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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Results(1-25 of 57) Sort By: Publication Date Relevance Took: 4.119 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 3 1 2 3 > (57 articles found) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Feb 2008 Julián Aragonés,Martin Schneider,Katie Van Geyte,Peter Fraisl,Tom Dresselaers,Massimiliano Mazzone,Ruud Dirkx,Serena Zacchigna,Hélène Lemieux,Nam Ho Jeoung,Diether Lambrechts,Tammie Bishop,Peggy Lafuste,Antonio Diez-Juan,Sarah K Harten,Pieter Van Noten,Katrien De Bock,Carsten Willam,Marc Tjwa,Alexandra Grosfeld,Rachel Navet,Lieve Moons,Thierry Vandendriessche,Christophe Deroose,Bhathiya Wijeyekoon,Johan Nuyts,Benedicte Jordan,Robert Silasi-Mansat,Florea Lupu,Mieke Dewerchin,Chris Pugh,Phil Salmon,Luc Mortelmans,Bernard Gallez,Frans Gorus,Johan Buyse,Francis Sluse,Robert A Harris,Erich Gnaiger,Peter Hespel,Paul Van Hecke,Frans Schuit,Paul Van Veldhoven,Peter Ratcliffe,Myriam Baes,Patrick Maxwell,Peter Carmeliet HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic AT... ( view more )P production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Correction of conebeam CT values using a planning CT for derivation of the "dose of the day". Nov 2007 Mathilda van Zijtveld,Maarten Dirkx,Ben Heijmen BACKGROUND AND PURPOSE: Verification of the actually delivered 3D dose distribution during each treatment fraction ("dose of the day") is the most complete and clinical relevant "in-vivo" check of an IMRT treatment. To do this, during patient treatment portal dose images are routinely acquired with... ( view more ) our electronic portal imaging device to derive the delivered fluence map for each treatment field. In addition, a conebeam CT scan is acquired just prior to treatment to derive the patient geometry at the time of treatment. However, the use of conebeam CT scans for dose calculation is hampered by inaccuracies in the conversion of CT values to electron densities due to an enlarged scatter contribution. MATERIALS AND METHODS: In this work, a method is described for mapping of Hounsfield Units of the planning CT to the conebeam CT scan, while accounting for non-rigidity in the anatomy, e.g. related to weight loss, in an approximate way. The method was validated for head and neck cancer patients by comparing dose distributions calculated using adjusted Hounsfield Units with a golden standard. RESULTS AND CONCLUSIONS: The observed dose differences were less than 1% in the majority of points, and in at least 96% of the points a 3D gamma analysis resulted in gamma values of less than 1 when applying a 2%/2mm criterion, showing that this straightforward approach allows for an accurate dose calculation based on conebeam CT scans. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beta-oxidation in hepatocyte cultures from mice with peroxisomal gene knockouts. Jun 8, 2007 Ruud Dirkx,Els Meyhi,Stanny Asselberghs,Janardan Reddy,Myriam Baes,Paul P Van Veldhoven Beta-oxidation of carboxylates takes place both in mitochondria and peroxisomes and in each pathway parallel enzymes exist for each conversion step. In order to better define the substrate specificities of these enzymes and in particular the elusive role of peroxisomal MFP-1, hepatocyte cultures fr... ( view more )om mice with peroxisomal gene knockouts were used to assess the consequences on substrate degradation. Hepatocytes from mice with liver selective elimination of peroxisomes displayed severely impaired oxidation of 2-methylhexadecanoic acid, the bile acid intermediate trihydroxycholestanoic acid (THCA), and tetradecanedioic acid. In contrast, mitochondrial beta-oxidation rates of palmitate were doubled, despite the severely affected inner mitochondrial membrane. As expected, beta-oxidation of the branched chain compounds 2-methylhexadecanoic acid and THCA was reduced in hepatocytes from mice with inactivation of MFP-2. More surprisingly, dicarboxylic fatty acid oxidation was impaired in MFP-1 but not in MFP-2 knockout hepatocytes, indicating that MFP-1 might play more than an obsolete role in peroxisomal beta-oxidation. ( view less ) View Full Abstract View Article Details   Related Articles 3D dose reconstruction for clinical evaluation of IMRT pretreatment verification with an EPID. Feb 2007 Mathilda van Zijtveld,Maarten L P Dirkx,Hans C J de Boer,Ben J M Heijmen BACKGROUND AND PURPOSE: Pretreatment verification with an electronic portal imaging device is an important part of our patient-specific quality assurance program for advanced treatment techniques. Up to now, this verification has been performed for over 400 IMRT patient plans. For every treatment f... ( view more )ield, a 2D portal dose image (PDI) is measured and compared with a predicted PDI. Often it is not straightforward to interpret dose deviations found in these 2D comparisons in terms of clinical implications for the patient. Therefore, a method to derive the 3D patient dose based on the measured PDIs was implemented. METHODS AND MATERIALS: For reconstruction of the 3D patient dose, the actual fluences delivered by the accelerator are derived from measured portal dose images using an iterative method. The derived fluence map for each beam direction is then used as input for the treatment planning system to generate an adapted 3D patient dose distribution. The accuracy of this method was assessed by measurements in a water phantom. Clinical evaluation of the 3D dose reconstruction was performed for 17 IMRT patients with different tumor sites. Dose differences with respect to the original treatment plan were evaluated in individual CT slices using dose difference maps and a 3D gamma analysis and by comparing dose-volume histograms (DVHs). RESULTS: The measurements indicated that the accuracy of the 3D dose reconstruction was within 2%/2mm. For the patients observed dose differences with respect to the original plan were generally within 2%, except at the field edges and in the sharp dose gradients around the planning target volume (PTV). Gamma analysis showed that the dose differences were within 2%/2mm for more than 95% of the points in all cases. Differences in DVH parameters for the PTV and organs at risk were also within 2% in nearly all cases. CONCLUSION: A method to derive actual delivered fluence maps from measured PDIs and to use them to reconstruct the 3D patient dose was implemented. The reconstruction eases the estimation of the clinical relevance of observed dose differences in the pretreatment measurements. ( view less ) View Full Abstract View Article Details   Related Articles Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Dec 2006 Anita E M Dirkx,Mirjam G A Oude Egbrink,John Wagstaff,Arjan W Griffioen The role of a tumor immune infiltrate in cancer progression and metastasis has been debated frequently. Although often considered to be associated with improved prognosis and leading to the enhanced survival of cancer patients, inflammatory cells have also been described to assist the tumor's capab... ( view more )ilities to progress, proliferate, and metastasize. Tumor-associated macrophages (TAMs), for example, have been shown to be symbiotically related to tumor cells: Tumor cells recruit TAMs and provide them with survival factors, and TAMs in turn produce a variety of angiogenic factors in response to the tumor microenvironment. This review will describe the composition of an immune infiltrate in tumors and the angiogenic and angiostatic properties of the cells present. Special emphasis will be on the angiogenesis-associated activities of TAMs. The development of immunotherapy and gene therapy using TAMs to mediate tumor cytotoxicity or to deliver gene constructs will be discussed as well. As immunotherapy has so far not been as effective as anticipated, a combination therapy in which angiostatic agents are used as well is put forward as a novel strategy to treat cancer. ( view less ) View Full Abstract View Article Details   Related Articles Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin matrix of a plasma clot. Nov 10, 2006 D C Rijken,S P G Dirkx,T M Luider,F W G Leebeek In order to study the multiple functions of fibrinogen and fibrin, we are investigating which proteins bind to the fibrin matrix of a plasma clot by using a proteomic approach. Extracts from washed plasma clots were analysed by 2-D gel electrophoresis. A relatively abundant spot was identified as h... ( view more )epatocyte-derived fibrinogen-related protein-1 (HFREP-1) by MALDI-TOF analysis, molecular mass (34 kDa), iso-electric point (pI 5.5) as well as by Western blot analysis. HFREP-1 in plasma almost completely bound to the fibrin matrix during clot formation. Several purified fibrinogen preparations proved to be contaminated with HFREP-1. It is concluded that HFREP-1 (also named hepassocin), a protein with liver cell growth regulatory properties, occurs in plasma and strongly associates with fibrin and possibly fibrinogen. ( view less ) View Full Abstract View Article Details   Related Articles Dosimetric pre-treatment verification of IMRT using an EPID; clinical experience. Nov 2006 Mathilda van Zijtveld,Maarten L P Dirkx,Hans C J de Boer,Ben J M Heijmen BACKGROUND AND PURPOSE: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment si... ( view more )mulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. MATERIALS AND METHODS: Most of our analyses are performed using the gamma index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the gamma values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having gamma values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. RESULTS: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean gamma value inside the field was 0.43 +/- 0.13 (1SD) and only 6.1 +/- 6.8% of pixels had a gamma value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. CONCLUSION: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload. ( view less ) View Full Abstract View Article Details   Related Articles Fast, daily linac verification for segmented IMRT using electronic portal imaging. Jul 2006 Sandra C Vieira,René A Bolt,Maarten L P Dirkx,Andries G Visser,Ben J M Heijmen PURPOSE: Intensity modulated radiotherapy (IMRT) requires dedicated quality assurance (QA). Recently, we have published a method for fast (1-2 min) and accurate linac quality control for dynamic multileaf collimation, using a portal imaging device. This method is in routine use for daily leaf motio... ( view more )n verification. The purpose of the present study was to develop an equivalent procedure for QA of IMRT with segmented (static) multileaf collimation (SMLC). MATERIALS AND METHODS: The QA procedure is based on measurements performed during 3- to 8-month periods at Elekta, Siemens and Varian accelerators. On each measurement day, images were acquired for a field consisting of five 3 x 22 cm(2) segments. These 10 monitor unit (MU) segments were delivered in SMLC mode, moving the leaves from left to right. Deviations of realized leaf gap widths from the prescribed width were analysed to study the leaf positioning accuracy. To assess hysteresis in leaf positioning, the sequential delivery of the SMLC segments was also inverted. A static 20 x 20 cm(2) field was delivered with exposures between 1 and 50 MU to study the beam output and beam profile at low exposures. Comparisons with an ionisation chamber were made to verify the EPID dose measurements at low MU. Dedicated software was developed to improve the signal-to-noise ratio and to correct for image distortion. RESULTS AND CONCLUSIONS: The observed long-term leaf gap reproducibility (1 standard deviation) was 0.1 mm for the Varian, and 0.2 mm for the Siemens and the Elekta accelerators. In all cases the hysteresis was negligible. Down to the lowest MU, beam output measurements performed with the EPID agreed within 1+/-1% (1SD) with ionisation chamber measurements. These findings led to a fast (3-4 min) procedure for accurate, daily linac quality control for SMLC. ( view less ) View Full Abstract View Article Details   Related Articles Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. Apr 2006 Anita E M Dirkx,Mirjam G A oude Egbrink,Karolien Castermans,Daisy W J van der Schaft,Victor L J L Thijssen,Ruud P M Dings,Lucy Kwee,Kevin H Mayo,John Wagstaff,Jessica C A Bouma-ter Steege,Arjan W Griffioen Tumor escape from immunity, as well as the failure of several anti-cancer vaccination and cellular immunotherapy approaches, is suggested to be due to the angiogenesis-mediated suppression of endothelial cell (EC) adhesion molecules involved in leukocyte-vessel wall interactions. We hypothesized th... ( view more )at inhibition of angiogenesis would overcome this escape from immunity. We investigated this in vivo by means of intravital microscopy and ex vivo by immunohistochemistry in two mouse tumor models. Angiogenesis inhibitors anginex, endostatin, and angiostatin, and the chemotherapeutic agent paclitaxel were found to significantly stimulate leukocyte-vessel wall interactions by circumvention of EC anergy in vivo, i.e., by the up-regulation of endothelial adhesion molecules in tumor vessels. This was confirmed by in vitro studies of cultured EC at the protein and mRNA levels. The new angiostatic designer peptide anginex was most potent at overcoming EC anergy; the enhanced leukocyte-vessel interactions led to an increase in the numbers of tumor infiltrating leukocytes. While anginex inhibited tumor growth and microvessel density significantly, the amount of infiltrated leukocytes (CD45), as well as the number of CD8+ cytotoxic T lymphocytes, was enhanced markedly. The current results suggest that immunotherapy strategies can be improved by combination with anti-angiogenesis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Improvement of radiotherapy treatment delivery accuracy using an electronic portal imaging device. 2006 M L P Dirkx,J C J de Boer,B J M Heijmen Reliable application of advanced external beam techniques for the treatment of patients with cancer, such as intensity modulated radiotherapy, requires an adequate quality assurance programme for the verification of the dose delivery. Accurate patient positioning is mandatory because of the steep d... ( view more )ose gradients outside the tumour volume. Owing to the increased complexity of the treatment planning and delivery techniques, verification of the dose delivery before and during the actual patient treatment is equally important. For this purpose, a quality assurance programme has been established in our clinic that is primarily based on measurements with electronic portal imaging devices. To minimise systematic set-up errors, the patient positioning is measured in the first few treatment fractions and a set-up correction is applied in the subsequent ones. Before the first treatment fraction, portal dose measurements are performed for each treatment field with the electronic portal imaging device to verify that the planned fluence distribution is correctly delivered at the treatment unit. Dosimetric measurements are also performed during patient treatment to derive the actually delivered fluence maps. By combining this information with knowledge on the patient set-up, the delivered 3-D dose distribution to both the tumour and sensitive organs may be assessed. However, for the highest accuracy, exact knowledge on the (internal) patient geometry during treatment, e.g. using a cone-beam CT, is required. ( view less ) View Full Abstract View Article Details   Related Articles Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities. Apr 2005 Ruud Dirkx,Ilse Vanhorebeek,Katrin Martens,Arno Schad,Markus Grabenbauer,Dariush Fahimi,Peter Declercq,Paul P Van Veldhoven,Myriam Baes Peroxisome deficiency in men causes severe pathology in several organs, particularly in the brain and liver, but it is still unknown how metabolic abnormalities trigger these defects. In the present study, a mouse model with hepatocyte-selective elimination of peroxisomes was generated by inbreedin... ( view more )g Pex5-loxP and albumin-Cre mice to investigate the consequences of peroxisome deletion on the functioning of hepatocytes. Besides the absence of catalase-positive peroxisomes, multiple ultrastructural alterations were noticed, including hepatocyte hypertrophy and hyperplasia, smooth endoplasmic reticulum proliferation, and accumulation of lipid droplets and lysosomes. Most prominent was the abnormal structure of the inner mitochondrial membrane, which bore some similarities with changes observed in Zellweger patients. This was accompanied by severely reduced activities of complex I, III, and V and a collapse of the mitochondrial inner membrane potential. Surprisingly, these abnormalities provoked no significant disturbances of adenosine triphosphate (ATP) levels and redox state of the liver. However, a compensatory increase of glycolysis as an alternative source of ATP and mitochondrial proliferation were observed. No evidence of oxidative damage to proteins or lipids nor elevation of oxidative stress defence mechanisms were found. Altered expression of peroxisome proliferator-activated receptor alpha (PPAR-alpha) regulated genes indicated that PPAR-alpha is activated in the peroxisome-deficient cells. In conclusion, the absence of peroxisomes from mouse hepatocytes has an impact on several other subcellular compartments and metabolic pathways but is not detrimental to the function of the liver parenchyma. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). ( view less ) View Full Abstract View Article Details View Coded Data Related Articles GRP1 pleckstrin homology domain: activation parameters and novel search mechanism for rare target lipid. Dec 28, 2004 John A Corbin,Ronald A Dirkx,Joseph J Falke Pleckstrin homology (PH) domains play a central role in a wide array of signaling pathways by binding second messenger lipids of the phosphatidylinositol phosphate (PIP) lipid family. A given type of PIP lipid is formed in a specific cellular membrane where it is generally a minor component of the ... ( view more )bulk lipid mixture. For example, the signaling lipid PI(3,4,5)P(3) (or PIP(3)) is generated primarily in the inner leaflet of the plasma membrane where it is believed to never exceed 0.02% of the bulk lipid. The present study focuses on the PH domain of the general receptor for phosphoinositides, isoform 1 (GRP1), which regulates the actin cytoskeleton in response to PIP(3) signals at the plasma membrane surface. The study systematically analyzes both the equilibrium and kinetic features of GRP1-PH domain binding to its PIP lipid target on a bilayer surface. Equilibrium binding measurements utilizing protein-to-membrane fluorescence resonance energy transfer (FRET) to detect GRP1-PH domain docking to membrane-bound PIP lipids confirm specific binding to PIP(3). A novel FRET competitive binding measurement developed to quantitate docking affinity yields a K(D) of 50 +/- 10 nM for GRP1-PH domain binding to membrane-bound PIP(3) in a physiological lipid mixture approximating the composition of the plasma membrane inner leaflet. This observed K(D) lies in a suitable range for regulation by physiological PIP(3) signals. Interestingly, the affinity of the interaction decreases at least 12-fold when the background anionic lipids phosphatidylserine (PS) and phosphatidylinositol (PI) are removed from the lipid mixture. Stopped-flow kinetic studies using protein-to-membrane FRET to monitor association and dissociation time courses reveal that this affinity decrease arises from a corresponding decrease in the on-rate for GRP1-PH domain docking with little or no change in the off-rate for domain dissociation from membrane-bound PIP(3). Overall, these findings indicate that the PH domain interacts not only with its target lipid, but also with other features of the membrane surface. The results are consistent with a previously undescribed type of two-step search mechanism for lipid binding domains in which weak, nonspecific electrostatic interactions between the PH domain and background anionic lipids facilitate searching of the membrane surface for PIP(3) headgroups, thereby speeding the high-affinity, specific docking of the domain to its rare target lipid. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles SIFT: a method to verify the IMRT fluence delivered during patient treatment using an electronic portal imaging device. Nov 1, 2004 Sandra C Vieira,Maarten L P Dirkx,Ben J M Heijmen,Hans C J de Boer PURPOSE: Radiotherapy patients are increasingly treated with intensity-modulated radiotherapy (IMRT) and high tumor doses. As part of our quality control program to ensure accurate dose delivery, a new method was investigated that enables the verification of the IMRT fluence delivered during patien... ( view more )t treatment using an electronic portal imaging device (EPID), irrespective of changes in patient geometry. METHODS AND MATERIALS: Each IMRT treatment field is split into a static field and a modulated field, which are delivered in sequence. Images are acquired for both fields using an EPID. The portal dose image obtained for the static field is used to determine changes in patient geometry between the planning CT scan and the time of treatment delivery. With knowledge of these changes, the delivered IMRT fluence can be verified using the portal dose image of the modulated field. This method, called split IMRT field technique (SIFT), was validated first for several phantom geometries, followed by clinical implementation for a number of patients treated with IMRT. RESULTS: The split IMRT field technique allows for an accurate verification of the delivered IMRT fluence (generally within 1% [standard deviation]), even if large interfraction changes in patient geometry occur. For interfraction radiological path length changes of 10 cm, deliberately introduced errors in the delivered fluence could still be detected to within 1% accuracy. Application of SIFT requires only a minor increase in treatment time relative to the standard IMRT delivery. CONCLUSIONS: A new technique to verify the delivered IMRT fluence from EPID images, which is independent of changes in the patient geometry, has been developed. SIFT has been clinically implemented for daily verification of IMRT treatment delivery. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in vitro and in vivo: implications for AIDS-associated vasculopathy. Sep 1, 2004 Kathrin Matzen,Anita E M Dirkx,Mirjam G A oude Egbrink,Cornelia Speth,Matthias Götte,Gudrun Ascherl,Thomas Grimm,Arjan W Griffioen,Michael Stürzl HIV-1-infected patients exhibit severe damages of the aortic endothelium, develop angioproliferative lesions such as Kaposi's sarcoma (KS), and have an increased risk of cardiovascular diseases and atherosclerosis. An increased adhesion of leukocytes to the endothelium is a common pathogenic parame... ( view more )ter of AIDS-associated vascular diseases. Here we show that the HIV-1 Tat protein, a regulatory protein of HIV-1 released by infected cells, and TNF-alpha, a cytokine increased in sera and tissues of HIV-1-infected patients, activate synergistically the adhesion of leukocytes to endothelial cells both in vitro and in vivo. This effect is selectively mediated by HIV-1 Tat, since HIV-1 Nef, another HIV-1 regulatory protein, and the HIV-1 envelope protein gp41, had no effect. In vitro adhesion assays with PBMC and quantitative cell type analysis of adherent cells by FACS demonstrated that HIV-1 Tat selectively activates the adhesion of T-cells and monocytes but not of B-cells. Intravital microscopic studies in mice confirmed the synergistic activity of HIV-1 Tat and TNF-alpha on leukocyte adhesion to the endothelium in vivo. These data indicate that HIV-1 Tat in cooperation with TNF-alpha may contribute to the vascular damage and cardiovascular diseases observed in AIDS patients but also to the prominent extravasation of T-cells and monocytes which is a key process in the formation and progression of KS lesions. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A treatment planning study evaluating a 'simultaneous integrated boost' technique for accelerated radiotherapy of stage III non-small cell lung cancer. Jul 2004 Maarten L P Dirkx,John R van Sörnsen De Koste,Suresh Senan PURPOSE: As local tumour control is poor in stage III non-small cell lung cancer (NSCLC), a radiotherapy planning study was performed to evaluate the potential for treatment acceleration by using a simultaneous integrated boost (SIB) technique in patients who had completed induction chemotherapy. M... ( view more )ETHODS AND MATERIALS: Co-registered pre- and post-chemotherapy planning CT scans from 10 patients who showed tumour regression after induction chemotherapy were used to compare different treatment schedules: (a) a sequential boost plan delivering, in 2 Gy per fraction, 50 Gy to the pre-chemotherapy tumour volume, followed by a sequential boost of 20 Gy to the post-chemotherapy tumour volume; (b) a SIB technique in which the pre- and post-chemotherapy tumour volumes were treated to different dose levels during each treatment fraction using identical total doses and number of fractions as above; (c) progressively more hypofractionated schedules that delivered the SIB technique in 25 and 20 once-daily fractions; (d) the actual clinical treatment plan in which 70 Gy was delivered to the pre-chemotherapy tumour volume in 35 daily fractions. Differences in the fractionation schemes used for these plans were accounted for by using the normalised total dose (NTD) for comparison, thereby assuming an alpha/beta ratio of 10 Gy for tumour and 3 Gy for normal tissues. The risk of normal tissue toxicity was estimated using the average lung NTD, the lung volume receiving NTD > 20 Gy, the oesophageal volume receiving NTD > 50 Gy, and the length of full circumference irradiated to at least 50 Gy. RESULTS: With respect to the sequential boost technique, the SIB technique improved the sparing of the normal tissues in all patients. In most patients, the SIB plan could also be delivered in 25 fractions without increasing the estimated normal tissue toxicity. With SIB25, the mean lung NTD was reduced from 12.1 to 11.7 Gy, and the fraction of healthy lung tissue receiving NTD > 20 Gy by 2% on average. Although the length and volume of oesophagus irradiated to at least 50 Gy increased for some of the patients, the observed values were less than that was the case for the actual delivered treatment. However, special care should be taken to avoid exceeding the spinal cord tolerance in patients whose tumours are located close to the cord. CONCLUSIONS: A SIB technique that delivers at least 50 Gy to the pre-chemotherapy tumour volume permits accelerated radiotherapy in patients with stage III NSCLC without increasing the expected risks of normal tissue toxicity. By reducing the overall treatment time, the SIB technique may improve local tumour control and survival. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Two-dimensional measurement of photon beam attenuation by the treatment couch and immobilization devices using an electronic portal imaging device. Nov 2003 Sandra C Vieira,Robert S J P Kaatee,Maarten L P Dirkx,Ben J M Heijmen In our institution, an individualized dosimetric quality assurance protocol for intensity modulated radiotherapy (IMRT) is being implemented. This protocol includes dosimetric measurements with a fluoroscopic electronic portal imaging device (EPID) for all IMRT fields while the patient is being irr... ( view more )adiated. For some of the first patients enrolled in this protocol, significant beam attenuation by (carbon fiber) components of the treatment couch was observed. To study this beam attenuation in two-dimensional, EPID images were also acquired in absence of the patient, both with and without treatment couch and immobilization devices, as positioned during treatment. For treatments of head and neck cancer patients with a 6 MV photon beam, attenuation of up to 15% was detected. These findings led to the development of new tools and procedures for planning and treatment delivery to avoid underdosages in the tumor. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Tumor angiogenesis modulates leukocyte-vessel wall interactions in vivo by reducing endothelial adhesion molecule expression. May 1, 2003 Anita E M Dirkx,Mirjam G A Oude Egbrink,Marijke J E Kuijpers,Sandra T van der Niet,Viviane V T Heijnen,Jessica C A Bouma-ter Steege,John Wagstaff,Arjan W Griffioen The expression of endothelial cell (EC) adhesion molecules involved in leukocyte-vessel wall interactions is suppressed in malignancies. In the present study, we investigated in vivo the regulation of leukocyte-vessel wall interactions by the presence of a tumor. By means of intravital microscopy, ... ( view more )tumor necrosis factor alpha-stimulated leukocyte-vessel wall interactions were studied in ear skin microvessels of nude mice bearing small human LS174T colon carcinomas and in C57Bl/6 mice bearing murine B16F10 melanomas. Leukocyte-vessel wall interactions were studied both within and outside small tumors growing in the ear, and in ear microvessels of mice with a large tumor growing on their flank. Tumor-free mice were used as controls. Compared with values measured at the edge of the ear and in the contralateral ear, leukocyte adhesion was found to be diminished significantly in vessels inside the ear tumor in both mouse models. This reduction disappeared with increasing distance from the tumor. Surprisingly, the level of leukocyte adhesion in ear venules of mice with a large flank tumor was also reduced significantly. Leukocyte rolling, i.e., the step preceding adhesion, was not influenced by the presence of a tumor in nude mice, but was down-regulated in immune-competent C57Bl/6 mice. Treatment of mice bearing a small ear tumor with a humanized antivascular endothelial growth factor antibody prevented the down-regulation of leukocyte-vessel wall interactions inside the tumor vessels compared with the nontreated group. Fluorescence-activated cell sorter analysis showed that isolated tumor ECs have suppressed levels of intercellular adhesion molecule 1 as compared with ECs from normal mouse tissues. In cultured b.END5 cells the tumor necrosis factor alpha-induced up-regulation of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 was reduced in ECs that were preincubated with basic fibroblast growth factor or vascular endothelial growth factor. The current results may have an impact on the effectiveness of clinical immunotherapeutic treatment protocols, because immune effector cells may not be able to enter tumor tissue. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Dosimetric verification of x-ray fields with steep dose gradients using an electronic portal imaging device. Jan 21, 2003 S C Vieira,M L P Dirkx,K L Pasma,B J M Heijmen Regions with steep dose gradients are often encountered in clinical x-ray beams, especially with the growing use of intensity modulated radiotherapy (IMRT). Such regions are present both at field edges and, for IMRT, in the vicinity of the projection of sensitive anatomical structures in the treatm... ( view more )ent field. Dose measurements in these regions are often difficult and labour intensive, while dose prediction may be inaccurate. A dedicated algorithm developed in our institution for conversion of pixel values, measured with a charged coupled device camera based fluoroscopic electronic portal imaging device (EPID), into absolute absorbed doses at the EPID plane has an accuracy of 1-2% for flat and smoothly modulated fields. However, in the current algorithm there is no mechanism to correct for the (short-range) differences in lateral electron transport between water and the metal plate with the fluorescent layer in the EPID. Moreover, lateral optical photon transport in the fluorescent layer is not taken into account. This results in large deviations (>10%) in the penumbra region of these fields. We have investigated the differences between dose profiles measured in water and with the EPID for small heavily peaked fields. A convolution kernel has been developed to empirically describe these differences. After applying the derived kernel to raw EPID images, a general agreement within 2% was obtained with the water measurements in the central region of the fields, and within 0.03 cm in the penumbra region. These results indicate that the EPID is well suited for accurate dosimetric verification of steep gradient x-ray fields. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Fast and accurate leaf verification for dynamic multileaf collimation using an electronic portal imaging device. Sep 2002 Sandra C Vieira,Maarten L P Dirkx,Kasper L Pasma,Ben J M Heijmen A prerequisite for accurate dose delivery of IMRT profiles produced with dynamic multileaf collimation (DMLC) is highly accurate leaf positioning. In our institution, leaf verification for DMLC was initially done with film and ionization chamber. To overcome the limitations of these methods, a fast... ( view more ), accurate and two-dimensional method for daily leaf verification, using our CCD-camera based electronic portal imaging device (EPID), has been developed. This method is based on a flat field produced with a 0.5 cm wide sliding gap for each leaf pair. Deviations in gap widths are detected as deviations in gray scale value profiles derived from the EPID images, and not by directly assessing leaf positions in the images. Dedicated software was developed to reduce the noise level in the low signal images produced with the narrow gaps. The accuracy of this quality assurance procedure was tested by introducing known leaf position errors. It was shown that errors in leaf gap as small as 0.01-0.02 cm could be detected, which is certainly adequate to guarantee accurate dose delivery of DMLC treatments, even for strongly modulated beam profiles. Using this method, it was demonstrated that both short and long term reproducibility in leaf positioning were within 0.01 cm (1sigma) for all gantry angles, and that the effect of gravity was negligible. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Commissioning of a commercially available system for intensity-modulated radiotherapy dose delivery with dynamic multileaf collimation. Aug 2001 M Essers,M de Langen,M L Dirkx,B J Heijmen PURPOSE: To commission commercially available equipment for intensity-modulated radiotherapy (IMRT) using dynamic multileaf collimation (DMLC). MATERIALS AND METHODS: First, the stability in leaf positioning and in realized IMRT profiles on a Varian 2300 C/D machine were determined as a function of... ( view more ) time and gantry angle, and as a result of treatment interrupts. Second, dose distributions calculated with the CadPlan (Varian) treatment planning system, using leaf trajectories calculated with the leaf motion calculator (LMC) algorithm, were compared with distributions realized at the 2300 C/D unit. RESULTS: Day-to-day and gantry angle variations in leaf positioning and dose delivery were very small (less than 0.1-0.2 mm and 2%). The effect of treatment interrupts on measured dose distributions was less than 2%. The agreement between the final dose distribution calculated by CadPlan and the measured dose was generally within 2%, or 2 mm at steep dose gradients, using a leaf transmission value of 1.8% and a leaf separation value of 2 mm in LMC. For narrow peaks, deviations of up to 6% were observed. LMC does not synchronize adjacent leaf trajectories resulting in tongue-and-groove underdosages of up to 29% for extreme cases. CONCLUSIONS: The 2300 C/D machine is suitable for accurate and reproducible DMLC treatments. The agreement between dose predictions with LMC and CadPlan, and realized doses at this unit is clinically acceptable for most cases. However, differences between calculated and actual dose values may exist in peaked fluences or due to tongue-and-groove effects. Therefore, pretreatment dosimetric verification for each patient is recommended. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles An evaluation of two techniques for beam intensity modulation in patients irradiated for stage III non-small cell lung cancer. May 2001 J van Sörnsen de Koste,P Voet,M Dirkx,J van Meerbeeck,S Senan,Rotterdam Oncological Thoracic Study Group In locally advanced lung cancer, the use of high dose radiotherapy (RT) and/or concurrent chemo-RT is associated with significant pulmonary and esophageal toxicity. Despite a 3D conformal RT technique and the omission of elective mediastinal fields, three (of ten) patients with inoperable stage 3 N... ( view more )SCLC who were treated with induction chemotherapy (carboplatin-paclitaxel) followed by RT to 70 Gy, developed symptomatic radiation pneumonitis. In this planning study, the actual treatment plans of all ten patients were compared to plans derived using two beam intensity-modulated (BIM) techniques, for which similar geometrical beam setup parameters were used. In the first technique (BF-BIM), cranial and caudal boost fields were applied in order to allow field length reduction. The second technique (C-BIM) utilised 3-D missing-tissue compensators for all radiation beams. Both BIM techniques resulted in a significant sparing of critical normal tissues and the C-BIM technique was superior in all cases. When compared to the actual RT technique used for treatment, a reduction of 8.1+/-4.7% (1 S.D.) was observed in the mean lung dose for the BF-BIM plan, vs. 20.3+/-5.8% (1 S.D.) for the C-BIM plan. Similar reductions were observed in the percentage of the total lung volume exceeding 20 Gy (V(20)) for these techniques. BIM techniques appear to be a promising tool for enabling radiation dose-escalation and/or intensive concurrent chemo-RT in inoperable lung cancer. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Testing of the stability of intensity modulated beams generated with dynamic multileaf collimation, applied to the MM50 racetrack microtron. Dec 2000 M L Dirkx,B J Heijmen Recently, we have published a method for the calculation of required leaf trajectories to generate optimized intensity modulated x-ray beams by means of dynamic multileaf collimation [Phys. Med. Biol. 43, 1171-1184 (1998)]. For the MM50 Racetrack Microtron it has been demonstrated that the dosimetr... ( view more )ic accuracy of this method, in combination with the dose calculation algorithm of the Cadplan 3D treatment planning system, is adequate for a clinical application (within 2% or 0.2 cm). Prior to initiating patient treatment with dynamic multileaf collimation (DMLC), tests have been performed to investigate the stability of DMLC fields generated at the MM50, (i) in time, (ii) subject to gantry rotation and (iii) in case of treatment interrupts, e.g., caused by an error detected by the treatment machine. The stability of relative dose profiles, normalized to a reference point in a relatively flat part of the modulated beam profile, was assessed from measurements with an electronic portal imaging device (EPID), with a linear diode array attached to the collimator and with film. The dose in the reference point was monitored using an ionization chamber. Tests were performed for several intensity modulated fields using 10 and 25 MV photon beams. Based on film measurements for sweeping 0.1 cm leaf gaps it was concluded that in an 80 days period the variation in leaf positioning was within 0.05 cm, without requiring any recalibration. For a uniform 10x10 cm2 field, realized dynamically by a scanning 0.4x10 cm2 slit beam, a maximum variation in slit width of 0.01 cm was derived from ionization chamber measurements, both in time and for gantry rotation. For a clinical example, the dose in the reference point reproduced within 0.2% (1 SD) over a period of 100 days. Apart from regions with very large dose gradients, variations in the relative beam profiles measured with the EPID were generally less than 1% (1 SD). For different gantry angles the dose profiles also reproduced within 1%, showing that gravity has a negligible influence. No significant deviations between uninterrupted and interrupted treatments could be observed, indicating that the effects of acceleration and deceleration of the leaves are negligible and that a DMLC treatment can be finished correctly after a treatment interrupt. Our previous and present studies have demonstrated that the dosimetric accuracy and stability of intensity modulated beams, generated at the MM50 by means of dynamic multileaf collimation, are adequate for clinical use. Patient treatment using dynamic multileaf collimation has been started in our clinic. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. Nov 27, 2000 S Berghs,D Aggujaro,R Dirkx,E Maksimova,P Stabach,J M Hermel,J P Zhang,W Philbrick,V Slepnev,T Ort,M Solimena We report the identification of betaIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The betaIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of betaIV spectrin generates ... ( view more )at least four distinct isoforms, numbered betaIVSigma1-betaIVSigma4 spectrin. The longest isoform (betaIVSigma1 spectrin) includes an actin-binding domain, followed by 17 spectrin repeats, a specific domain in which the amino acid sequence ERQES is repeated four times, several putative SH3-binding sites and a pleckstrin homology domain. betaIVSigma2 and betaIVSigma3 spectrin encompass the NH(2)- and COOH-terminal halves of betaIVSigma1 spectrin, respectively, while betaIVSigma4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of betaIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, betaIVSigma1 spectrin is recognized as a protein of 250 kD. Anti-betaIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from betaIVSigma1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for betaIV spectrin is more prominent in alpha than in beta cells. In brain, betaIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrin(G) 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, betaIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, betaIVSigma1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that betaIVSigma1 spectrin interacts with ankyrin(G) 480/270-kD and participates in the clustering of voltage-gated Na(+) channels and cell-adhesion molecules at initial segments and nodes of Ranvier. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells. Sep 2000 T Ort,E Maksimova,R Dirkx,A M Kachinsky,S Berghs,S C Froehner,M Solimena Islet cell autoantigen (ICA) 512 of type I diabetes is a receptor tyrosine phosphatase-like protein associated with the secretory granules of neurons and endocrine cells including insulin-secreting beta-cells of the pancreas. Here we show that in a yeast two-hybrid assay its cytoplasmic domain bind... ( view more )s beta2-syntrophin, a modular adapter which in muscle cells interacts with members of the dystrophin family including utrophin, as well as the signaling molecule neuronal nitric oxide synthase (nNOS). The cDNA isolated by two-hybrid screening corresponded to a novel beta2-syntrophin isoform with a predicted molecular mass of 28 kDa. This isoform included the PDZ domain, but not the C-terminal region, which in full-length beta2-syntrophin is responsible for binding dystrophin-related proteins. In vitro binding of the beta2-syntrophin PDZ domain to ICA512 required both ICA512's C-terminal region and an internal polypeptide preceding its tyrosine phosphatase-like domain. Immunomicroscopy and co-immunoprecipitations from insulinoma INS-1 cells confirmed the occurrence of ICA512-beta2-syntrophin complexes in vivo. ICA512 also interacted in vitro with the PDZ domain of nNOS and ICA512-nNOS complexes were co-immunoprecipitated from INS-1 cells. Finally, we show that INS-1 cells, like muscle cells, contain beta2-syntrophin-utrophin oligomers. Thus, we propose that ICA512, through beta2-syntrophin and nNOS, links secretory granules with the actin cytoskeleton and signaling pathways involving nitric oxide. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beam intensity modulation for penumbra enhancement and field length reduction in lung cancer treatments: a dosimetric study. Aug 2000 M L Dirkx,B J Heijmen BACKGROUND AND PURPOSE: In a recent treatment planning study, a previously published technique for superior-inferior field length reduction for prostate cancer patients, based on penumbra enhancement using static beam intensity modulation (BIM) with a multileaf collimator, was investigated for lung... ( view more ) cancer treatments. For the patient group studied, the field lengths could be reduced by 1.4 cm and an average dose escalation of 6 Gy (maximum 16 Gy) appeared to be possible without any increase in the calculated risk of radiation pneumonitis. However, this planning study was performed with a treatment planning system that does not correctly account for the increased lateral secondary electron transport in lung tissue, resulting in too steep beam penumbrae. Therefore, prior to clinical implementation, an extensive dosimetric study was performed to evaluate and optimize BIM for penumbra enhancement and superior-inferior field length reduction in lung cancer treatments. MATERIALS AND METHODS: Film dosimetry was performed in several phantoms consisting of water equivalent and lung equivalent materials, both for a 6 and a 10 MV photon beam. Measured dose distributions were used to (i) adapt the BIM technique to properly account for increased lateral secondary electron transport, (ii) compare BIM dose distributions in lung material with dose distributions of standard treatment fields, and (iii) investigate the use of our treatment planning system for the design of BIM plans for lung cancer patients. RESULTS: Compared with our treatment planning study the superior and inferior boost fields, used in the BIM technique for penumbra enhancement, had to be longer and of a higher weight to compensate for the increased lateral secondary electron transport in lung tissue. With these modifications in the BIM technique, field lengths could indeed be reduced by 1.4 cm compared with treatment with standard fields, without the appearance of underdosages in the most superior and inferior target areas, whilst better sparing the healthy lung tissue. Practical rules were derived to use our treatment planning system for the design of BIM treatment plans. CONCLUSIONS: In spite of the increased lateral secondary electron transport in lung tissue, static BIM with a multileaf collimator may effectively be used for penumbra enhancement and superior-inferior field length reduction in lung cancer treatments. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 3 1 2 3 > (57 articles found)

      
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