with the OTA concentration in the range of 0.01-1.0 ng/mL with a detection limit of 2 pg/mL. This innovative system not only expands the immobilization-free sensors in the electrochemiluminescent fields, but also can be developed for the

Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer.

PubMed

Magnuson, William J; Urban, Erich; Bayliss, R Adam; Harari, Paul M

2015-06-01

There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm(3) (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

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

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

2014-01-15

and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

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

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Role of structural barriers for carotenoid bioaccessibility upon high pressure homogenization.

PubMed

Palmero, Paola; Panozzo, Agnese; Colle, Ines; Chigwedere, Claire; Hendrickx, Marc; Van Loey, Ann

2016-05-15

A specific approach to investigate the effect of high pressure homogenization on the carotenoid bioaccessibility in tomato-based products was developed. Six different tomato-based model systems were reconstituted in order to target the specific role of the natural structural barriers (chromoplast substructure/cell wall) and of the phases (soluble/insoluble) in determining the carotenoid bioaccessibility and viscosity changes upon high pressure homogenization. Results indicated that in the absence of natural structural barriers (carotenoid enriched oil), the soluble and insoluble phases determined the carotenoid bioaccessibility upon processing whereas, in their presence, these barriers governed the bioaccessibility. Furthermore, it was shown that the increment of the viscosity upon high pressure homogenization is determined by the presence of insoluble phase, however, this result was related to the initial ratio of the soluble:insoluble phases in the system. In addition, no relationship between the changes in viscosity and carotenoid bioaccessibility upon high pressure homogenization was found. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

DTIC Science & Technology

2009-06-01

imagining) into the HDR brachytherapy treatment planning has been demonstrated. Using the inverse planning program IPSA , dose escalation of target...Principles and Clinical Applications of IPSA ; Nucletron International Physics Seminar, Vaals, Netherlands, Sept 13-16, 2006. 7 IPSA ...experience with IPSA for prostate cancer treatment in HDR Brachytherapy, 4ième séminaire francophone de curiethérapie, Arcachon, France, June 15, 2006

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Development and Validation of a Novel Vancomycin Dosing Nomogram for Achieving High-Target Trough Levels at 2 Canadian Teaching Hospitals

PubMed Central

Thalakada, Rosanne; Legal, Michael; Lau, Tim T Y; Luey, Tiffany; Batterink, Josh; Ensom, Mary H H

2012-01-01

Background: Recent guidelines recommend a vancomycin trough (predose) level between 15 and 20 mg/L in the treatment of invasive gram-positive infections, but most initial dosing nomograms are designed to achieve lower targets (5–15 mg/L). Clinicians need guidance about appropriate initial dosing to achieve the higher target. Objective: To develop and validate a high-target vancomycin dosing nomogram to achieve trough levels of 15–20 mg/L. Methods: A retrospective study was conducted at 2 teaching hospitals, St Paul’s Hospital and Vancouver General Hospital in Vancouver, British Columbia. Patients who were treated with vancomycin between January 2008 and June 2010 and who had achieved a trough level of 14.5–20.5 mg/L were identified. Demographic and clinical data were collected. Multiple linear regression was used to develop a vancomycin dosing nomogram for each hospital site. An integrated nomogram was constructed by merging the data from the 2 hospitals. A unique set of patients at each institution was used for validating their respective nomograms and a pooled group of patients for validating the integrated nomogram. Predictive success was evaluated, and a nomogram was deemed significantly different from another nomogram if p < 0.05 via “χ2 testing. Results: Data from 78 patients at one hospital and 91 patients at the other were used in developing the respective institutional nomograms. For each hospital’s data set, both age and initial serum creatinine were significantly associated with the predicted dosing interval (p < 0.001). Validation in a total of 105 test patients showed that the integrated nomogram had a predictive success rate of 56%. Conclusions: A novel vancomycin dosing nomogram was developed and validated at 2 Canadian teaching hospitals. This integrated nomogram is a tool that clinicians can use in selecting appropriate initial vancomycin regimens on the basis of age and serum creatinine, to achieve high-target levels of 15–20 mg

Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

DTIC Science & Technology

2008-08-01

AD_________________ Award Number: W81XWH-04-1-0697 TITLE: Alpha -v Integrin Targeted PET Imaging of...SUBTITLE 5a. CONTRACT NUMBER Alpha -v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low- Dose Metronomic Anti-Angiogenic...Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer” was published in Eur J Nucl

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

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

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

2014-06-15

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

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

PubMed Central

Lee, T-F; Ting, H-M; Chao, P-J; Wang, H-Y; Shieh, C-S; Horng, M-F; Wu, J-M; Yeh, S-A; Cho, M-Y; Huang, E-Y; Huang, Y-J; Chen, H-C; Fang, F-M

2012-01-01

Objective We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). Methods The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle3® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V20 Gy and V30 Gy of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. Results Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V20 Gy, and heart V30 Gy in the DV-gEUD plan were lower than those in the DV plan (p<0.05). Conclusions A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV. PMID:23091290

WE-EF-BRA-02: A Monte Carlo Study of Macroscopic and Microscopic Dose Descriptors for Kilovoltage Cellular Dosimetry

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

Oliver, P; Thomson, R

2015-06-15

Purpose: To investigate how doses to cellular (microscopic) targets depend on cell morphology, and how cellular doses relate to doses to bulk tissues and water for 20 to 370 keV photon sources using Monte Carlo (MC) simulations. Methods: Simulation geometries involve cell clusters, single cells, and single nuclear cavities embedded in various healthy and cancerous bulk tissue phantoms. A variety of nucleus and cytoplasm elemental compositions are investigated. Cell and nucleus radii range from 5 to 10 microns and 2 to 9 microns, respectively. Doses to water and bulk tissue cavities are compared to nucleus and cytoplasm doses. Results: Variationsmore » in cell dose with simulation geometry are most pronounced for lower energy sources. Nuclear doses are sensitive to the surrounding geometry: the nuclear dose in a multicell model differs from the dose to a cavity of nuclear medium in an otherwise homogeneous bulk tissue phantom by more than 7% at 20 keV. Nuclear doses vary with cell size by up to 20% at 20 keV, with 10% differences persisting up to 90 keV. Bulk tissue and water cavity doses differ from cellular doses by up to 16%. MC results are compared to cavity theory predictions; large and small cavity theories qualitatively predict nuclear doses for energies below and above 50 keV, respectively. Burlin’s (1969) intermediate cavity theory best predicts MC results with an average discrepancy of 4%. Conclusion: Cellular doses vary as a function of source energy, subcellular compartment size, elemental composition, and tissue morphology. Neither water nor bulk tissue is an appropriate surrogate for subcellular targets in radiation dosimetry. The influence of microscopic inhomogeneities in the surrounding environment on the nuclear dose and the importance of the nucleus as a target for radiation-induced cell death emphasizes the potential importance of cellular dosimetry for understanding radiation effects. Funded by the Natural Sciences and Engineering Research

Continuous Toxicological Dose-Response Relationships Are Pretty Homogeneous (Society for Risk Analysis Annual Meeting)

EPA Science Inventory

Dose-response relationships for a wide range of in vivo and in vitro continuous datasets are well-described by a four-parameter exponential or Hill model, based on a recent analysis of multiple historical dose-response datasets, mostly with more than five dose groups (Slob and Se...

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug

PubMed Central

Alyami, Hamad; Dahmash, Eman; Bowen, James

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation. PMID:28609454

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug.

PubMed

Alyami, Hamad; Dahmash, Eman; Bowen, James; Mohammed, Afzal R

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

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

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

Homogenizing Advanced Alloys: Thermodynamic and Kinetic Simulations Followed by Experimental Results

NASA Astrophysics Data System (ADS)

Jablonski, Paul D.; Hawk, Jeffrey A.

2017-01-01

Segregation of solute elements occurs in nearly all metal alloys during solidification. The resultant elemental partitioning can severely degrade as-cast material properties and lead to difficulties during post-processing (e.g., hot shorts and incipient melting). Many cast articles are subjected to a homogenization heat treatment in order to minimize segregation and improve their performance. Traditionally, homogenization heat treatments are based upon past practice or time-consuming trial and error experiments. Through the use of thermodynamic and kinetic modeling software, NETL has designed a systematic method to optimize homogenization heat treatments. Use of the method allows engineers and researchers to homogenize casting chemistries to levels appropriate for a given application. The method also allows for the adjustment of heat treatment schedules to fit limitations on in-house equipment (capability, reliability, etc.) while maintaining clear numeric targets for segregation reduction. In this approach, the Scheil module within Thermo-Calc is used to predict the as-cast segregation present within an alloy, and then diffusion controlled transformations is used to model homogenization kinetics as a function of time and temperature. Examples of computationally designed heat treatments and verification of their effects on segregation and properties of real castings are presented.

Technical Note: The impact of deformable image registration methods on dose warping.

PubMed

Qin, An; Liang, Jian; Han, Xiao; O'Connell, Nicolette; Yan, Di

2018-03-01

The purpose of this study was to investigate the clinical-relevant discrepancy between doses warped by pure image based deformable image registration (IM-DIR) and by biomechanical model based DIR (BM-DIR) on intensity-homogeneous organs. Ten patients (5Head&Neck, 5Prostate) were included. A research DIR tool (ADMRIE_v1.12) was utilized for IM-DIR. After IM-DIR, BM-DIR was carried out for organs (parotids, bladder, and rectum) which often encompass sharp dose gradient. Briefly, high-quality tetrahedron meshes were generated and deformable vector fields (DVF) from IM-DIR were interpolated to the surface nodes of the volume meshes as boundary condition. Then, a FEM solver (ABAQUS_v6.14) was used to simulate the displacement of internal nodes, which were then interpolated to image-voxel grids to get the more physically plausible DVF. Both geometrical and subsequent dose warping discrepancies were quantified between the two DIR methods. Target registration discrepancy(TRD) was evaluated to show the geometry difference. The re-calculated doses on second CT were warped to the pre-treatment CT via two DIR. Clinical-relevant dose parameters and γ passing rate were compared between two types of warped dose. The correlation was evaluated between parotid shrinkage and TRD/dose discrepancy. The parotid shrunk to 75.7% ± 9% of its pre-treatment volume and the percentage of volume with TRD>1.5 mm) was 6.5% ± 4.7%. The normalized mean-dose difference (NMDD) of IM-DIR and BM-DIR was -0.8% ± 1.5%, with range (-4.7% to 1.5%). 2 mm/2% passing rate was 99.0% ± 1.4%. A moderate correlation was found between parotid shrinkage and TRD and NMDD. The bladder had a NMDD of -9.9% ± 9.7%, with BM-DIR warped dose systematically higher. Only minor deviation was observed for rectum NMDD (0.5% ± 1.1%). Impact of DIR method on treatment dose warping is patient and organ-specific. Generally, intensity-homogeneous organs, which undergo larger deformation/shrinkage during

SU-F-T-574: MLC Based SRS Beam Commissioning - Minimum Target Size Investigation

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

Zakikhani, R; Able, C

2016-06-15

Purpose: To implement a MLC accelerator based SRS program using small fields down to 1 cm × 1 cm and to determine the smallest target size safe for clinical treatment. Methods: Computerized beam scanning was performed in water using a diode detector and a linac-head attached transmission ion chamber to characterize the small field dosimetric aspects of a 6 MV photon beam (Trilogy-Varian Medical Systems, Inc.). The output factors, PDD and profiles of field sizes 1, 2, 3, 4, and 10 cm{sup 2} were measured and utilized to create a new treatment planning system (TPS) model (AAA ver 11021). Staticmore » MLC SRS treatment plans were created and delivered to a homogeneous phantom (Cube 20, CIRS, Inc.) for a 1.0 cm and 1.5 cm “PTV” target. A 12 field DMLC plan was created for a 2.1 cm target. Radiochromic film (EBT3, Ashland Inc.) was used to measure the planar dose in the axial, coronal and sagittal planes. A micro ion chamber (0.007 cc) was used to measure the dose at isocenter for each treatment delivery. Results: The new TPS model was validated by using a tolerance criteria of 2% dose and 2 mm distance to agreement. For fields ≤ 3 cm{sup 2}, the max PDD, Profile and OF difference was 0.9%, 2%/2mm and 1.4% respectively. The measured radiochromic film planar dose distributions had gamma scores of 95.3% or higher using a 3%/2mm criteria. Ion chamber measurements for all 3 test plans effectively met our goal of delivering the dose accurately to within 5% when compared to the expected dose reported by the TPS (1 cm plan Δ= −5.2%, 1.5 cm plan Δ= −2.0%, 2 cm plan Δ= 1.5%). Conclusion: End to end testing confirmed that MLC defined SRS for target sizes ≥ 1.0 cm can be safely planned and delivered.« less

Development of a homogeneous immunoassay system using protein A fusion fragmented Renilla luciferase.

PubMed

Mie, Masayasu; Thuy, Ngo Phan Bich; Kobatake, Eiry

2012-03-07

A homogeneous immunoassay system was developed using fragmented Renilla luciferase (Rluc). The B domain of protein A was fused to two Rluc fragments. When complexes between an antibody and fragmented Rluc fusion proteins bind to target molecules, the Rluc fragments come into close proximity and the luminescence activity of fragmented Rluc is restored by complementation. As proof-of-principle, this fragmented Rluc system was used to detect E. coli homogeneously using an anti-E. coli antibody.

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

PubMed

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

PubMed Central

Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

PubMed

Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Effect of lipid viscosity and high-pressure homogenization on the physical stability of "Vitamin E" enriched emulsion.

PubMed

Alayoubi, Alaadin; Abu-Fayyad, Ahmed; Rawas-Qalaji, Mutasem M; Sylvester, Paul W; Nazzal, Sami

2015-01-01

Recently there has been a growing interest in vitamin E for its potential use in cancer therapy. The objective of this work was therefore to formulate a physically stable parenteral lipid emulsion to deliver higher doses of vitamin E than commonly used in commercial products. Specifically, the objectives were to study the effects of homogenization pressure, number of homogenizing cycles, viscosity of the oil phase, and oil content on the physical stability of emulsions fortified with high doses of vitamin E (up to 20% by weight). This was done by the use of a 27-run, 4-factor, 3-level Box-Behnken statistical design. Viscosity, homogenization pressure, and number of cycles were found to have a significant effect on particle size, which ranged from 213 to 633 nm, and on the percentage of vitamin E remaining emulsified after storage, which ranged from 17 to 100%. Increasing oil content from 10 to 20% had insignificant effect on the responses. Based on the results it was concluded that stable vitamin E rich emulsions could be prepared by repeated homogenization at higher pressures and by lowering the viscosity of the oil phase, which could be adjusted by blending the viscous vitamin E with medium-chain triglycerides (MCT).

Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD

NASA Astrophysics Data System (ADS)

Cantley, Justin L.; Hanlon, Justin; Chell, Erik; Lee, Choonsik; Smith, W. Clay; Bolch, Wesley E.

2013-10-01

Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay® Radiotherapy System, developed by Oraya® Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye—total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18° to 34° in 2° increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26° or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.

Improvement of dose calculation in radiation therapy due to metal artifact correction using the augmented likelihood image reconstruction.

PubMed

Ziemann, Christian; Stille, Maik; Cremers, Florian; Buzug, Thorsten M; Rades, Dirk

2018-04-17

Metal artifacts caused by high-density implants lead to incorrectly reconstructed Hounsfield units in computed tomography images. This can result in a loss of accuracy in dose calculation in radiation therapy. This study investigates the potential of the metal artifact reduction algorithms, Augmented Likelihood Image Reconstruction and linear interpolation, in improving dose calculation in the presence of metal artifacts. In order to simulate a pelvis with a double-sided total endoprosthesis, a polymethylmethacrylate phantom was equipped with two steel bars. Artifacts were reduced by applying the Augmented Likelihood Image Reconstruction, a linear interpolation, and a manual correction approach. Using the treatment planning system Eclipse™, identical planning target volumes for an idealized prostate as well as structures for bladder and rectum were defined in corrected and noncorrected images. Volumetric modulated arc therapy plans have been created with double arc rotations with and without avoidance sectors that mask out the prosthesis. The irradiation plans were analyzed for variations in the dose distribution and their homogeneity. Dosimetric measurements were performed using isocentric positioned ionization chambers. Irradiation plans based on images containing artifacts lead to a dose error in the isocenter of up to 8.4%. Corrections with the Augmented Likelihood Image Reconstruction reduce this dose error to 2.7%, corrections with linear interpolation to 3.2%, and manual artifact correction to 4.1%. When applying artifact correction, the dose homogeneity was slightly improved for all investigated methods. Furthermore, the calculated mean doses are higher for rectum and bladder if avoidance sectors are applied. Streaking artifacts cause an imprecise dose calculation within irradiation plans. Using a metal artifact correction algorithm, the planning accuracy can be significantly improved. Best results were accomplished using the Augmented Likelihood Image

Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

PubMed

Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

2017-10-21

Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was

Comparison of different treatment planning optimization methods for vaginal HDR brachytherapy with multichannel applicators: A reduction of the high doses to the vaginal mucosa is possible.

PubMed

Carrara, Mauro; Cusumano, Davide; Giandini, Tommaso; Tenconi, Chiara; Mazzarella, Ester; Grisotto, Simone; Massari, Eleonora; Mazzeo, Davide; Cerrotta, Annamaria; Pappalardi, Brigida; Fallai, Carlo; Pignoli, Emanuele

2017-12-01

A direct planning approach with multi-channel vaginal cylinders (MVCs) used for HDR brachytherapy of vaginal cancers is particularly challenging. Purpose of this study was to compare the dosimetric performances of different forward and inverse methods used for the optimization of MVC-based vaginal treatments for endometrial cancer, with a particular attention to the definition of strategies useful to limit the high doses to the vaginal mucosa. Twelve postoperative vaginal HDR brachytherapy treatments performed with MVCs were considered. Plans were retrospectively optimized with three different methods: Dose Point Optimization followed by Graphical Optimization (DPO + GrO), Inverse Planning Simulated Annealing with two different class solutions as starting conditions (surflPSA and homogIPSA) and Hybrid Inverse Planning Optimization (HIPO). Several dosimetric parameters related to target coverage, hot spot extensions and sparing of organs at risk were analyzed to evaluate the quality of the achieved treatment plans. Dose homogeneity index (DHI), conformal index (COIN) and a further parameter quantifying the proportion of the central catheter loading with respect to the overall loading (i.e., the central catheter loading index: CCLI) were also quantified. The achieved PTV coverage parameters were highly correlated with each other but uncorrelated with the hot spot quantifiers. HomogIPSA and HIPO achieved higher DHIs and CCLIs and lower volumes of high doses than DPO + GrO and surflPSA. Within the investigated optimization methods, HIPO and homoglPSA showed the highest dose homogeneity to the target. In particular, homogIPSA resulted also the most effective in reducing hot spots to the vaginal mucosa. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nonclinical dose formulation analysis method validation and sample analysis.

PubMed

Whitmire, Monica Lee; Bryan, Peter; Henry, Teresa R; Holbrook, John; Lehmann, Paul; Mollitor, Thomas; Ohorodnik, Susan; Reed, David; Wietgrefe, Holly D

2010-12-01

Nonclinical dose formulation analysis methods are used to confirm test article concentration and homogeneity in formulations and determine formulation stability in support of regulated nonclinical studies. There is currently no regulatory guidance for nonclinical dose formulation analysis method validation or sample analysis. Regulatory guidance for the validation of analytical procedures has been developed for drug product/formulation testing; however, verification of the formulation concentrations falls under the framework of GLP regulations (not GMP). The only current related regulatory guidance is the bioanalytical guidance for method validation. The fundamental parameters for bioanalysis and formulation analysis validations that overlap include: recovery, accuracy, precision, specificity, selectivity, carryover, sensitivity, and stability. Divergence in bioanalytical and drug product validations typically center around the acceptance criteria used. As the dose formulation samples are not true "unknowns", the concept of quality control samples that cover the entire range of the standard curve serving as the indication for the confidence in the data generated from the "unknown" study samples may not always be necessary. Also, the standard bioanalytical acceptance criteria may not be directly applicable, especially when the determined concentration does not match the target concentration. This paper attempts to reconcile the different practices being performed in the community and to provide recommendations of best practices and proposed acceptance criteria for nonclinical dose formulation method validation and sample analysis.

Homogenization of Mammalian Cells.

PubMed

de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

2015-11-02

Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

Consequences of additional use of PET information for target volume delineation and radiotherapy dose distribution for esophageal cancer.

PubMed

Muijs, Christina T; Schreurs, Liesbeth M; Busz, Dianne M; Beukema, Jannet C; van der Borden, Arnout J; Pruim, Jan; Van der Jagt, Eric J; Plukker, John Th; Langendijk, Johannes A

2009-12-01

To determine the consequences of target volume (TV) modifications, based on the additional use of PET information, on radiation planning, assuming PET/CT-imaging represents the true extent of the tumour. For 21 patients with esophageal cancer, two separate TV's were retrospectively defined based on CT (CT-TV) and co-registered PET/CT images (PET/CT-TV). Two 3D-CRT plans (prescribed dose 50.4 Gy) were constructed to cover the corresponding TV's. Subsequently, these plans were compared for target coverage, normal tissue dose-volume histograms and the corresponding normal tissue complication probability (NTCP) values. The addition of PET led to the modification of CT-TV with at least 10% in 12 of 21 patients (57%) (reduction in 9, enlargement in 3). PET/CT-TV was inadequately covered by the CT-based treatment plan in 8 patients (36%). Treatment plan modifications resulted in significant changes (p<0.05) in dose distributions to heart and lungs. Corresponding changes in NTCP values ranged from -3% to +2% for radiation pneumonitis and from -0.2% to +1.2% for cardiac mortality. This study demonstrated that TV's based on CT might exclude PET-avid disease. Consequences are under dosing and thereby possibly ineffective treatment. Moreover, the addition of PET in radiation planning might result in clinical important changes in NTCP.

A knowledge-based approach to improving and homogenizing intensity modulated radiation therapy planning quality among treatment centers: an example application to prostate cancer planning.

PubMed

Good, David; Lo, Joseph; Lee, W Robert; Wu, Q Jackie; Yin, Fang-Fang; Das, Shiva K

2013-09-01

Intensity modulated radiation therapy (IMRT) treatment planning can have wide variation among different treatment centers. We propose a system to leverage the IMRT planning experience of larger institutions to automatically create high-quality plans for outside clinics. We explore feasibility by generating plans for patient datasets from an outside institution by adapting plans from our institution. A knowledge database was created from 132 IMRT treatment plans for prostate cancer at our institution. The outside institution, a community hospital, provided the datasets for 55 prostate cancer cases, including their original treatment plans. For each "query" case from the outside institution, a similar "match" case was identified in the knowledge database, and the match case's plan parameters were then adapted and optimized to the query case by use of a semiautomated approach that required no expert planning knowledge. The plans generated with this knowledge-based approach were compared with the original treatment plans at several dose cutpoints. Compared with the original plan, the knowledge-based plan had a significantly more homogeneous dose to the planning target volume and a significantly lower maximum dose. The volumes of the rectum, bladder, and femoral heads above all cutpoints were nominally lower for the knowledge-based plan; the reductions were significantly lower for the rectum. In 40% of cases, the knowledge-based plan had overall superior (lower) dose-volume histograms for rectum and bladder; in 54% of cases, the comparison was equivocal; in 6% of cases, the knowledge-based plan was inferior for both bladder and rectum. Knowledge-based planning was superior or equivalent to the original plan in 95% of cases. The knowledge-based approach shows promise for homogenizing plan quality by transferring planning expertise from more experienced to less experienced institutions. Copyright © 2013 Elsevier Inc. All rights reserved.

Homogeneous electrochemical detection of ochratoxin A in foodstuff using aptamer-graphene oxide nanosheets and DNase I-based target recycling reaction.

PubMed

Sun, Ai-Li; Zhang, Yan-Fang; Sun, Guo-Peng; Wang, Xuan-Nian; Tang, Dianping

2017-03-15

A simple and feasible homogeneous electrochemical sensing protocol was developed for the detection of ochratoxin A (OTA) in foodstuff on the immobilization-free aptamer-graphene oxide nanosheets coupling with DNase I-based cycling signal amplification. Thionine-labeled OTA aptamers were attached to the surface of nanosheets because of the strong noncovalent binding of graphene oxide nanosheets with nucleobases and aromatic compounds. The electronic signal was acquired via negatively charged screen-printed carbon electrode (SPCE) toward free thionine molecules. Initially, the formed thionine-aptamer/graphene nanocomposites were suspended in the detection solution and far away from the electrode, thereby resulting in a weak electronic signal. Upon addition of target OTA, the analyte reacted with the aptamer and caused the dissociation of thionine-aptamer from the graphene oxide nanosheets. The newly formed thionine-aptamer/OTA could be readily cleaved by DNase I and released target OTA, which could retrigger thionine-aptamer/graphene nanocomposites with target recycling to generate numerous free thionine molecules. Free thionine molecules were captured by negatively charged SPCE, each of which could produce an electrochemical signal within the applied potentials. Under optimal conditions, graphene-based aptasensing platform could exhibit good electrochemical responses for the detection of OTA at a concentration as low as 5.6pg/mL. The reproducibility, precision and selectivity of the system were acceptable. Importantly, the method accuracy was comparable with commercialized OTA ELISA kit when using for quantitative monitoring of contaminated wheat samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells.

PubMed

Hatada, Seigo; Subramanian, Aparna; Mandefro, Berhan; Ren, Songyang; Kim, Ho Won; Tang, Jie; Funari, Vincent; Baloh, Robert H; Sareen, Dhruv; Arumugaswami, Vaithilingaraja; Svendsen, Clive N

2015-09-01

Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells. ©AlphaMed Press.

SU-E-T-318: The Effect of Patient Positioning Errors On Target Coverage and Cochlear Dose in Stereotactic Radiosurgery Treatment of Acoustic Neuromas

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

Dellamonica, D.; Luo, G.; Ding, G.

Purpose: Setup errors on the order of millimeters may cause under-dosing of targets and significant changes in dose to critical structures especially when planning with tight margins in stereotactic radiosurgery. This study evaluates the effects of these types of patient positioning uncertainties on planning target volume (PTV) coverage and cochlear dose for stereotactic treatments of acoustic neuromas. Methods: Twelve acoustic neuroma patient treatment plans were retrospectively evaluated in Brainlab iPlan RT Dose 4.1.3. All treatment beams were shaped by HDMLC from a Varian TX machine. Seven patients had planning margins of 2mm, five had 1–1.5mm. Six treatment plans were createdmore » for each patient simulating a 1mm setup error in six possible directions: anterior-posterior, lateral, and superiorinferior. The arcs and HDMLC shapes were kept the same for each plan. Change in PTV coverage and mean dose to the cochlea was evaluated for each plan. Results: The average change in PTV coverage for the 72 simulated plans was −1.7% (range: −5 to +1.1%). The largest average change in coverage was observed for shifts in the patient's superior direction (−2.9%). The change in mean cochlear dose was highly dependent upon the direction of the shift. Shifts in the anterior and superior direction resulted in an average increase in dose of 13.5 and 3.8%, respectively, while shifts in the posterior and inferior direction resulted in an average decrease in dose of 17.9 and 10.2%. The average change in dose to the cochlea was 13.9% (range: 1.4 to 48.6%). No difference was observed based on the size of the planning margin. Conclusion: This study indicates that if the positioning uncertainty is kept within 1mm the setup errors may not result in significant under-dosing of the acoustic neuroma target volumes. However, the change in mean cochlear dose is highly dependent upon the direction of the shift.« less

Response functions for computing absorbed dose to skeletal tissues from neutron irradiation

NASA Astrophysics Data System (ADS)

Bahadori, Amir A.; Johnson, Perry; Jokisch, Derek W.; Eckerman, Keith F.; Bolch, Wesley E.

2011-11-01

Spongiosa in the adult human skeleton consists of three tissues—active marrow (AM), inactive marrow (IM) and trabecularized mineral bone (TB). AM is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM50), defined as all tissues lying within the first 50 µm of the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent micro-CT imaging of a 40 year old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton (Hough et al 2011 Phys. Med. Biol. 56 2309-46). This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fraction (SAF) values for protons originating in axial and appendicular bone sites (Jokisch et al 2011 Phys. Med. Biol. 56 6857-72). These proton SAFs, bone masses, tissue compositions and proton production cross sections, were subsequently used to construct neutron dose-response functions (DRFs) for both AM and TM50 targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, AM, TM50 and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM50 DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged-particle equilibrium is established across the bone site. In the range of 10 eV to 100 Me

RESPONSE FUNCTIONS FOR COMPUTING ABSORBED DOSE TO SKELETAL TISSUES FROM NEUTRON IRRADIATION

PubMed Central

Bahadori, Amir A.; Johnson, Perry; Jokisch, Derek W.; Eckerman, Keith F.; Bolch, Wesley E.

2016-01-01

Spongiosa in the adult human skeleton consists of three tissues - active marrow (AM), inactive marrow (IM), and trabecularized mineral bone (TB). Active marrow is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM50), defined as all tissues laying within the first 50 μm the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent microCT imaging of a 40-year-old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton [Hough et al PMB (2011)]. This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fractions (SAF) values for protons originating in axial and appendicular bone sites [Jokisch et al PMB (submitted)]. These proton SAFs, bone masses, tissue compositions, and proton production cross-sections, were subsequently used to construct neutron dose response functions (DRFs) for both AM and TM50 targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, active marrow, total shallow marrow, and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM50 DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged particle equilibrium (CPE) is established across the bone site. In the range of 10 eV to 100 Me

Response functions for computing absorbed dose to skeletal tissues from neutron irradiation.

PubMed

Bahadori, Amir A; Johnson, Perry; Jokisch, Derek W; Eckerman, Keith F; Bolch, Wesley E

2011-11-07

Spongiosa in the adult human skeleton consists of three tissues-active marrow (AM), inactive marrow (IM) and trabecularized mineral bone (TB). AM is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM(50)), defined as all tissues lying within the first 50 µm of the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent micro-CT imaging of a 40 year old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton (Hough et al 2011 Phys. Med. Biol. 56 2309-46). This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fraction (SAF) values for protons originating in axial and appendicular bone sites (Jokisch et al 2011 Phys. Med. Biol. 56 6857-72). These proton SAFs, bone masses, tissue compositions and proton production cross sections, were subsequently used to construct neutron dose-response functions (DRFs) for both AM and TM(50) targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, AM, TM(50) and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM(50) DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged-particle equilibrium is established across the bone site. In the range of 10 eV to 100 Me

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

PubMed

Hirayama, Shusuke; Matsuura, Taeko; Ueda, Hideaki; Fujii, Yusuke; Fujii, Takaaki; Takao, Seishin; Miyamoto, Naoki; Shimizu, Shinichi; Fujimoto, Rintaro; Umegaki, Kikuo; Shirato, Hiroki

2018-05-22

To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LET d ) is required. In this study, we have developed the analytical LET d calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LET d value for the lateral distribution of a pencil beam, the actual LET d increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LET d behavior, we have assumed that the LETs of primary and halo components can take different values (LET p and LET halo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LET d distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LET d distributions and mean LET d (LET d,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. In the homogeneous phantom, the LET d profiles obtained by the dual-LET kernels

The assumption of heterogeneous or homogeneous radioactive contamination in soil/sediment: does it matter in terms of the external exposure of fauna?

PubMed

Beaugelin-Seiller, K

2014-12-01

The classical approach to environmental radioprotection is based on the assumption of homogeneously contaminated media. However, in soils and sediments there may be a significant variation of radioactivity with depth. The effect of this heterogeneity was investigated by examining the external exposure of various sediment and soil organisms, and determining the resulting dose rates, assuming a realistic combination of locations and radionuclides. The results were dependent on the exposure situation, i.e., the organism, its location, and the quality and quantity of radionuclides. The dose rates ranged over three orders of magnitude. The assumption of homogeneous contamination was not consistently conservative (if associated with a level of radioactivity averaged over the full thickness of soil or sediment that was sampled). Dose assessment for screening purposes requires consideration of the highest activity concentration measured in a soil/sediment that is considered to be homogeneously contaminated. A more refined assessment (e.g., higher tier of a graded approach) should take into consideration a more realistic contamination profile, and apply different dosimetric approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.

The dose distribution of low dose rate Cs-137 in intracavitary brachytherapy: comparison of Monte Carlo simulation, treatment planning calculation and polymer gel measurement

NASA Astrophysics Data System (ADS)

Fragoso, M.; Love, P. A.; Verhaegen, F.; Nalder, C.; Bidmead, A. M.; Leach, M.; Webb, S.

2004-12-01

In this study, the dose distribution delivered by low dose rate Cs-137 brachytherapy sources was investigated using Monte Carlo (MC) techniques and polymer gel dosimetry. The results obtained were compared with a commercial treatment planning system (TPS). The 20 mm and the 30 mm diameter Selectron vaginal applicator set (Nucletron) were used for this study. A homogeneous and a heterogeneous—with an air cavity—polymer gel phantom was used to measure the dose distribution from these sources. The same geometrical set-up was used for the MC calculations. Beyond the applicator tip, differences in dose as large as 20% were found between the MC and TPS. This is attributed to the presence of stainless steel in the applicator and source set, which are not considered by the TPS calculations. Beyond the air cavity, differences in dose of around 5% were noted, due to the TPS assuming a homogeneous water medium. The polymer gel results were in good agreement with the MC calculations for all the cases investigated.

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being

Homogeneous Characterization of Transiting Exoplanet Systems

NASA Astrophysics Data System (ADS)

Gomez Maqueo Chew, Yilen; Faedi, Francesca; Hebb, Leslie; Pollacco, Don; Stassun, Keivan; Ghezzi, Luan; Cargile, Phillip; Barros, Susana; Smalley, Barry; Mack, Claude

2012-02-01

We aim to obtain a homogeneous set of high resolution, high signal- to-noise (S/N) spectra for a large and diverse sample of stars with transiting planets, using the Kitt Peak 4-m echelle spectrograph for bright Northern targets (7.7homogeneous analysis of this high-quality dataset, we will be able to investigate any systematic uncertainties on the derived stellar properties, and consequently, on the planetary properties derived from the iterative combination of our spectral analysis with the best available radial velocity data and transit photometry. % to derive a homogeneous set of properties for the transiting systems. The resulting consistent set of physical properties will allow us to further explore known correlations, e.g., core-size of the planet and stellar metallicity, and to newly identify subtle relationships providing insight into our understanding of planetary formation, structure, and evolution. Our pilot study analyzing our WASP-13 HIRES spectrum (R 48 000, S/N>150) in combination with high precision light curves shows an improvement in the precision of the stellar parameters of 60% in Teff, 75% in FeH, 82% in mstar, and 73% in rstar, which translates into a 64% improvement in the precision of rpl, and more than 2% on mpl, relative to the discovery paper's values.

Monte Carlo modeling of the MammoSite(Reg) treatments: Dose effects of air pockets

NASA Astrophysics Data System (ADS)

Huang, Yu-Huei Jessica

In the treatment of early-stage breast cancer, MammoSiteRTM has been used as one of the partial breast irradiation techniques after breast-conserving surgery. The MammoSiteRTM applicator is a single catheter with an inflatable balloon at its distal end that can be placed in the resected cavity (tumor bed). The treatment is performed by delivering the Ir-192 high-dose-rate source through the center lumen of the catheter by a remote afterloader while the balloon is inflated in the tumor bed cavity. In the MammoSiteRTM treatment, it has been found that air pockets occasionally exist and can be seen and measured in CT images. Experiences have shown that about 90% of the patients have air pockets when imaged two days after the balloon placement. The criterion for the air pocket volume is less than or equal to 10% of the planning target volume in volume. The purpose of this study is to quantify dose errors occurring at the interface of the air pocket in MammoSiteRTM treatments with Monte Carlo calculations, so that the dosimetric effects from the air pocket can be fully understood. Modern brachytherapy treatment planning systems typically consider patient anatomy as a homogeneous water medium, and incorrectly model lateral and backscatter radiation during treatment delivery. Heterogeneities complicate the problem and may result in overdosage to the tissue located near the medium interface. This becomes a problem in MammoSiteRTM brachytherapy when air pocket appears during the treatment. The resulting percentage dose difference near the air-tissue interface is hypothesized to be greater than 10% when comparing Monte Carlo N-Particle (version 5) with current treatment planning systems. The specific aims for this study are: (1) Validate Monte Carlo N-Particle (Version 5) source modeling. (2) Develop phantom. (3) Calculate phantom doses with Monte Carlo N-Particle (Version 5) and investigate doses difference between thermoluminescent dosimeter measurement, treatment planning

Monte Carlo dose distribution calculation at nuclear level for Auger-emitting radionuclide energies.

PubMed

Di Maria, S; Belchior, A; Romanets, Y; Paulo, A; Vaz, P

2018-05-01

The distribution of radiopharmaceuticals in tumor cells represents a fundamental aspect for a successful molecular targeted radiotherapy. It was largely demonstrated at microscopic level that only a fraction of cells in tumoral tissues incorporate the radiolabel. In addition, the distribution of the radionuclides at sub-cellular level, namely inside each nucleus, should also be investigated for accurate dosimetry estimation. The most used method to perform cellular dosimetry is the MIRD one, where S-values are able to estimate cellular absorbed doses for several electron energies, nucleus diameters, and considering homogeneous source distributions. However the radionuclide distribution inside nuclei can be also highly non-homogeneous. The aim of this study is to show in what extent a non-accurate cellular dosimetry could lead to misinterpretations of surviving cell fraction vs dose relationship; in this context, a dosimetric case study with 99m Tc is also presented. The state-of-art MCNP6 Monte Carlo simulation was used in order to model cell structures both in MIRD geometry (MG) and MIRD modified geometries (MMG), where also entire mitotic chromosome volumes were considered (each structure was modeled as liquid water material). In order to simulate a wide energy range of Auger emitting radionuclides, four mono energetic electron emissions were considered, namely 213eV, 6keV, 11keV and 20keV. A dosimetric calculation for 99m Tc undergoing inhomogeneous nuclear internalization was also performed. After a successful validation step between MIRD and our computed S-values for three Auger-emitting radionuclides ( 99m Tc, 125 I and 64 Cu), absorbed dose results showed that the standard MG could differ from the MMG from one to three orders of magnitude. These results were also confirmed by considering the 99m Tc spectrum emission (Auger and internal conversion electrons). Moreover, considering an inhomogeneous radionuclide distribution, the average electron energy that

Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways.

PubMed

Donnelley, M; Siu, K K W; Jamison, R A; Parsons, D W

2012-01-01

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.

Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation

PubMed Central

Tang, Liang; Cheng, Pengle

2017-01-01

Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC) is extracted with the periodic boundary condition applied on it. An elastic–plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM) model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM) model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis. PMID:28746390

Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation.

PubMed

Tang, Liang; Zhang, Jinjie; Cheng, Pengle

2017-01-01

Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC) is extracted with the periodic boundary condition applied on it. An elastic-plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM) model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM) model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis.

Homogeneous Yang-Baxter deformations as generalized diffeomorphisms

NASA Astrophysics Data System (ADS)

Sakamoto, Jun-ichi; Sakatani, Yuho; Yoshida, Kentaroh

2017-10-01

Yang-Baxter (YB) deformations of string sigma model provide deformed target spaces. We propose that homogeneous YB deformations always lead to a certain class of β-twisted backgrounds and represent the bosonic part of the supergravity fields in terms of the classical r-matrix associated with the YB deformation. We then show that various β-twisted backgrounds can be realized by considering generalized diffeomorphisms in the undeformed background. Our result extends the notable relation between the YB deformations and (non-commuting) TsT transformations. We also discuss more general deformations beyond the YB deformations.

Dose calculation and verification of the Vero gimbal tracking treatment delivery

NASA Astrophysics Data System (ADS)

Prasetio, H.; Wölfelschneider, J.; Ziegler, M.; Serpa, M.; Witulla, B.; Bert, C.

2018-02-01

The Vero linear accelerator delivers dynamic tumor tracking (DTT) treatment using a gimbal motion. However, the availability of treatment planning systems (TPS) to simulate DTT is limited. This study aims to implement and verify the gimbal tracking beam geometry in the dose calculation. Gimbal tracking was implemented by rotating the reference CT outside the TPS according to the ring, gantry, and gimbal tracking position obtained from the tracking log file. The dose was calculated using these rotated CTs. The geometric accuracy was verified by comparing calculated and measured film response using a ball bearing phantom. The dose was verified by comparing calculated 2D dose distributions and film measurements in a ball bearing and a homogeneous phantom using a gamma criterion of 2%/2 mm. The effect of implementing the gimbal tracking beam geometry in a 3D patient data dose calculation was evaluated using dose volume histograms (DVH). Geometrically, the gimbal tracking implementation accuracy was  <0.94 mm. The isodose lines agreed with the film measurement. The largest dose difference of 9.4% was observed at maximum tilt positions with an isocenter and target separation of 17.51 mm. Dosimetrically, gamma passing rates were  >98.4%. The introduction of the gimbal tracking beam geometry in the dose calculation shifted the DVH curves by 0.05%-1.26% for the phantom geometry and by 5.59% for the patient CT dataset. This study successfully demonstrates a method to incorporate the gimbal tracking beam geometry into dose calculations. By combining CT rotation and MU distribution according to the log file, the TPS was able to simulate the Vero tracking treatment dose delivery. The DVH analysis from the gimbal tracking dose calculation revealed changes in the dose distribution during gimbal DTT that are not visible with static dose calculations.

A similarity based approach to identify homogeneous regions for seasonal forecasting

NASA Astrophysics Data System (ADS)

Schick, Simon; Rössler, Ole; Weingartner, Rolf

2015-04-01

Seasonal runoff forecasting using statistical models is challenged by a large number of candidate predictors and a general weak predictor-predictand relationship. As the area of the target basin increases, often also the available data sets do, thus reinforcing the predictor selection challenge. We propose an approach which follows the idea of 'divide and conquer' as developed in computational sciences and machine learning: First, the macroscale target basin is partitioned into homogeneous regions using all its gauged mesoscale subbasins. Second, one representative subbasin per homogeneous region is identified, for which models are fitted and applied. Third, the resulting forecasts are combined at the scale of the macroscale target basin. This approach requires a suitable method to identify homogeneous regions and representative subbasins. We suggest a way based on hydrological similarity, as catchment similarity estimated with respect to physiographic-climatic descriptors does not necessarily imply similar runoff response. Each descriptor is derived from daily runoff series and aimed to reflect a specific catchment characteristic: autocorrelation coefficient, parameters of fitted Gamma distribution and low/high flow indices (based on daily runoff values) fluctuation of the standard deviation within the yearly cycle (based on weekly runoff values) dominant harmonics obtained from the discrete Fourier transform (based on monthly runoff values) long term trend (based on yearly runoff values) Where necessary, the runoff series first need to be standardized, aggregated, detrended or deseasonalized. As a preliminary study we present the results of a cluster analysis for the Swiss Rhine River as macroscale target basin, which leads to about 40 mesoscale subbasins with runoff series for the period 1991-2010. Problems we have to address include the choice of a clustering algorithm, the identification of an appropriate number of regions and the selection of representative

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

PubMed

Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

2013-11-04

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low‐density media

PubMed Central

Leung, Lucullus H.T.; Yu, Peter K.N.

2013-01-01

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric‐modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no‐air) for RapidArc planning in targets with low‐density media of different sizes and complexities. The performance of PRO10_no‐air and PRO10_air was initially compared using single‐arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple‐arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non‐small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no‐air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low‐density media were present in or adjacent to the target volume, the use of the air cavity correction option in PROIO was shown to be beneficial. For NPC cases or cases for which small volumes of both low‐ and high‐density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan

SU-F-J-133: Adaptive Radiation Therapy with a Four-Dimensional Dose Calculation Algorithm That Optimizes Dose Distribution Considering Breathing Motion

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

Ali, I; Algan, O; Ahmad, S

Purpose: To model patient motion and produce four-dimensional (4D) optimized dose distributions that consider motion-artifacts in the dose calculation during the treatment planning process. Methods: An algorithm for dose calculation is developed where patient motion is considered in dose calculation at the stage of the treatment planning. First, optimal dose distributions are calculated for the stationary target volume where the dose distributions are optimized considering intensity-modulated radiation therapy (IMRT). Second, a convolution-kernel is produced from the best-fitting curve which matches the motion trajectory of the patient. Third, the motion kernel is deconvolved with the initial dose distribution optimized for themore » stationary target to produce a dose distribution that is optimized in four-dimensions. This algorithm is tested with measured doses using a mobile phantom that moves with controlled motion patterns. Results: A motion-optimized dose distribution is obtained from the initial dose distribution of the stationary target by deconvolution with the motion-kernel of the mobile target. This motion-optimized dose distribution is equivalent to that optimized for the stationary target using IMRT. The motion-optimized and measured dose distributions are tested with the gamma index with a passing rate of >95% considering 3% dose-difference and 3mm distance-to-agreement. If the dose delivery per beam takes place over several respiratory cycles, then the spread-out of the dose distributions is only dependent on the motion amplitude and not affected by motion frequency and phase. This algorithm is limited to motion amplitudes that are smaller than the length of the target along the direction of motion. Conclusion: An algorithm is developed to optimize dose in 4D. Besides IMRT that provides optimal dose coverage for a stationary target, it extends dose optimization to 4D considering target motion. This algorithm provides alternative to motion

Real-time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program.

PubMed

Zelefsky, Michael J; Cohen, Gilad N; Taggar, Amandeep S; Kollmeier, Marisa; McBride, Sean; Mageras, Gig; Zaider, Marco

Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program. Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed. When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%. In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce

Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target.

PubMed

Budiarto, E; Keijzer, M; Storchi, P R M; Heemink, A W; Breedveld, S; Heijmen, B J M

2014-01-20

Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.

Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts.

PubMed

O'Donnell, Robert T; Ma, Yunpeng; McKnight, Hayes C; Pearson, David; Tuscano, Joseph M

2009-12-01

CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm(3) had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled-HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7.

Direct current dielectric barrier assistant discharge to get homogeneous plasma in capacitive coupled discharge

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

Du, Yinchang, E-mail: ycdu@mail.ustc.edu.cn; Max-Planck Institute for Extraterrestrial Physics, D-85748 Garching; Li, Yangfang

In this paper, we propose a method to get more homogeneous plasma in the geometrically asymmetric capacitive coupled plasma (CCP) discharge. The dielectric barrier discharge (DBD) is used for the auxiliary discharge system to improve the homogeneity of the geometrically asymmetric CCP discharge. The single Langmuir probe measurement shows that the DBD can increase the electron density in the low density volume, where the DBD electrodes are mounted, when the pressure is higher than 5 Pa. By this manner, we are able to improve the homogeneity of the plasma production and increase the overall density in the target volume. At last,more » the finite element simulation results show that the DC bias, applied to the DBD electrodes, can increase the homogeneity of the electron density in the CCP discharge. The simulation results show a good agreement with the experiment results.« less

Study of Variation in Dose Calculation Accuracy Between kV Cone-Beam Computed Tomography and kV fan-Beam Computed Tomography

PubMed Central

Kaliyaperumal, Venkatesan; Raphael, C. Jomon; Varghese, K. Mathew; Gopu, Paul; Sivakumar, S.; Boban, Minu; Raj, N. Arunai Nambi; Senthilnathan, K.; Babu, P. Ramesh

2017-01-01

Cone-beam computed tomography (CBCT) images are presently used for geometric verification for daily patient positioning. In this work, we have compared the images of CBCT with the images of conventional fan beam CT (FBCT) in terms of image quality and Hounsfield units (HUs). We also compared the dose calculated using CBCT with that of FBCT. Homogenous RW3 plates and Catphan phantom were scanned by FBCT and CBCT. In RW3 and Catphan phantom, percentage depth dose (PDD), profiles, isodose distributions (for intensity modulated radiotherapy plans), and calculated dose volume histograms were compared. The HU difference was within ± 20 HU (central region) and ± 30 HU (peripheral region) for homogeneous RW3 plates. In the Catphan phantom, the difference in HU was ± 20 HU in the central area and peripheral areas. The HU differences were within ± 30 HU for all HU ranges starting from −1000 to 990 in phantom and patient images. In treatment plans done with simple symmetric and asymmetric fields, dose difference (DD) between CBCT plan and FBCT plan was within 1.2% for both phantoms. In intensity modulated radiotherapy (IMRT) treatment plans, for different target volumes, the difference was <2%. This feasibility study investigated HU variation and dose calculation accuracy between FBCT and CBCT based planning and has validated inverse planning algorithms with CBCT. In our study, we observed a larger deviation of HU values in the peripheral region compared to the central region. This is due to the ring artifact and scatter contribution which may prevent the use of CBCT as the primary imaging modality for radiotherapy treatment planning. The reconstruction algorithm needs to be modified further for improving the image quality and accuracy in HU values. However, our study with TG-119 and intensity modulated radiotherapy test targets shows that CBCT can be used for adaptive replanning as the recalculation of dose with the anisotropic analytical algorithm is in full accord

Homogeneous crystal nucleation in polymers.

PubMed

Schick, C; Androsch, R; Schmelzer, J W P

2017-11-15

The pathway of crystal nucleation significantly influences the structure and properties of semi-crystalline polymers. Crystal nucleation is normally heterogeneous at low supercooling, and homogeneous at high supercooling, of the polymer melt. Homogeneous nucleation in bulk polymers has been, so far, hardly accessible experimentally, and was even doubted to occur at all. This topical review summarizes experimental findings on homogeneous crystal nucleation in polymers. Recently developed fast scanning calorimetry, with cooling and heating rates up to 10 6 K s -1 , allows for detailed investigations of nucleation near and even below the glass transition temperature, including analysis of nuclei stability. As for other materials, the maximum homogeneous nucleation rate for polymers is located close to the glass transition temperature. In the experiments discussed here, it is shown that polymer nucleation is homogeneous at such temperatures. Homogeneous nucleation in polymers is discussed in the framework of the classical nucleation theory. The majority of our observations are consistent with the theory. The discrepancies may guide further research, particularly experiments to progress theoretical development. Progress in the understanding of homogeneous nucleation is much needed, since most of the modelling approaches dealing with polymer crystallization exclusively consider homogeneous nucleation. This is also the basis for advancing theoretical approaches to the much more complex phenomena governing heterogeneous nucleation.

Mt-Insar Landslide Monitoring with the Aid of Homogeneous Pixels Filter

NASA Astrophysics Data System (ADS)

Liu, X. J.; Zhao, C. Y.; Wang, B. H.; Zhu, W. F.

2018-04-01

SAR interferograms are often contaminated by random noises related to temporal decorrelation, geometrical decorrelation and thermal noises, which makes the fringes obscured and greatly decreases the density of the coherent target and the accuracy of InSAR deformation results, especially for the landslide monitoring in vegetated region and in rainy season. Two different SAR interferogram filtering methods, that is Goldstein filter and homogeneous pixels filter, for one specific landslide are compared. The results show that homogeneous pixels filter is better than Goldstein one for small-scale loess landslide monitoring, which can increase the density of monitoring points. Moreover, the precision of InSAR result can reach millimeter by comparing with GPS time series measurements.

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

SU-E-CAMPUS-I-06: Y90 PET/CT for the Instantaneous Determination of Both Target and Non-Target Absorbed Doses Following Hepatic Radioembolization

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

Pasciak, A; Kao, J

2014-06-15

Purpose The process of converting Yttrium-90 (Y90) PET/CT images into 3D absorbed dose maps will be explained. The simple methods presented will allow the medical physicst to analyze Y90 PET images following radioembolization and determine the absorbed dose to tumor, normal liver parenchyma and other areas of interest, without application of Monte-Carlo radiation transport or dose-point-kernel (DPK) convolution. Methods Absorbed dose can be computed from Y90 PET/CT images based on the premise that radioembolization is a permanent implant with a constant relative activity distribution after infusion. Many Y90 PET/CT publications have used DPK convolution to obtain 3D absorbed dose maps.more » However, this method requires specialized software limiting clinical utility. The Local Deposition method, an alternative to DPK convolution, can be used to obtain absorbed dose and requires no additional computer processing. Pixel values from regions of interest drawn on Y90 PET/CT images can be converted to absorbed dose (Gy) by multiplication with a scalar constant. Results There is evidence that suggests the Local Deposition method may actually be more accurate than DPK convolution and it has been successfully used in a recent Y90 PET/CT publication. We have analytically compared dose-volume-histograms (DVH) for phantom hot-spheres to determine the difference between the DPK and Local Deposition methods, as a function of PET scanner point-spread-function for Y90. We have found that for PET/CT systems with a FWHM greater than 3.0 mm when imaging Y90, the Local Deposition Method provides a more accurate representation of DVH, regardless of target size than DPK convolution. Conclusion Using the Local Deposition Method, post-radioembolization Y90 PET/CT images can be transformed into 3D absorbed dose maps of the liver. An interventional radiologist or a Medical Physicist can perform this transformation in a clinical setting, allowing for rapid prediction of treatment efficacy

Biotic homogenization of three insect groups due to urbanization.

PubMed

Knop, Eva

2016-01-01

Cities are growing rapidly, thereby expected to cause a large-scale global biotic homogenization. Evidence for the homogenization hypothesis is mostly derived from plants and birds, whereas arthropods have so far been neglected. Here, I tested the homogenization hypothesis with three insect indicator groups, namely true bugs, leafhoppers, and beetles. In particular, I was interested whether insect species community composition differs between urban and rural areas, whether they are more similar between cities than between rural areas, and whether the found pattern is explained by true species turnover, species diversity gradients and geographic distance, by non-native or specialist species, respectively. I analyzed insect species communities sampled on birch trees in a total of six Swiss cities and six rural areas nearby. In all indicator groups, urban and rural community composition was significantly dissimilar due to native species turnover. Further, for bug and leafhopper communities, I found evidence for large-scale homogenization due to urbanization, which was driven by reduced species turnover of specialist species in cities. Species turnover of beetle communities was similar between cities and rural areas. Interestingly, when specialist species of beetles were excluded from the analyses, cities were more dissimilar than rural areas, suggesting biotic differentiation of beetle communities in cities. Non-native species did not affect species turnover of the insect groups. However, given non-native arthropod species are increasing rapidly, their homogenizing effect might be detected more often in future. Overall, the results show that urbanization has a negative large-scale impact on the diversity specialist species of the investigated insect groups. Specific measures in cities targeted at increasing the persistence of specialist species typical for the respective biogeographic region could help to stop the loss of biodiversity. © 2015 John Wiley & Sons Ltd.

Benchmarking monthly homogenization algorithms

NASA Astrophysics Data System (ADS)

Venema, V. K. C.; Mestre, O.; Aguilar, E.; Auer, I.; Guijarro, J. A.; Domonkos, P.; Vertacnik, G.; Szentimrey, T.; Stepanek, P.; Zahradnicek, P.; Viarre, J.; Müller-Westermeier, G.; Lakatos, M.; Williams, C. N.; Menne, M.; Lindau, R.; Rasol, D.; Rustemeier, E.; Kolokythas, K.; Marinova, T.; Andresen, L.; Acquaotta, F.; Fratianni, S.; Cheval, S.; Klancar, M.; Brunetti, M.; Gruber, C.; Prohom Duran, M.; Likso, T.; Esteban, P.; Brandsma, T.

2011-08-01

The COST (European Cooperation in Science and Technology) Action ES0601: Advances in homogenization methods of climate series: an integrated approach (HOME) has executed a blind intercomparison and validation study for monthly homogenization algorithms. Time series of monthly temperature and precipitation were evaluated because of their importance for climate studies and because they represent two important types of statistics (additive and multiplicative). The algorithms were validated against a realistic benchmark dataset. The benchmark contains real inhomogeneous data as well as simulated data with inserted inhomogeneities. Random break-type inhomogeneities were added to the simulated datasets modeled as a Poisson process with normally distributed breakpoint sizes. To approximate real world conditions, breaks were introduced that occur simultaneously in multiple station series within a simulated network of station data. The simulated time series also contained outliers, missing data periods and local station trends. Further, a stochastic nonlinear global (network-wide) trend was added. Participants provided 25 separate homogenized contributions as part of the blind study as well as 22 additional solutions submitted after the details of the imposed inhomogeneities were revealed. These homogenized datasets were assessed by a number of performance metrics including (i) the centered root mean square error relative to the true homogeneous value at various averaging scales, (ii) the error in linear trend estimates and (iii) traditional contingency skill scores. The metrics were computed both using the individual station series as well as the network average regional series. The performance of the contributions depends significantly on the error metric considered. Contingency scores by themselves are not very informative. Although relative homogenization algorithms typically improve the homogeneity of temperature data, only the best ones improve precipitation data

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

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

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription

Multiple anatomy optimization of accumulated dose

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

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

PubMed

Girst, S; Marx, C; Bräuer-Krisch, E; Bravin, A; Bartzsch, S; Oelfke, U; Greubel, C; Reindl, J; Siebenwirth, C; Zlobinskaya, O; Multhoff, G; Dollinger, G; Schmid, T E; Wilkens, J J

2015-09-01

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

PubMed

Horsley, Patrick J; Aherne, Noel J; Edwards, Grace V; Benjamin, Linus C; Wilcox, Shea W; McLachlan, Craig S; Assareh, Hassan; Welshman, Richard; McKay, Michael J; Shakespeare, Thomas P

2015-03-01

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles. © 2014 Wiley Publishing Asia Pty Ltd.

Dose distribution for dental cone beam CT and its implication for defining a dose index

PubMed Central

Pauwels, R; Theodorakou, C; Walker, A; Bosmans, H; Jacobs, R; Horner, K; Bogaerts, R

2012-01-01

Objectives To characterize the dose distribution for a range of cone beam CT (CBCT) units, investigating different field of view sizes, central and off-axis geometries, full or partial rotations of the X-ray tube and different clinically applied beam qualities. The implications of the dose distributions on the definition and practicality of a CBCT dose index were assessed. Methods Dose measurements on CBCT devices were performed by scanning cylindrical head-size water and polymethyl methacrylate phantoms, using thermoluminescent dosemeters, a small-volume ion chamber and radiochromic films. Results It was found that the dose distribution can be asymmetrical for dental CBCT exposures throughout a homogeneous phantom, owing to an asymmetrical positioning of the isocentre and/or partial rotation of the X-ray source. Furthermore, the scatter tail along the z-axis was found to have a distinct shape, generally resulting in a strong drop (90%) in absorbed dose outside the primary beam. Conclusions There is no optimal dose index available owing to the complicated exposure geometry of CBCT and the practical aspects of quality control measurements. Practical validation of different possible dose indices is needed, as well as the definition of conversion factors to patient dose. PMID:22752320

BY HOW MUCH DO SHAPES OF TOXICOLOGICAL DOSE-RESPONSE RELATIONSHIPS VARY? (SOT)

EPA Science Inventory

A re-analysis of a large number of historical dose-response data for continuous endpoints showed that the shapes of the dose-response relationships were surprisingly homogenous. The datasets were selected on the sole criterion that they were expected to provide relatively good in...

Phage therapy dosing: The problem(s) with multiplicity of infection (MOI).

PubMed

Abedon, Stephen T

2016-01-01

The concept of bacteriophage multiplicity of infection (MOI) - ratios of phages to bacteria - historically has been less easily applied than many phage workers would prefer or, perhaps, may be aware. Here, toward clarification of the concept, I discuss multiplicity of infection in terms of semantics, history, mathematics, pharmacology, and actual practice. For phage therapy and other biocontrol purposes it is desirable, especially, not to solely employ MOI to describe what phage quantities have been applied during dosing. Why? Bacterial densities can change between bacterial challenge and phage application, may not be easily determined immediately prior to phage dosing, and/or target bacterial populations may not be homogeneous with regard to phage access and thereby inconsistent in terms of what MOI individual bacteria experience. Toward experiment reproducibility and as practiced generally for antibacterial application, phage dosing instead should be described in terms of concentrations of formulations (phage titers) as well as volumes applied and, in many cases, absolute numbers of phages delivered. Such an approach typically will be far more desirable from a pharmacological perspective than solely indicating ratios of agents to bacteria. This essay was adapted, with permission, from an appendix of the 2011 monograph, Bacteriophages and Biofilms , Nova Science Publishers.

SU-E-T-287: Dose Verification On the Variation of Target Volume and Organ at Risk in Preradiation Chemotherapy IMRT for Nasopharyngeal Cancer

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

Zhang, X; Kong, L; Wang, J

2015-06-15

Purpose: To quantify the target volume and organ at risk of nasopharyngeal carcinoma (NPC) patients with preradiation chemotherapy based on CT scanned during intensity-modulated radiotherapy (IMRT), and recalculate the dose distribution. Methods: Seven patients with NPC and preradiation chemotherapy, treated with IMRT (35 to 37 fractions) were reviewed. Repeat CT scanning was required to all of the patients during the radiotherapy, and the number of repeat CTs varies from 2 to 6. The plan CT and repeat CT were generated by different CT scanner. To ensure crespectively on the same IMPT plan. The real dose distribution was calculated by deformablemore » registration and weighted method in Raystation (v 4.5.1). The fraction of each dose is based on radiotherapy record. The volumetric and dose differences among these images were calculated for nascIpharyngeal tumor and retro-pharyngeal lymph nodes (GTV-NX), neck lymph nodes(GTV-ND), and parotid glands. Results: The volume variation in GTV-NX from CT1 to CT2 was 1.15±3.79%, and in GTV-LN −0.23±4.93%. The volume variation in left parotid from CT1 to CT2 was −6.79±11.91%, and in right parotid −3.92±8.80%. In patient 2, the left parotid volume were decreased remarkably, as a Result, the V30 and V40 of it were increased as well. Conclusion: The target volume of patients with NPC varied lightly during IMRT. It shows that preradiation chemotherapy can control the target volume variation and perform a good dose repeatability. Also, the decreasing volume of parotid in some patient might increase the dose of it, which might course potential complications.« less

Immortal homogeneous Ricci flows

NASA Astrophysics Data System (ADS)

Böhm, Christoph; Lafuente, Ramiro A.

2018-05-01

We show that for an immortal homogeneous Ricci flow solution any sequence of parabolic blow-downs subconverges to a homogeneous expanding Ricci soliton. This is established by constructing a new Lyapunov function based on curvature estimates which come from real geometric invariant theory.

Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique

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

Sampson, Andrew; Le Yi; Williamson, Jeffrey F.

2012-02-15

Purpose: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. Methods: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, {Delta}D, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled inmore » a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 {sup 125}I seeds. The breast case consisted of 87 Model-200 {sup 103}Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D{sub 90}, as well as for various anatomical regions. Results: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 x 1 x 1 mm{sup 3} dose grid, efficiency gains were realized in all structures with 38.1- and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous

Pesticide Dose - A Parameter with Many Implications

USDA-ARS?s Scientific Manuscript database

Like pharmaceuticals, pesticides can have unintended effects, even when used at the proper dose. For pesticides, the possible effects are even more diverse, because the chemicals are released immediately into the environment and the dose reaching the intended target(s) and unintended targets can var...

Moderate-dose sedation and analgesia during targeted temperature management after cardiac arrest.

PubMed

May, Teresa L; Seder, David B; Fraser, Gilles L; Stone, Philip; McCrum, Barbara; Riker, Richard R

2015-02-01

Sedation and analgesia regimens during targeted temperature management (TTM), after cardiac arrest varies widely, are poorly described in the literature and may have a negative impact on outcome. Since implementing TTM in 2005, we have used moderate-dose sedation and describe our experience with this approach. In this retrospective review, we included patients treated with TTM for cardiac arrest at our institution for 2008-2012. Patients received TTM if they did not follow verbal commands following cardiac arrest, regardless of place of arrest or rhythm. Utstein-compatible data were prospectively entered into the International Cardiac Arrest Registry, supplemented by review of nursing, pharmacy, and physical therapy records. We report analgesic and sedative medications and doses during the 24 h of active TTM at 33 °C, resource utilization, and important clinical events. 166 patients treated with TTM after in- and out-of-hospital cardiac arrest with complete data were included. Overall survival was 42 %, median time to following commands was 3 h after rewarming (-6, 14), time to spontaneous breathing trial was 19 h (5-35), time to extubation was 28 h (9-60), and 59 % of survivors were discharged directly home at 13 (10-20) days. The incidence of seizure was 6 %, septic shock 4 %, and pneumonia 32 %. Four survivors required tracheostomy at 8, 8, 12, and 16 days. A moderate-dose sedation and analgesia regimen was well tolerated and effective during therapeutic hypothermia after cardiac arrest and is an effective alternative to very deep sedation. We recommend more complete description of sedation and analgesia protocols in future studies, including expanded outcome reporting to include variables affected by sedation therapy. Further study is required to define which sedation approach for TTM may be best.

High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

NASA Astrophysics Data System (ADS)

Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

2017-01-01

Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

NASA Astrophysics Data System (ADS)

Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.

2015-09-01

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation.

PubMed

Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M

2015-09-07

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Determination of alkylphenols and 17beta-estradiol in fish homogenate. Extraction and clean-up strategies.

PubMed

Navarro, P; Bustamante, J; Vallejo, A; Prieto, A; Usobiaga, A; Arrasate, S; Anakabe, E; Puy-Azurmendi, E; Zuloaga, O

2010-09-17

The determination of target analytes such as nonyl- and octylphenols and 17beta-estradiol in fish homogenate require of solid-liquid extraction step. In this work microwave-assisted extraction (MAE) and focused-ultrasound liquid extraction (FUSLE) were studied as two different alternatives for extraction of the target compounds in zebrafish (Danio rerio) homogenate. In this work solid phase extraction (SPE) using 5-g and 10-g Florisil cartridges and gel permeation chromatography (GPC) were studied for the clean-up of the MAE and FUSLE extracts due to the non-selective extraction step. Although good recoveries were obtained both for SPE (106% and 126% range) and GPC (79% and 100% range) clean-up procedures, cleaner chromatograms were obtained after SPE and finally 5-g Florisil cartridges were tested since no improvement was observed when 10-g Florisil cartridges were used. Under optimized clean-up conditions, MAE and FUSLE provided comparable results for 4nOP and NP, while more accurate results were obtained for 4tOP and E2 after FUSLE. Finally, the method was applied to the determination of alkylphenols and 17beta-estradiol in zebrafish homogenate that had been exposed to known concentrations of the target analytes. In the case of alkylphenols two different isomers of nonyl- and octylphenol (4-(3',6'-dimethyl-3'-hepthyl)phenol, 363-NP, and 4-(3'-methyl-3'-hepthyl)phenol, 33-OP) were studied. 2010 Elsevier B.V. All rights reserved.

Investigations of different kilovoltage x-ray energy for three-dimensional converging stereotactic radiotherapy system: Monte Carlo simulations with CT data

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

Deloar, Hossain M.; Kunieda, Etsuo; Kawase, Takatsugu

2006-12-15

We are investigating three-dimensional converging stereotactic radiotherapy (3DCSRT) with suitable medium-energy x rays as treatment for small lung tumors with better dose homogeneity at the target. A computed tomography (CT) system dedicated for non-coplanar converging radiotherapy was simulated with BEAMnrc (EGS4) Monte-Carlo code for x-ray energy of 147.5, 200, 300, and 500 kilovoltage (kVp). The system was validated by comparing calculated and measured percentage of depth dose in a water phantom for the energy of 120 and 147.5 kVp. A thorax phantom and CT data from lung tumors (<20 cm{sup 3}) were used to compare dose homogeneities of kVp energiesmore » with MV energies of 4, 6, and 10 MV. Three non-coplanar arcs (0 deg. and {+-}25 deg. ) around the center of the target were employed. The Monte Carlo dose data format was converted to the XiO RTP format to compare dose homogeneity, differential, and integral dose volume histograms of kVp and MV energies. In terms of dose homogeneity and DVHs, dose distributions at the target of all kVp energies with the thorax phantom were better than MV energies, with mean dose absorption at the ribs (human data) of 100%, 85%, 50%, 30% for 147.5, 200, 300, and 500 kVp, respectively. Considering dose distributions and reduction of the enhanced dose absorption at the ribs, a minimum of 500 kVp is suitable for the lung kVp 3DCSRT system.« less

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Kotsuma, Tadayuki; Akiyama, Hironori; Takenaka, Tadashi; Masui, Koji; Yoshioka, Yasuo; Uesugi, Yasuo; Shimbo, Taiju; Yoshikawa, Nobuhiko; Yoshioka, Hiroto; Arika, Takumi; Tanaka, Eiichi; Narumi, Yoshifumi

2017-02-01

We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.

Monte Carlo simulations of patient dose perturbations in rotational-type radiotherapy due to a transverse magnetic field: A tomotherapy investigation

PubMed Central

Yang, Y. M.; Geurts, M.; Smilowitz, J. B.; Sterpin, E.; Bednarz, B. P.

2015-01-01

Purpose: Several groups are exploring the integration of magnetic resonance (MR) image guidance with radiotherapy to reduce tumor position uncertainty during photon radiotherapy. The therapeutic gain from reducing tumor position uncertainty using intrafraction MR imaging during radiotherapy could be partially offset if the negative effects of magnetic field-induced dose perturbations are not appreciated or accounted for. The authors hypothesize that a more rotationally symmetric modality such as helical tomotherapy will permit a systematic mediation of these dose perturbations. This investigation offers a unique look at the dose perturbations due to homogeneous transverse magnetic field during the delivery of Tomotherapy® Treatment System plans under varying degrees of rotational beamlet symmetry. Methods: The authors accurately reproduced treatment plan beamlet and patient configurations using the Monte Carlo code geant4. This code has a thoroughly benchmarked electromagnetic particle transport physics package well-suited for the radiotherapy energy regime. The three approved clinical treatment plans for this study were for a prostate, head and neck, and lung treatment. The dose heterogeneity index metric was used to quantify the effect of the dose perturbations to the target volumes. Results: The authors demonstrate the ability to reproduce the clinical dose–volume histograms (DVH) to within 4% dose agreement at each DVH point for the target volumes and most planning structures, and therefore, are able to confidently examine the effects of transverse magnetic fields on the plans. The authors investigated field strengths of 0.35, 0.7, 1, 1.5, and 3 T. Changes to the dose heterogeneity index of 0.1% were seen in the prostate and head and neck case, reflecting negligible dose perturbations to the target volumes, a change from 5.5% to 20.1% was observed with the lung case. Conclusions: This study demonstrated that the effect of external magnetic fields can be

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.

SU-F-T-314: Estimation of Dose Distributions with Different Types of Breast Implants in Various Radiation Treatment Techniques for Breast Cancer

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

Lee, M; Lee, S; Suh, T

Purpose: This study investigates the effects of different kinds and designs of commercialized breast implants on the dose distributions in breast cancer radiotherapy under a variety of conditions. Methods: The dose for the clinical conventional tangential irradiation, Intensity Modulated Radiation Therapy (IMRT), volumetric modulated arc therapy (VMAT) breast plans was measured using radiochromic films and stimulated luminescence dosimeter (OSLD). The radiochromic film was used as an integrating dosimeter, while the OSLDs were used for real-time dosimetry to isolate the contribution of dose from individual segment. The films were placed at various slices in the Rando phantom and between the bodymore » and breast surface OSLDs were used to measure skin dose at 18 positions spaced on the two (right/left) breast. The implant breast was placed on the left side and the phantom breast was remained on the right side. Each treatment technique was performed on different size of the breasts and different shape of the breast implant. The PTV dose was prescribed 50.4 Gy and V47.88≥95%. Results: In different shapes of the breast implant, because of the shadow formed extensive around the breast implant, dose variation was relatively higher that of prescribed dose. As the PTV was delineated on the whole breast, maximum 5% dose error and average 3% difference was observed averagely. VMAT techniques largely decrease the contiguous hot spot in the skin by an average of 25% compared with IMRT. The both IMRT and VMAT techniques resulted in lower doses to normal critical structures than tangential plans for nearly all dose analyzation. Conclusion: Compared to the other technique, IMRT reduced radiation dose exposure to normal tissues and maintained reasonable target homogeneity and for the same target coverage, VMAT can reduce the skin dose in all the regions of the body.« less

Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

PubMed

Norris, David C

2017-01-01

Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to

Dose calculations using artificial neural networks: A feasibility study for photon beams

NASA Astrophysics Data System (ADS)

Vasseur, Aurélien; Makovicka, Libor; Martin, Éric; Sauget, Marc; Contassot-Vivier, Sylvain; Bahi, Jacques

2008-04-01

Direct dose calculations are a crucial requirement for Treatment Planning Systems. Some methods, such as Monte Carlo, explicitly model particle transport, others depend upon tabulated data or analytic formulae. However, their computation time is too lengthy for clinical use, or accuracy is insufficient, especially for recent techniques such as Intensity-Modulated Radiotherapy. Based on artificial neural networks (ANNs), a new solution is proposed and this work extends the properties of such an algorithm and is called NeuRad. Prior to any calculations, a first phase known as the learning process is necessary. Monte Carlo dose distributions in homogeneous media are used, and the ANN is then acquired. According to the training base, it can be used as a dose engine for either heterogeneous media or for an unknown material. In this report, two networks were created in order to compute dose distribution within a homogeneous phantom made of an unknown material and within an inhomogeneous phantom made of water and TA6V4 (titanium alloy corresponding to hip prosthesis). All NeuRad results were compared to Monte Carlo distributions. The latter required about 7 h on a dedicated cluster (10 nodes). NeuRad learning requires between 8 and 18 h (depending upon the size of the training base) on a single low-end computer. However, the results of dose computation with the ANN are available in less than 2 s, again using a low-end computer, for a 150×1×150 voxels phantom. In the case of homogeneous medium, the mean deviation in the high dose region was less than 1.7%. With a TA6V4 hip prosthesis bathed in water, the mean deviation in the high dose region was less than 4.1%. Further improvements in NeuRad will have to include full 3D calculations, inhomogeneity management and input definitions.

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Limitations of current dosimetry for intracavitary accelerated partial breast irradiation with high dose rate iridium-192 and electronic brachytherapy sources

NASA Astrophysics Data System (ADS)

Raffi, Julie A.

Intracavitary accelerated partial breast irradiation (APBI) is a method of treating early stage breast cancer using a high dose rate (HDR) brachytherapy source positioned within the lumpectomy cavity. An expandable applicator stretches the surrounding tissue into a roughly spherical or elliptical shape and the dose is prescribed to 1 cm beyond the edge of the cavity. Currently, dosimetry for these treatments is most often performed using the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism. The TG-43 dose-rate equation determines the dose delivered to a homogeneous water medium by scaling the measured source strength with standardized parameters that describe the radial and angular features of the dose distribution. Since TG-43 parameters for each source model are measured or calculated in a homogeneous water medium, the dosimetric effects of the patient's dimensions and composition are not accounted for. Therefore, the accuracy of TG-43 calculations for intracavitary APBI is limited by the presence of inhomogeneities in and around the target volume. Specifically, the breast is smaller than the phantoms used to determine TG-43 parameters and is surrounded by air, ribs, and lung tissue. Also, the composition of the breast tissue itself can affect the dose distribution. This dissertation is focused on investigating the limitations of TG-43 dosimetry for intracavitary APBI for two HDR brachytherapy sources: the VariSource TM VS2000 192Ir source and the AxxentRTM miniature x-ray source. The dose for various conditions was determined using thermoluminescent dosimeters (TLDs) and Monte Carlo (MC) calculations. Accurate measurements and calculations were achieved through the implementation of new measurement and simulation techniques and a novel breast phantom was developed to enable anthropomorphic phantom measurements. Measured and calculated doses for phantom and patient geometries were compared with TG-43 calculated doses to

Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations.

PubMed

Preuss, Nora; van der Veen, Jan Willem; Carlson, Paul J; Shen, Jun; Hasler, Gregor

2013-12-01

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0mg, 150mg and 300mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system. © 2013 Elsevier B.V. All rights reserved.

Homogeneous anisotropic solutions of topologically massive gravity with a cosmological constant and their homogeneous deformations

NASA Astrophysics Data System (ADS)

Moutsopoulos, George

2013-06-01

We solve the equations of topologically massive gravity (TMG) with a potentially non-vanishing cosmological constant for homogeneous metrics without isotropy. We only reproduce known solutions. We also discuss their homogeneous deformations, possibly with isotropy. We show that de Sitter space and hyperbolic space cannot be infinitesimally homogeneously deformed in TMG. We clarify some of their Segre-Petrov types and discuss the warped de Sitter spacetime.

Out of Field Doses in Clinical Photon and Proton Beam

NASA Astrophysics Data System (ADS)

Kubančák, Ján

2010-01-01

Out-of-field doses in homogenous cubical polymethylmethacrylate (PMMA) phantom were studied in this work. Measurements were performed in clinical 171 MeV proton and megavoltae photon beam. As detectors, CaSO:Dy thermoluminescent detectors were used. According to expectancy, results showed that out-of-field doses are substantially lower for clinical proton beam in comparison with clinical proton beam.

Benchmarking homogenization algorithms for monthly data

NASA Astrophysics Data System (ADS)

Venema, V. K. C.; Mestre, O.; Aguilar, E.; Auer, I.; Guijarro, J. A.; Domonkos, P.; Vertacnik, G.; Szentimrey, T.; Stepanek, P.; Zahradnicek, P.; Viarre, J.; Müller-Westermeier, G.; Lakatos, M.; Williams, C. N.; Menne, M. J.; Lindau, R.; Rasol, D.; Rustemeier, E.; Kolokythas, K.; Marinova, T.; Andresen, L.; Acquaotta, F.; Fratiannil, S.; Cheval, S.; Klancar, M.; Brunetti, M.; Gruber, C.; Prohom Duran, M.; Likso, T.; Esteban, P.; Brandsma, T.; Willett, K.

2013-09-01

The COST (European Cooperation in Science and Technology) Action ES0601: Advances in homogenization methods of climate series: an integrated approach (HOME) has executed a blind intercomparison and validation study for monthly homogenization algorithms. Time series of monthly temperature and precipitation were evaluated because of their importance for climate studies. The algorithms were validated against a realistic benchmark dataset. Participants provided 25 separate homogenized contributions as part of the blind study as well as 22 additional solutions submitted after the details of the imposed inhomogeneities were revealed. These homogenized datasets were assessed by a number of performance metrics including i) the centered root mean square error relative to the true homogeneous values at various averaging scales, ii) the error in linear trend estimates and iii) traditional contingency skill scores. The metrics were computed both using the individual station series as well as the network average regional series. The performance of the contributions depends significantly on the error metric considered. Although relative homogenization algorithms typically improve the homogeneity of temperature data, only the best ones improve precipitation data. Moreover, state-of-the-art relative homogenization algorithms developed to work with an inhomogeneous reference are shown to perform best. The study showed that currently automatic algorithms can perform as well as manual ones.

Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.

PubMed

Takeda, Atsuya; Oku, Yohei; Sanuki, Naoko; Eriguchi, Takahisa; Aoki, Yousuke; Enomoto, Tatsuji; Kaneko, Takeshi; Nishimura, Shuichi; Kunieda, Etsuo

2014-09-01

We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

A dose error evaluation study for 4D dose calculations

NASA Astrophysics Data System (ADS)

Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

2014-10-01

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

A dose error evaluation study for 4D dose calculations.

PubMed

Milz, Stefan; Wilkens, Jan J; Ullrich, Wolfgang

2014-11-07

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms.The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms.The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm; 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex programming

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

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

2009-11-01

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

Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?☆

PubMed Central

Little, M.P.

2011-01-01

In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose–response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10

Effective inactivation of Saccharomyces cerevisiae in minimally processed Makgeolli using low-pressure homogenization-based pasteurization.

PubMed

Bak, Jin Seop

2015-01-01

In order to address the limitations associated with the inefficient pasteurization platform used to make Makgeolli, such as the presence of turbid colloidal dispersions in suspension, commercially available Makgeolli was minimally processed using a low-pressure homogenization-based pasteurization (LHBP) process. This continuous process demonstrates that promptly reducing the exposure time to excessive heat using either large molecules or insoluble particles can dramatically improve internal quality and decrease irreversible damage. Specifically, optimal homogenization increased concomitantly with physical parameters such as colloidal stability (65.0% of maximum and below 25-μm particles) following two repetitions at 25.0 MPa. However, biochemical parameters such as microbial population, acidity, and the presence of fermentable sugars rarely affected Makgeolli quality. Remarkably, there was a 4.5-log reduction in the number of Saccharomyces cerevisiae target cells at 53.5°C for 70 sec in optimally homogenized Makgeolli. This value was higher than the 37.7% measured from traditionally pasteurized Makgeolli. In contrast to the analytical similarity among homogenized Makgeollis, our objective quality evaluation demonstrated significant differences between pasteurized (or unpasteurized) Makgeolli and LHBP-treated Makgeolli. Low-pressure homogenization-based pasteurization, Makgeolli, minimal processing-preservation, Saccharomyces cerevisiae, suspension stability.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient

Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

PubMed Central

Norris, David C.

2017-01-01

Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically

MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

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

Wu, Q; Snyder, K; Liu, C

Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas weremore » the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.« less

Study of dose calculation on breast brachytherapy using prism TPS

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

Fendriani, Yoza; Haryanto, Freddy

2015-09-30

PRISM is one of non-commercial Treatment Planning System (TPS) and is developed at the University of Washington. In Indonesia, many cancer hospitals use expensive commercial TPS. This study aims to investigate Prism TPS which been applied to the dose distribution of brachytherapy by taking into account the effect of source position and inhomogeneities. The results will be applicable for clinical Treatment Planning System. Dose calculation has been implemented for water phantom and CT scan images of breast cancer using point source and line source. This study used point source and line source and divided into two cases. On the firstmore » case, Ir-192 seed source is located at the center of treatment volume. On the second case, the source position is gradually changed. The dose calculation of every case performed on a homogeneous and inhomogeneous phantom with dimension 20 × 20 × 20 cm{sup 3}. The inhomogeneous phantom has inhomogeneities volume 2 × 2 × 2 cm{sup 3}. The results of dose calculations using PRISM TPS were compared to literature data. From the calculation of PRISM TPS, dose rates show good agreement with Plato TPS and other study as published by Ramdhani. No deviations greater than ±4% for all case. Dose calculation in inhomogeneous and homogenous cases show similar result. This results indicate that Prism TPS is good in dose calculation of brachytherapy but not sensitive for inhomogeneities. Thus, the dose calculation parameters developed in this study were found to be applicable for clinical treatment planning of brachytherapy.« less

Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy.

PubMed

Wu, Vincent W C; Kwong, Dora L W; Sham, Jonathan S T

2004-05-01

Dose conformity to the planning target volume is an important criterion in radiotherapy treatment planning, for which the conformity index is a useful assessment tool. The purpose of this study is to compare the differences in CI for the treatment planning of four cancers including the nasopharynx, oesophagus, lung and prostate. Seventy patients with cancers of nasopharynx (30), oesophagus (15), lung (15) and prostate (10) were recruited. Each of these patients was planned with three sets of treatment plans using the FOCUS treatment planning system: the forward and inverse 3DCRT plans and the IMRT plan. The CI was generated for each treatment plan. The mean CI from each cancer patient group was calculated and compared with the other three cancer groups. The mean value of CI was also compared among the three planning methods. The oesophageal and lung cancers demonstrated relatively higher overall mean CI values (0.64 and 0.62, respectively), whereas that of the nasopharynx and prostate were lower (0.54 and 0.50, respectively). With regards to the planning method groups, the IMRT plans produced the highest overall mean CI (0.62), while those for the forward and inverse 3DCRT were similar (0.57 and 0.55, respectively). For the four selected cancers, oesophageal and lung cancers were easier to conform than the nasopharyngeal and prostate cancers. The IMRT plans were more effective in achieving better dose conformity than that of the 3DCRT.

TH-AB-BRA-05: Lung Cannot Be Treated as Homogeneous in Radiation Transport Simulations in Magnetic Fields

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

Malkov, V; Rogers, D; Jaffray, D

2016-06-15

Purpose: Magnetic fields in MRgRT are known to induce dose perturbations near lung-tissue interfaces. The goal of this study is to determine if the heterogeneous structure of the lung influences the dose distribution in a magnetic field. Method: The dose distribution from a 4 cm X 4 cm 6 MV photon beam in a 0, 0.6, or 1.5 T magnetic field in a homogeneous lung density (0.333 g/cm{sup 3}) geometry is compared to that in a heterogeneous segmented slab configuration. The heterogeneous phantom is composed of 2/3 water vapour and 1/3 liquid water such that the overall density of themore » lung regions in the two phantoms are equivalent. The EGSnrc DOSXYZnrc user code is used with a previously implemented magnetic field transport code. Results: For water vapour gap thickness of 2 mm, compared to the homogeneous lung case (which already exhibits significant dose perturbations in a magnetic field) differences as large as 12.3 ± 0.2 % are observed for a 0.6 T field and 9.3 ± 0.1 % for a 1.5 T field at the tissuelung interface, and on the order of several percent within the lung-like tissue region for both magnetic fields. Thicker gaps produced larger deviations while a gap thickness of 0.2 mm does not result in notable differences. Regardless of gap thickness, the heterogeneities had little effect on the 0 T simulations. Further, using smaller scoring regions revealed that dose averaging effects could obscure dose differences as large as 10 – 20 % within the heterogeneous structures of the lung-like media. Conclusions: This simple model demonstrates that media heterogeneities can play an important role in MRgRT dose distributions, and care must be taken in setting up any dose calculation in the lung in the presence of a magnetic field, especially for air regions larger than 2 mm.« less

Orthogonality Measurement for Homogenous Projects-Bases

ERIC Educational Resources Information Center

Ivan, Ion; Sandu, Andrei; Popa, Marius

2009-01-01

The homogenous projects-base concept is defined. Next, the necessary steps to create a homogenous projects-base are presented. A metric system is built, which then will be used for analyzing projects. The indicators which are meaningful for analyzing a homogenous projects-base are selected. The given hypothesis is experimentally verified. The…

ORANGE: a Monte Carlo dose engine for radiotherapy.

PubMed

van der Zee, W; Hogenbirk, A; van der Marck, S C

2005-02-21

This study presents data for the verification of ORANGE, a fast MCNP-based dose engine for radiotherapy treatment planning. In order to verify the new algorithm, it has been benchmarked against DOSXYZ and against measurements. For the benchmarking, first calculations have been done using the ICCR-XIII benchmark. Next, calculations have been done with DOSXYZ and ORANGE in five different phantoms (one homogeneous, two with bone equivalent inserts and two with lung equivalent inserts). The calculations have been done with two mono-energetic photon beams (2 MeV and 6 MeV) and two mono-energetic electron beams (10 MeV and 20 MeV). Comparison of the calculated data (from DOSXYZ and ORANGE) against measurements was possible for a realistic 10 MV photon beam and a realistic 15 MeV electron beam in a homogeneous phantom only. For the comparison of the calculated dose distributions and dose distributions against measurements, the concept of the confidence limit (CL) has been used. This concept reduces the difference between two data sets to a single number, which gives the deviation for 90% of the dose distributions. Using this concept, it was found that ORANGE was always within the statistical bandwidth with DOSXYZ and the measurements. The ICCR-XIII benchmark showed that ORANGE is seven times faster than DOSXYZ, a result comparable with other accelerated Monte Carlo dose systems when no variance reduction is used. As shown for XVMC, using variance reduction techniques has the potential for further acceleration. Using modern computer hardware, this brings the total calculation time for a dose distribution with 1.5% (statistical) accuracy within the clinical range (less then 10 min). This means that ORANGE can be a candidate for a dose engine in radiotherapy treatment planning.

Bioimmunological responses to Schistosoma mansoni and Fasciola gigantica worm homogenates either with or without saponin.

PubMed

Maghraby, Amany Sayed; Hamed, Manal Abdel-Aziz; Ali, Sanaa Ahmed

2010-06-03

In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. The immunization schedule was based on subcutaneous administration of two doses (50 microg /100 microl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator

PubMed Central

Wack, L.; Ngwa, W.; Tryggestad, E.; Tsiamas, P.; Berbeco, R.; Ng, S.K.; Hesser, J.

2013-01-01

Purpose We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilo-voltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. Methods We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multichannel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm2. The results were compared against Monte Carlo simulations. Results Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%–3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. Conclusions EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated. PMID:23510532

Feasibility and Initial Dosimetric Findings for a Randomized Trial Using Dose-Painted Multiparametric Magnetic Resonance Imaging–Defined Targets in Prostate Cancer

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

Bossart, Elizabeth L., E-mail: EBossart@med.miami.edu; Stoyanova, Radka; Sandler, Kiri

2016-06-01

Purpose: To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials: Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15)more » consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results: For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions: The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.« less

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

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

Yim, Jackie; Suttie, Clare; Bromley, Regina

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with themore » 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.« less

Analysis of the Body Distribution of Absorbed Dose in the Organs of Three Species of Fish from Sepetiba Bay

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

Pereira, Wagner de S; Universidade Federal Fluminense, Programa de Pos-graduacao em Biologia Marinha; Kelecom, Alphonse

2008-08-07

The body distribution of Polonium-210 in three fishes from the Sepetiba Bay (Macrodon ancylodon, Micropogonias furnieri and Mugil curema) has been studied under the approach of the Department of Energy of the United States of America (DOE) that set the limit of absorbed dose rate in biota equal to 3.5x10{sup 3} {mu}Gy/y, and that also established the relation between dose rate (D) and radionuclide concentration (c) on a fish muscle fresh weight basis, as follows: D = 5.05 ExNxC, assuming that the radionuclide distribution is homogenous among organs. Two hypotheses were tested here, using statistical tools: 1) is the bodymore » distribution of absorbed dose homogenous among organs? and 2) is the body distribution of absorbed dose identical among studied fishes? It was concluded, as expected, that the distribution among organs is heterogeneous; but, unexpectedly, that the three fishes display identical body distribution pattern, although they belong to different trophic levels. Hence, concerning absorbed dose calculation, the statement that data distribution is homogenous must be understood merely as an approximation, at least in the case of Polonium-210.« less

Internal homogenization: effective permittivity of a coated sphere.

PubMed

Chettiar, Uday K; Engheta, Nader

2012-10-08

The concept of internal homogenization is introduced as a complementary approach to the conventional homogenization schemes, which could be termed as external homogenization. The theory for the internal homogenization of the permittivity of subwavelength coated spheres is presented. The effective permittivity derived from the internal homogenization of coreshells is discussed for plasmonic and dielectric constituent materials. The effective model provided by the homogenization is a useful design tool in constructing coated particles with desired resonant properties.

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle - an update.

PubMed

Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve A C; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald A H

2012-12-05

To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure. Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size. Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.

Validation of an improved helical diode array and dose reconstruction software using TG-244 datasets and stringent dose comparison criteria.

PubMed

Ahmed, Saeed; Nelms, Benjamin; Kozelka, Jakub; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2016-11-08

The original helical ArcCHECK (AC) diode array and associated software for 3D measurement-guided dose reconstruction were characterized and validated; however, recent design changes to the AC required that the subject be revisited. The most important AC change starting in 2014 was a significant reduction in the overresponse of diodes to scattered radiation outside of the direct beam, accom-plished by reducing the amount of high-Z materials adjacent to the diodes. This change improved the diode measurement accuracy, but in the process invalidated the dose reconstruction models that were assembled based on measured data acquired with the older version of the AC. A correction mechanism was intro-duced in the reconstruction software (3DVH) to accommodate this and potential future design changes without requiring updating model parameters. For each permutation of AC serial number and beam model, the user can define in 3DVH a single correction factor which will be used to compensate for the difference in the out-of-field response between the new and original AC designs. The exact value can be determined by minimizing the dose-difference with an ionization chamber or another independent dosimeter. A single value of 1.17, corresponding to the maximum measured out-of-field response difference between the new and old AC, provided satisfactory results for all studied energies (6X, 15X, and flatten-ing filter-free 10XFFF). A library of standard cases recommended by the AAPM TG-244 Report was used for reconstructed dose verification. The overall difference between reconstructed dose and an ion chamber in a water-equivalent phantom in the targets was 0.0% ± 1.4% (1 SD). The reconstructed dose on a homogeneous phantom was also compared to a biplanar diode dosimeter (Delta4) using gamma analysis with 2% (local dose-error normalization) / 2 mm / 10% cutoff criteria. The mean agreement rate was 96.7% ± 3.7%. For the plans common with the previous comparison, the mean agreement

Assessment of Volumetric-Modulated Arc Therapy for Constant and Variable Dose Rates

PubMed Central

De Ornelas-Couto, Mariluz; Mihaylov, Ivaylo; Dogan, Nesrin

2017-01-01

Purpose: The aim of this study is to compare the effects of dose rate on volumetric-modulated arc therapy plans to determine optimal dose rates for prostate and head and neck (HN) cases. Materials and Methods: Ten prostate and ten HN cases were retrospectively studied. For each case, seven plans were generated: one variable dose rate (VDR) and six constant dose rate (CDR) (100–600 monitor units [MUs]/min) plans. Prescription doses were: 80 Gy to planning target volume (PTV) for the prostate cases, and 70, 60, and 54 Gy to PTV1, PTV2, and PTV3, respectively, for HN cases. Plans were normalized to 95% of the PTV and PTV1, respectively, with the prescription dose. Plans were assessed using Dose-Volume-Histogram metrics, homogeneity index, conformity index, MUs, and delivery time. Results: For the prostate cases, significant differences were found for rectum D35 between VDR and all CDR plans, except CDR500. Furthermore, VDR was significantly different than CDR100 and 200 for bladder D50. Delivery time for all CDR plans and MUs for CDR400–600 were significantly higher when compared to VDR. HN cases showed significant differences between VDR and CDR100, 500 and 600 for D2 to the cord and brainstem. Significant differences were found for delivery time and MUs for all CDR plans, except CDR100 for number of MUs. Conclusion: The most significant differences were observed in delivery time and number of MUs. All-in-all, the best CDR for prostate cases was found to be 300 MUs/min and 200 or 300 MUs/min for HN cases. However, VDR plans are still the choice in terms of MU efficiency and plan quality. PMID:29296033

Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

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

Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.

2007-11-01

Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with lowmore » dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.« less

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

PubMed Central

2014-01-01

Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in

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

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

Koivula, Lauri

Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity valuesmore » of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1

Benchmarking homogenization algorithms for monthly data

NASA Astrophysics Data System (ADS)

Venema, V. K. C.; Mestre, O.; Aguilar, E.; Auer, I.; Guijarro, J. A.; Domonkos, P.; Vertacnik, G.; Szentimrey, T.; Stepanek, P.; Zahradnicek, P.; Viarre, J.; Müller-Westermeier, G.; Lakatos, M.; Williams, C. N.; Menne, M. J.; Lindau, R.; Rasol, D.; Rustemeier, E.; Kolokythas, K.; Marinova, T.; Andresen, L.; Acquaotta, F.; Fratianni, S.; Cheval, S.; Klancar, M.; Brunetti, M.; Gruber, C.; Prohom Duran, M.; Likso, T.; Esteban, P.; Brandsma, T.

2012-01-01

The COST (European Cooperation in Science and Technology) Action ES0601: advances in homogenization methods of climate series: an integrated approach (HOME) has executed a blind intercomparison and validation study for monthly homogenization algorithms. Time series of monthly temperature and precipitation were evaluated because of their importance for climate studies and because they represent two important types of statistics (additive and multiplicative). The algorithms were validated against a realistic benchmark dataset. The benchmark contains real inhomogeneous data as well as simulated data with inserted inhomogeneities. Random independent break-type inhomogeneities with normally distributed breakpoint sizes were added to the simulated datasets. To approximate real world conditions, breaks were introduced that occur simultaneously in multiple station series within a simulated network of station data. The simulated time series also contained outliers, missing data periods and local station trends. Further, a stochastic nonlinear global (network-wide) trend was added. Participants provided 25 separate homogenized contributions as part of the blind study. After the deadline at which details of the imposed inhomogeneities were revealed, 22 additional solutions were submitted. These homogenized datasets were assessed by a number of performance metrics including (i) the centered root mean square error relative to the true homogeneous value at various averaging scales, (ii) the error in linear trend estimates and (iii) traditional contingency skill scores. The metrics were computed both using the individual station series as well as the network average regional series. The performance of the contributions depends significantly on the error metric considered. Contingency scores by themselves are not very informative. Although relative homogenization algorithms typically improve the homogeneity of temperature data, only the best ones improve precipitation data

Monte Carlo N Particle code - Dose distribution of clinical electron beams in inhomogeneous phantoms

PubMed Central

Nedaie, H. A.; Mosleh-Shirazi, M. A.; Allahverdi, M.

2013-01-01

Electron dose distributions calculated using the currently available analytical methods can be associated with large uncertainties. The Monte Carlo method is the most accurate method for dose calculation in electron beams. Most of the clinical electron beam simulation studies have been performed using non- MCNP [Monte Carlo N Particle] codes. Given the differences between Monte Carlo codes, this work aims to evaluate the accuracy of MCNP4C-simulated electron dose distributions in a homogenous phantom and around inhomogeneities. Different types of phantoms ranging in complexity were used; namely, a homogeneous water phantom and phantoms made of polymethyl methacrylate slabs containing different-sized, low- and high-density inserts of heterogeneous materials. Electron beams with 8 and 15 MeV nominal energy generated by an Elekta Synergy linear accelerator were investigated. Measurements were performed for a 10 cm × 10 cm applicator at a source-to-surface distance of 100 cm. Individual parts of the beam-defining system were introduced into the simulation one at a time in order to show their effect on depth doses. In contrast to the first scattering foil, the secondary scattering foil, X and Y jaws and applicator provide up to 5% of the dose. A 2%/2 mm agreement between MCNP and measurements was found in the homogenous phantom, and in the presence of heterogeneities in the range of 1-3%, being generally within 2% of the measurements for both energies in a "complex" phantom. A full-component simulation is necessary in order to obtain a realistic model of the beam. The MCNP4C results agree well with the measured electron dose distributions. PMID:23533162

Sewage sludge solubilization by high-pressure homogenization.

PubMed

Zhang, Yuxuan; Zhang, Panyue; Guo, Jianbin; Ma, Weifang; Fang, Wei; Ma, Boqiang; Xu, Xiangzhe

2013-01-01

The behavior of sludge solubilization using high-pressure homogenization (HPH) treatment was examined by investigating the sludge solid reduction and organics solubilization. The sludge volatile suspended solids (VSS) decreased from 10.58 to 6.67 g/L for the sludge sample with a total solids content (TS) of 1.49% after HPH treatment at a homogenization pressure of 80 MPa with four homogenization cycles; total suspended solids (TSS) correspondingly decreased from 14.26 to 9.91 g/L. About 86.15% of the TSS reduction was attributed to the VSS reduction. The increase of homogenization pressure from 20 to 80 MPa or homogenization cycle number from 1 to 4 was favorable to the sludge organics solubilization, and the protein and polysaccharide solubilization linearly increased with the soluble chemical oxygen demand (SCOD) solubilization. More proteins were solubilized than polysaccharides. The linear relationship between SCOD solubilization and VSS reduction had no significant change under different homogenization pressures, homogenization cycles and sludge solid contents. The SCOD of 1.65 g/L was solubilized for the VSS reduction of 1.00 g/L for the three experimental sludge samples with a TS of 1.00, 1.49 and 2.48% under all HPH operating conditions. The energy efficiency results showed that the HPH treatment at a homogenization pressure of 30 MPa with a single homogenization cycle for the sludge sample with a TS of 2.48% was the most energy efficient.

Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer

PubMed Central

Grassberger, Clemens; Dowdell, Stephen; Lomax, Antony; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald

2013-01-01

Purpose Quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy. Methods and Materials 4D Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3cc) and motion amplitudes (3-30mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity and 2-year local control rate (2y-LC). Results Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (σ≈3mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor ~2.8 compared to a larger spot size (σ≈13mm). Using a smaller spot size to treat a tumor with 30mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V20 are <0.6Gy(RBE) and <1.7% respectively. Conclusions For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments employing smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y

U.S. Joint Special Operations Forces: Two Few, Overworked, Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War?

DTIC Science & Technology

2008-05-28

OVERWORKED , YOUNG, HOMOGENOUS, & MACHO TO FULFILL THE UNCONVENTIONAL DEMANDS OF THE LONG WAR? SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR...U.S. Joint Special Operations Forces: Two Few, Overworked , Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War? 5a...to be the targets of nearly daily mortar, improvised explosive devices (IEDs), and occasional suicide vehicle-borne IED (SVBIED) attacks. It

The impacts of dental filling materials on RapidArc treatment planning and dose delivery: Challenges and solution

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

Mail, Noor; Al-Ghamdi, S.; Saoudi, A.

examined initially and weekly during the course of radiotherapy.Results: For a RapidArc treatment technique, the backscatter dose from the DFM insert was measured to be 9.25 ± 2.17 in the IMRT-verification-phantom. The measured backscatter upstream dose from DFM for a single-field was 22% higher than without the DFM, whereas the downstream dose was lower by 14%. The values of homogeneity index for the plans with and without the application of mask were 0.09 and 0.14, respectively. The calculated mean treatment planning volume (PTV) dose differed from the delivered dose by 13% and was reduced to 2% when using the mask and virtual filter together. A grade 3 mucosa reaction was observed in the control group after 22–24 fractions (44–48 Gy). In contrast, no grade 3 mucositis was observed in the patients wearing the PDM after 25–26 fractions (50–52 Gy).Conclusions: The backscatter from the DFM for a single, parallel-opposed fields, and RapidArc treatment technique was found significant. The application of mask in replacing streaking artifacts can be useful in improving dose homogeneity in the PTV. The use of a virtual filter around the teeth during the planning phase reduces the target underdosage issue in the phantom. Furthermore, a reduction in mucositis is observed in the head and neck patients with the use of PDM.« less

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

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

Liu, J; Eldib, A; Ma, C

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number wasmore » used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.« less

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

PubMed

Iwata, Hiromitsu; Inoue, Mitsuhiro; Shiomi, Hiroya; Murai, Taro; Tatewaki, Koshi; Ohta, Seiji; Okawa, Kohei; Yokota, Naoki; Shibamoto, Yuta

2016-02-01

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable. © The Author(s) 2014.

Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

PubMed

Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel

2016-10-01

Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

PubMed

Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

2016-11-01

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate

Mechanized syringe homogenization of human and animal tissues.

PubMed

Kurien, Biji T; Porter, Andrew C; Patel, Nisha C; Kurono, Sadamu; Matsumoto, Hiroyuki; Scofield, R Hal

2004-06-01

Tissue homogenization is a prerequisite to any fractionation schedule. A plethora of hands-on methods are available to homogenize tissues. Here we report a mechanized method for homogenizing animal and human tissues rapidly and easily. The Bio-Mixer 1200 (manufactured by Innovative Products, Inc., Oklahoma City, OK) utilizes the back-and-forth movement of two motor-driven disposable syringes, connected to each other through a three-way stopcock, to homogenize animal or human tissue. Using this method, we were able to homogenize human or mouse tissues (brain, liver, heart, and salivary glands) in 5 min. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric enzyme assay for prolidase, we have found that the homogenates obtained were as good or even better than that obtained used a manual glass-on-Teflon (DuPont, Wilmington, DE) homogenization protocol (all-glass tube and Teflon pestle). Use of the Bio-Mixer 1200 to homogenize animal or human tissue precludes the need to stay in the cold room as is the case with the other hands-on homogenization methods available, in addition to freeing up time for other experiments.

Total skin electron irradiation: evaluation of dose uniformity throughout the skin surface.

PubMed

Anacak, Yavuz; Arican, Zumre; Bar-Deroma, Raquel; Tamir, Ada; Kuten, Abraham

2003-01-01

In this study, in vivo dosimetic data of 67 total skin electron irradiation (TSEI) treatments were analyzed. Thermoluminescent dosimetry (TLD) measurements were made at 10 different body points for every patient. The results demonstrated that the dose inhomogeneity throughout the skin surface is around 15%. The homogeneity was better at the trunk than at the extratrunk points, and was worse when a degrader was used. There was minimal improvement of homogeneity in subsequent days of treatment.

Recent developments in human biomonitoring: non-invasive assessment of target tissue dose and effects of pneumotoxic metals.

PubMed

Mutti, A; Corradi, M

2006-01-01

Tobacco smoke and polluted environments substantially increase the lung burden of pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a better understanding of the early events between exposure to inhaled toxicants and the onset of adverse effects on the lung, the characterization of dose at the target organ would be extremely useful. Exhaled breath condensate (EBC), obtained by cooling exhaled air under conditions of spontaneous breathing, is a novel technique that could provide a non-invasive assessment of pulmonary pathobiology. Considering that EBC is water practically free of interfering solutes, it represents an ideal biological matrix for elemental characterization. Published data show that several toxic metals and trace elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of pneumotoxic substances. This novel approach may represent a significant advance over the analysis of alternative media (blood, serum, urine, hair), which are not as reliable (owing to interfering substances in the complex matrix) and reflect systemic rather than lung (target tissue) levels of both toxic metals and essential trace elements. Data obtained among workers occupationally exposed to either hard metals or chromium (VI) and in smokers with or without chronic obstructive pulmonary disease (COPD) are reviewed to show that--together with biomarkers of exposure--EBC also allows the simultaneous quantification of biomarkers of effect directly sampled from the epithelial lining fluid, thus providing novel insights on both kinetic and dynamic aspects of metal toxicology.

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

PubMed

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Homogenous assay for protein detection based on proximity DNA hybridization and isothermal circular strand displacement amplification reaction.

PubMed

Zhang, Manjun; Li, Ruimin; Ling, Liansheng

2017-06-01

This work proposed a homogenous fluorescence assay for proteins, based on the target-triggered proximity DNA hybridization in combination with strand displacement amplification (SDA). It benefited from target-triggered proximity DNA hybridization to specifically recognize the target and SDA making recycling signal amplification. The system included a molecular beacon (MB), an extended probe (EP), and an assistant probe (AP), which were not self-assembly in the absence of target proteins, due to the short length of the designed complementary sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP are bound to the target proteins, which induced the occurrence of proximity hybridization between MB, EP, and AP and followed by strand displacement amplification. Through the primer extension, a tripartite complex of probes and target was displaced and recycled to hybridize with another MB, and the more opened MB enabled the detection signal to amplify. Under optimum conditions, it was used for the detection of streptavidin and thrombin. Fluorescence intensity was proportional to the concentration of streptavidin and thrombin in the range of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method has a good selectivity, in which the fluorescence intensity of thrombin was ~37-fold or even larger than that of the other proteins at the same concentration. It is a new and simple method for SDA-involved target protein detection and possesses a great potential for other protein detection in the future. Graphical abstract A homogenous assay for protein detection is based on proximity DNA hybridization and strand displacement amplification reaction.

A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy

NASA Astrophysics Data System (ADS)

Koger, B.; Kirkby, C.

2016-03-01

Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP.

Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy.

PubMed

Moore, Caroline M; Azzouzi, Abel-Rahmene; Barret, Eric; Villers, Arnauld; Muir, Gordon H; Barber, Neil J; Bott, Simon; Trachtenberg, John; Arumainayagam, Nimalan; Gaillac, Bertrand; Allen, Clare; Schertz, Avigdor; Emberton, Mark

2015-12-01

To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%). © 2014 The Authors BJU International © 2014 BJU

Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2018-01-01

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

Enhancement of anaerobic sludge digestion by high-pressure homogenization.

PubMed

Zhang, Sheng; Zhang, Panyue; Zhang, Guangming; Fan, Jie; Zhang, Yuxuan

2012-08-01

To improve anaerobic sludge digestion efficiency, the effects of high-pressure homogenization (HPH) conditions on the anaerobic sludge digestion were investigated. The VS and TCOD were significantly removed with the anaerobic digestion, and the VS removal and TCOD removal increased with increasing the homogenization pressure and homogenization cycle number; correspondingly, the accumulative biogas production also increased with increasing the homogenization pressure and homogenization cycle number. The optimal homogenization pressure was 50 MPa for one homogenization cycle and 40 MPa for two homogenization cycles. The SCOD of the sludge supernatant significantly increased with increasing the homogenization pressure and homogenization cycle number due to the sludge disintegration. The relationship between the biogas production and the sludge disintegration showed that the accumulative biogas and methane production were mainly enhanced by the sludge disintegration, which accelerated the anaerobic digestion process and improved the methane content in the biogas. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nanosecond laser ablation of target Al in a gaseous medium: explosive boiling

NASA Astrophysics Data System (ADS)

Mazhukin, V. I.; Mazhukin, A. V.; Demin, M. M.; Shapranov, A. V.

2018-03-01

An approximate mathematical description of the processes of homogeneous nucleation and homogeneous evaporation (explosive boiling) of a metal target (Al) under the influence of ns laser radiation is proposed in the framework of the hydrodynamic model. Within the continuum approach, a multi-phase, multi-front hydrodynamic model and a computational algorithm are designed to simulate nanosecond laser ablation of the metal targets immersed in gaseous media. The proposed approach is intended for modeling and detailed analysis of the mechanisms of heterogeneous and homogeneous evaporation and their interaction with each other. It is shown that the proposed model and computational algorithm allow modeling of interrelated mechanisms of heterogeneous and homogeneous evaporation of metals, manifested in the form of pulsating explosive boiling. Modeling has shown that explosive evaporation in metals is due to the presence of a near-surface temperature maximum. It has been established that in nanosecond pulsed laser ablation, such exposure regimes can be implemented in which phase explosion is the main mechanism of material removal.

Voluntary Deep Inspiration Breath-hold Reduces the Heart Dose Without Compromising the Target Volume Coverage During Radiotherapy for Left-sided Breast Cancer.

PubMed

Al-Hammadi, Noora; Caparrotti, Palmira; Naim, Carole; Hayes, Jillian; Rebecca Benson, Katherine; Vasic, Ana; Al-Abdulla, Hissa; Hammoud, Rabih; Divakar, Saju; Petric, Primoz

2018-03-01

During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique. Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/- regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control. Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/- 2.5 to 3.2 +/- 1.4 Gy (p < 0.001), maximum cardiac dose from 51.1 +/- 1.4 to 48.5 +/- 6.8 Gy (p = 0.005) and cardiac V25Gy from 8.5 +/- 4.2 to 3.2 +/- 2.5% (p < 0.001). Heart volumes receiving low (10-20 Gy) and high (30-50 Gy) doses were also significantly reduced. Mean dose to the left anterior coronary artery was 23.0 (+/- 6.7) Gy and 14.8 (+/- 7.6) Gy on FB and V-DIBH, respectively (p < 0.001). Differences between FB- and V-DIBH-derived mean lung dose (11.3 +/- 3.2 vs. 10.6 +/- 2.6 Gy), lung V20Gy (20.5 +/- 7 vs. 19.5 +/- 5.1 Gy) and V95% for the OPTV (95.6 +/- 4.1 vs. 95.2 +/- 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model.

PubMed

Zhou, Yu-Feng; Tao, Meng-Ting; He, Yu-Zhang; Sun, Jian; Liu, Ya-Hong; Liao, Xiao-Ping

2018-01-01

Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy ( R 2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log 10 and 2-log 10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli . Copyright © 2017 American Society for Microbiology.

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

PubMed

Xie, Chuanbin; Cong, Xiaohu; Xu, Shouping; Dai, Xiangkun; Wang, Yunlai; Han, Lu; Gong, Hanshun; Ju, Zhongjian; Ge, Ruigang; Ma, Lin

2015-03-01

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

PubMed Central

Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

2013-01-01

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

Dose calculations accounting for breathing motion in stereotactic lung radiotherapy based on 4D-CT and the internal target volume.

PubMed

Admiraal, Marjan A; Schuring, Danny; Hurkmans, Coen W

2008-01-01

The purpose of this study was to determine the 4D accumulated dose delivered to the CTV in stereotactic radiotherapy of lung tumours, for treatments planned on an average CT using an ITV derived from the Maximum Intensity Projection (MIP) CT. For 10 stage I lung cancer patients, treatment plans were generated based on 4D-CT images. From the 4D-CT scan, 10 time-sorted breathing phases were derived, along with the average CT and the MIP. The ITV with a margin of 0mm was used as a PTV to study a worst case scenario in which the differences between 3D planning and 4D dose accumulation will be largest. Dose calculations were performed on the average CT. Dose prescription was 60Gy to 95% of the PTV, and at least 54Gy should be received by 99% of the PTV. Plans were generated using the inverse planning module of the Pinnacle(3) treatment planning system. The plans consisted of nine coplanar beams with two segments each. After optimisation, the treatment plan was transferred to all breathing phases and the delivered dose per phase was calculated using an elastic body spline model available in our research version of Pinnacle (8.1r). Then, the cumulative dose to the CTV over all breathing phases was calculated and compared to the dose distribution of the original treatment plan. Although location, tumour size and breathing-induced tumour movement varied widely between patients, the PTV planning criteria could always be achieved without compromising organs at risk criteria. After 4D dose calculations, only very small differences between the initial planned PTV coverage and resulting CTV coverage were observed. For all patients, the dose delivered to 99% of the CTV exceeded 54Gy. For nine out of 10 patients also the criterion was met that the volume of the CTV receiving at least the prescribed dose was more than 95%. When the target dose is prescribed to the ITV (PTV=ITV) and dose calculations are performed on the average CT, the cumulative CTV dose compares well to the

Nonstationary homogeneous nucleation

NASA Technical Reports Server (NTRS)

Harstad, K. G.

1974-01-01

The theory of homogeneous condensation is reviewed and equations describing this process are presented. Numerical computer solutions to transient problems in nucleation (relaxation to steady state) are presented and compared to a prior computation.

A novel dose-based positioning method for CT image-guided proton therapy

PubMed Central

Cheung, Joey P.; Park, Peter C.; Court, Laurence E.; Ronald Zhu, X.; Kudchadker, Rajat J.; Frank, Steven J.; Dong, Lei

2013-01-01

Purpose: Proton dose distributions can potentially be altered by anatomical changes in the beam path despite perfect target alignment using traditional image guidance methods. In this simulation study, the authors explored the use of dosimetric factors instead of only anatomy to set up patients for proton therapy using in-room volumetric computed tomographic (CT) images. Methods: To simulate patient anatomy in a free-breathing treatment condition, weekly time-averaged four-dimensional CT data near the end of treatment for 15 lung cancer patients were used in this study for a dose-based isocenter shift method to correct dosimetric deviations without replanning. The isocenter shift was obtained using the traditional anatomy-based image guidance method as the starting position. Subsequent isocenter shifts were established based on dosimetric criteria using a fast dose approximation method. For each isocenter shift, doses were calculated every 2 mm up to ±8 mm in each direction. The optimal dose alignment was obtained by imposing a target coverage constraint that at least 99% of the target would receive at least 95% of the prescribed dose and by minimizing the mean dose to the ipsilateral lung. Results: The authors found that 7 of 15 plans did not meet the target coverage constraint when using only the anatomy-based alignment. After the authors applied dose-based alignment, all met the target coverage constraint. For all but one case in which the target dose was met using both anatomy-based and dose-based alignment, the latter method was able to improve normal tissue sparing. Conclusions: The authors demonstrated that a dose-based adjustment to the isocenter can improve target coverage and/or reduce dose to nearby normal tissue. PMID:23635262

Two-Dimensional Homogeneous Fermi Gases

NASA Astrophysics Data System (ADS)

Hueck, Klaus; Luick, Niclas; Sobirey, Lennart; Siegl, Jonas; Lompe, Thomas; Moritz, Henning

2018-02-01

We report on the experimental realization of homogeneous two-dimensional (2D) Fermi gases trapped in a box potential. In contrast to harmonically trapped gases, these homogeneous 2D systems are ideally suited to probe local as well as nonlocal properties of strongly interacting many-body systems. As a first benchmark experiment, we use a local probe to measure the density of a noninteracting 2D Fermi gas as a function of the chemical potential and find excellent agreement with the corresponding equation of state. We then perform matter wave focusing to extract the momentum distribution of the system and directly observe Pauli blocking in a near unity occupation of momentum states. Finally, we measure the momentum distribution of an interacting homogeneous 2D gas in the crossover between attractively interacting fermions and bosonic dimers.

Improving homogeneity by dynamic speed limit systems.

PubMed

van Nes, Nicole; Brandenburg, Stefan; Twisk, Divera

2010-05-01

Homogeneity of driving speeds is an important variable in determining road safety; more homogeneous driving speeds increase road safety. This study investigates the effect of introducing dynamic speed limit systems on homogeneity of driving speeds. A total of 46 subjects twice drove a route along 12 road sections in a driving simulator. The speed limit system (static-dynamic), the sophistication of the dynamic speed limit system (basic roadside, advanced roadside, and advanced in-car) and the situational condition (dangerous-non-dangerous) were varied. The homogeneity of driving speed, the rated credibility of the posted speed limit and the acceptance of the different dynamic speed limit systems were assessed. The results show that the homogeneity of individual speeds, defined as the variation in driving speed for an individual subject along a particular road section, was higher with the dynamic speed limit system than with the static speed limit system. The more sophisticated dynamic speed limit system tested within this study led to higher homogeneity than the less sophisticated systems. The acceptance of the dynamic speed limit systems used in this study was positive, they were perceived as quite useful and rather satisfactory. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Searching regional rainfall homogeneity using atmospheric fields

NASA Astrophysics Data System (ADS)

Gabriele, Salvatore; Chiaravalloti, Francesco

2013-03-01

The correct identification of homogeneous areas in regional rainfall frequency analysis is fundamental to ensure the best selection of the probability distribution and the regional model which produce low bias and low root mean square error of quantiles estimation. In an attempt at rainfall spatial homogeneity, the paper explores a new approach that is based on meteo-climatic information. The results are verified ex-post using standard homogeneity tests applied to the annual maximum daily rainfall series. The first step of the proposed procedure selects two different types of homogeneous large regions: convective macro-regions, which contain high values of the Convective Available Potential Energy index, normally associated with convective rainfall events, and stratiform macro-regions, which are characterized by low values of the Q vector Divergence index, associated with dynamic instability and stratiform precipitation. These macro-regions are identified using Hot Spot Analysis to emphasize clusters of extreme values of the indexes. In the second step, inside each identified macro-region, homogeneous sub-regions are found using kriging interpolation on the mean direction of the Vertically Integrated Moisture Flux. To check the proposed procedure, two detailed examples of homogeneous sub-regions are examined.

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Sojourning with the Homogeneous Poisson Process.

PubMed

Liu, Piaomu; Peña, Edsel A

2016-01-01

In this pedagogical article, distributional properties, some surprising, pertaining to the homogeneous Poisson process (HPP), when observed over a possibly random window, are presented. Properties of the gap-time that covered the termination time and the correlations among gap-times of the observed events are obtained. Inference procedures, such as estimation and model validation, based on event occurrence data over the observation window, are also presented. We envision that through the results in this paper, a better appreciation of the subtleties involved in the modeling and analysis of recurrent events data will ensue, since the HPP is arguably one of the simplest among recurrent event models. In addition, the use of the theorem of total probability, Bayes theorem, the iterated rules of expectation, variance and covariance, and the renewal equation could be illustrative when teaching distribution theory, mathematical statistics, and stochastic processes at both the undergraduate and graduate levels. This article is targeted towards both instructors and students.

Propagation and immunization of infection on general networks with both homogeneous and heterogeneous components

NASA Astrophysics Data System (ADS)

Liu, Zonghua; Lai, Ying-Cheng; Ye, Nong

2003-03-01

We consider the entire spectrum of architectures of general networks, ranging from being heterogeneous (scale-free) to homogeneous (random), and investigate the infection dynamics by using a three-state epidemiological model that does not involve the mechanism of self-recovery. This model is relevant to realistic situations such as the propagation of a flu virus or information over a social network. Our heuristic analysis and computations indicate that (1) regardless of the network architecture, there exists a substantial fraction of nodes that can never be infected and (2) heterogeneous networks are relatively more robust against spreads of infection as compared with homogeneous networks. We have also considered the problem of immunization for preventing wide spread of infection, with the result that targeted immunization is effective for heterogeneous networks.

Quantitative Homogenization in Nonlinear Elasticity for Small Loads

NASA Astrophysics Data System (ADS)

Neukamm, Stefan; Schäffner, Mathias

2018-04-01

We study quantitative periodic homogenization of integral functionals in the context of nonlinear elasticity. Under suitable assumptions on the energy densities (in particular frame indifference; minimality, non-degeneracy and smoothness at the identity; {p ≥q d} -growth from below; and regularity of the microstructure), we show that in a neighborhood of the set of rotations, the multi-cell homogenization formula of non-convex homogenization reduces to a single-cell formula. The latter can be expressed with the help of correctors. We prove that the homogenized integrand admits a quadratic Taylor expansion in an open neighborhood of the rotations - a result that can be interpreted as the fact that homogenization and linearization commute close to the rotations. Moreover, for small applied loads, we provide an estimate on the homogenization error in terms of a quantitative two-scale expansion.

Dosimetric quality endpoints for low-dose-rate prostate brachytherapy using biological effective dose (bed) vs. conventional dose

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

Singh, Rachana; Al-Hallaq, Hania; Pelizzari, Charles A.

2003-12-31

The purpose of this study was to compare conventional low-dose-rate prostate brachytherapy dosimetric quality parameters with their biological effective dose (BED) counterparts. To validate a model for transformation from conventional dose to BED, the postimplant plans of 31 prostate brachytherapy patients were evaluated using conventional dose-volume histogram (DVH) quality endpoints and analogous BED-DVH endpoints. Based on CT scans obtained 4 weeks after implantation, DVHs were computed and standard dosimetric endpoints V100 (volume receiving 100% of the prescribed dose), V150, V200, HI (1-[V150/V100]), and D90 (dose that 90% of the target volume received) were obtained for quality analysis. Using known andmore » reported transformations, dose grids were transformed to BED-early ({alpha}/{beta} = 10 Gy) and BED-late ({alpha}/{beta} = 3 Gy) grids, and the same dosimetric endpoints were analyzed. For conventional, BED-early and BED-late DVHs, no differences in V100 were seen (0.896, 0.893, and 0.894, respectively). However, V150 and V200 were significantly higher for both BED-early (0.582 and 0.316) and BED-late (0.595 and 0.337), compared with the conventional (0.539 and 0.255) DVHs. D90 was significantly lower for the BED-early (103.1 Gy) and BED-late transformations (106.9 Gy) as compared with the conventional (119.5 Gy) DVHs. The conventional prescription parameter V100 is the same for the corresponding BED-early and BED-late transformed DVHs. The toxicity parameters V150 and V200 are slightly higher using the BED transformations, suggesting that the BED doses are somewhat higher than predicted using conventional DVHs. The prescription/quality parameter D90 is slightly lower, implying that target coverage is lower than predicted using conventional DVHs. This methodology can be applied to analyze BED dosimetric endpoints to improve clinical outcome and reduce complications of prostate brachytherapy.« less

Intensity Modulated Radiotherapy Improves Target Coverage and Parotid Gland Sparing When Delivering Total Mucosal Irradiation in Patients With Squamous Cell Carcinoma of Head and Neck of Unknown Primary Site

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

Bhide, Shreerang; Clark, Catherine; Harrington, Kevin

2007-10-01

Head and neck squamous cell carcinoma with occult primary site represents a controversial clinical problem. Conventional total mucosal irradiation (TMI) maximizes local control, but at the expense of xerostomia. IMRT has been shown to spare salivary tissue in head and cancer patients. This study has been performed to investigate the potential of IMRT to perform nodal and TMI and also allow parotid gland sparing in this patient group. Conventional radiotherapy (CRT) and IMRT plans were produced for six patients to treat the ipsilateral (involved) post-operative neck (PTV1) and the un-operated contralateral neck and mucosal axis (PTV2). Plans were produced withmore » and without the inclusion of nasopharynx in the PTV2. The potential to improve target coverage and spare the parotid glands was investigated for the IMRT plans. There was no significant difference in the mean doses to the PTV1 using CRT and IMRT (59.7 and 60.0 respectively, p = 0.5). The maximum doses to PTV1 and PTV2 were lower for the IMRT technique as compared to CRT (P = 0.008 and P < 0.0001), respectively, and the minimum doses to PTV1 and PTV2 were significantly higher for IMRT as compared to CRT (P = 0.001 and P = 0.001), respectively, illustrating better dose homogeneity with IMRT. The mean dose to the parotid gland contralateral to PTV1 was significantly lower for IMRT (23.21 {+-} 0.7) as compared to CRT (50.5 {+-} 5.8) (P < 0.0001). There was a significant difference in parotid dose between plans with and without the inclusion of the nasopharynx. IMRT offers improved dose homogeneity in PTV1 and PTV2 and allows for parotid sparing.« less

High-NA optical CD metrology on small in-cell targets enabling improved higher order dose control and process control for logic

NASA Astrophysics Data System (ADS)

Cramer, Hugo; Mc Namara, Elliott; van Laarhoven, Rik; Jaganatharaja, Ram; de la Fuente, Isabel; Hsu, Sharon; Belletti, Filippo; Popadic, Milos; Tu, Ward; Huang, Wade

2017-03-01

The logic manufacturing process requires small in-device metrology targets to exploit the full dose correction potential of the modern scanners and process tools. A high-NA angular resolved scatterometer (YieldStar S-1250D) was modified to demonstrate the possibility of OCD measurements on 5x5µm2 targets. The results obtained on test wafers in a logic manufacturing environment, measured after litho and after core etch, showed a good correlation to larger reference targets and AEI to ADI intra-field CDU correlation, thereby demonstrating the feasibility of OCD on such small targets. The data was used to determine a reduction potential of 55% for the intra-field CD variation, using 145 points per field on a few inner fields, and 33% of the process induced across wafer CD variation using 16 points per field full wafer. In addition, the OCD measurements reveal valuable information on wafer-to-wafer layer height variations within a lot.

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

Krayenbuehl, Jerome; Hartmann, Matthias; Lomax, Anthony J.

Purpose: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. Methods and Materials: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. Results: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The meanmore » dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm{sup 3}), decreasing from 0 to 18.5 cm{sup 3}/day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. Conclusion: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.« less

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

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

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

PubMed Central

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

PubMed

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

Evolution of resistance to anti-cancer therapy during general dosing schedules

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

Anti-cancer drugs targeted to specific oncogenic pathways have shown promising therapeutic results in the past few years; however, drug resistance remains an important obstacle for these therapies. Resistance to these drugs can emerge due to a variety of reasons including genetic or epigenetic changes which alter the binding site of the drug target, cellular metabolism or export mechanisms. Obtaining a better understanding of the evolution of resistant populations during therapy may enable the design of more effective therapeutic regimens which prevent or delay progression of disease due to resistance. In this paper, we use stochastic mathematical models to study the evolutionary dynamics of resistance under time-varying dosing schedules and pharmacokinetic effects. The populations of sensitive and resistant cells are modeled as multi-type non-homogeneous birth-death processes in which the drug concentration affects the birth and death rates of both the sensitive and resistant cell populations in continuous time. This flexible model allows us to consider the effects of generalized treatment strategies as well as detailed pharmacokinetic phenomena such as drug elimination and accumulation over multiple doses. We develop estimates for the probability of developing resistance and moments of the size of the resistant cell population. With these estimates, we optimize treatment schedules over a subspace of tolerated schedules to minimize the risk of disease progression due to resistance as well as locate ideal schedules for controlling the population size of resistant clones in situations where resistance is inevitable. Our methodology can be used to describe dynamics of resistance arising due to a single (epi)genetic alteration in any tumor type. PMID:20004211

Surface dose measurement for helical tomotherapy.

PubMed

Snir, Jonatan A; Mosalaei, Homeira; Jordan, Kevin; Yartsev, Slav

2011-06-01

To compare the surface dose measurements made by different dosimeters for the helical tomotherapy (HT) plan in the case of the target close to the surface. Surface dose measurements in different points for the HT plan to deliver 2 Gy to the planning target volume (PTV) at 5 mm below the surface of the cylindrical phantom were performed by radiochromic films, single use metal oxide semiconductor field-effect transistor (MOSFET) dosimeters, silicon IVD QED diode, and optically stimulated luminescence (OSL) dosimeters. The measured doses by all dosimeters were within 12 +/- 8% difference of each other. Radiochromic films, EBT, and EBT2, provide high spatial resolution, although it is difficult to get accurate measurements of dose. Both the OSL and QED measured similar dose to that of the MOSFET detectors. The QED dosimeter is promising as a reusable on-line wireless dosimeter, while the OSL dosimeters are easier to use, require minimum setup time and are very precise.

Sensitivity of liquid clouds to homogenous freezing parameterizations.

PubMed

Herbert, Ross J; Murray, Benjamin J; Dobbie, Steven J; Koop, Thomas

2015-03-16

Water droplets in some clouds can supercool to temperatures where homogeneous ice nucleation becomes the dominant freezing mechanism. In many cloud resolving and mesoscale models, it is assumed that homogeneous ice nucleation in water droplets only occurs below some threshold temperature typically set at -40°C. However, laboratory measurements show that there is a finite rate of nucleation at warmer temperatures. In this study we use a parcel model with detailed microphysics to show that cloud properties can be sensitive to homogeneous ice nucleation as warm as -30°C. Thus, homogeneous ice nucleation may be more important for cloud development, precipitation rates, and key cloud radiative parameters than is often assumed. Furthermore, we show that cloud development is particularly sensitive to the temperature dependence of the nucleation rate. In order to better constrain the parameterization of homogeneous ice nucleation laboratory measurements are needed at both high (>-35°C) and low (<-38°C) temperatures. Homogeneous freezing may be significant as warm as -30°CHomogeneous freezing should not be represented by a threshold approximationThere is a need for an improved parameterization of homogeneous ice nucleation.

SEMICONDUCTOR TECHNOLOGY: An efficient dose-compensation method for proximity effect correction

NASA Astrophysics Data System (ADS)

Ying, Wang; Weihua, Han; Xiang, Yang; Renping, Zhang; Yang, Zhang; Fuhua, Yang

2010-08-01

A novel simple dose-compensation method is developed for proximity effect correction in electron-beam lithography. The sizes of exposed patterns depend on dose factors while other exposure parameters (including accelerate voltage, resist thickness, exposing step size, substrate material, and so on) remain constant. This method is based on two reasonable assumptions in the evaluation of the compensated dose factor: one is that the relation between dose factors and circle-diameters is linear in the range under consideration; the other is that the compensated dose factor is only affected by the nearest neighbors for simplicity. Four-layer-hexagon photonic crystal structures were fabricated as test patterns to demonstrate this method. Compared to the uncorrected structures, the homogeneity of the corrected hole-size in photonic crystal structures was clearly improved.

Variability of surface and center position radiation dose in MDCT: Monte Carlo simulations using CTDI and anthropomorphic phantoms

PubMed Central

Zhang, Di; Savandi, Ali S.; Demarco, John J.; Cagnon, Chris H.; Angel, Erin; Turner, Adam C.; Cody, Dianna D.; Stevens, Donna M.; Primak, Andrew N.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

2009-01-01

The larger coverage afforded by wider z-axis beams in multidetector CT (MDCT) creates larger cone angles and greater beam divergence, which results in substantial surface dose variation for helical and contiguous axial scans. This study evaluates the variation of absorbed radiation dose in both cylindrical and anthropomorphic phantoms when performing helical or contiguous axial scans. The approach used here was to perform Monte Carlo simulations of a 64 slice MDCT. Simulations were performed with different radiation profiles (simulated beam widths) for a given collimation setting (nominal beam width) and for different pitch values and tube start angles. The magnitude of variation at the surface was evaluated under four different conditions: (a) a homogeneous CTDI phantom with different combinations of pitch and simulated beam widths, (b) a heterogeneous anthropomorphic phantom with one measured beam collimation and various pitch values, (c) a homogeneous CTDI phantom with fixed beam collimation and pitch, but with different tube start angles, and (d) pitch values that should minimize variations of surface dose—evaluated for both homogeneous and heterogeneous phantoms. For the CTDI phantom simulations, peripheral dose patterns showed variation with percent ripple as high as 65% when pitch is 1.5 and simulated beam width is equal to the nominal collimation. For the anterior surface dose on an anthropomorphic phantom, the percent ripple was as high as 40% when the pitch is 1.5 and simulated beam width is equal to the measured beam width. Low pitch values were shown to cause beam overlaps which created new peaks. Different x-ray tube start angles create shifts of the peripheral dose profiles. The start angle simulations showed that for a given table position, the surface dose could vary dramatically with minimum values that were 40% of the peak when all conditions are held constant except for the start angle. The last group of simulations showed that an �

Validation of an improved helical diode array and dose reconstruction software using TG‐244 datasets and stringent dose comparison criteria

PubMed Central

Ahmed, Saeed; Nelms, Benjamin; Kozelka, Jakub; Zhang, Geoffrey; Moros, Eduardo

2016-01-01

The original helical ArcCHECK (AC) diode array and associated software for 3D measurement‐guided dose reconstruction were characterized and validated; however, recent design changes to the AC required that the subject be revisited. The most important AC change starting in 2014 was a significant reduction in the overresponse of diodes to scattered radiation outside of the direct beam, accomplished by reducing the amount of high‐Z materials adjacent to the diodes. This change improved the diode measurement accuracy, but in the process invalidated the dose reconstruction models that were assembled based on measured data acquired with the older version of the AC. A correction mechanism was introduced in the reconstruction software (3DVH) to accommodate this and potential future design changes without requiring updating model parameters. For each permutation of AC serial number and beam model, the user can define in 3DVH a single correction factor which will be used to compensate for the difference in the out‐of‐field response between the new and original AC designs. The exact value can be determined by minimizing the dose‐difference with an ionization chamber or another independent dosimeter. A single value of 1.17, corresponding to the maximum measured out‐of‐field response difference between the new and old AC, provided satisfactory results for all studied energies (6X, 15X, and flattening filter‐free 10XFFF). A library of standard cases recommended by the AAPM TG‐244 Report was used for reconstructed dose verification. The overall difference between reconstructed dose and an ion chamber in a water‐equivalent phantom in the targets was 0.0% ± 1.4% (1 SD). The reconstructed dose on a homogeneous phantom was also compared to a biplanar diode dosimeter (Delta4) using gamma analysis with 2% (local dose‐error normalization)/2 mm/10% cutoff criteria. The mean agreement rate was 96.7% ± 3.7%. For the plans common with the previous

Ridge filter design and optimization for the broad-beam three-dimensional irradiation system for heavy-ion radiotherapy.

PubMed

Schaffner, B; Kanai, T; Futami, Y; Shimbo, M; Urakabe, E

2000-04-01

The broad-beam three-dimensional irradiation system under development at National Institute of Radiological Sciences (NIRS) requires a small ridge filter to spread the initially monoenergetic heavy-ion beam to a small spread-out Bragg peak (SOBP). A large SOBP covering the target volume is then achieved by a superposition of differently weighted and displaced small SOBPs. Two approaches were studied for the definition of a suitable ridge filter and experimental verifications were performed. Both approaches show a good agreement between the calculated and measured dose and lead to a good homogeneity of the biological dose in the target. However, the ridge filter design that produces a Gaussian-shaped spectrum of the particle ranges was found to be more robust to small errors and uncertainties in the beam application. Furthermore, an optimization procedure for two fields was applied to compensate for the missing dose from the fragmentation tail for the case of a simple-geometry target. The optimized biological dose distributions show that a very good homogeneity is achievable in the target.

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Radiomics based targeted radiotherapy planning (Rad-TRaP): a computational framework for prostate cancer treatment planning with MRI.

PubMed

Shiradkar, Rakesh; Podder, Tarun K; Algohary, Ahmad; Viswanath, Satish; Ellis, Rodney J; Madabhushi, Anant

2016-11-10

Radiomics or computer - extracted texture features have been shown to achieve superior performance than multiparametric MRI (mpMRI) signal intensities alone in targeting prostate cancer (PCa) lesions. Radiomics along with deformable co-registration tools can be used to develop a framework to generate targeted focal radiotherapy treatment plans. The Rad-TRaP framework comprises three distinct modules. Firstly, a module for radiomics based detection of PCa lesions on mpMRI via a feature enabled machine learning classifier. The second module comprises a multi-modal deformable co-registration scheme to map tissue, organ, and delineated target volumes from MRI onto CT. Finally, the third module involves generation of a radiomics based dose plan on MRI for brachytherapy and on CT for EBRT using the target delineations transferred from the MRI to the CT. Rad-TRaP framework was evaluated using a retrospective cohort of 23 patient studies from two different institutions. 11 patients from the first institution were used to train a radiomics classifier, which was used to detect tumor regions in 12 patients from the second institution. The ground truth cancer delineations for training the machine learning classifier were made by an experienced radiation oncologist using mpMRI, knowledge of biopsy location and radiology reports. The detected tumor regions were used to generate treatment plans for brachytherapy using mpMRI, and tumor regions mapped from MRI to CT to generate corresponding treatment plans for EBRT. For each of EBRT and brachytherapy, 3 dose plans were generated - whole gland homogeneous ([Formula: see text]) which is the current clinical standard, radiomics based focal ([Formula: see text]), and whole gland with a radiomics based focal boost ([Formula: see text]). Comparison of [Formula: see text] against conventional [Formula: see text] revealed that targeted focal brachytherapy would result in a marked reduction in dosage to the OARs while ensuring that the

Shock effects in particle beam fusion targets

NASA Astrophysics Data System (ADS)

Sweeney, M. A.; Perry, F. C.; Asay, J. R.; Widner, M. M.

1982-04-01

At Sandia National Laboratorics we are assessing the response of fusion target materials to shock loading with the particle beam accelerators HYDRA and PROTO I and the gas gun facility. Nonlinear shock-accelerated unstable growth of fabriction irregularities has been demonstrated, and jetting is found to occur in imploding targets because of asymmetric beam deposition. Cylindrical ion targets display an instability due either to beam or target nonuniformity. However, the data suggest targets with aspect ratios of 30 may implode stably. The first time- and space-resolved measurements of shock-induced vaporization have been made. A homogeneous mixed phase EOS model cannot adequately explain the results because of the kinetic effects of vapor formation and expansion.

Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization.

PubMed

Pavan, Ana Luiza Menegatti; Rosa, Maria Eugênia Dela; Giacomini, Guilherme; Bacchim Neto, Fernando Antonio; Yamashita, Seizo; Vulcano, Luiz Carlos; Duarte, Sergio Barbosa; Miranda, José Ricardo de Arruda; de Pina, Diana Rodrigues

2016-01-01

Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures.

Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization

PubMed Central

2016-01-01

Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures. PMID:27101001

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats.

PubMed

López de las Hazas, Maria-Carmen; Rubió, Laura; Kotronoulas, Aristotelis; de la Torre, Rafael; Solà, Rosa; Motilva, Maria-José

2015-07-01

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols

Differential pencil beam dose computation model for photons.

PubMed

Mohan, R; Chui, C; Lidofsky, L

1986-01-01

Differential pencil beam (DPB) is defined as the dose distribution relative to the position of the first collision, per unit collision density, for a monoenergetic pencil beam of photons in an infinite homogeneous medium of unit density. We have generated DPB dose distribution tables for a number of photon energies in water using the Monte Carlo method. The three-dimensional (3D) nature of the transport of photons and electrons is automatically incorporated in DPB dose distributions. Dose is computed by evaluating 3D integrals of DPB dose. The DPB dose computation model has been applied to calculate dose distributions for 60Co and accelerator beams. Calculations for the latter are performed using energy spectra generated with the Monte Carlo program. To predict dose distributions near the beam boundaries defined by the collimation system as well as blocks, we utilize the angular distribution of incident photons. Inhomogeneities are taken into account by attenuating the primary photon fluence exponentially utilizing the average total linear attenuation coefficient of intervening tissue, by multiplying photon fluence by the linear attenuation coefficient to yield the number of collisions in the scattering volume, and by scaling the path between the scattering volume element and the computation point by an effective density.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on

Homogenization patterns of the world's freshwater fish faunas.

PubMed

Villéger, Sébastien; Blanchet, Simon; Beauchard, Olivier; Oberdorff, Thierry; Brosse, Sébastien

2011-11-01

The world is currently undergoing an unprecedented decline in biodiversity, which is mainly attributable to human activities. For instance, nonnative species introduction, combined with the extirpation of native species, affects biodiversity patterns, notably by increasing the similarity among species assemblages. This biodiversity change, called taxonomic homogenization, has rarely been assessed at the world scale. Here, we fill this gap by assessing the current homogenization status of one of the most diverse vertebrate groups (i.e., freshwater fishes) at global and regional scales. We demonstrate that current homogenization of the freshwater fish faunas is still low at the world scale (0.5%) but reaches substantial levels (up to 10%) in some highly invaded river basins from the Nearctic and Palearctic realms. In these realms experiencing high changes, nonnative species introductions rather than native species extirpations drive taxonomic homogenization. Our results suggest that the "Homogocene era" is not yet the case for freshwater fish fauna at the worldwide scale. However, the distressingly high level of homogenization noted for some biogeographical realms stresses the need for further understanding of the ecological consequences of homogenization processes.

Homogeneous buoyancy-generated turbulence

NASA Technical Reports Server (NTRS)

Batchelor, G. K.; Canuto, V. M.; Chasnov, J. R.

1992-01-01

Using a theoretical analysis of fundamental equations and a numerical simulation of the flow field, the statistically homogeneous motion that is generated by buoyancy forces after the creation of homogeneous random fluctuations in the density of infinite fluid at an initial instant is examined. It is shown that analytical results together with numerical results provide a comprehensive description of the 'birth, life, and death' of buoyancy-generated turbulence. Results of numerical simulations yielded the mean-square density mean-square velocity fluctuations and the associated spectra as functions of time for various initial conditions, and the time required for the mean-square density fluctuation to fall to a specified small value was estimated.

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

NASA Technical Reports Server (NTRS)

Chappell, Lori J.; Cucinotta, Francis A.

2010-01-01

There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

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

Carlsson Tedgren, A; Persson, M; Nilsson, J

Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT imagesmore » in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined.« less

Comparison of microdosimetry-based absorbed doses to control tumours and clinically obtained tumour absorbed doses in treatments with ²²³Ra.

PubMed

Minguez Gabina, Pablo; Roeske, John C; Mínguez, Ricardo; Gomez de Iturriaga, Alfonso; Rodeño, Emilia

2018-06-20

We performed Monte Carlo simulations in order to determine by means of microdosimetry calculations the average number of hits to the cell nucleus required to reach a tumour control probability (TCP) of 0.9, 〈n_0.9 〉, for the source geometry of a nucleus embedded in a homogeneous distribution of ²²³Ra atoms. From the results obtained and following the MIRD methodology, we determined the values of lesion absorbed doses needed to reach a TCP of 0.9, D_0.9, for different values of mass density, cell radiosensitivity, nucleus radius and lesion volume. The greatest variation of those absorbed doses occurred with cell radiosensitivity and no dependence was found on mass density. The source geometry used was chosen because we aimed to compare the values of D_0.9 with the lesion absorbed doses obtained from image-based macrodosimetry in treatments of metastatic castration-resistant prostate cancer with ²²³Ra which were obtained assuming a homogeneous distribution of ²²³Ra atoms within the lesion. In a comparison with a study including 29 lesions, results showed that even for the case of the most radiosensitive cells simulated, 45% of the lesions treated following a schedule of two cycles of 110 kBq/kg body mass would receive absorbed doses below the values of D_0.9 determined in this study. © 2018 Institute of Physics and Engineering in Medicine.

Visualization of a variety of possible dosimetric outcomes in radiation therapy using dose-volume histogram bands.

PubMed

Trofimov, Alexei; Unkelbach, Jan; DeLaney, Thomas F; Bortfeld, Thomas

2012-01-01

Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quality of a clinical treatment plan. However, when delivery uncertainties are present, the DVH may not always accurately describe the dose distribution actually delivered to the patient. We present a method, based on DVH formalism, to visualize the variability in the expected dosimetric outcome of a treatment plan. For a case of chordoma of the cervical spine, we compared 2 intensity modulated proton therapy plans. Treatment plan A was optimized based on dosimetric objectives alone (ie, desired target coverage, normal tissue tolerance). Plan B was created employing a published probabilistic optimization method that considered the uncertainties in patient setup and proton range in tissue. Dose distributions and DVH for both plans were calculated for the nominal delivery scenario, as well as for scenarios representing deviations from the nominal setup, and a systematic error in the estimate of range in tissue. The histograms from various scenarios were combined to create DVH bands to illustrate possible deviations from the nominal plan for the expected magnitude of setup and range errors. In the nominal scenario, the DVH from plan A showed superior dose coverage, higher dose homogeneity within the target, and improved sparing of the adjacent critical structure. However, when the dose distributions and DVH from plans A and B were recalculated for different error scenarios (eg, proton range underestimation by 3 mm), the plan quality, reflected by DVH, deteriorated significantly for plan A, while plan B was only minimally affected. In the DVH-band representation, plan A produced wider bands, reflecting its higher vulnerability to delivery errors, and uncertainty in the dosimetric outcome. The results illustrate that comparison of DVH for the nominal scenario alone does not provide any information about the relative sensitivity of dosimetric outcome to delivery uncertainties. Thus, such

Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry.

PubMed

Weber, D C; Nouet, P; Kurtz, J M; Allal, A S

2001-04-01

To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the

Regional Homogeneity

PubMed Central

Jiang, Lili; Zuo, Xi-Nian

2015-01-01

Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004

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.

SU-E-T-285: Dose Variation at Bone in Small-Animal Irradiation: A Monte Carlo Study Using Monoenergetic Photon Beams

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

Vuong, A; Chow, J

Purpose: The aim of this study is to investigate the variation of bone dose on photon beam energy (keV – MeV) in small-animal irradiation. Dosimetry of homogeneous and inhomogeneous phantoms as per the same mouse computed tomography image set were calculated using the DOSCTP and DOSXYZnrc based on the EGSnrc Monte Carlo code. Methods: Monte Carlo simulations for the homogeneous and inhomogeneous mouse phantom irradiated by a 360 degree photon arc were carried out. Mean doses of the bone tissue in the irradiated volumes were calculated at various photon beam energies, ranging from 50 keV to 1.25 MeV. The effectmore » of bone inhomogeneity was examined through the Inhomogeneous Correction Factor (ICF), a dose ratio of the inhomogeneous to the homogeneous medium. Results: From our Monte Carlo results, higher mean bone dose and ICF were found when using kilovoltage photon beams compared to megavoltage. In beam energies ranging from 50 keV to 200 keV, the bone dose was found maximum at 50 keV, and decreased significantly from 2.6 Gy to 0.55 Gy, when 2 Gy was delivered at the center of the phantom (isocenter). Similarly, the ICF were found decreasing from 4.5 to 1 when the photon beam energy was increased from 50 keV to 200 keV. Both mean bone dose and ICF remained at about 0.5 Gy and 1 from 200 keV to 1.25 MeV with insignificant variation, respectively. Conclusion: It is concluded that to avoid high bone dose in the small-animal irradiation, photon beam energy higher than 200 keV should be used with the ICF close to one, and bone dose comparable to the megavoltage beam where photoelectric effect is not dominant.« less

Proof of concept and dose estimation with binary responses under model uncertainty.

PubMed

Klingenberg, B

2009-01-30

This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors.

PubMed

Moore, Kathleen N; Borghaei, Hossein; O'Malley, David M; Jeong, Woondong; Seward, Shelly M; Bauer, Todd M; Perez, Raymond P; Matulonis, Ursula A; Running, Kelli L; Zhang, Xiaoyan; Ponte, Jose F; Ruiz-Soto, Rodrigo; Birrer, Michael J

2017-08-15

Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors. Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme. The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Secondary objectives were to determine safety and tolerability, to characterize the pharmacokinetic profile, and to describe preliminary clinical activity. In total, 44 patients received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug accumulation was observed with the dosing regimen of once every 3 weeks. The most common treatment-related adverse events were fatigue, blurred vision, and diarrhea, the majority of which were grade 1 or 2. The dose-limiting toxicities observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian cancer, achieved confirmed tumor responses according to Response Evaluation Criteria in Solid Tumors 1.1, and each was a partial response. IMGN853 demonstrated a manageable safety profile and encouraging preliminary clinical activity, particularly in patients with ovarian cancer. The results establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body weight) once every 3 weeks. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3080-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Colorimetric Aptasensor Using Unmodified Gold Nanoparticles for Homogeneous Multiplex Detection

PubMed Central

Niu, Shucao; Lv, Zhenzhen; Liu, Jinchuan; Bai, Wenhui; Yang, Shuming; Chen, Ailiang

2014-01-01

Colorimetric aptasensors using unmodified gold nanoparticles (AuNPs) have attracted much attention because of their low cost, simplicity, and practicality, and they have been developed for various targets in the past several years. However, previous research has focused on developing single-target assays. Here, we report the development of a homogeneous multiplex aptasensor by using more than one class of aptamers to stabilize AuNPs. Using sulfadimethoxine (SDM), kanamycin (KAN) and adenosine (ADE) as example targets, a KAN aptamer (750 nM), an SDM aptamer (250 nM) and an ADE aptamer (500 nM) were mixed at a 1∶1∶1 volume ratio and adsorbed directly onto the surface of unmodified AuNPs by electrostatic interaction. Upon the addition of any of the three targets, the conformation of the corresponding aptamer changed from a random coil structure to a rigid folded structure, which could not adsorb and stabilize AuNPs. The AuNPs aggregated in a specific reaction buffer (20 mM Tris-HCl containing 20 mM NaCl and 5 mM KCl), which led to a color change from red to purple/blue. These results demonstrate that the multiplex colorimetric aptasensor detected three targets simultaneously while maintaining the same sensitivity as a single-target aptasensor for each individual target. The multiplex aptasensor could be extended to other aptamers for various molecular detection events. Due to its simple design, easy operation, fast response, cost effectiveness and lack of need for sophisticated instrumentation, the proposed strategy provides a powerful tool to examine large numbers of samples to screen for a small number of potentially positive samples containing more than one analyte, which can be further validated using sophisticated instruments. PMID:25279730

Cosmic homogeneity: a spectroscopic and model-independent measurement

NASA Astrophysics Data System (ADS)

Gonçalves, R. S.; Carvalho, G. C.; Bengaly, C. A. P., Jr.; Carvalho, J. C.; Bernui, A.; Alcaniz, J. S.; Maartens, R.

2018-03-01

Cosmology relies on the Cosmological Principle, i.e. the hypothesis that the Universe is homogeneous and isotropic on large scales. This implies in particular that the counts of galaxies should approach a homogeneous scaling with volume at sufficiently large scales. Testing homogeneity is crucial to obtain a correct interpretation of the physical assumptions underlying the current cosmic acceleration and structure formation of the Universe. In this letter, we use the Baryon Oscillation Spectroscopic Survey to make the first spectroscopic and model-independent measurements of the angular homogeneity scale θh. Applying four statistical estimators, we show that the angular distribution of galaxies in the range 0.46 < z < 0.62 is consistent with homogeneity at large scales, and that θh varies with redshift, indicating a smoother Universe in the past. These results are in agreement with the foundations of the standard cosmological paradigm.

Measurement and comparison of skin dose using OneDose MOSFET and Mobile MOSFET for patients with acute lymphoblastic leukemia.

PubMed

Mattar, Essam H; Hammad, Lina F; Al-Mohammed, Huda I

2011-07-01

Total body irradiation is a protocol used to treat acute lymphoblastic leukemia in patients prior to bone marrow transplant. It is involved in the treatment of the whole body using a large radiation field with extended source-skin distance. Therefore measuring and monitoring the skin dose during the treatment is important. Two kinds of metal oxide semiconductor field effect transistor (OneDose MOSFET and mobile MOSEFT) dosimeter are used during the treatment delivery to measure the skin dose to specific points and compare it with the target prescribed dose. The objective of this study was to compare the variation of skin dose in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using OneDose MOSFET detectors and Mobile MOSFET, and then compare both results with the target prescribed dose. The measurements involved 32 patient's (16 males, 16 females), aged between 14-30 years, with an average age of 22.41 years. One-Dose MOSFET and Mobile MOSFET dosimetry were performed at 10 different anatomical sites on every patient. The results showed there was no variation between skin dose measured with OneDose MOSFET and Mobile MOSFET in all patients. Furthermore, the results showed for every anatomical site selected there was no significant difference in the dose delivered using either OneDose MOSFET detector or Mobile MOSFET as compared to the prescribed dose. The study concludes that One-Dose MOSFET detectors and Mobile MOSFET both give a direct read-out immediately after the treatment; therefore both detectors are suitable options when measuring skin dose for total body irradiation treatment.

Cosmological models with homogeneous and isotropic spatial sections

NASA Astrophysics Data System (ADS)

Katanaev, M. O.

2017-05-01

The assumption that the universe is homogeneous and isotropic is the basis for the majority of modern cosmological models. We give an example of a metric all of whose spatial sections are spaces of constant curvature but the space-time is nevertheless not homogeneous and isotropic as a whole. We give an equivalent definition of a homogeneous and isotropic universe in terms of embedded manifolds.

A targeted and adjuvanted nanocarrier lowers the effective dose of liposomal amphotericin B and enhances adaptive immunity in murine cutaneous leishmaniasis.

PubMed

Daftarian, Pirouz M; Stone, Geoffrey W; Kovalski, Leticia; Kumar, Manoj; Vosoughi, Aram; Urbieta, Maitee; Blackwelder, Pat; Dikici, Emre; Serafini, Paolo; Duffort, Stephanie; Boodoo, Richard; Rodríguez-Cortés, Alhelí; Lemmon, Vance; Deo, Sapna; Alberola, Jordi; Perez, Victor L; Daunert, Sylvia; Ager, Arba L

2013-12-01

Amphotericin B (AmB), the most effective drug against leishmaniasis, has serious toxicity. As Leishmania species are obligate intracellular parasites of antigen presenting cells (APC), an immunopotentiating APC-specific AmB nanocarrier would be ideally suited to reduce the drug dosage and regimen requirements in leishmaniasis treatment. Here, we report a nanocarrier that results in effective treatment shortening of cutaneous leishmaniasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infected host. We used a Pan-DR-binding epitope (PADRE)-derivatized-dendrimer (PDD), complexed with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic efficacy of low-dose PDD/LAmB vs full dose LAmB. PDD was shown to escort LAmB to APCs in vivo, enhanced the drug efficacy by 83% and drug APC targeting by 10-fold and significantly reduced parasite burden and toxicity. Fortuitously, the PDD immunopotentiating effect significantly enhanced parasite-specific T-cell responses in immunocompetent infected mice. PDD reduced the effective dose and toxicity of LAmB and resulted in elicitation of strong parasite specific T-cell responses. A reduced effective therapeutic dose was achieved by selective LAmB delivery to APC, bypassing bystander cells, reducing toxicity and inducing antiparasite immunity.

Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

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

Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo

Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using {sup 60}Co or {sup 192}Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes frommore » an adult reference man defined in ICRP Publication 89. Point sources of {sup 60}Co or {sup 192}Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by {sup 60}Co source were smaller (8%-19%) than from {sup 192}Ir. However, as the distance increases, the more penetrating gamma rays produced by {sup 60}Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a {sup 60}Co source (11.1 mSv/Gy) is lower than from a {sup 192}Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

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

Al-Qaisieh, Bashar; Mason, Josh, E-mail: joshua.mason@nhs.net; Bownes, Peter

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focalmore » (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a

Limitations of analytical dose calculations for small field proton radiosurgery.

PubMed

Geng, Changran; Daartz, Juliane; Lam-Tin-Cheung, Kimberley; Bussiere, Marc; Shih, Helen A; Paganetti, Harald; Schuemann, Jan

2017-01-07

The purpose of the work was to evaluate the dosimetric uncertainties of an analytical dose calculation engine and the impact on treatment plans using small fields in intracranial proton stereotactic radiosurgery (PSRS) for a gantry based double scattering system. 50 patients were evaluated including 10 patients for each of 5 diagnostic indications of: arteriovenous malformation (AVM), acoustic neuroma (AN), meningioma (MGM), metastasis (METS), and pituitary adenoma (PIT). Treatment plans followed standard prescription and optimization procedures for PSRS. We performed comparisons between delivered dose distributions, determined by Monte Carlo (MC) simulations, and those calculated with the analytical dose calculation algorithm (ADC) used in our current treatment planning system in terms of dose volume histogram parameters and beam range distributions. Results show that the difference in the dose to 95% of the target (D95) is within 6% when applying measured field size output corrections for AN, MGM, and PIT. However, for AVM and METS, the differences can be as great as 10% and 12%, respectively. Normalizing the MC dose to the ADC dose based on the dose of voxels in a central area of the target reduces the difference of the D95 to within 6% for all sites. The generally applied margin to cover uncertainties in range (3.5% of the prescribed range  +  1 mm) is not sufficient to cover the range uncertainty for ADC in all cases, especially for patients with high tissue heterogeneity. The root mean square of the R90 difference, the difference in the position of distal falloff to 90% of the prescribed dose, is affected by several factors, especially the patient geometry heterogeneity, modulation and field diameter. In conclusion, implementation of Monte Carlo dose calculation techniques into the clinic can reduce the uncertainty of the target dose for proton stereotactic radiosurgery. If MC is not available for treatment planning, using MC dose distributions to

A generalized target theory and its applications.

PubMed

Zhao, Lei; Mi, Dong; Hu, Bei; Sun, Yeqing

2015-09-28

Different radiobiological models have been proposed to estimate the cell-killing effects, which are very important in radiotherapy and radiation risk assessment. However, most applied models have their own scopes of application. In this work, by generalizing the relationship between "hit" and "survival" in traditional target theory with Yager negation operator in Fuzzy mathematics, we propose a generalized target model of radiation-induced cell inactivation that takes into account both cellular repair effects and indirect effects of radiation. The simulation results of the model and the rethinking of "the number of targets in a cell" and "the number of hits per target" suggest that it is only necessary to investigate the generalized single-hit single-target (GSHST) in the present theoretical frame. Analysis shows that the GSHST model can be reduced to the linear quadratic model and multitarget model in the low-dose and high-dose regions, respectively. The fitting results show that the GSHST model agrees well with the usual experimental observations. In addition, the present model can be used to effectively predict cellular repair capacity, radiosensitivity, target size, especially the biologically effective dose for the treatment planning in clinical applications.

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

2017-08-01

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method.

PubMed

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A; Purdie, Thomas G

2017-07-06

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

Optimal Normal Tissue Sparing in Craniospinal Axis Irradiation Using IMRT With Daily Intrafractionally Modulated Junction(s)

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

Kusters, Johannes M.A.M.; Louwe, Rob J.W.; Kollenburg, Peter G.M. van

2011-12-01

Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). Methods and Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques.more » Results: The maximum dose with IMRT was <107% in all patients. V{sub <95} and V{sub >107} were <1 cm{sup 3} for IMRT compared with 3-9 cm{sup 3} for the craniospinal and 26-43 cm{sup 3} for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V{sub 75} for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V{sub 75} for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.« less

Noncompetitive Homogeneous Detection of Small Molecules Using Synthetic Nanopeptamer-Based Luminescent Oxygen Channeling.

PubMed

Lassabe, Gabriel; Kramer, Karl; Hammock, Bruce D; González-Sapienza, Gualberto; González-Techera, Andrés

2018-05-15

Our group has previously developed immunoassays for noncompetitive detection of small molecules based on the use of phage borne anti-immunocomplex peptides. Recently, we substituted the phage particles by biotinylated synthetic anti-immunocomplex peptides complexed with streptavidin and named these constructs nanopeptamers. In this work, we report the results of combining AlphaLisa, a commercial luminescent oxygen channeling bead system, with nanopeptamers for the development of a noncompetitive homogeneous assay for the detection of small molecules. The signal generation of AlphaLisa assays relies on acceptor-donor bead proximity induced by the presence of the analyte (a macromolecule) simultaneously bound by antibodies immobilized on the surface of these beads. In the developed assay, termed as nanoAlphaLisa, bead proximity is sustained by the presence of a small model molecule (atrazine, MW = 215) using an antiatrazine antibody captured on the acceptor bead and an atrazine nanopeptamer on the donor bead. Atrazine is one of the most used pesticides worldwide, and its monitoring in water has relevant human health implications. NanoAlphaLisa allowed the homogeneous detection of atrazine down to 0.3 ng/mL in undiluted water samples in 1 h, which is 10-fold below the accepted limit in drinking water. NanoAlphaLisa has the intrinsic advantages for automation and high-throughput, simple, and fast homogeneous detection of target analytes that AlphaLisa assay provides.

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

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

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

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

SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

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

Menten, MJ; Fast, MF; Nill, S

Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin:more » 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting

Homogeneity and Entropy

NASA Astrophysics Data System (ADS)

Tignanelli, H. L.; Vazquez, R. A.; Mostaccio, C.; Gordillo, S.; Plastino, A.

1990-11-01

RESUMEN. Presentamos una metodologia de analisis de la homogeneidad a partir de la Teoria de la Informaci6n, aplicable a muestras de datos observacionales. ABSTRACT:Standard concepts that underlie Information Theory are employed in order design a methodology that enables one to analyze the homogeneity of a given data sample. Key : DATA ANALYSIS

Homogeneous Atomic Fermi Gases

NASA Astrophysics Data System (ADS)

Mukherjee, Biswaroop; Yan, Zhenjie; Patel, Parth B.; Hadzibabic, Zoran; Yefsah, Tarik; Struck, Julian; Zwierlein, Martin W.

2017-03-01

We report on the creation of homogeneous Fermi gases of ultracold atoms in a uniform potential. In the momentum distribution of a spin-polarized gas, we observe the emergence of the Fermi surface and the saturated occupation of one particle per momentum state: the striking consequence of Pauli blocking in momentum space for a degenerate gas. Cooling a spin-balanced Fermi gas at unitarity, we create homogeneous superfluids and observe spatially uniform pair condensates. For thermodynamic measurements, we introduce a hybrid potential that is harmonic in one dimension and uniform in the other two. The spatially resolved compressibility reveals the superfluid transition in a spin-balanced Fermi gas, saturation in a fully polarized Fermi gas, and strong attraction in the polaronic regime of a partially polarized Fermi gas.

Neutrons in active proton therapy: Parameterization of dose and dose equivalent.

PubMed

Schneider, Uwe; Hälg, Roger A; Lomax, Tony

2017-06-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160MeV or 177MeV instead of 138MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy. Copyright © 2016. Published by Elsevier GmbH.

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95