2024-03-29T00:31:56Z
http://ir.lib.uwo.ca/do/oai/
oai:works.bepress.com:edwardyu-1105
2015-01-20T16:07:58Z
publication:edwardyu
Time Interval From Conservative Breast Surgery To Breast Irradiation In Early Stage Node Negative Breast Cancer: 17-Year Follow-Up Results And Patterns Of Recurrence
Vujovic, Olga
Yu, Edward
Cherian, Anil
Dar, Rashid
Stitt, Larry
Perera, Francisco
Purpose: A retrospective chart review was conducted to determine if the time interval from conservative breast surgery to breast irradiation (surgery – radiotherapy interval) in early stage node negative breast cancer had any detrimental effect on recurrence rates. Materials and Methods: There were 566 patients with T1-T3, N0 breast cancer treated with breast conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery – radiotherapy intervals used for analysis were: 0-8 weeks (201 patients), >8-12 weeks (233 patients), >12-16 weeks (91 patients) and >16 weeks (41 patients). Kaplan-Meir estimates of time to local-recurrence, disease-free survival, distant-free survival, cause-specific survival and overall survival rates were calculated. Results: Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of patient characteristics and pathologic features. There was no statistically significant difference between the 4 time groups in local-recurrence (p=0.67) or disease-free survival (p=0.45). The local recurrence rate at 5, 10 and 15 years was 4.9%, 11.5% and 15.0% respectively. The distant-disease relapse rate at 5, 10 and 15 years was 10.6%, 15.4% and 18.5% respectively. The disease-free failure rate at 5, 10 and 15 years was 20%, 32.3% and 39.8% respectively. Cause-specific survival at 5, 10 and 15 years was 92%, 84.6 % and 79.8% respectively. The overall survival at 5, 10 and 15 years was 89.3%, 79.2% and 66.9%. Conclusion: Surgery-radiotherapy intervals up to 16 weeks from definitive breast surgery are not associated with any increased risk of recurrence in early stage node negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.
2015-02-01T08:00:00Z
text
https://works.bepress.com/edwardyu/94
http://www.sciencedirect.com/science/article/pii/S0360301614042576
Edward Yu
SelectedWorks
17-year radiation wait time results
Breast Cancer
Oncology
oai:ir.lib.uwo.ca:medpub-1001
2009-05-06T03:32:00Z
publication:rwkex
publication:med
publication:biophysics
publication:robartspub
publication:rwkex_researcharticles
publication:biophysicspub
publication:medimagingpub
publication:robarts
publication:medimaging
publication:institutes
publication:faculties
publication:medpub
Abnormal Myocardial Perfusion in Hypertrophic Cardiomyopathy: Preliminary Findings of a Cardiovascular MRI Study
White, James A.
Armstrong, Sarah
Al-Admawi, Mohammed
Rambihar, Sherryn
Wisenberg, Gerald
Verschuur, Ivonna
MacDonald, Anna
Harper-Little, Cyndi
So, Aaron
Lee, Ting-Yim
Prato, Frank
Thompson, Terry
Background: Reduced myocardial perfusion has been speculated as a potential mechanism for the development and/or propagation of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). This study aims to evaluate the prevalence, distribution and extent of stress-induced perfusion abnormalities and their relationship to underlying fibrosis in patients with HCM using magnetic resonance imaging.
Methods: 15 patients with echocardiographically diagnosed HCM have been enrolled. Cine imaging, first-pass stress perfusion imaging using vasodilator stress (Dipyridamole), and delayed gadolinium enhancement imaging were performed. Stress hypoperfusion and delayed enhancement images were assessed both quantitatively and visually using a 16-segment model. Conversion of segmental visual scoring to % of LV by volume was achieved for both hypoperfusion (HP) and late enhancement (LE) using a standardized scoring system. For quantitative assessment prospectively defined cut-offs for LE and HP were used.
Results: Maximal wall thickness ranged from 13 to 22 mm (mean 17 ± 2.6 mm). Non-ischemic pattern LE was present in 70% of patients. Perfusion abnormalities were identified on stress perfusion images in 80% of patients using visual analysis and 87% of patients using quantitative analysis. Perfusion abnormalities were predominantly subendocardial, and were regionally associated with segments containing LE (p < 0.01). Mean percent HP and mean percent LE were 17 ± 8.4% and 10 ± 9.3%, respectively by visual estimation and 20.0 ± 12.1% and 14.0 ± 7.4%, respectively by quantitative assessment. Figure 1.
Conclusion: These preliminary results suggest that patients with HCM have a high prevalence of stress-induced myocardial hypoperfusion as represented by reduced first-pass gadolinium enhancement during vasodilator stress. This hypoperfusion appears to extend beyond regions of established LE suggesting a potential contribution of ischemia in the development and/or propagation of myocardial fibrosis in patients with HCM.
2009-01-28T08:00:00Z
article
https://ir.lib.uwo.ca/medpub/2
http://jcmr-online.com/content/11/S1/P55
Department of Medicine Publications
Scholarship@Western
Myocardial perfusion
Myocardial fibrosis
Hypertrophic cardiomyopathy
Cardiology
Other Medical Sciences
oai:ir.lib.uwo.ca:medpub-1002
2009-05-06T03:31:14Z
publication:rwkex
publication:med
publication:biophysics
publication:rwkex_researcharticles
publication:biophysicspub
publication:medimagingpub
publication:medimaging
publication:faculties
publication:medpub
Is Hemorrhage in Acute Reperfused Myocardial Infarction a New Marker for the Severity of Tissue Injury?
Kumar, Andreas
Green, Jordin D.
Sykes, Jane M.
Mitchell, Andrea
Wisenberg, Gerald
Friedrich, Matthias G.
Introduction: Reperfusion injury in myocardial infarction leads to microvascular obstruction, which can occur with or without gross reperfusion hemorrhage. The incidence and implications of reperfusion hemorrhage are not well investigated. A recently described in vivo imaging approach using T2*-weighted cardiovascular magnetic resonance can help investigate the pathophysiology of reperfusion hemorrhage in vivo.
Hypothesis: We hypothesized that hemorrhage reflects a severer from of reperfusion injury and therefore occurs with larger infarct size and worse LV function as compared to reperfusion injury without hemorrhage.
Methods: In 14 female mongrel dogs, myocardial infarction was induced by ligation of the left anterior descending coronary artery for 2–4 hours, followed by reperfusion. On day 3 ± 1, a cardiovascular magnetic resonance study was performed in vivo to (1) assess presence of microvascular obstruction, defining reperfusion injury (2) assess presence of reperfusion hemorrhage (3) quantify left ventricular end-diastolic volume, ejection fraction and cardiac output and (4) quantify infarct size with late enhancement. An independent-samples t-test was performed to compare these parameters in dogs with and without hemorrhage in reperfusion injury.
Results: From 14 dogs, 9 had microvascular obstruction, and 4/9 had reperfusion hemorrhage in addition to microvascular obstruction.
Dogs with hemorrhagic infarcts had significantly larger infarct size (26.1 ± 6.6 g vs. 5.5 ± 3.9 g, p < 0.05), lower LV ejection fraction (28 ± 7% vs. 53 ± 12%, p < 0.05), and lower cardiac output (1.9 ± 0.2 l/min vs. 2.8 ± 0.5 l/min, p < 0.05). There were no differences in LV end-diastolic volume and LV mass.
Discussion and conclusion: In this dog model of ischemia/reperfusion injury, gross hemorrhage was associated with significantly larger infarct size and worse LV functional parameters. This supports the hypothesis that hemorrhage may occur with advanced, severe ischemic tissue injury only.
2009-01-28T08:00:00Z
article
https://ir.lib.uwo.ca/medpub/3
http://jcmr-online.com/content/11/S1/P65
Department of Medicine Publications
Scholarship@Western
Microvascular obstruction
Reperfusion hemorrhage
In vivo imaging
Cardiology
Other Medical Specialties
oai:ir.lib.uwo.ca:robartspub-1000
2018-02-16T17:05:01Z
publication:physics
publication:anatomy
publication:robartspub
publication:biophysicspub
publication:pmid
publication:faculties
publication:physicspub
publication:electricalpub
publication:medpub
publication:anatomypub
publication:med
publication:biophysics
publication:biochempub
publication:electrical
publication:robarts
publication:biochem
publication:institutes
Clinical Field-strength MRI of Amyloid Plaques Induced by Low-level Cholesterol Feeding in Rabbits
Ronald, John A.
Chen, Yuanxin
Bernas, Lisa
Kitzler, Hagen H.
Rogers, Kem A.
Hegele, Robert A.
Rutt, Brian K.
Two significant barriers have limited the development of effective treatment of Alzheimer’s disease. First, for many cases the aetiology is unknown and likely multi-factorial. Among these factors, hypercholesterolemia is a known risk predictor and has been linked to the formation of b-amyloid plaques, a pathological hallmark this disease. Second, standardized diagnostic tools are unable to definitively diagnose this disease prior to death; hence new diagnostic tools are urgently needed. Magnetic resonance imaging (MRI) using high field-strength scanners has shown promise for direct visualization of b-amyloid plaques, allowing in vivo longitudinal tracking of disease progression in mouse models. Here, we present a new rabbit model for studying the relationship between cholesterol and Alzheimer’s disease development and new tools for direct visualization of b-amyloid plaques using clinical field-strength MRI. New Zealand white rabbits were fed either a low-level (0.125–0.25% w/w) cholesterol diet (n = 5) or normal chow (n = 4) for 27 months. High-resolution (66x66x100 mm3; scan time = 96 min) ex vivo MRI of brains was performed using a 3-Tesla (T) MR scanner interfaced with customized gradient and radiofrequency coils. b-Amyloid-42 immunostaining and Prussian blue iron staining were performed on brain sections and MR and histological images were manually registered. MRI revealed distinct signal voids throughout the brains of cholesterol-fed rabbits, whereas minimal voids were seen in control rabbit brains. These voids corresponded directly to small clusters of extracellular b-amyloid-positive plaques, which were consistently identified as iron-loaded (the presumed source of MR contrast). Plaques were typically located in the hippocampus, parahippocampal gyrus, striatum, hypothalamus and thalamus. Quantitative analysis of the number of histologically positive b-amyloid plaques (P50.0001) and MR-positive signal voids (P50.05) found in cholesterol-fed and control rabbit brains corroborated our qualitative observations. In conclusion, long-term, low-level cholesterol feeding was sufficient to promote the formation of extracellular b-amyloid plaque formation in rabbits, supporting the integral role of cholesterol in the aetiology of Alzheimer’s disease. We also present the first evidence that MRI is capable of detecting iron-associated b-amyloid plaques in a rabbit model of Alzheimer’s disease and have advanced the sensitivity of MRI for plaque detection to a new level, allowing clinical field-strength scanners to be employed. We believe extension of these technologies to an in vivo setting in rabbits is feasible and that our results support future work exploring the role of MRI as a leading imaging tool for this debilitating and life-threatening disease.
2009-05-01T07:00:00Z
article
application/pdf
https://ir.lib.uwo.ca/robartspub/1
https://ir.lib.uwo.ca/context/robartspub/article/1000/viewcontent/awp031.pdf
Robarts Imaging Publications
Scholarship@Western
Alzheimer’s disease
Cholesterol
Rabbit model
Magnetic resonance imaging
b-amyloid plaques
Other Medical Sciences
Other Medical Specialties
oai:ir.lib.uwo.ca:biophysicspub-1000
2009-05-23T01:29:06Z
publication:biophysicspub
publication:pmid
publication:faculties
publication:psychologypub
publication:biophysics
publication:psychology
The Effect of Forearm Posture on Wrist Flexion in Computer Workers with Chronic Upper Extremity Musculoskeletal Disorders
Burgess, Ronald A.
Thompson, R. Terry
Rollman, Gary B.
Background: Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/ or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.
Methods: We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.
Results: The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.
Conclusion: The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.
2008-04-11T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/1
http://www.biomedcentral.com/1471-2474/9/47
Medical Biophysics Publications
Scholarship@Western
Upper extremity musculoskeletal disorder
UEMSD
Wrist flexion
Forearm posture
Medical Biophysics
Musculoskeletal, Neural, and Ocular Physiology
oai:ir.lib.uwo.ca:biophysicspub-1001
2009-05-26T21:44:41Z
publication:kin
publication:biophysicspub
publication:pmid
publication:faculties
publication:kinpub
publication:biophysics
Changes in Tissue Water Content Measured with Multiple-frequency Bioimpedance and Metabolism Measured with 31P-MRS during Progressive Forearm Exercise
Raja, Mohan K.
Raymer, Graydon H.
Moran, Gerald R.
Marsh, Greg
Thompson, R. Terry
Multiple-frequency bioimpedance analysis (MFBIA) has been used to determine the cellular water composition in the human body. It is noninvasive and has demonstrated good correlations with other invasive measures of tissue water. However, the ability of this method to study transient changes in tissue water in specific muscle groups has not been explored. In this study, MFBIA was used to assess changes in forearm intracellular water (ICW), extracellular water (ECW), and total water (TW) in seven healthy volunteers during and after a progressive wrist flexion exercise protocol. In an identical trial, 31P magnetic resonance spectroscopy (31P-MRS) was used to assess changes in intracellular pH and phosphocreatine (PCr). At the completion of exercise, forearm ICW increased 12.6% (SD 0.07, P = 0.003), TW increased 10.1% (SD 0.06, P = 0.005), and no significant changes were recorded for ECW. A significant correlation was found between the changes in intracellular pH and changes in ICW during exercise (r = –0.84, P = 0.018). With the use of regression analysis, average changes in Pi, PCr, and pH were found to predict changes in ICW (R2 = 0.98, P = 0.005). In conclusion, MFBIA was sensitive enough to measure transient changes in the exercising forearm muscle. The changes seen were consistent with the hypothesis that intracellular acidification and PCr hydrolysis are important mediators of cellular osmolality and therefore may be responsible for the increased volume of water in the intracellular space that is often recorded after short-term high-intensity exercise.
2006-06-22T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/2
http://jap.physiology.org/cgi/content/full/101/4/1070
Medical Biophysics Publications
Scholarship@Western
Intracellular water
Extracellular water
Phosphorus-31 magnetic resonance spectroscopy
Intracellular pH
Phosphocreatine
Bioimaging and Biomedical Optics
Kinesiology
Medical Biophysics
oai:ir.lib.uwo.ca:biochempub-1018
2009-07-25T20:37:01Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:surgery
publication:biochem
A Novel Mass Spectrometry-based Assay for GSK-3β Activity
Bowley, Erin
Mulvihill, Erin
Howard, Jeffrey C.
Pak, Brian J.
Gan, Bing Siang
O'Gorman, David B.
Background: As a component of the progression from genomic to proteomic analysis, there is a need for accurate assessment of protein post-translational modifications such as phosphorylation. Traditional kinase assays rely heavily on the incorporation of γ-P32 radiolabeled isotopes, monoclonal anti-phospho-protein antibodies, or gel shift analysis of substrate proteins. In addition to the expensive and time consuming nature of these methods, the use of radio-ligands imposes restrictions based on the half-life of the radionucleotides and pose potential health risks to researchers. With the shortcomings of traditional assays in mind, the aim of this study was to develop a high throughput, non-radioactive kinase assay for screening Glycogen Synthase Kinase-3beta (GSK-3β) activity.
Results: Synthetic peptide substrates designed with a GSK-3β phosphorylation site were assayed with both recombinant enzyme and GSK-3β immunoprecipitated from NIH 3T3 fibroblasts. A molecular weight shift equal to that of a single phosphate group (80 Da.) was detected by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) in a GSK-3β target peptide (2B-Sp). Not only was there a dose-dependent response in molecular weight shift to the amount of recombinant GSK-3β used in this assay, this shift was also inhibited by lithium chloride (LiCl), in a dose-dependent manner.
Conclusion: We present here a novel method to sensitively measure peptide phosphorylation by GSK-3β that, due to the incorporation of substrate controls, is applicable to either purified enzyme or cell extracts. Future studies using this method have the potential to elucidate the activity of GSK-3β in vivo, and to screen enzyme activity in relation to a variety of GSK-3β related disorders.
2005-12-16T08:00:00Z
article
https://ir.lib.uwo.ca/biochempub/18
http://www.biomedcentral.com/1471-2091/6/29
Biochemistry Publications
Scholarship@Western
kinase assay
Glycogen Synthase Kinase-3beta activity
Biochemistry
Medical Physiology
Surgery
oai:ir.lib.uwo.ca:oncpub-1002
2009-07-31T19:41:52Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:surgery
publication:onc
Tumour Dormancy in Breast Cancer: An Update
Brackstone, Muriel
Townson, Jason L.
Chambers, Ann F.
Delayed recurrences, common in breast cancer, are well explained by the concept of tumour dormancy. Numerous publications describe clinical times to disease recurrence or death, using mathematical approaches to infer mechanisms responsible for delayed recurrences. However, most of the clinical literature discussing tumour dormancy uses data from over a half century ago and much has since changed. This review explores how current breast cancer treatment could change our understanding of the biology of breast cancer tumour dormancy, and summarizes relevant experimental models to date. Current knowledge gaps are highlighted and potential areas of future research are identified.
2007-05-31T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/2
http://breast-cancer-research.com/content/9/3/208
Oncology Publications
Scholarship@Western
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Cyclophosphamide
Female
Fluorouracil
Humans
Methotrexate
Neoplasm
Residual
Recurrence
Time Factors
Neoplasm, Residual
Medical Biophysics
Oncology
Surgery
oai:ir.lib.uwo.ca:biophysicspub-1002
2009-09-26T00:58:42Z
publication:rwkex_researcharticles
publication:biophysicspub
publication:anesthesia
publication:pmid
publication:anesthesiapub
publication:faculties
publication:rwkex
publication:biophysics
Bench-to-bedside Review: Microvascular Dysfunction in Sepsis--Hemodynamics, Oxygen Transport, and Nitric Oxide
Bateman, Ryon M.
Sharpe, Michael D.
Ellis, Christopher G.
The microcirculation is a complex and integrated system that supplies and distributes oxygen throughout the tissues. The red blood cell (RBC) facilitates convective oxygen transport via co-operative binding with hemoglobin. In the microcirculation oxygen diffuses from the RBC into neighboring tissues, where it is consumed by mitochondria. Evidence suggests that the RBC acts as deliverer of oxygen and 'sensor' of local oxygen gradients. Within vascular beds RBCs are distributed actively by arteriolar tone and passively by rheologic factors, including vessel geometry and RBC deformability. Microvascular oxygen transport is determined by microvascular geometry, hemodynamics, and RBC hemoglobin oxygen saturation. Sepsis causes abnormal microvascular oxygen transport as significant numbers of capillaries stop flowing and the microcirculation fails to compensate for decreased functional capillary density. The resulting maldistribution of RBC flow results in a mismatch of oxygen delivery with oxygen demand that affects both critical oxygen delivery and oxygen extraction ratio. Nitric oxide (NO) maintains microvascular homeostasis by regulating arteriolar tone, RBC deformability, leukocyte and platelet adhesion to endothelial cells, and blood volume. NO also regulates mitochondrial respiration. During sepsis, NO over-production mediates systemic hypotension and microvascular reactivity, and is seemingly protective of microvascular blood flow.
2003-07-28T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/3
http://ccforum.com/content/7/5/359
Medical Biophysics Publications
Scholarship@Western
Hemodynamics
Humans
Microcirculation
Nitric Oxide
Oxygen
Sepsis
Anesthesiology
Medical Biophysics
oai:ir.lib.uwo.ca:surgerypub-1006
2009-09-16T00:32:03Z
publication:mnipub
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:mni
publication:biochem
publication:surgery
Elevated Levels of β-catenin and Fibronectin in Three-dimensional Collagen Cultures of Dupuytren's Disease Cells are Regulated by Tension in Vitro
Howard, Jeffrey C.
Varallo, Vincenzo M.
Ross, Douglas C.
Roth, James H.
Faber, Kenneth J.
Alman, Benjamin
Gan, Bing Siang
Background: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that beta-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in beta-catenin and fibronectin levels.
Methods: Western blots of beta-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed.
Results: Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in beta-catenin and fibronectin levels, including a transient increase in beta-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and beta-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices.
Conclusion: Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of beta-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension.
2003-07-16T07:00:00Z
article
https://ir.lib.uwo.ca/surgerypub/7
http://www.biomedcentral.com/1471-2474/4/16
Surgery Publications
Scholarship@Western
Biomechanics
Cells
Cultured
Collagen
Cytoskeletal Proteins
Dupuytren's Contracture
Fibroblasts
Fibronectins
Humans
Trans-Activators
beta Catenin
Cells, Cultured
Surgery
oai:ir.lib.uwo.ca:medpub-1011
2009-09-19T03:17:32Z
publication:biophysicspub
publication:physpharmpub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:physpharm
publication:biophysics
publication:apmaths
publication:apmathspub
Erythropoietin Improves Skeletal Muscle Microcirculation and Tissue Bioenergetics in a Mouse Sepsis Model
Kao, Raymond
Xenocostas, Anargyros
Rui, Tao
Yu, Pei
Huang, Weixiong
Rose, James
Martin, Claudio M.
Introduction: The relationship between oxygen delivery and consumption in sepsis is impaired, suggesting a microcirculatory perfusion defect. Recombinant human erythropoietin (rHuEPO) regulates erythropoiesis and also exerts complex actions promoting the maintenance of homeostasis of the organism under stress. The objective of this study was to test the hypothesis that rHuEPO could improve skeletal muscle capillary perfusion and tissue oxygenation in sepsis.
Methods: Septic mice in three experiments received rHu-EPO 400 U/kg subcutaneously 18 hours after cecal ligation and perforation (CLP). The first experiment measured the acute effects of rHuEPO on hemodynamics, blood counts, and arterial lactate level. The next two sets of experiments used intravital microscopy to observe capillary perfusion and nicotinamide adenine dinucleotide (NADH) fluorescence post-CLP after treatment with rHuEPO every 10 minutes for 40 minutes and at 6 hours. Perfused capillary density during a three-minute observation period and NADH fluorescence were measured.
Results: rHuEPO did not have any effects on blood pressure, lactate level, or blood cell numbers. CLP mice demonstrated a 22% decrease in perfused capillary density compared to the sham group (28.5 versus 36.6 capillaries per millimeter; p < 0.001). Treatment of CLP mice with rHuEPO resulted in an immediate and significant increase in perfused capillaries in the CLP group at all time points compared to baseline from 28.5 to 33.6 capillaries per millimeter at 40 minutes; p < 0.001. A significant increase in baseline NADH, suggesting tissue hypoxia, was noted in the CLP mice compared to the sham group (48.3 versus 43.9 fluorescence units [FU]; p = 0.03) and improved with rHuEPO from 48.3 to 44.4 FU at 40 minutes (p = 0.02). Six hours after treatment with rHuEPO, CLP mice demonstrated a higher mean perfused capillary density (39.4 versus 31.7 capillaries per millimeter; p < 0.001) and a lower mean NADH fluorescence as compared to CLP+normal saline mice (49.4 versus 52.7 FU; p = 0.03).
Conclusion: rHuEPO produced an immediate increase in capillary perfusion and decrease in NADH fluorescence in skeletal muscle. Thus, it appears that rHuEPO improves tissue bioenergetics, which is sustained for at least six hours in this murine sepsis model.
2007-05-18T07:00:00Z
article
https://ir.lib.uwo.ca/medpub/7
http://ccforum.com/content/11/3/R58
Department of Medicine Publications
Scholarship@Western
Animals
Disease Models
Animal
Energy Metabolism
Erythropoietin
Mice
Mice
Inbred C57BL
Microcirculation
Muscle
Skeletal
Sepsis
Treatment Outcome
Disease Models, Animal
Mice, Inbred C57BL
Muscle, Skeletal
Medical Sciences
Musculoskeletal, Neural, and Ocular Physiology
oai:ir.lib.uwo.ca:robartspub-1001
2023-03-16T14:07:28Z
publication:robartspub
publication:rwkex_researcharticles
publication:biophysicspub
publication:pmid
publication:medimaging
publication:faculties
publication:medpub
publication:rwkex
publication:med
publication:biophysics
publication:medimagingpub
publication:robarts
publication:institutes
Carotid Ultrasound Phenotypes in Vulnerable Populations
Riccio, Silvia A.
House, Andrew A.
Spence, J. David
Fenster, Aaron
Parraga, Grace
Background: Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT) to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT), total plaque volume (TPV) and total plaque area (TPA) in two separate populations, both vulnerable to carotid atherosclerosis. Methods: In total, 88 subjects (mean age 72.8) with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9) with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed. Results: IMT and TPV were only modestly correlated in the two separate populations (r = .6, p < .01). ANOVA analyses indicated that both IMT and TPV were significantly associated with age (p < .001) and Framingham score (p < .05), but only TPV was associated with diabetes (p < .001) and presence of plaque ulcerations (p < .01) Conclusion: IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.
2006-11-13T08:00:00Z
article
https://ir.lib.uwo.ca/robartspub/2
info:doi/10.1186/1476-7120-4-44
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1657034/
Robarts Imaging Publications
Scholarship@Western
Aged
Carotid Stenosis
Diabetic Nephropathies
Female
Humans
Image Interpretation
Computer-Assisted
Male
Phenotype
Prognosis
Reproducibility of Results
Risk Assessment
Risk Factors
Sensitivity and Specificity
Ultrasonography
Doppler
Color
Image Interpretation, Computer-Assisted
Ultrasonography, Doppler, Color
Bioimaging and Biomedical Optics
Biomedical Engineering and Bioengineering
oai:ir.lib.uwo.ca:medpub-1016
2009-10-12T04:11:55Z
publication:anatomy
publication:biophysicspub
publication:pmid
publication:faculties
publication:medpub
publication:anatomypub
publication:med
publication:biophysics
Cell Tracking and Therapy Evaluation of Bone Marrow Monocytes and Stromal Cells Using SPECT and CMR in a Canine Model of Myocardial Infarction
Wisenberg, Gerald
Lekx, Katie
Zabel, Pam
Kong, Huafu
Mann, Rupinder
Zeman, Peter R.
Datta, Sudip
Culshaw, Caroline N.
Merrifield, Peter
Bureau, Yves
Wells, Glenn
Sykes, Jane
Prato, Frank S.
Background: The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu.
Objectives: To establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling.
Methods: We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells.
Results: In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67-88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment.
Conclusion: This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.
2009-04-27T07:00:00Z
article
https://ir.lib.uwo.ca/medpub/10
http://www.jcmr-online.com/content/11/1/11
Department of Medicine Publications
Scholarship@Western
Analysis of Variance
Animals
Bone Marrow Transplantation
Cell Survival
Dogs
Female
Image Processing
Computer-Assisted
Indium Radioisotopes
Magnetic Resonance Imaging
Cine
Monocytes
Myocardial Infarction
Organic Chemicals
Stromal Cells
Tomography
Emission-Computed
Single-Photon
Transplantation
Autologous
Ventricular Dysfunction
Left
Image Processing, Computer-Assisted
Magnetic Resonance Imaging, Cine
Tomography, Emission-Computed, Single-Photon
Transplantation, Autologous
Ventricular Dysfunction, Left
Cardiology
oai:ir.lib.uwo.ca:surgerypub-1015
2009-09-23T00:46:56Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:faculties
publication:physpharm
publication:biophysics
publication:surgery
Wnt Expression Is Not Correlated with β-catenin Dysregulation in Dupuytren's Disease
O'Gorman, David B.
Wu, Yan
Seney, Shannon
Zhu, Rebecca D.
Gan, Bing Siang
Background: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular β-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular β-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures.
Results: The Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis.
Conclusion: These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of β-catenin expression in DD.
2006-08-30T07:00:00Z
article
https://ir.lib.uwo.ca/surgerypub/12
http://www.jnrbm.com/content/5/1/13
Surgery Publications
Scholarship@Western
Wnt expression
?-catenin
Dupuytren's Disease
Medical Biophysics
Medical Physiology
Surgery
oai:ir.lib.uwo.ca:surgerypub-1016
2009-10-10T03:22:14Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:biochem
publication:surgery
Type-1 Collagen Differentially Alters Beta-catenin Accumulation in Primary Dupuytren's Disease Cord and Adjacent Palmar Fascia Cells
Vi, Linda
Njarlangattil, Anna
Wu, Yan
Gan, Bing Siang
O'Gorman, David B.
Background: Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased transforming growth factor-beta levels and beta-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered beta-catenin accumulation by primary DD cells in the presence or absence of transforming growth factor-beta.
Methods: Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and transforming growth factor-beta1. beta-catenin and alpha-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.
Results: DD cells display a rapid depletion of cellular beta-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of transforming growth factor-beta1 to DD cells in collagen culture negates the loss of beta-catenin accumulation. Transforming growth factor-beta1-induced alpha-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.
Conclusion: Our findings implicate type-1 collagen as a previously unrecognized regulator of beta-catenin accumulation and a modifier of TGF-beta1 signaling specifically in primary DD cells. These data have implications for current treatment modalities as well as the design of in vitro models for research into the molecular mechanisms of DD.
2009-06-19T07:00:00Z
article
https://ir.lib.uwo.ca/surgerypub/16
http://www.biomedcentral.com/1471-2474/10/72
Surgery Publications
Scholarship@Western
Actins
Case-Control Studies
Cells
Cultured
Collagen Type I
Dupuytren's Contracture
Fascia
Humans
Recombinant Proteins
Time Factors
Transforming Growth Factor beta1
beta Catenin
Cells, Cultured
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
oai:ir.lib.uwo.ca:immunologypub-1015
2009-10-12T23:32:06Z
publication:mnipub
publication:anatomy
publication:biophysicspub
publication:pmid
publication:immunologypub
publication:faculties
publication:medpub
publication:anatomypub
publication:med
publication:biophysics
publication:biochempub
publication:mni
publication:robarts
publication:biochem
publication:institutes
Wilms’ Tumor 1–Associating Protein Regulates the Proliferation of Vascular Smooth Muscle Cells
Small, Theodore W.
Bolender, Zuzana
Bueno, Clara
O'Neil, Caroline
Nong, Zengxuan
Rushlow, Walter
Rajakumar, Nagalingham
Kandel, Christopher
Strong, Jennifer
Madrenas, Joaquin
Pickering, J. Geoffrey
Smooth muscle cells (SMCs) are called on to proliferate during vascular restructuring but must return to a nonproliferative state if remodeling is to appropriately terminate. To identify mediators of the reacquisition of replicative quiescence, we undertook gene expression screening in a uniquely plastic human SMC line. As proliferating SMCs shifted to a contractile and nonproliferative state, expression of TIMP-3, Axl, and KIAA0098 decreased whereas expression of complement C1s, cathepsin B, cellular repressor of E1A-activated genes increased. Wilms' tumor 1-associating protein (WTAP), a nuclear constituent of unknown function, was also upregulated as SMCs became nonproliferative. Furthermore, WTAP in the intima of injured arteries was substantially upregulated in the late stages of repair. Introduction of WTAP complementary DNA into human SMCs inhibited their proliferation, with a corresponding decrease in DNA synthesis and an increase in apoptosis. Knocking down endogenous WTAP increased SMC proliferation, because of increased DNA synthesis and G(1)/S phase transition, together with reduced apoptosis. WTAP was found to associate with the Wilms' tumor-1 protein in human SMCs and WTAP overexpression inhibited the binding of WT1 to an oligonucleotide containing a consensus WT1 binding site, whereas WTAP knockdown accentuated this interaction. Expression of the WT1 target genes, amphiregulin and Bcl-2, was suppressed in WTAP-overexpressing SMCs and increased in WTAP-deficient SMCs. Moreover, exogenous amphiregulin rescued the antiproliferative effect of WTAP. These findings identify WTAP as a novel regulator of the cell cycle and cell survival and implicate a WTAP-WT1 axis as a novel pathway for controlling vascular SMC phenotype.
2006-12-08T08:00:00Z
article
https://ir.lib.uwo.ca/immunologypub/14
http://circres.ahajournals.org/cgi/content/abstract/99/12/1338
Robarts Immunology and Transplantation Publications
Scholarship@Western
Angioplasty
Balloon
Animals
Aorta
Thoracic
Apoptosis
Carotid Artery Injuries
Carrier Proteins
Cell Division
Cell Line
DNA-Binding Proteins
Gene Silencing
Glycoproteins
Humans
Intercellular Signaling Peptides and Proteins
Male
Muscle
Smooth
Vascular
Nuclear Proteins
Rats
Rats
Inbred WKY
Rats
Sprague-Dawley
Transcription
Genetic
Up-Regulation
WT1 Proteins
Angioplasty, Balloon
Aorta, Thoracic
Muscle, Smooth, Vascular
Rats, Inbred WKY
Rats, Sprague-Dawley
Transcription, Genetic
Immunology and Infectious Disease
Medical Anatomy
Medical Biochemistry
Medical Biophysics
oai:ir.lib.uwo.ca:biophysicspub-1003
2009-10-15T22:26:07Z
publication:rwkex_researcharticles
publication:biophysicspub
publication:anesthesia
publication:pmid
publication:anesthesiapub
publication:faculties
publication:rwkex
publication:biophysics
The Microcirculation as a Functional System
Ellis, Christopher G.
Jagger, Justin
Sharpe, Michael
This review examines experimental evidence that the microvascular dysfunction that occurs early in sepsis is the critical first stage in tissue hypoxia and organ failure. A functional microvasculature maintains tissue oxygenation despite limitations on oxygen delivery from blood to tissue imposed by diffusion; the density of perfused (functional) capillaries is high enough to ensure appropriate diffusion distances, and arterioles regulate the distribution of oxygen within the organ precisely to where it is needed. Key components of this regulatory system are the endothelium, which communicates and integrates signals along the microvascular network, and the erythrocytes, which directly monitor and regulate oxygen delivery. During hypovolemic shock, a functional microvasculature responds to diminish the impact of a decrease in oxygen supply on tissue perfusion. However, within hours of the onset of sepsis, a dysfunctional microcirculation is, due to a loss of functional capillary density and impaired regulation of oxygen delivery, unable to maintain capillary oxygen saturation levels and prevent the rapid onset of tissue hypoxia despite adequate oxygen supply to the organ. The mechanism(s) responsible for this dysfunctional microvasculature must be understood in order to develop appropriate management strategies for sepsis.
2005-08-25T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/4
http://ccforum.com/content/9/S4/S3
Medical Biophysics Publications
Scholarship@Western
Animals
Erythrocytes
Humans
Microcirculation
Models
Cardiovascular
Oxygen Consumption
Sepsis
Models, Cardiovascular
Medical Biophysics
oai:ir.lib.uwo.ca:oncpub-1010
2009-10-24T03:18:49Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:surgery
publication:onc
publication:epidempub
Post-Operative Extended Volume External Beam Radiation Therapy in High Risk Esophageal Cancer Patients: A Prospective Experience
Yu, E.
Tai, P.
Younus, J.
Malthaner, R.
Truong, P.
Stitt, L.
Rodrigues, G.
Ash, R.
Dar, R.
Yaremko, B.
Tomiak, A.
Dingle, B.
Sanatani, M.
Vincent, M.
Kocha, W.
Fortin, D.
Inculet, R.
Background and purpose: Extended volume external beam radiation therapy (RT) following esophagectomy is controversial. This prospective study evaluates the feasibility of extended volume RT treatment in high-risk esophagectomy patients with cervical anastomosis receiving post–operative combined chemo-radiation therapy. Patients and methods: From 2001-2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study, to evaluate the adverse effects of extended volume RT. Eligibility criteria were pathologically proven esophageal malignancy, T3-4, N0-1, disease amenable to surgical resection and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 patients received four cycles of 5-fluorouracil-based chemotherapy. External beam RT utilized conformal computerized tomography (CT) planning, with multi-field arrangement tailored to the pathological findings with clinical target volume encompassing the primary tumour bed and anastomotic site in the neck. The radiation therapy dose was 50.40Gy at 1.8Gy per fraction, delivered concurrently with the third cycle of chemotherapy. Outcomes were disease-free survival (DFS) and overall survival (OS), calculated by Kaplan–Meier method. Treatment-related toxicities were assessed using NCI-CTC Grading System. Results: There were 10 male and 5 female patients. The median age was 64 years (ranging 48 to 80 years). The TNM stages included one T3N0, two T2N1, eleven T3N1 and one T4N1. The histopathology included 5 adenocarcinomas and 10 squamous cell carcinomas. Resection margins were clear in 10 patients. The median follow up time was 19 months (range: 3.5-53.4 months). Delay in chemotherapy occurred in 20% of patients and dose reduction was required in 13.3% of patients prior to radiation therapy. During the concurrent chemo-radiation therapy phase, 20% and 6.6% had chemotherapy delay and dose reduction, respectively. No patient experienced treatment related acute and chronic esophagitis of > Grade 2. Disease recurrence occurred in 40% (6/15) and the median time to relapse was 24 months. There was no tumour recurrence at the anastomotic site. The median DFS and OS rate were 23 months and 21 months, respectively. Conclusion: Extended volume external beam radiation therapy encompassing the tumour bed and the anastomotic site is feasible and safe after esophagectomy. These findings support proceeding with a larger trial to assess its efficacy in patients with high-risk esophageal cancer.
2009-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/10
http://www.current-oncology.com/index.php/oncology/article/view/355
Oncology Publications
Scholarship@Western
Pilot study
cancer
esophagus
extended volume
irradiation
Medical Biophysics
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1011
2009-10-24T03:37:20Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:surgery
publication:onc
publication:epidempub
Is Extended Volume External Beam Radiation Therapy Covering the Anastomotic Site Beneficial in Post-esophagectomy High Risk Patients?
Yu, Edward
Dar, Rashid
Rodrigues, George B.
Stitt, Larry
Videtic, Gregory M. M.
Truong, Pauline
Tomiak, Anna
Ash, Robert
Brecevic, Ed
Inculet, Richard
Malthaner, Richard
Vincent, Mark
Craig, Ian
Kocha, Walter
Lefcoe, Michael
Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.
Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment fields tailored to the pathologic findings and location of the anastomosis. CT planning was used in all patients to design spinal cord sparing beam arrangements. First relapse rate (first incidence of an event), disease specific survival and overall survival were calculated by Chi-Square, Log-Rank, and Kaplan-Meier (K-M) methods.
Results: During the study period, 72 patients had underwent esophagectomy and were considered for adjuvant chemoradiation therapy. Three patients were excluded due to disease progression prior to therapy. The 69 remaining patients formed the study cohort for the present analysis. The median age of the study group was 60 years (range 35-82 years). Pathologic stage distribution (AJCC 1997 staging) was T(2,3) N(1) in 94% patients, 65% of the cases were adenocarcinoma and had undergone transhiatal esophagectomy (86%) with positive/close margins in 34 (49%) patients. Median follow-up was 30.5 months (range 3.4-116.3 months). Two- and 5-year actuarial overall survivals rates were 50 and 31%, respectively. First relapse rate after adjuvant therapy was 63.7% (n = 44) and median time to relapse was 27.2 months. Anastomosis recurrence rates were 29% with small volume and 0% with extended volume RT (P = 0.041). Local and regional relapse occurred in 74.2% of patients treated with small volume RT compared to 15.4% in patients treated with extended volume RT (P < 0.001). After adjusting for resection margin status, the local control benefit of extended volume RT remained significant (P = 0.003). Treatment interruptions and late gastrointestinal toxicity were not significantly increased with the use of extended volume RT.
Conclusions: A significant decrease in local and regional relapse without added late toxicity was achieved with the use of extended volume RT encompassing the anastomotic site post-operatively in high risk esophageal cancer patients.
2004-11-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/11
http://dx.doi.org/10.1016/j.radonc.2004.08.024
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Anastomosis
Surgical
Brachytherapy
Combined Modality Therapy
Esophageal Neoplasms
Esophagectomy
Female
Humans
Male
Middle Aged
Neoplasm Recurrence
Local
Neoplasm Staging
Probability
Prognosis
Radiotherapy Dosage
Radiotherapy
Adjuvant
Registries
Retrospective Studies
Risk Assessment
Sensitivity and Specificity
Survival Analysis
Time Factors
Treatment Outcome
Aged, 80 and over
Anastomosis, Surgical
Neoplasm Recurrence, Local
Radiotherapy, Adjuvant
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1014
2009-10-26T00:38:55Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Eleven-year Follow-up Results in the Delay of Breast Irradiation after Conservative Breast Surgery in Node-negative Breast Cancer Patients
Vujovic, Olga
Yu, Edward
Cherian, Anil
Dar, A. Rashid
Stitt, Larry
Perera, Francisco
Purpose: This retrospective review was conducted to determine if delay in the start of radiotherapy after conservative breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients.
Methods and materials: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy, between January 1, 1985 and December 31, 1992 at the London Regional Cancer Centre. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0 to 8 weeks (201 patients), greater than 8 to 12 weeks (235 patients), greater than 12 to 16 weeks (91 patients), and greater than 16 weeks (41 patients). Kaplan-Meier estimates of time to local-recurrence and disease-free survival rates were calculated.
Results: Median follow-up was 11.2 years. Patients in all 4 time intervals were similar in terms of age and pathologic features. No statistically significant difference was seen between the 4 groups in local recurrence or disease-free survival with surgery radiotherapy interval (p = 0.521 and p = 0.222, respectively). The overall local-recurrence rate at 5 and 10 years was 4.6% and 11.3%, respectively. The overall disease-free survival at 5 and 10 years was 79.6% and 67.0%, respectively.
Conclusion: This retrospective study suggests that delay in the start of breast irradiation of up to 16 weeks from definitive surgery does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results is limited by the retrospective nature of this analysis.
2006-03-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/14
http://dx.doi.org/10.1016/j.ijrobp.2005.08.004
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Breast Neoplasms
Carcinoma
Ductal
Breast
Carcinoma
Lobular
Combined Modality Therapy
Disease-Free Survival
Female
Follow-Up Studies
Humans
Mastectomy
Segmental
Middle Aged
Neoplasm Recurrence
Local
Regression Analysis
Retrospective Studies
Time Factors
Aged, 80 and over
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Mastectomy, Segmental
Neoplasm Recurrence, Local
Oncology
oai:ir.lib.uwo.ca:oncpub-1013
2009-10-26T00:26:47Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
The Role of High-dose-rate Brachytherapy in the Palliation of Symptoms in Patients with Non-small-cell Lung Cancer: A Systematic Review
Ung, Yee C.
Yu, Edward
Falkson, Conrad
Haynes, Adam E.
Stys-Norman, Denise
Evans, William K.
Cancer Care Ontario's Program in Evidence-based Care, McMaster University
Purpose: This review addresses the role of high-dose-rate endobronchial brachytherapy (HDREB) for symptom palliation in patients with non-small-cell lung cancer.
Methods and materials: Relevant trials were identified through a systematic search of the literature.
Results: Twenty-nine trials were eligible. Six randomized trials involved HDREB alone or with external beam radiation therapy (EBR) or laser therapy. Median and 1-year survival ranged from 4 to 10 months and from 11% to 38%, respectively. Symptoms controlled by HDREB were dyspnea, cough, chest pain, and hemoptysis. Fatal hemoptysis ranged from 7% to 22%. Better overall symptom palliation and fewer retreatments were required in previously untreated patients using EBR alone or EBR with HDREB.
Conclusions: EBR alone is more effective than HDREB for symptom palliation in previously untreated patients with endobronchial non-small-cell lung cancer. HDREB with EBR seems to provide better symptom relief than EBR alone. HDREB is recommended for symptomatic patients with recurrent endobronchial obstruction previously treated by EBR, providing it is technically feasible.
2006-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/13
http://dx.doi.org/10.1016/j.brachy.2006.05.001
Oncology Publications
Scholarship@Western
Brachytherapy
Carcinoma
Non-Small-Cell Lung
Dose-Response Relationship
Radiation
Humans
Lung Neoplasms
Palliative Care
Treatment Outcome
Carcinoma, Non-Small-Cell Lung
Dose-Response Relationship, Radiation
Oncology
oai:ir.lib.uwo.ca:oncpub-1012
2009-10-26T00:13:46Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:faculties
publication:biophysics
publication:epidem
publication:surgery
publication:onc
publication:epidempub
Definitive Radiation Therapy Management for Medically Non-resectable Clinically Localised Non-small Cell Lung Cancer: Results & Prognostic Factors
Yu, Edward
Tai, Patricia
Ash, Robert
Lee, Michael
Stitt, Larry
Rodrigues, George
Dar, Rashid
Vincent, Mark
Inculet, Richard
Malthaner, Richard
The aim of this paper is to review the experience of radical radiation therapy and the prognostic factors of patient outcome for clinically localised, medically inoperable non-small cell lung cancer (NSCLC) patients. Clinically staged node-negative NSCLC patients who were not a surgical candidates due to co-morbid diseases but who were eligible for curative treatment, were reviewed in the London Regional Cancer Program (LRCP). This study population was treated between 1st Jan 1985 to 31st Jan 2004. Patients were excluded if they were previously treated with chest radiotherapy. Patients with localised disease, but who refused surgery, were also included in the study. Eligible patients received radiation therapy which was given via localised portals and underwent simulation prior to therapy. The dose prescription range was from 50 Gy in 2.5 Gy per fraction to 60 Gy in 2 Gy per fraction. Hazard ratios and P-values were determined for time to recurrence and patient survival. A total of 74 patients met the study eligibility criteria. The median age of the cohort was 70 years (range 38-92 years). The cohort consisted of 52 males and 22 females. 39/74 (53%) had a pathological diagnosis of squamous cell carcinoma. Clinical stages were 21 (28%) T1 , 40 (54%) T2 , and 13 (18%) T3 , respectively. 59/74 (78%) completed their planned radical radiotherapy but 15/74 declined radiotherapy. The median follow-up time was 17.6 months (range 0.4-123.6 months). For patients who completed radiotherapy, the two-year and five-year disease-free survival (DFS) rates were 38.1% and 11.4%. Overall survival (OS) two-year and five-year rates were 33.2% and 6.9%, respectively. The median DFS and OS for T1 , T2 , and T3 were 18.7, 14, 15 months; and 23.1, 18.5, 14.5 months, respectively. Patients who received radiotherapy compared to those who did not, had median lung cancer-specific survival (CSS) times of 21 months and 4.9 months (P<0.001); OS times of 20 months and 5 months (P<0.001), respectively. Tumour size had impact on patient survival in univariate (P=0.004) and multivariate (P=0.002) analyses. In conclusion, radical radiotherapy significantly improves survival for patients with medically inoperable clinically staged localised NSCLC, and tumour size is a predictor of patient outcome. The OS, CSS, and DFS rates for patients with tumour size greater than 6 cm are significantly worse than those with smaller size tumours.
2007-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/12
http://www.nowotwory.edu.pl/files/pdf/s_263e_Yu_-_Definitive_radiation.pdf
Oncology Publications
Scholarship@Western
radiation therapy
lung cancer
Epidemiology
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1015
2010-08-13T23:25:06Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Practice Guideline on Prophylactic Cranial Irradiation in Small-cell Lung Cancer
Kotalik, Jaro
Yu, Edward
Markman, Barbara R.
Evans, William K.
Cancer Care Ontario, Toronto, ON
Purpose: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest.
Methods and materials: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline.
Results: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30-36 Gy in 2-3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial irradiation does not produce significant late neurotoxicity. There is evidence from one trial that prophylactic cranial irradiation does not have a detrimental effect on quality of life in the first 12 months following the completion of therapy. There is insufficient evidence to comment on the long-term effects of prophylactic cranial irradiation on quality of life.
Conclusion: For adult patients with limited or extensive SCLC who achieve a complete remission with induction therapy, PCI is recommended.
2001-06-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/15
info:doi/10.1016/S0360-3016(01)01448-1
http://dx.doi.org/10.1016/S0360-3016(01)01448-1
Oncology Publications
Scholarship@Western
Carcinoma
Small Cell
Cognition
Cranial Irradiation
Disease-Free Survival
Dose-Response Relationship
Radiation
Evidence-Based Medicine
Humans
Lung Neoplasms
Meta-Analysis as Topic
Physician's Practice Patterns
Practice Guidelines as Topic
Quality of Life
Randomized Controlled Trials as Topic
Survival Rate
Carcinoma, Small Cell
Dose-Response Relationship, Radiation
Oncology
oai:ir.lib.uwo.ca:oncpub-1016
2009-10-26T01:16:21Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:faculties
publication:biophysics
publication:epidem
publication:surgery
publication:onc
publication:epidempub
The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake
Ung, Y. C.
Yu, E.
Malthaner, R.
Burkes, R.
Ellis, P.
Goss, G.
Solow, H.
Irvine, S.
Laffan, S.
The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake focused on the themes of innova- tions in the management of lung cancer, controversies in the management of esophageal cancer, and molecu- lar targeted therapies in lung cancer. This conference summary highlights the presentations and provides clinicians with a referenced update on these topics.
2009-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/16
http://www.current-oncology.com/index.php/oncology/article/view/516
Oncology Publications
Scholarship@Western
lung cancer
esophageal cancer
molecular targeted therapies
Oncology
oai:ir.lib.uwo.ca:oncpub-1018
2009-11-23T01:24:18Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Impact of Radiation Therapy Fraction Size on Local Control of Early Glottic Carcinoma
Yu, Edward
Shenouda, George
Beaudet, Marie P.
Black, Martin J.
Purpose: Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients.
Methods and materials: A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 Gy with once-daily 2.5-Gy fractions, and 30 received 65.25 Gy in 29 fractions of 2.25 Gy each), and 32 patients were treated to a dose of 66 Gy in 33 fractions with 2 Gy/fraction. Patients' characteristics of prognostic importance were equally distributed between the two fractionation groups.
Results: At a median follow-up of 84 months, the 10-year disease-free survival and overall survival were 76% and 93%, respectively. Local control for patients treated with > 2 Gy fraction was 84%, compared to 65.6% for those treated with 2-Gy fractions (p = 0.026). Among the prognostic factors tested, such as gender, age, stage, anterior and posterior commissure involvement, smoking history, and fraction size, the latter was the only significant predictor of local control for the whole group of patients in univariate (p = 0.041) and multivariate (p = 0.023) analysis. There was no observed difference in the incidence of complications between the two fractionation groups.
Conclusions: From the results of this retrospective review of patients treated with radiotherapy for T1 true vocal cord cancer, and within the range of total doses and overall treatment times used in our patients, it was found that fractionation schedules using daily fraction size > 2 Gy are associated with a better local control than schedules delivering 2 Gy/fraction, with no increase in toxicity.
1997-02-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/18
info:doi/10.1016/S0360-3016(96)00578-0
http://www.redjournal.org/article/S0360-3016%2896%2900578-0/abstract
Oncology Publications
Scholarship@Western
Carcinoma
Squamous Cell
Disease-Free Survival
Female
Follow-Up Studies
Humans
Laryngeal Neoplasms
Male
Middle Aged
Neoplasm Staging
Radiotherapy Dosage
Retrospective Studies
Sex Factors
Treatment Failure
Vocal Cords
Carcinoma, Squamous Cell
Oncology
oai:ir.lib.uwo.ca:oncpub-1017
2009-11-15T11:01:35Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Chemotherapy in Neuroendocrine/Merkel Cell Carcinoma of the Skin: Case Series and Review of 204 Cases
Tai, Patricia T. H.
Yu, Edward
Winquist, Eric
Hammond, Alex
Stitt, Larry
Tonita, Jon
Gilchrist, Jim
Purpose: To study the use of chemotherapy for Merkel cell carcinoma (MCC) of the skin.
Patients and methods: Twenty-five cases of MCC were treated at the London Regional Cancer Center between 1987 and 1997. Thirteen cases treated with chemotherapy were reviewed with 191 cases from the literature.
Results: At presentation, 24 patients had localized skin lesions (stage I) and one had locoregional involvement (stage II). Among the nine cases with recurrent nodal disease, six had chemotherapy as a component of salvage treatment. They were all free of disease at a median of 19 months (range, 12 to 37 months). In contrast, two patients who had salvage radiotherapy alone died of disease. Overall survival (OS) and disease-free survival (DFS) were 59% and 43%, respectively, at two years. Median OS and DFS were 29 months (range, 1 to 133 months) and 9 months (range, 1 to 133 months), respectively. Nodal disease developed in 12 (50%) of 24 patients with stage I disease, and distant metastases developed in six (25%) of 24. Including those from the literature, there were 204 cases treated with chemotherapy. Cyclophosphamide/doxorubicin (or epirubicin)/vincristine combination +/- prednisone was the most commonly used chemotherapy regimen (47 cases), with an overall response rate of 75.7% (35.1% complete, 35. 1% partial, and 5.4% minor responses). Etoposide/cisplatin (or carboplatin) was the next most commonly used regimen (27 cases), with an overall response rate of 60% (36% complete and 24% partial responses). The difference in response rate was not statistically significant (P =.19). Among the 204 cases, there were seven (3.4%) toxic deaths.
Conclusion:: Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.
2000-06-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/17
http://jco.ascopubs.org/cgi/content/abstract/18/12/2493
Oncology Publications
Scholarship@Western
Aged
Aged
80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Merkel Cell
Combined Modality Therapy
Disease-Free Survival
Female
Humans
Karnofsky Performance Status
Male
Middle Aged
Neoplasm Staging
Prognosis
Skin Neoplasms
Treatment Outcome
Aged, 80 and over
Carcinoma, Merkel Cell
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1019
2009-10-28T06:37:28Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Accelerated Fractionation in Inoperable Non-small Cell Lung Cancer. A Phase I/II Study
Yu, Edward
Souhami, Luis
Guerra, Julio
Clark, Brenda
Gingras, Carole
Fava, Palma
Background: A prospective, single-treatment-arm, Phase I/II trial was performed to determine the tumor response to an accelerated regimen and assess the feasibility and toxic effects of this approach in patients with inoperable non-small cell lung cancer (NSCLC).
Methods: Thirty-seven previously untreated patients with inoperable NSCLC who had no evidence of metastatic disease entered the study. All patients were able to walk and had disease that was measurable or assessable. Patients with palpable supraclavicular disease and weight loss were also eligible. Radiation therapy consisted of an altered fractionation regimen with a concomitant boost technique. The original lung volume received a dose of 40 Gy in 20 daily fractions to the computerized axial tomography (CT)-defined primary tumor and mediastinal nodes. The boost dose (10 Gy) was administered concomitantly with the last five fractions of the original volume treatments, with an interfraction interval of 6-8 hours. The maximal allowed dose to the cord was 46 Gy.
Results: At a median follow-up of 36 months, complete response was achieved in 29% (9 of 31) of the patients and a partial response in 42% (13 of 31). The overall survival rate at 36 months was 10% (median survival time, 8 months). Survival rates were 25%, 8%, and 0% for the complete responders, partial responders, and nonresponders, respectively. Local failure alone was observed in 35.5% of all patients, local and distant failure in 42%, and distant failure only in 13%. Treatments were well tolerated, and all patients were able to complete the planned regimen. Grade 1 and 2 esophagitis occurred in 65% and 26% of the patients, respectively. The clinical condition of two patients (6%) was compatible with radiation pneumonitis. Moist desquamation of the skin occurred in two patients, but most had either mild (55%) or moderate (19%) skin erythema. Late complications have been limited to radiologically detected lung fibrosis.
Conclusions: The accelerated fractionation schedule used in this trial was well tolerated with shortening of overall treatment time. Local tumor control and overall survival are similar to those resulting from conventional fractionation without an increase in normal tissue effects. These results are encouraging, and additional studies testing higher tumor doses are warranted.
1993-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/19
http://www3.interscience.wiley.com/journal/112675825/abstract
Oncology Publications
Scholarship@Western
Aged
Carcinoma
Non-Small-Cell Lung
Feasibility Studies
Female
Follow-Up Studies
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Prospective Studies
Radiation Injuries
Radiotherapy Dosage
Survival Rate
Treatment Failure
Carcinoma, Non-Small-Cell Lung
Oncology
oai:ir.lib.uwo.ca:oncpub-1020
2009-10-28T06:52:41Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
The Role of Biogenic Amines in the Regulation of Exocrine Gland Function: A Possible Mechanism for the Pathogenesis of Cystic Fibrosis
Tenenhouse, A.
Yu, E. W.-T.
1984-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/20
http://journals.lww.com/jpgn/Citation/1984/00031/The_Role_of_Biogenic_Amines_in_the_Regulation_of.6.aspx
Oncology Publications
Scholarship@Western
Animals
Biogenic Amines
Cystic Fibrosis
Pancreas
Pancreatic Ducts
Rats
Oncology
Pharmacology, Toxicology and Environmental Health
oai:ir.lib.uwo.ca:oncpub-1021
2009-10-28T07:02:18Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Decarboxylation of L-Dopa and 5-Hydroxytryptophan in Dispersed Rat Pancreas Acinar Cells
Yu, E. W.-T.
Stern, L.
Tenenhouse, A.
Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other and the decarboxylation of each is inhibited by NSD-1055. The estimated Km and Vmax are, for L-dopa, 4.8 X 10(-5) M and 2.5 nmol/mg protein/min and for 5-hydroxytryptophan, 2.9 X 10(-5) M and 0.3 nmol/mg protein/min. The pH optimum for 5-hydroxytryptophan decarboxylation is from 7.0-8.5 while that for L-dopa is 7.0. It is concluded that pancreas acinar cells possess a single aromatic amino acid decarboxylase specific for the hydroxylated amino acids L-dopa and 5-hydroxytryptophan, and which is similar in all properties studied to the aromatic amino acid decarboxylase found in several other mammalian tissues.
1984-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/21
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=138011&Ausgabe=236604&ProduktNr=224274
Oncology Publications
Scholarship@Western
Animals
Aromatic-L-Amino-Acid Decarboxylases
Binding
Competitive
Decarboxylation
Female
Histidine
Levodopa
Pancreas
Rats
Rats
Inbred Strains
Serotonin
Tryptophan
Tyrosine
Binding, Competitive
Rats, Inbred Strains
Oncology
Pharmacology, Toxicology and Environmental Health
oai:ir.lib.uwo.ca:oncpub-1022
2009-10-29T05:30:49Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Lung Cancer Trends. Part 1: North America
Tai, P.
Yu, E.
2004-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/25
http://www.current-oncology.com/
Oncology Publications
Scholarship@Western
lung cancer
North America
Oncology
oai:ir.lib.uwo.ca:oncpub-1024
2009-10-29T05:37:32Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Malignant Pleural Mesothelioma: World Trends
Tai, P.
Yu, E.
2004-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/23
http://www.current-oncology.com/
Oncology Publications
Scholarship@Western
Pleural mesothelioma
Oncology
oai:ir.lib.uwo.ca:oncpub-1023
2009-10-29T05:33:49Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Lung Cancer Trends. Part 2: Beyond North America
Tai, P.
Yu, E.
2005-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/24
http://www.current-oncology.com/
Oncology Publications
Scholarship@Western
lung cancer
Oncology
oai:ir.lib.uwo.ca:oncpub-1025
2009-10-29T05:51:44Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Altered Fractionation of Radical Radiation Therapy in the Management of Unresectable Non-Small Cell Lung Cancer
Yu, E.
Lochrin, K.
Dixon, P.
Ung, Y.
Gagliardi, A.
Evans, W. K.
2000-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/22
http://www.cma.ca/index.cfm/ci_id/54490/la_id/1.htm?cpgId=3278
Oncology Publications
Scholarship@Western
lung cancer
radiation therapy
Oncology
oai:ir.lib.uwo.ca:oncpub-1027
2009-11-02T00:24:14Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Cardiac Tumours
Tai, Patricia
Yu, Edward
Primary cardiac neoplasms are rare and they are not covered comprehensively in the literature, including textbooks. A Medline search from January 2007 to July 2008 was performed to update the existing literature. Cardiac tumour manifestation may mimic other conditions. It may lead to fatal complications like sudden death, and because the tumour can act as a nidus for the formation of fibrin-platelet aggregates, embolic events occur. Its rarity means that an average physician would have minimal experience with its management. This review will serve as a useful reference.
2009-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/27
http://www.nowotwory.edu.pl/files/pdf/2009/plik_s1e_Cardiac.pdf
Oncology Publications
Scholarship@Western
cardiac tumours
prognostic factors
diagnosis
treatment
Oncology
oai:ir.lib.uwo.ca:oncpub-1029
2011-05-05T01:16:53Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
A Long-Term Study of Radiation Therapy in T1-2 Node-Negative Breast Cancer Patients in Relation to the Number of Axillary Nodes Examined
Tai, Patricia
Yu, Edward
Sadikov, Evgeny
Joseph, Kurian
Purpose: The optimal number of axillary nodes to be resected is controversial. This large series investigated the effect of surgery with or without adjuvant radiotherapy among node-negative breast cancer patients in relation to the number of nodes examined.
Methods and materials: Node-negative patients from the Saskatchewan registry of 1981-1995 were studied. Because nodal status may be more reliable with more number of nodes examined, we analyzed T1-2 age < 90 patients with < 10 nodes examined treated with surgery alone (Group A_S, n = 509) vs. surgery and adjuvant radiotherapy (Group A_S+R, n = 342); and T1-2 age < 90 patients with > or = 10 nodes examined treated with surgery alone (Group B_S, n = 902) vs. surgery and adjuvant radiotherapy (Group B_S+R, n = 596).
Results: For the two radiotherapy groups, patients with < 10 nodes (Group A_S+R) vs. > or = 10 nodes (Group B_S+R), there was no difference in overall survival (p = 0.14). In the two nonradiotherapy groups (A_S and B_S), there is a statistically significant decrease in overall survival for patients with < 10 nodes removed (p < 0.001, log-rank test). The optimal number of axillary nodes examined could be 8 nodes with adjuvant radiotherapy (p = 0.05, logrank test) and 12 nodes without adjuvant radiotherapy (p = 0.02, log-rank test).
Conclusions: The poorer prognosis of a lesser number of nodes resected was overcome partly by the use of radiotherapy, raising the possibility of micrometastases in lymph nodes not removed. The optimal number of axillary nodes examined could be 8 nodes with adjuvant radiotherapy and 12 nodes without adjuvant radiotherapy.
2009-06-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/29
info:doi/10.1016/j.ijrobp.2008.08.035
http://dx.doi.org/10.1016/j.ijrobp.2008.08.035
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Axilla
Breast Neoplasms
Female
Humans
Lymph Node Excision
Lymph Nodes
Lymphatic Metastasis
Mastectomy
Segmental
Middle Aged
Prospective Studies
Radiotherapy
Adjuvant
Registries
Saskatchewan
Survival Analysis
Aged, 80 and over
Mastectomy, Segmental
Radiotherapy, Adjuvant
Oncology
oai:ir.lib.uwo.ca:oncpub-1028
2009-11-02T00:38:49Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:surgery
publication:onc
publication:epidempub
Management and Prognosis in Synchronous Solitary Resected Brain Metastasis from Non–Small-Cell Lung Cancer
Louie, Alexander V.
Rodrigues, George
Yaremko, Brian
Yu, Edward
Dar, A. Rashid
Dingle, Brian
Vincent, Mark
Sanatani, Michael
Malthaner, Richard
Inculet, Richard
Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.
Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm.
Results: Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery (P = .0033), primary lung treatment > 8 weeks after brain surgery (P = .0128), and stage I/II disease (P = .0467) were predictive of overall survival.
Conclusion: Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.
2009-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/28
http://cigjournals.metapress.com/content/506526020m5610k1/?p=5f802118b7d04304af4114dab0debb4cπ=5
Oncology Publications
Scholarship@Western
Adult
Aged
Brain Neoplasms
Carcinoma
Non-Small-Cell Lung
Cranial Irradiation
Humans
Infant
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Prognosis
Retrospective Studies
Carcinoma, Non-Small-Cell Lung
Epidemiology
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1026
2009-11-02T00:14:35Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Effect of Interval to Definitive Breast Surgery on Clinical Presentation and Survival in Early-Stage Invasive Breast Cancer
Vujovic, Olga
Yu, Edward
Cherian, Anil
Perera, Francisco
Dar, A. Rashid
Stitt, Larry
Hammond, A.
Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer.
Methods and materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival.
Results: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041).
Conclusion: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.
2009-11-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/26
http://www.redjournal.org/article/S0360-3016%2808%2903837-6/abstract
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Axilla
Breast Neoplasms
Disease-Free Survival
Female
Follow-Up Studies
Humans
Lymph Node Excision
Mammography
Middle Aged
Neoplasm Recurrence
Local
Neoplasm Staging
Palpation
Radiotherapy Dosage
Regression Analysis
Retrospective Studies
Time Factors
Aged, 80 and over
Neoplasm Recurrence, Local
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1030
2009-11-02T01:59:40Z
publication:physics
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:medimagingpub
publication:robarts
publication:institutes
publication:onc
The Use of CT Density Changes at Internal Tissue Interfaces to Correlate Internal Organ Motion with an External Surrogate
Gaede, Stewart
Carnes, Gregory
Yu, Edward
Van Dyk, Jake
Battista, Jerry
Lee, Ting-Yim
The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a ciné mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing on multiple axial slices and measured the mean CT number versus respiratory phase. Tumour motion was directly correlated with external marker motion, acquired simultaneously, using the sample coefficient of determination, r(2). Only three of the ten patients showed correlation higher than r(2) = 0.80 between tumour motion and external marker position. However, after taking into account time shifts (ranging between 0 s and 0.4 s) between the two data sets, all ten patients showed correlation better than r(2) = 0.8. This non-invasive method for monitoring the motion of internal organs is an effective tool that can assess the use of external markers for 4D-CT imaging and respiratory-gated radiotherapy on a patient-specific basis.
2009-01-21T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/30
http://www.iop.org/EJ/abstract/0031-9155/54/2/006
Oncology Publications
Scholarship@Western
Biophysical Phenomena
Humans
Imaging
Three-Dimensional
Lung Neoplasms
Movement
Organ Specificity
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Computer-Assisted
Respiration
Respiratory Mechanics
Tomography Scanners
X-Ray Computed
Tomography
X-Ray Computed
Imaging, Three-Dimensional
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Computer-Assisted
Tomography Scanners, X-Ray Computed
Tomography, X-Ray Computed
Bioimaging and Biomedical Optics
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:biophysicspub-1004
2009-11-02T02:00:48Z
publication:physics
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:medimagingpub
publication:robarts
publication:institutes
publication:onc
A Fully Automated Non-external Marker 4D-CT Sorting Algorithm Using a Serial Cine Scanning Protocol
Carnes, Greg
Gaede, Stewart
Yu, Edward
Van Dyk, Jake
Battista, Jerry
Lee, Ting-Yim
Current 4D-CT methods require external marker data to retrospectively sort image data and generate CT volumes. In this work we develop an automated 4D-CT sorting algorithm that performs without the aid of data collected from an external respiratory surrogate. The sorting algorithm requires an overlapping cine scan protocol. The overlapping protocol provides a spatial link between couch positions. Beginning with a starting scan position, images from the adjacent scan position (which spatial match the starting scan position) are selected by maximizing the normalized cross correlation (NCC) of the images at the overlapping slice position. The process was continued by 'daisy chaining' all couch positions using the selected images until an entire 3D volume was produced. The algorithm produced 16 phase volumes to complete a 4D-CT dataset. Additional 4D-CT datasets were also produced using external marker amplitude and phase angle sorting methods. The image quality of the volumes produced by the different methods was quantified by calculating the mean difference of the sorted overlapping slices from adjacent couch positions. The NCC sorted images showed a significant decrease in the mean difference (p < 0.01) for the five patients.
2009-04-07T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/5
http://www.iop.org/EJ/abstract/0031-9155/54/7/013
Medical Biophysics Publications
Scholarship@Western
Algorithms
Artifacts
Automation
Humans
Image Processing
Computer-Assisted
Neoplasms
Radiography
Thoracic
Reference Standards
Respiration
Tomography
X-Ray Computed
Image Processing, Computer-Assisted
Radiography, Thoracic
Tomography, X-Ray Computed
Bioimaging and Biomedical Optics
Medical Biophysics
oai:ir.lib.uwo.ca:oncpub-1031
2010-07-27T19:59:37Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
The Number of Axillary Nodes Removed as a Predictor of Regional Recurrence in Node Negative Breast Cancer
Vujovic, Olga
Yu, Edward
Cherian, Anil
Dar, A. Rashid
Stitt, Larry
Perera, Francisco
Purpose: To determine if the number of axillary nodes removed is a predictor of recurrence in node negative breast cancer.
Materials and methods: Five hundred thirty-six patients with T1-T2, N0 invasive breast cancer, treated with lumpectomy and axillary node dissection (AND), were reviewed from January 1, 1986 to December 31, 1992. Patients received radiation to whole breast only, without regional nodal radiation. There was no adjuvant chemotherapy or Tamoxifen given. Patients were grouped according to the number of axillary nodes dissected as follows: 1-5 nodes (91 patients), 6-10 nodes (225 patients) and > 10 nodes (220 patients). Hazard ratios and p-values were determined for time to local recurrence, regional recurrence and for disease specific survival.
Results: Median follow-up was 11.2 years. The overall local recurrence and regional recurrence rates for the three groups were: 1-5 nodes, 9.9% and 8.8%, respectively, 6-10 nodes, 10.2% and 2.2%, respectively, and > 10 nodes, 11.8% and 2.7%, respectively. The effect of number of axillary nodes removed was statistically significant only for regional recurrence (p = 0.017). There was no adverse effect on disease specific survival (p = 0.363).
Conclusion: The number of axillary nodes removed predicts only for regional recurrence in node negative breast cancer patients, with less than 6 nodes removed associated with higher regional recurrence. This may have clinical implications with the current practice of sentinel node biopsy (SNB) replacing axillary node dissection in early stage breast cancer.
2009-04-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/31
info:doi/10.1016/j.radonc.2008.05.003
http://dx.doi.org/10.1016/j.radonc.2008.05.003
Oncology Publications
Scholarship@Western
Adult
Axilla
Breast Neoplasms
Female
Follow-Up Studies
Humans
Lymph Node Excision
Lymphatic Metastasis
Neoplasm Recurrence
Local
Neoplasm Staging
Predictive Value of Tests
Proportional Hazards Models
Survival Rate
Neoplasm Recurrence, Local
Epidemiology
Oncology
oai:ir.lib.uwo.ca:epidempub-1018
2012-03-29T00:14:24Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Dosimetric Evaluation of Helical Tomotherapy Treatment Planning for Non-small Cell Lung Cancer
Chu, Karen
Rodrigues, George
Yartsev, Slav
Dar, A. Rashid
Yu, Edward
Ash, Robert
Yaremko, Brian
MacKenzie, Marc
Quon, Harvey
Bauman, Glenn
Roa, Wilson
Helical tomotherapy (HT) is a novel technique to deliver intensity modulated radiation therapy guided by 3D megavoltage CT imaging. The purpose of our study is to assess the dosimetric parameters related to HT and 3DCRT in advanced non-small cell lung cancer (NSCLC). Eleven patients from the London Regional Cancer Centre and the Cross Cancer Institute with NSCLC underwent individualized treatment planning on both HT and 3DCRT. Corresponding HT and 3DCRT plans for each patient were analyzed using dose-volume histograms for GTV, PTV (median dose 60Gy/30 fractions), and critical structures (lung V5-30, esophageal V50-60, and spinal cord D1). Observed differences in tumor and normal tissue dosimetry were assessed for statistical significance using paired t-tests. A statistically significant improvement on GTV homogeneity but not PTV homogeneity was found in relation with HT. 3DCRT was associated with improved V5 (14%, p = 0.02), V10 (9%, p = 0.04) and V15 (6%, p = 0.04). However, there was no difference in V20 (2%, p = NS); while HT demonstrated superior V30 (5%, p = 0.002). HT achieved excellent tumor coverage relative to 3DCRT in the setting of routinely clinically planned radiation therapy with improvements in the V30 lung parameter. This was at the expense of a modest increase in V5-V15 total lung dose.
2008-09-01T07:00:00Z
article
https://ir.lib.uwo.ca/epidempub/18
http://www.cancer-therapy.org/CT/v6/B/PDF/60._Chu_et_al,_571-576.pdf
Epidemiology and Biostatistics Publications
Scholarship@Western
Helical tomotherapy
non-small cell lung cancer
Three-dimensional Conformal Radiotherapy
Dosimetric Comparison
Lung Cancer
Biostatistics
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1032
2010-11-15T04:53:01Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Nodal Ratios in Node-Positive Breast Cancer—Long-Term Study to Clarify Discrepancy of Role of Supraclavicular and Axillary Regional Radiotherapy
Tai, Patricia
Joseph, Kurian
Sadikov, Evgeny
Mahmood, Shazia
Lien, Francis
Yu, Edward
Purpose: To study the absolute number of involved nodes/the number of nodes examined or the nodal ratio (NR) in breast cancer. The primary study endpoint was to evaluate the role of supraclavicular and axillary radiotherapy (SART) according to the NR.
Methods and materials: From the Saskatchewan provincial registry of 1981-1995, the charts of 5,996 consecutive patients were retrieved to collect detailed prognostic factors. Among these patients, 1,985 were node positive. Because the NRs are more reliable the greater the number of nodes examined, we analyzed 1,255 patients with > or =10 nodes examined. Of these 1,255 patients, 667, 389, and 199 were categorized into three NR groups--low (< or =25%), medium (>25% to < or =75%), and high (>75%) nodal involvement, respectively.
Results: The NR correlated significantly with the primary tumor size (< or =2 cm, >2 to < or =5 cm, and >5 cm; p = 2.2 x 10(-16)), clinical stage group (p = 5.5 x 10(-16)), pathologic stage group (p < 2.2 x 10(-16)), and the risk of any first recurrence (p = 5.0 x 10(-15)) using chi-square tests. For a low NR, the 10-year overall survival rate with and without SART was 57% and 58% (p = 0.18), and the cause-specific survival rate was 68% and 71% (p = 0.32), respectively. For a medium NR, the 10-year overall survival rate with and without SART was 48% and 34% (p = 0.007), and the cause-specific survival rate was 57% and 43% (p = 0.002), respectively. For a high NR, the 10-year overall survival rate with and without SART was 19% and 10% (p = 0.005), and the cause-specific survival rate was 26% and 14% (p = 0.005), respectively.
Conclusion: This is the first study demonstrating that for patients with > or =10 nodes examined, SART significantly improved the survival for the median and high NR groups but not for the low NR group.
2007-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/32
info:doi/10.1016/j.ijrobp.2007.01.057
http://dx.doi.org/10.1016/j.ijrobp.2007.01.057
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Axilla
Breast Neoplasms
Clavicle
Female
Humans
Longitudinal Studies
Lymph Nodes
Lymphatic Metastasis
Middle Aged
Neoplasm Recurrence
Local
Radiotherapy
Risk Assessment
Risk Factors
Saskatchewan
Survival Analysis
Survival Rate
Treatment Outcome
Aged, 80 and over
Neoplasm Recurrence, Local
Oncology
oai:ir.lib.uwo.ca:oncpub-1033
2009-11-04T07:54:51Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Radiotherapy for Merkel Cell Carcinoma of the Skin
Tai, Patricia
Yu, Edward
Pacella, Juan
We examine the impact of radiotherapy in the treatment of Merkel cell carcinoma (MCC) of the skin. Data at two Canadian institutions (Allan Blair Cancer Centre and London Regional Cancer Program) were collected and charts were retrieved from the registry of 1987 to 2005. A total of 79 patients with definite MCC were studied. All except three had a primary skin lesion. Six patients presented with nodal metastases and three patients with distant metastases. Fourteen patients were referred to the cancer centers at the time of recurrence: 2/14 with local recurrence, 8/14 with nodal recurrence, 2/14 with both local and nodal recurrence, and 2/14 with distant recurrence. The series consisted of 40 males and 39 females with a median age of 80 years (range 48-94). The median follow up was 21 months (range 0.5-150.4).
Twenty-two patients (group A) received radiotherapy at the time of presentation,21 being post-operative adjuvant treatment and one being primary treatment without surgery. The 5-year cause-specific survival rate (CSSR) was 42%. The 5-year rates equals the 10-year rate since the CSSR plateaus at a survival of 4.5 years and thereafter, patients died from causes other than MCC. The 5-year overall survival rate (OSR) was 19% for group A.
Fifty-seven patients (group B) had surgery alone without post-operative adjuvant radiotherapy. 5-year and 10-year CSSRs were both 63% (P=0.8, using the logrank test when comparing the two groups of patients). The 5-year OSR was 30% and the 10-year OSR was 13% (P=0.6, group A versus group B). Morbidity from radiotherapy was minimal. Only one patient with an ankle lesion did not take the skin graft well and had drainage for one year before healing. One patient had lymphoedema of the arm (which required a pressure garment) after axillary dissection and radiotherapy of 50 Gy in 25 fractions over 35 days. Radiotherapy after surgical excision is well tolerated. It is recommended if there are high risk factors for recurrence and radiotherapy should be started as soon as possible after referral.
2006-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/33
http://www.nowotwory.edu.pl/files/pdf/s%20637%20Radiotherapy%20for%20Merkel.pdf
Oncology Publications
Scholarship@Western
Merkel cell carcinoma
skin
radiotherapy
prognostic factors
Oncology
oai:ir.lib.uwo.ca:oncpub-1034
2009-11-06T08:09:56Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
The Role of Radiation Therapy in Malignant Pleural Mesothelioma: A Systematic Review
Ung, Yee C.
Yu, Edward
Falkson, Conrad
Haynes, Adam E.
Stys-Norman, Denise
Evans, William K.
Cancer Care Ontario Program in Evidence-based Care, McMaster University
Introduction: Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM.
Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed.
Results: Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis found no significant reduction in the frequency of procedure tract metastases. Four non-comparative studies have shown that hemithoracic irradiation alone resulted in significant toxicity, including radiation-induced pulmonary fibrosis, radiation pneumonitis, and bronchopleural fistula, without any survival benefit. Few of the identified studies reported on symptom control, and no studies included formal measures of quality of life.
Conclusion: There is limited evidence for the role of radiotherapy in the management of patients with MPM. Future studies including radiotherapy for the treatment of such patients should include formal measures of quality of life and symptom control.
2006-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/34
http://dx.doi.org/10.1016/j.radonc.2006.06.002
Oncology Publications
Scholarship@Western
Clinical Trials as Topic
Databases
Bibliographic
Humans
Mesothelioma
Pleural Neoplasms
Prospective Studies
Quality of Life
Radiation Oncology
Radiotherapy
Randomized Controlled Trials as Topic
Time Factors
Treatment Outcome
Databases, Bibliographic
Oncology
oai:ir.lib.uwo.ca:oncpub-1035
2009-11-08T08:35:56Z
publication:physics
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:robarts
publication:surgery
publication:institutes
publication:onc
publication:epidempub
3D Thoracoscopic Ultrasound Volume Measurement Validation in an Ex Vivo and In Vivo Porcine Model of Lung Tumours
Hornblower, V. D. M.
Yu, E.
Fenster, A.
Battista, J. J.
Malthaner, R. A.
The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure "tumour" volumes both in vivo and ex vivo.
2007-01-07T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/35
http://www.iop.org/EJ/abstract/0031-9155/52/1/007
Oncology Publications
Scholarship@Western
Agar
Algorithms
Animals
Automation
Humans
Image Processing
Computer-Assisted
Imaging
Three-Dimensional
Lung
Lung Neoplasms
Neoplasm Transplantation
Phantoms
Imaging
Reproducibility of Results
Swine
Ultrasonography
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Phantoms, Imaging
Bioimaging and Biomedical Optics
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1037
2009-11-08T09:08:17Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Patients with Limited Stage Small Cell Lung Cancer
Tai, Patricia
Yu, Edward
Jones, Kurian
Sadikov, Evgeny
Mahmood, Shazia
Tonita, Jon
A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era.
From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH.
There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance.
Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence.
Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.
2006-08-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/37
http://dx.doi.org/10.1016/j.lungcan.2006.05.009
Oncology Publications
Scholarship@Western
Aged
Biological Markers
Carcinoma
Small Cell
Female
Humans
Inappropriate ADH Syndrome
Lung Neoplasms
Male
Medical Records
Middle Aged
Neoplasm Recurrence
Local
Neoplasm Staging
Recurrence
Retrospective Studies
Sickness Impact Profile
Survival Analysis
Carcinoma, Small Cell
Neoplasm Recurrence, Local
Oncology
oai:ir.lib.uwo.ca:oncpub-1036
2009-11-08T08:54:56Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
The Effect of Timing of Radiotherapy after Breast-conserving Surgery in Patients with Positive or Close Resection Margins, Young Age, and Node-negative Disease, with Long Term Follow-up
Vujovic, Olga
Cherian, Anil
Yu, Edward
Dar, A. Rashid
Stitt, Larry
Perera, Francisco
Purpose: The aim of this study was to determine the effect of timing of radiotherapy after conservative breast surgery on local recurrence in women with positive resection margins and young age, treated without systemic therapy.
Methods and Materials: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, between January 1, 1985, and December 31, 1992, at the London Regional Cancer Centre. 63 patients (11.1%) had positive/close resection margins (< 2 mm) and 48 patients (8.4%) were age < or = 40 years. For patients with positive resection margins, the time intervals from breast surgery to breast irradiation used for analysis were, 0 to 8 weeks, > 8 to 12 weeks and > 12 weeks. For patients < or = 40 years, the intervals used for analysis were 0 to 8 weeks and > 8 weeks.
Results: Median follow up was 11.2 years. For patients < or = 40 years, local recurrence rate at 5 and 10 years was 17.2% and 19.8% respectively. Four patients (17.4%) treated in the 0-week to 8-week interval and 7 patients (28.0%) treated in the > 8 week interval had local recurrences. For patients < or = 40 years with positive resection margins, the local recurrence rate was 25.0%. For patients with positive resection margins, 5-year and 10-year local recurrence rates were as follows: 0 to 8 weeks, 0% and 10.5% respectively; > 8 to 12 weeks, 10.3% and 10.3% respectively; and > 12 weeks, 13.3% and 20.0% respectively.
Conclusion: Patients < or = 40 years have an increased local recurrence rate which occurs early. Patients with positive resection margins have higher local recurrence rates that become apparent when breast irradiation is delayed.
2006-11-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/36
http://www.redjournal.org/article/S0360-3016%2806%2900978-3/abstract
Oncology Publications
Scholarship@Western
Adult
Age Factors
Aged
Aged
80 and over
Breast Neoplasms
Carcinoma
Ductal
Breast
Carcinoma
Lobular
Disease-Free Survival
Female
Follow-Up Studies
Humans
Mastectomy
Segmental
Middle Aged
Neoplasm Recurrence
Local
Neoplasm
Residual
Time Factors
Aged, 80 and over
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Mastectomy, Segmental
Neoplasm Recurrence, Local
Neoplasm, Residual
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1038
2009-11-09T00:09:32Z
publication:physics
publication:rwkex_researcharticles
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:rwkex
publication:biophysics
publication:medimagingpub
publication:onc
Comparative Planning Evaluation of Intensity-modulated Radiotherapy Techniques for Complex Lung Cancer Cases
Yartsev, Slav
Chen, Jeff
Yu, Edward
Kron, Tomas
Rodrigues, George
Coad, Terry
Trenka, Kristina
Wong, Eugene
Bauman, Glenn
Van Dyk, Jake
Background and Purpose: Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance.
Patients and Methods: Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate PTV2 and 1cm margin around elective nodes for PTV1 resulting in PTV1 volumes larger than 1000 cm(3) in 13 of the 15 patients. 3D conformal and IMRT plans were generated on a commercial treatment planning system (TheraPlan Plus, Nucletron) with various combinations of beam energies and gantry angles. A 'dose quality factor' (DQF) was introduced to correlate the plan quality with patient specific parameters.
Results: A good correlation was found between the quality of the plans and the overlap between PTV1 and lungs. The patient feature factor (PFF), which is a product of several pertinent characteristics, was introduced to facilitate the choice of a particular technique for a particular patient.
Conclusions: This approach may allow the evaluation of different treatment options prior to actual planning, subject to validation in larger prospective data sets.
2006-02-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/38
http://dx.doi.org/10.1016/j.radonc.2005.12.007
Oncology Publications
Scholarship@Western
Carcinoma
Non-Small-Cell Lung
Esophagus
Female
Heart
Humans
Imaging
Three-Dimensional
Lung
Lung Neoplasms
Lymph Nodes
Male
Neoplasm Staging
Radiotherapy Dosage
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Conformal
Radiotherapy
High-Energy
Radiotherapy
Intensity-Modulated
Spinal Cord
Carcinoma, Non-Small-Cell Lung
Imaging, Three-Dimensional
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Conformal
Radiotherapy, High-Energy
Radiotherapy, Intensity-Modulated
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1040
2009-11-09T00:48:36Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Evaluation of Intra- and Inter-fraction Motion in Breast Radiotherapy Using Electronic Portal Cine Imaging
Kron, Tomas
Lee, Chrison
Perera, Francisco
Yu, Edward
Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters.
EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD linear accelerator. Depending on the incident dose and the angle of the wedge, between 4 and 16 images could be acquired in one session using an EPI device based on liquid ionization chambers (Varian).
The border between lung and chest-wall could be easily detected in all images and quantitative measurements were taken for the amount of lung in the field and the distance of the breast tissue from the field edges. Inter-fraction variability was found to be about twice as large as intra-fraction variability. The largest variability was detected in cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/- 1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm intra- and inter-fraction, respectively. This indicates that the effect of breathing motion on the amount of radiated lung was not of major concern in the patients studied. Of other patient specific parameters such as body weight, breast separation, field size and location of the target, only increasing age was significantly correlated with larger inter-fraction motion.
Acquisition of EPI cine loops proved to be a quick and easy technique to establish the amount of patient movement during breast radiotherapy. The relatively small variability found in the present pilot study justifies considerations for more conformal dose delivery.
2004-10-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/40
http://www.tcrt.org/index.cfm?d=3018&c=4161&p=12478&do=detail
Oncology Publications
Scholarship@Western
Aged
Breast Neoplasms
Female
Humans
Image Processing
Computer-Assisted
Middle Aged
Observer Variation
Radiotherapy Planning
Computer-Assisted
Reproducibility of Results
Image Processing, Computer-Assisted
Radiotherapy Planning, Computer-Assisted
Oncology
oai:ir.lib.uwo.ca:oncpub-1039
2009-11-09T00:32:16Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Does Sex Influence the Impact that Smoking, Treatment Interruption and Impaired Pulmonary Function Have on Outcomes in Limited Stage Small Cell Lung Cancer Treatment?
Videtic, Gregory M. M.
Truong, Pauline T.
Ash, Robert B.
Yu, Edward W.
Kocha, Walter I.
Vincent, Mark D.
Tomiak, Anna T.
Dar, A Rashid
Whiston, Frances
Stitt, Larry W.
PURPOSE: To look for survival differences between men and women with limited stage small cell lung cancer (LS-SCLC) by examining stratified variables that impair treatment efficacy.
METHODS: A retrospective review of 215 LS-SCLC patients treated from 1989 to 1999 with concurrent chemotherapy-radiotherapy modelled on the 'early-start' thoracic radiotherapy arm of a National Cancer Institute of Canada randomized trial.
RESULTS: Of 215 LS-SCLC patients, 126 (58.6%) were men and 89 (41.4%) were women. Smoking status during treatment for 186 patients (86.5%) was: 107 (58%) nonsmoking (NS) (76 [71%] male [M]; 31 [29%] female [F]) and 79 (42%) smoking (S) (36 M [46%]; 43 F [54%]) (continuing-to-smoke F versus M, P=0.001). Fifty-six patients (26%) had radiotherapy interruptions (RTI) during chemotherapy-radiotherapy because of toxicity. Radiotherapy breaks were not associated with sex (P=0.95). Survival by sex and smoking status at two years was: F + NS = 38.7%; F + S = 21.6%; M + NS = 22.9%; and M + S = 9.1% (P=0.0046). Survival by sex and RTI status at two years was: F + no RTI = 32.4%; F + RTI = 23.6%; M + no RTI = 23.0%; and M + RTI = 3.8% (P=0.0025). Diffusion capacity for carbon monoxide (DLCO) was recorded for 86 patients (40%) and median survival by sex and DLCO was F = 16.7 months and M = 12.1 months for a DLCO less than 60%; and for a DLCO 60% or more, F = 15.1 months and M = 15.3 months. First relapses were recorded in 132 cases (61%), with chest failure in men (45%) greater than for women (35%) and cranial failure rates similar between sexes (48%). Upon multivariable analysis, continued smoking was the strongest negative factor affecting survival.
CONCLUSIONS: In LS-SCLC, women overall do better than men, with or without a negative variable. The largest quantifiable improvement in survival for women came from smoking cessation, and for men from avoidance of breaks during treatment.
2005-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/39
http://www.pulsus.com/journals/abstract.jsp?sCurrPg=abstract&jnlKy=4&atlKy=1191&isuKy=357&isArt=t&fromfold=
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Carcinoma
Small Cell
Female
Humans
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Radiotherapy Dosage
Retrospective Studies
Sex Factors
Smoking
Survival Analysis
Aged, 80 and over
Carcinoma, Small Cell
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1041
2009-11-09T01:01:58Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:medimagingpub
publication:onc
Planning Evaluation of Radiotherapy for Complex Lung Cancer Cases Using Helical Tomotherapy
Kron, Tomas
Grigorov, Grigor
Yu, Edward
Yartsev, Slav
Chen, Jeff Z.
Wong, Eugene
Rodrigues, George
Trenka, Kris
Coad, Terry
Bauman, Glenn
Van Dyk, Jake
Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/-4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.
2004-08-21T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/41
http://www.iop.org/EJ/abstract/0031-9155/49/16/014
Oncology Publications
Scholarship@Western
Carcinoma
Non-Small-Cell Lung
Dose-Response Relationship
Radiation
Female
Hot Temperature
Humans
Lung
Lung Neoplasms
Lymphatic Metastasis
Male
Models
Statistical
Radiometry
Radiotherapy
Radiotherapy Dosage
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Computer-Assisted
Radiotherapy
Conformal
Time Factors
Carcinoma, Non-Small-Cell Lung
Dose-Response Relationship, Radiation
Models, Statistical
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Computer-Assisted
Radiotherapy, Conformal
Bioimaging and Biomedical Optics
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1042
2009-11-11T08:21:16Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:medimagingpub
publication:onc
Radiation Treatment of Lung Cancer--Patterns of Practice in Canada
Tai, Patricia
Yu, Edward
Battista, Jerry
Van Dyk, Jake
BACKGROUND AND PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat lung cancers.
PATIENTS AND METHODS: A questionnaire detailing different aspects of radiation treatment of lung cancer was mailed to all radiation oncologists treating lung cancer in Canada. Seventy-two percent (74/103) of radiation oncologists who treat lung cancer from all 34 Canadian cancer centres replied to the questionnaire.
RESULTS: (a) Radiotherapy regimens in Canadian cancer centres are in accordance with several major randomised studies. There is still some variation in treatment practice that may be due to unresolved controversies or limited resources. The most frequently used prescription dose was 40Gy/15f/3w (where f stands for fractions and w stands for weeks) for small cell lung cancer (SCLC) and 60Gy/30f/6w for non-small cell lung cancer (NSCLC). If there were no resource constraints, 30% (22/74) and 20% (15/74) would prefer to use a different dose-fractionation scheme for SCLC and NSCLC, respectively; 95% (70/74) would prefer to use 3D-conformal or intensity-modulated radiotherapy. (b) Among the various modern technologies assessed by respondents, CT (computed tomography) simulator, multi-leaf collimator, on-line electronic portal imaging and PET (positron-emission tomography) scanning were rated the highest in terms of potential patient benefit. Discrepancy between demand and availability of technology was greatest for PET scanning.
CONCLUSIONS: Canadian practice in the treatment of lung cancers shows some variations although it is consistent with the trends in the literature. The lack of some modern technologies and human resources is an ongoing concern, especially the lack of PET imaging equipment.
2004-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/42
info:doi/10.1016/j.radonc.2003.11.021
http://dx.doi.org/10.1016/j.radonc.2003.11.021
Oncology Publications
Scholarship@Western
Adult
Attitude of Health Personnel
Female
Health Care Surveys
Humans
Lung Neoplasms
Male
Middle Aged
Ontario
Physician's Practice Patterns
Quality of Health Care
Questionnaires
Radiation Oncology
Radiotherapy Dosage
Radiotherapy
Conformal
Risk Assessment
Radiotherapy, Conformal
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:epidempub-1020
2009-11-11T08:11:40Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Prediction of Radiation Pneumonitis by Dose-volume Histogram Parameters in Lung Cancer--A Systematic Review
Rodrigues, George
Lock, Michael
D'Souza, David
Yu, Edward
Van Dyk, Jake
BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.
METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data were abstracted from the various reports to calculate operating characteristics and odds ratios for the different DVH metrics.
RESULTS: A total of 12 published studies and two abstracts were identified. Eleven studies assessed V(dose), seven assessed MLD, and eight assessed NTCP. Nine studies exclusively analyzed the association between various DVH metrics and RP risk. Five studies also analyzed other patient, tumor, and treatment variables in conjunction with standard DVH metrics. A direct comparison between studies and the generation of summary statistics (i.e. meta-analysis) could not be achieved due to significant predictive and outcome variable heterogeneity. Most studies did show an association between DVH parameters and RP risk. However, overall accuracy, sensitivity, specificity, and positive predictive value were generally poor to fair for all three classes of DVH metrics.
CONCLUSIONS: An association between DVH parameters and RP risk has been demonstrated in the literature. However, the ideal DVH metric with excellent operating characteristics, either alone or in a model with other predictive variables, for RP risk prediction has not yet been identified. Several recommendations for reporting and conduct of future research into the association between DVH metrics and RP risk are provided.
2004-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/epidempub/20
info:doi/10.1016/j.radonc.2004.02.015
http://dx.doi.org/10.1016/j.radonc.2004.02.015
Epidemiology and Biostatistics Publications
Scholarship@Western
Carcinoma
Non-Small-Cell Lung
Carcinoma
Small Cell
Dose-Response Relationship
Radiation
Female
Humans
Lung
Lung Neoplasms
Male
Predictive Value of Tests
Prognosis
Radiation Pneumonitis
Radiation Tolerance
Radiotherapy Dosage
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Conformal
Randomized Controlled Trials as Topic
Risk Assessment
Severity of Illness Index
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Dose-Response Relationship, Radiation
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Conformal
Biostatistics
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1043
2009-11-12T03:25:15Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Shifting from Hypofractionated to "Conventionally" Fractionated Thoracic Radiotherapy: A Single Institution's 10-year Experience in the Management of Limited-stage Small-cell Lung Cancer Using Concurrent Chemoradiation
Videtic, Gregory M. M.
Truong, Pauline T.
Dar, A. Rashid
Yu, Edward W.
Stitt, Larry W.
PURPOSE: To perform a retrospective review of a single institution's 10-year experience in treating limited-stage small-cell lung cancer (LS-SCLC) with a concurrent chemoradiation regimen modeled after the experimental arm of a randomized National Cancer Institute of Canada trial in which hypofractionated radiotherapy started with cycle 2 of chemotherapy. We then looked at the impact on patient outcomes of changing the RT during the course of the decade to a "conventionally" (2 Gy) fractionated regimen, with a focus on toxicity and survival rates.
METHODS AND MATERIALS: Between 1989 and 1999, 215 LS-SCLC patients received six cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and vincristine alternating with etoposide and cisplatin every 3 weeks. Thoracic RT was administered concurrently with etoposide and cisplatin (at cycle 2 or 3) only and consisted of either 40 Gy in 15 fractions for 3 weeks or 50 Gy in 25 fractions for 5 weeks. RT fields encompassed gross and suspected microscopic disease with 2-cm margins. Prophylactic cranial irradiation (PCI) was offered to complete responders according to clinician preference. RT interruption during concurrent chemoradiation was used as the "marker" for treatment toxicity. The analysis compared the RT schedules for differences in toxicity, survival, and recurrence patterns.
RESULTS: The overall survival rate for 215 patients at 2 and 5 years was 22.7% and 7.2%, respectively, with a median survival of 14.7 months. Thoracic RT consisted of 40 Gy in 3 weeks for 122 patients (57%) and 50 Gy in 5 weeks for 92 patients (43%). PCI was administered to 21 (44%) and 47 (56%) patients receiving 40 Gy and 50 Gy, respectively. The patient- and treatment-related variables were comparable between the two cohorts treated with the different RT prescriptions. RT interruptions during concurrent chemoradiation were recorded in 56 cases (26%), with a median duration of 5 days (range 1-18). No differences in treatment-related toxicity rates were demonstrated between the two dose cohorts (p = 0.35). The overall and disease-free survival rates (patients stratified by PCI use) at 5 years for the 40- and 50-Gy schedules were 14.3% and 12.0% (p = 0.71) and 20.7% and 22.2% (p = 0.76), respectively. Sites of first failure were recorded in 132 patients (61%). Comparing the 40-Gy and 50-Gy cohorts, the rate of any first relapse was 40% vs. 42% and the chest as the first relapse site was 34% vs. 45% (patients stratified by PCI use), respectively. The brain failure rate reflected PCI use and was not related to the thoracic RT schedule.
CONCLUSION: Changing from a hypofractionated to a conventionally fractionated RT thoracic prescription did not alter outcomes because the survival, thoracic control, and toxicity rates were statistically similar. This suggests that the hypofractionated schedule remains practicable and should be considered in the setting of randomized clinical trials. In view of the benefits that accelerated schedules provide for both patients and cost containment, clinicians may opt to use this tolerable regimen in managing LS-SCLC. Regarding the future development of novel chemoradiation programs, the most critical factor in ensuring improved outcomes for LS-SCLC may be limiting the duration of RT and overall treatment time.
2003-11-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/43
info:doi/10.1016/S0360-3016(03)00635-7
http://www.redjournal.org/article/S0360-3016%2803%2900635-7/abstract
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Small Cell
Cisplatin
Cyclophosphamide
Dose Fractionation
Doxorubicin
Etoposide
Female
Humans
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Neoplasm Staging
Retrospective Studies
Survival Rate
Vincristine
Aged, 80 and over
Carcinoma, Small Cell
Epidemiology
Oncology
oai:ir.lib.uwo.ca:epidempub-1021
2009-11-12T03:14:21Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Impaired Diffusion Capacity Predicts for Decreased Treatment Tolerance and Survival in Limited Stage Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiation
Videtic, Gregory M. M.
Stitt, Larry W.
Ash, Robert B.
Truong, Pauline T.
Dar, A. Rashid
Yu, Edward W.
Whiston, Frances
PURPOSE: To determine if stratification of limited stage small cell lung cancer (LSCLC) patients by pre-treatment pulmonary function test (PFT) prognostic indicators predicts for treatment-related toxicity risks and survival following concurrent chemoradiation.
MATERIALS AND METHODS: From 1989 to 1999, 215 LSCLC patients received six cycles of alternating cyclophosphamide/doxorubicin/vincristine and etoposide/cisplatin (EP). Thoracic radiation (RT) was initiated only with EP and at cycle 2 or 3. RT dose was: 40 Gy/15 fractions/3 weeks or 50 Gy/25 fractions/5 weeks. RT fields encompassed gross and suspected microscopic disease with a 2 cm margin. Pre-treatment PFT values analyzed included forced expiratory volume in 1s (FEV1) (in liter and as % predicted) and diffusion capacity for carbon monoxide (DLCO) (as % predicted). The "marker" for toxicity during concurrent chemoradiation was the duration of any RT breaks initiated for severe hematologic or locoregional symptomatology. Patient outcomes were analyzed for associations between recognized PFT cut-offs (FEV1 <2l, > or =2l; FEV1 <60%, > or =60% predicted; DLCO <60%, > or =60% predicted), toxicity rates, and survival.
RESULTS: For the whole study cohort, median, 2- and 5-year overall survivals were: 14.7 months, 22.7 and 7.2%, respectively. Fifty-six patients (26%) required treatment breaks due to toxicity. FEV1 and DLCO results were available for 96 (45%) and 86 (40%) patients, respectively. Two thirds of FEV1s measured were <2l. On statistical analysis, the incidence of toxicity-related interruptions was significant for DLCO<60% (P=0.043), suggestive for FEV1<2l (P=0.1) and non-significant for FEV1<60%. Patients with simultaneous DLCO<60% and FEV1<2l showed a trend toward increase toxicity risk (P=0.1). For selected PFT measures, median overall survivals were: 12.7 months versus 14.8 months for DLCO<60% versus > or =60%; 13.4 months versus 17.7 months for FEV1<2l versus> or =2l; 15.4 months versus 19.9 months for DLCO<60% + FEV1<2l versus DLCO> or =60% + FEV1> or =2l. Although absolute differences favored all patients with PFT values above the prognostic cut-offs, differences were not statistically significant on this analysis. Patients with both a treatment break and a DLCO<60% had the poorest median survival of all patient subsets, at 11.4 months (P=0.09).
CONCLUSIONS: Impaired DLCO (i.e. <60%) is a novel predictor of increased treatment-related toxicity leading to interruptions. The present study suggests a probable role for DLCO and FEV1 (in l) as prognostic factors for predicting survival but larger patient samples are required for confirmation. Patients with impaired DLCOs experiencing treatment interruptions have the poorest survival. Assessment of pre-treatment PFTs contributes to determining optimal management strategies for LSCLC patients receiving definitive chemoradiation.
2004-02-01T08:00:00Z
article
https://ir.lib.uwo.ca/epidempub/21
info:doi/10.1016/j.lungcan.2003.08.026
http://dx.doi.org/10.1016/j.lungcan.2003.08.026
Epidemiology and Biostatistics Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Algorithms
Antineoplastic Combined Chemotherapy Protocols
Cisplatin
Combined Modality Therapy
Cyclophosphamide
Doxorubicin
Etoposide
Female
Humans
Lung Neoplasms
Male
Middle Aged
Predictive Value of Tests
Prognosis
Radiation Injuries
Retrospective Studies
Risk Factors
Spirometry
Survival Analysis
Treatment Outcome
Vincristine
Aged, 80 and over
Epidemiology
Oncology
oai:ir.lib.uwo.ca:biophysicspub-1005
2010-02-05T03:25:20Z
publication:biophysicspub
publication:pmid
publication:faculties
publication:electricalpub
publication:biophysics
publication:electrical
Cardiac MR Elastography: Comparison with Left Ventricular Pressure Measurement
Elgeti, Thomas
Laule, Michael
Kaufels, Nikola
Schnorr, Jorg
Hamm, Bernd
Samani, Abbas
Braun, Jurgen
Sack, Ingolf
Purpose of the Study: To compare magnetic resonance elastography (MRE) with ventricular pressure changes in an animal model.
Methods: Three pigs of different cardiac physiology (weight, 25 to 53 kg; heart rate, 61 to 93 bpm; left ventricular [LV] end-diastolic volume, 35 to 70 ml) were subjected to invasive LV pressure measurement by catheter and noninvasive cardiac MRE. Cardiac MRE was performed in a short-axis view of the heart and applying a 48.3-Hz shear-wave stimulus. Relative changes in LV-shear wave amplitudes during the cardiac cycle were analyzed. Correlation coefficients between wave amplitudes and LV pressure as well as between wave amplitudes and LV diameter were determined.
Results: A relationship between MRE and LV pressure was observed in all three animals (R-square [greater than or equal to] 0.76). No correlation was observed between MRE and LV diameter (R-square [less than or equal to] 0.15). Instead, shear wave amplitudes decreased 102 +/- 58 ms earlier than LV diameters at systole and amplitudes increased 175 +/- 40 ms before LV dilatation at diastole. Amplitude ratios between diastole and systole ranged from 2.0 to 2.8, corresponding to LV pressure differences of 60 to 73 mmHg.
Conclusion: Externally induced shear waves provide information reflecting intraventricular pressure changes which, if substantiated in further experiments, has potential to make cardiac MRE a unique noninvasive imaging modality for measuring pressure-volume function of the heart.
2009-11-09T08:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/7
info:doi/10.1186/1532-429X-11-44
http://jcmr-online.com/content/11/1/44
Medical Biophysics Publications
Scholarship@Western
magnetic resonance elastography
left ventricular
Electrical and Computer Engineering
Medical Biophysics
oai:ir.lib.uwo.ca:oncpub-1045
2009-11-14T08:15:35Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:surgery
publication:onc
Patterns of Breast Recurrence in a Pilot Study of Brachytherapy Confined to the Lumpectomy Site for Early Breast Cancer with Six Years' Minimum Follow-up
Perera, Francisco
Yu, Edward
Engel, Jay
Holliday, Ronald
Scott, Leslie
Chisela, Frank
Venkatesan, Varagur
PURPOSE: In this pilot study of high-dose-rate brachytherapy to the lumpectomy site as the sole radiation, ipsilateral and contralateral breast recurrences are documented with specific attention to the location of recurrence relative to the lumpectomy site.
METHODS: Between March 1992 and January 1996, 39 patients with T1 (32 patients) and T2 breast cancers received 37.2 Gy in 10 fractions (b.i.d.) over 1 week prescribed to a volume encompassing the surgical clips. Thirteen received adjuvant tamoxifen, and 4 received chemotherapy. Follow-up included annual bilateral mammograms and clinical breast examination every 3 to 6 months. Whereas 13 patients had intraoperative implantation of the lumpectomy site, 26 had postoperative implantation. The latter group and 7 of the former group had surgical clips marking the lumpectomy site, which allowed estimates of the distance of any ipsilateral breast recurrence from the lumpectomy site, using the mediolateral and cranio-caudad mammographic views.
RESULTS: At a median follow-up of 91 months, 33 women are alive, 4 have died of disease, and 2 have died of other causes. The 5-year actuarial rate of ipsilateral breast recurrence was 16.2%. Of 6 ipsilateral recurrences, 2 occurred within the lumpectomy site (in-field recurrences). One of the 2 patients had a 1-mm microscopic margin at initial diagnosis; the recurrence was a 3.5-mm microscopic focus of duct carcinoma in situ. The other patient had a 1.5-cm, high-grade infiltrating mammary carcinoma with no residual at wider resection at first diagnosis; the 5-mm invasive recurrence was also of high grade. Four women developed invasive recurrences at least 1.6 cm or more from the lumpectomy site (out-of-field recurrences). Two of these women had gross multifocal recurrences with two cancers in each patient; 1 of the 2 patients had an extensive intraductal component at initial diagnosis. The estimated nearest distances between the out-of-field recurrences and the surgical clips were 1.6, 5.5, 7.7, and 12.0 cm. All ipsilateral breast recurrences were salvaged by mastectomy (4 patients) or by repeat lumpectomy (2 patients) and whole-breast radiation. The interval postdiagnosis to ipsilateral recurrence ranged from 20 months to 58 months. There were two contralateral breast recurrences at intervals of 34 and 36 months; 1 of these patients also had a multifocal, ipsilateral recurrence at 58 months, as previously described. Among patients with any breast recurrence, 1 patient had a family history of prostate cancer; there was no family history of breast or ovarian cancer. Of 17 patients who received adjuvant systemic therapy, only 1 had a breast recurrence.
CONCLUSIONS: In this pilot study, breast recurrences outside of the lumpectomy site were the predominant pattern of recurrence.
2003-12-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/44
info:doi/10.1016/S0360-3016(03)00816-2
http://dx.doi.org/10.1016/S0360-3016(03)00816-2
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Brachytherapy
Breast Neoplasms
Carcinoma in Situ
Carcinoma
Intraductal
Noninfiltrating
Chemotherapy
Adjuvant
Dose Fractionation
Female
Follow-Up Studies
Humans
Mastectomy
Segmental
Middle Aged
Neoplasm Recurrence
Local
Pilot Projects
Salvage Therapy
Treatment Failure
Aged, 80 and over
Carcinoma, Intraductal, Noninfiltrating
Chemotherapy, Adjuvant
Mastectomy, Segmental
Neoplasm Recurrence, Local
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1046
2009-11-14T08:24:01Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Twenty-year Follow-up Study of Long-term Survival of Limited-stage Small-cell Lung Cancer and Overview of Prognostic and Treatment Factors
Tai, Patricia
Tonita, Jon
Yu, Edward
Skarsgard, David
PURPOSE: To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer.
METHODS AND MATERIALS: Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method.
RESULTS: The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.
CONCLUSION: The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.
2003-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/45
info:doi/10.1016/S0360-3016(03)00070-1
http://dx.doi.org/10.1016/S0360-3016(03)00070-1
Oncology Publications
Scholarship@Western
Algorithms
Antineoplastic Combined Chemotherapy Protocols
Brain Neoplasms
Carcinoma
Small Cell
Cranial Irradiation
Follow-Up Studies
Humans
Lung Neoplasms
Models
Statistical
Multivariate Analysis
Prognosis
Radiotherapy Dosage
Salvage Therapy
Saskatchewan
Statistics as Topic
Survival Rate
Carcinoma, Small Cell
Models, Statistical
Oncology
oai:ir.lib.uwo.ca:oncpub-1044
2009-11-14T08:26:43Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Validation of the Lognormal Model for Prediction of Long-term Survival Rates from Short-term Follow up Data in Stages III and IV Breast Cancer
Tai, P.
Yu, E.
Skarsgard, D.
Tonita, J.
2003-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/46
http://www.current-oncology.com/index.php/oncology
Oncology Publications
Scholarship@Western
breast cancer
survival rate
Oncology
oai:ir.lib.uwo.ca:oncpub-1048
2009-11-22T04:43:25Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:onc
Monte Carlo Simulations of DNA Damage from Incorporated Cold Iodine Following Photoelectrically Induced Auger Electron Cascades
Moiseenko, V. V.
Karnas, S. J.
Yu, E.
Battista, J. J.
Radiation-induced damage in nucleosomal DNA from Auger electron cascades due to incorporated cold IUdR has been modelled through Monte Carlo simulations. Probabilities of DNA double strand break (DSB) production following a vacancy in the K, L, M and N shells of iodine are estimated. DSB complexity from the base damage accompanying a break was also estimated. Multiple DSB events were analysed for correlated breaks due to nucleosome periodicity. The probability of an Auger cascade causing at least one DSB strongly depended on the shell in which the initial vacancy was produced. This probability was approximately 0.35 for K and L shells and fell to 0.02 for the N shell. As expected, DSBs were predominantly induced in a nucleosome containing incorporated iodine and were accompanied with extensive base damage. Analysis of multiple DSB events showed that approximately 14% of the DSBs produced following a vacancy in the L1 orbital can be interpreted as correlated with base pair separation attributable to the nucleosome periodicity. The data generated in this work provide a basis for the development of photon-activation therapy using kilovoltage X rays incident upon IUdR sensitised tumours.
2002-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/48
http://rpd.oxfordjournals.org/cgi/content/abstract/99/1-4/113
Oncology Publications
Scholarship@Western
Computer Simulation
DNA Damage
Electrochemistry
Electrons
Iodine
Monte Carlo Method
Nucleosomes
Photochemistry
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1047
2009-11-15T10:02:12Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:medimaging
publication:faculties
publication:biophysics
publication:epidem
publication:medimagingpub
publication:surgery
publication:onc
publication:epidempub
Subsets More Likely to Benefit From Surgery or Prophylactic Cranial Irradiation After Chemoradiation for Localized Non-Small-Cell Lung Cancer
Keith, Bruce
Vincent, Mark
Stitt, Larry
Tomiak, Anna
Malthaner, Richard
Yu, Edward
Truong, Pauline
Inculet, Richard
Lefcoe, Michael
Dar, A. Rashid
Kocha, Walter
Craig, Ian
After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence and 15 had brain recurrences. In multivariable analysis, female gender and elevated LDH were found to be risk factors for brain recurrence. In the subset with stage III disease (n = 76), squamous cell histology was a risk factor for isolated initial local recurrence in both univariable and multivariable analysis. It is possible to identify subsets that may show increased benefit from PCI or surgery.
2002-12-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/47
http://journals.lww.com/amjclinicaloncology/Abstract/2002/12000/Subsets_More_Likely_to_Benefit_From_Surgery_or.11.aspx
Oncology Publications
Scholarship@Western
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Brain Neoplasms
Carcinoma
Non-Small-Cell Lung
Combined Modality Therapy
Cranial Irradiation
Female
Humans
L-Lactate Dehydrogenase
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Neoplasm Recurrence
Local
Pneumonectomy
Prognosis
Radiotherapy Dosage
Radiotherapy
Adjuvant
Retrospective Studies
Risk Factors
Carcinoma, Non-Small-Cell Lung
Neoplasm Recurrence, Local
Radiotherapy, Adjuvant
Epidemiology
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1050
2009-11-15T10:47:08Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Prophylactic Cranial Irradiation Revisited: Cost-effectiveness and Quality of Life in Small-cell Lung Cancer
Tai, T. H. Patricia
Yu, Edward
Dickof, Peter
Beck, Glen
Tonita, Jon
Ago, Tete
Skarsgard, David
Schmidt, Marlene
Schmid, Matthew
Liem, John S. K.
PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission.
METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis.
RESULTS: Among the 98 complete remission patients, the median OS for PCI+ and PCI- patients was 20.0 and 19.0 months, respectively (p > 0.05, nonsignificant). The median disease-free survival was 14.7 and 10.0 months, respectively (p < 0.05). The difference in the mean Q-TWiST survival was significant (p < 0.01). The mean marginal cost was $18,834/PCI+ patient and $17,885/PCI- patient (p > 0.05, nonsignificant). The cost-effectiveness ratio was $70/mo of incremental OS if u(tox) and u(rel) (the utility coefficients to reflect the value of time in health states of toxicity and relapse) were assumed to be 1.0.
CONCLUSION: PCI is a cost-effective treatment that improves the quality-of-life-adjusted survival for patients with a complete remission of SCLC.
2002-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/50
info:doi/10.1016/S0360-3016(01)01748-5
http://dx.doi.org/10.1016/S0360-3016(01)01748-5
Oncology Publications
Scholarship@Western
Aged
Antineoplastic Combined Chemotherapy Protocols
Brain Neoplasms
Carcinoma
Small Cell
Confidence Intervals
Cost-Benefit Analysis
Cranial Irradiation
Female
Humans
Lung Neoplasms
Male
Middle Aged
Prognosis
Quality of Life
Remission Induction
Retrospective Studies
Survival Rate
Carcinoma, Small Cell
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1051
2009-11-15T10:58:54Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:biophysics
publication:medimagingpub
publication:onc
Computed Tomography to Assess Pulmonary Injury Associated with Concurrent Chemo-radiotherapy for Inoperable Non-small Cell Lung Cancer
Aviram, Galit
Yu, Edward
Tai, Patricia
Lefcoe, Michael S.
OBJECTIVE: To characterize serial computed tomography (CT) findings of pulmonary injury after a uniform regimen of concurrent chemo-radiotherapy in inoperable non-small cell lung cancer, and to compare the radiation-induced lung toxicity with other concurrent chemo-radiation regimens.
METHODS: Twenty-four patients with advanced non-small cell lung cancer received 2 induction cycles of cisplatin and vinblastine, followed by 2 further cycles of cisplatin and vinblastine, concurrent with 60 Gy radiation at 2 Gy per fraction. Radiation-induced lung injury in the acute and chronic phases was assessed by serial CT scans and compared with preradiation baseline scans. Acute radiation pneumonitis was evaluated using the Common Toxicity Criteria, and chronic radiation fibrosis was graded according to the European Organisation for Research and Treatment of Cancer--Radiation Therapy Oncology Group Scale.
RESULTS: Seventeen (81%) patients had characteristic CT findings of radiation-induced pulmonary damage, which were confined to the radiation ports. Although patchy nonhomogeneous and air-space opacities characterized acute radiation pneumonitis, and homogeneous opacities with loss of volume were typical for chronic fibrosis, ground-glass opacities were found frequently in both phases. Acute radiation pneumonitis grade 1 was seen in 29% and grade 2 in 9.5%. Chronic radiation fibrosis grades 1, 2 and 3 were found in 14%, 33% and 19% of the patients respectively. Median survival time was 13 months.
CONCLUSION: CT enables detailed evaluation of radiation-induced pulmonary injury after concurrent chemo-radiation for inoperable non-small cell lung cancer. Although survival time with the present regimen is comparable to other concurrent chemo-radiation regimens, a high incidence of radiation injury was found, though the severity was not life threatening.
2001-12-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/51
http://www.carj.ca/issues/2001-Dec/385/385.html
Oncology Publications
Scholarship@Western
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Non-Small-Cell Lung
Chemotherapy
Adjuvant
Chronic Disease
Cisplatin
Combined Modality Therapy
Female
Follow-Up Studies
Humans
Lung Neoplasms
Male
Middle Aged
Radiation Pneumonitis
Vinblastine
Carcinoma, Non-Small-Cell Lung
Chemotherapy, Adjuvant
Bioimaging and Biomedical Optics
Oncology
oai:ir.lib.uwo.ca:oncpub-1049
2009-11-15T10:34:32Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:medimagingpub
publication:onc
publication:epidempub
Improving the Consistency in Cervical Esophageal Target Volume Definition by Special Training
Tai, Patricia
Van Dyk, Jake
Battista, Jerry
Yu, Edward
Stitt, Larry
Tonita, Jon
Agboola, Olusegun
Brierley, James
Dar, Rashid
Leighton, Christopher
Malone, Shawn
Strang, Barbara
Truong, Pauline
Videtic, Gregory
Wong, C. Shun
Wong, Rebecca
Youssef, Youssef
PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions.
METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared.
RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training.
CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.
2002-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/49
info:doi/10.1016/S0360-3016(02)02752-9
http://dx.doi.org/10.1016/S0360-3016(02)02752-9
Oncology Publications
Scholarship@Western
Education
Medical
Continuing
Esophageal Neoplasms
Humans
Imaging
Three-Dimensional
Physical Phenomena
Physics
Radiation Oncology
Radiotherapy
Conformal
Tomography
X-Ray Computed
Education, Medical, Continuing
Imaging, Three-Dimensional
Radiotherapy, Conformal
Tomography, X-Ray Computed
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:epidempub-1023
2009-11-15T09:44:50Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Continued Cigarette Smoking by Patients Receiving Concurrent Chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer Is Associated With Decreased Survival
Videtic, Gregory M. M.
Stitt, Larry W.
Dar, A. Rashid
Kocha, Walter I.
Tomiak, Anna T.
Truong, Pauline T.
Vincent, Mark D.
Yu, Edward W.
PURPOSE: To determine the impact of continued smoking by patients receiving chemotherapy (CHT) and radiotherapy (RT) for limited-stage small-cell lung cancer (LSCLC) on toxicity and survival.
PATIENTS AND METHODS: A retrospective review was carried out on 215 patients with LSCLC treated between 1989 and 1999. Treatment consisted of six cycles of alternating cyclophosphamide, doxorubicin, vincristine and etoposide, cisplatin (EP). Thoracic RT was concurrent with EP (cycle 2 or 3) only. Patients were known smokers, with their smoking status recorded at the start of chemoradiotherapy (CHT/RT). RT interruption during concurrent CHT/RT was used as the marker for treatment toxicity.
RESULTS: Of 215 patients, smoking status was recorded for 186 patients (86.5%), with 79 (42%) continuing to smoke and 107 (58%) abstaining during CHT/RT. RT interruptions were recorded in 38 patients (20.5%), with a median duration of 5 days (range, 1 to 18 days). Median survival for former smokers was greater than for continuing smokers (18 v 13.6 months), with 5-year actuarial overall survival of 8.9% versus 4%, respectively (log-rank P =.0017). Proportion of noncancer deaths was comparable between the two cohorts. Continuing smokers did not have a greater incidence of toxicity-related treatment breaks (P =.49), but those who continued to smoke and also experienced a treatment break had the poorest overall survival (median, 13.4 months; log-rank P =.0014).
CONCLUSION: LSCLC patients who continue to smoke during CHT/RT have poorer survival rates than those who do not. Smoking did not have an impact on the rate of treatment interruptions attributed to toxicity.
2003-04-15T07:00:00Z
article
https://ir.lib.uwo.ca/epidempub/22
http://jco.ascopubs.org/cgi/content/abstract/21/8/1544
Epidemiology and Biostatistics Publications
Scholarship@Western
Actuarial Analysis
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Small Cell
Chemotherapy
Adjuvant
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Radiotherapy
Adjuvant
Retrospective Studies
Smoking
Survival Analysis
Treatment Outcome
Carcinoma, Small Cell
Chemotherapy, Adjuvant
Radiotherapy, Adjuvant
Epidemiology
Oncology
oai:ir.lib.uwo.ca:biophysicspub-1006
2009-11-22T04:40:54Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Monte Carlo Simulations and Measurement of DNA Damage from X-ray-triggered Auger Cascades in Iododeoxyuridine (IUdR)
Karnas, S. J.
Moiseenko, V. V.
Yu, E.
Truong, P.
Battista, J. J.
We investigated the DNA damage from Auger electrons emitted from incorporated stable iodine (127I), following photoelectric absorption of external x-rays. The effectiveness of the Auger electrons in producing DNA double-strand breaks (DSB) was determined theoretically, using Monte Carlo simulations of the radiation physics and chemistry, and was shown to be in reasonable agreement with DNA damage measured using the comet assay. The DSB yields were measured in CHO cells for 60Co (as a non-Auger-promoting radiation) and for tungsten-filtered 100 kVp x-rays capable of producing Auger electron emission. The theoretical study showed that on average, 2.5 Auger electrons were emitted for N-shell orbital vacancies and up to 10 Auger electrons were emitted from L1-shell vacancies. These Auger bursts produced approximately 0.03 DSB per N-shell vacancy and 0.3 DSB per K-shell or L-shell vacancy. The calculated yield of DSB from Auger cascades per unit dose (1 Gy) in water was approximately 1.7 for tungsten-filtered 100 kVp x-rays, assuming 20% IUdR substitution of thymidine. The comet assay yielded an experimental value of 3.6+/-1.6 per 1 Gy for the same conditions. The Monte Carlo simulations also demonstrated a high complexity of DSB produced by Auger cascades with virtually all DSB from inner shell orbitals (i.e. K, L shells) accompanied by compounded strand breakage and base damage, indicating a difficult lesion to repair. This finding agrees well with comet assay results of DNA repair, where an increase in the DSB yield in IUdR-sensitized cells was shown to persist after a time of 24 h. We conclude that Auger cascades in iodine produce a modest increase in the number of initial strand breaks of the order of 10% but the complex nature of these DSB makes them very difficult to repair or potentially prone to misrepair. The accentuated DNA damage may have major consequences for cell survival and may be exploitable in kilovoltage photon activation therapy (PAT) of tumors sensitized with iodine.
2001-09-01T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/6
info:doi/10.1007/s004110100099
http://www.springerlink.com/content/5ymf312yyq3fv6p1/?p=11424eb5730942d0b6d15220b8bffebdπ=4
Medical Biophysics Publications
Scholarship@Western
Animals
CHO Cells
Comet Assay
Cricetinae
DNA Damage
Electrons
Idoxuridine
Models
Theoretical
Monte Carlo Method
Nucleic Acid Synthesis Inhibitors
Photons
Radiation-Sensitizing Agents
Tungsten
X-Rays
Models, Theoretical
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:epidempub-1024
2009-11-18T08:17:20Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Using Treatment Interruptions to Palliate the Toxicity from Concurrent Chemoradiation for Limited Small Cell Lung Cancer Decreases Survival and Disease Control
Videtic, Gregory M. M.
Fung, Karen
Tomiak, Anna T.
Stitt, Larry W.
Dar, A. Rashid
Truong, Pauline T.
Yu, Edward W.
Vincent, Mark D.
Kocha, Walter I.
BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years.
MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, delivered to a target volume encompassing gross disease and suspected microscopic disease with a 2 cm margin. Treatment breaks arising during concurrent ChT+RT were used to manage severe symptomatic or hematologic toxicities. We used the interruptions in thoracic RT as the 'marker' for any concurrent break and measured 'break duration' by the total length of time (in days) RT was interrupted, since that also signaled that ChT could be re-initiated. Patient results were analyzed for the impact of interruptions/treatment prolongation on overall and disease-free survival.
RESULTS: For all patients, 2-year and 5-year overall and disease-specific survivals were 22.7 and 7.2, 27.6 and 9.3%, respectively; overall and disease-specific median survivals were 14.7 months each. A total of 56 patients (26%) had treatment breaks due to toxicity. Hematologic depression caused the majority of breaks (88%). The median duration of breaks was 5 days (range 1-18). Patients with and without interruptions were compared for a range of prognostic factors and were not found to have any significant differences. Comparing interrupted/uninterrupted courses, median survivals were 13.8 versus 15.6 months, respectively, and 5-year overall survivals were 4.2 versus 8.3%, respectively. There was a statistical difference between overall survival curves which favored the uninterrupted group (P=0.01). When comparing a series of prognostic variables, multivariable analysis found that the most significant factor influencing survival in the present study was the presence of treatment breaks (P=0.006). There was a trend for development of any recurrence in the patients with breaks (P=0.08). When controlling for the use of prophylactic cranial irradiation (PCI) in the two groups, the rate of failure in the chest was higher in the patients with RT breaks (58 vs. 33%). The rate of failure in the brain was dependent on the use of PCI only.
CONCLUSIONS: Interruptions in treatment to palliate the toxicity from concurrent chemoradiation result in poorer local control and decreased survival.
2001-08-01T07:00:00Z
article
https://ir.lib.uwo.ca/epidempub/23
info:doi/10.1016/S0169-5002(00)00240-3
http://dx.doi.org/10.1016/S0169-5002(00)00240-3
Epidemiology and Biostatistics Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Small Cell
Cyclophosphamide
Doxorubicin
Epirubicin
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Recurrence
Local
Remission Induction
Survival Rate
Treatment Failure
Vincristine
Aged, 80 and over
Carcinoma, Small Cell
Neoplasm Recurrence, Local
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1052
2009-11-23T00:07:05Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Merkel Cell Carcinoma of the Skin
Tai, Patricia T. H.
Yu, Edward
Tonita, Jon
Gilchrist, James
Background: Neuroendocrine/Merkel cell carcinoma (MCC) of the skin is an uncommon tumour. Currently, there are only limited data available on the natural history, prognostic factors, and patient management of MCC.
Objective: To review our experience and build the largest database from the literature.
Methods: Twenty-eight cases from the London Regional Cancer Center were combined with 633 cases obtained from the literature searched in English, French, German, and Chinese for the years 1966 to 1998. The database included age, sex, initial disease status at presentation to the clinic, site of primary, any coexisting disease, any previous irradiation, sizes of primary/nodal/distant metas-tases, management details, and final disease status. A new modified staging system was used: stage Ia (primary disease only, size £ 2 cm), stage Ib (primary disease only, size > 2 cm); stage II (regional nodal disease), and stage III (beyond regional nodes and/or distant disease).
Results: Age > 65 years, male sex, size of primary > 2 cm, truncal site, nodal/distant disease at presentation, and duration of disease b e f o re presentation (£ 3 months) were poor prognostic factors. Surg e ry was the initial treatment of choice and it significantly impro v e d overall survival (p = .004).
Conclusion : We identified poor prognostic factors that may necessitate more aggressive treatment. The suggested staging system, incorporating primary tumour size, accurately predicted outcomes.
2000-10-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/52
http://www.dermweb.com/jcms/abstracts_4_4/186.html
Oncology Publications
Scholarship@Western
Merkel cell carcinoma
skin
prognostic factors
Oncology
oai:ir.lib.uwo.ca:biophysicspub-1007
2009-11-22T04:39:39Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:onc
Operational Characteristics of a Prototype X-ray Needle Device
Karnas, S. J.
Avvakumov, N.
Yu, E.
Battista, J. J.
A prototype x-ray needle, which emits 62.5 kVp x-rays at the tip of a 20 cm long, 4 mm diameter steel needle, has been developed by Titan Pulse Sciences Incorporated (PSI) (Albuquerque, NM) and was tested for its suitability in brachytherapy applications in comparison with a similar device by the Photoelectron Corporation. The depth dose profiles were also compared with those of two common brachytherapy sources (125I and 192Ir). The depth dose characteristics of the radiation were comparable with the two brachytherapy sources with a slightly reduced attenuation gradient. The dose rate from the x-ray needle tip was relatively isotropic at the needle tip and was continuously adjustable over the range of 0 cGy min(-1) to upwards of 62 cGy min(-1) at a reference distance of 1 cm in air. We detected a significant proportion of x-rays generated along the needle shaft, and not at the needle tip, as intended. The energy spectrum emitted from this device had a peak intensity at 21 keV and an average energy of 28 keV. The beam was attenuated in both aluminium (the first half-value layer being less than 0.1 mm) and in water (50% dose at approximately 2 mm). These studies confirm that although there is potential for a system similar to this one for clinical applications, the simplistic electron guidance used in this particular prototype device limits it to research applications. Further optimization is required in focusing and steering the electron beam to the target, improving x-ray production efficiency and using x-ray target cooling to achieve higher dose rates.
2001-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/8
info:doi/10.1088/0031-9155/46/1/307
http://www.iop.org/EJ/abstract/0031-9155/46/1/307
Medical Biophysics Publications
Scholarship@Western
Aluminum
Brachytherapy
Dose-Response Relationship
Radiation
Iodine Radioisotopes
Iridium Radioisotopes
Water
X-Rays
Dose-Response Relationship, Radiation
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:biophysicspub-1008
2009-11-22T04:49:49Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:onc
Optimal Photon Energies for IUdR K-edge Radiosensitization with Filtered X-ray and Radioisotope Sources
Karnas, S. J.
Yu, E.
McGarry, R. C.
Battista, J. J.
The purpose of this work is to determine the most physically effective radiation energy for K-edge absorption of x- or gamma-rays by iododeoxyuridine (IUdR) on Chinese hamster ovary (CHO) cells. Brachytherapy sources (Sm-145, I-125, Yb-169 and Am-241) and x-ray beams (30 kVp, 100 kVp and 100 kVp with gold, gadolinium, lead or tungsten filtration) were investigated for their preferential absorption qualities by IUdR sensitized DNA. The 30 kVp, 100 kVp and 100 kVp with tungsten filtration were then used to irradiate CHO cells, with or without IUdR incorporation (i.e. 10(-5) M of IUdR for 3 days). Radiation absorption calculations were performed to determine the increase in energy absorption in DNA with and without IUdR incorporated. In order to measure the in vitro biological effects of K-edge absorption, cell survival experiments were performed. The radiation physics calculations yielded an iodine dose enhancement ratio (DER) of 1.4+/-0.15. 1.8+/-0.15 and 2.7+/-0.15 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for 18% IUdR replacement of thymidine in DNA. The corresponding cell sensitization enhancement ratios (SER), determined from the cell survival assay, were determined to be 1.24+/-0.2, 1.8+/-0.2 and 2.3+/-0.3 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for cells with 18+/-2% IUdR incorporation. These SER values are in reasonable agreement with the DER values of 1.4, 1.8 and 2.7. From these radiation calculations and radiobiology experiments we confirm that using x-radiation energies above the K-edge of iodine (33.2 keV) can have a significant effect on cell survival. This effect is due mainly to the increase in the local dose to the DNA for IUdR-sensitized cells compared with the normal DNA which lacks the iodine contrast agent. Our results support the clinical application of IUdR and low-energy brachytherapy, perhaps using new technologies such as the x-ray needle or new isotopes such as Yb-169.
1999-10-01T07:00:00Z
article
https://ir.lib.uwo.ca/biophysicspub/9
info:doi/10.1088/0031-9155/44/10/312
http://www.iop.org/EJ/abstract/0031-9155/44/10/312
Medical Biophysics Publications
Scholarship@Western
Americium
Animals
Brachytherapy
CHO Cells
Cricetinae
DNA
Dose-Response Relationship
Radiation
Gamma Rays
Idoxuridine
Iodine Radioisotopes
Photons
Radiation-Sensitizing Agents
Radioisotopes
Samarium
X-Rays
Ytterbium
Dose-Response Relationship, Radiation
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1053
2009-11-23T00:23:24Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Functional Infrared Imaging of the Breast
Keyserlingk, J. R.
Ahlgren, P. D.
Yu, E.
Belliveau, N.
Yassa, M.
In order to re-assess the potential contribution of infrared (IR) imaging as a first-line component of a multi-imaging strategy using currently available technology, we first review the history of its introduction and clinical application, including the results of the Breast Cancer Detection Demonstration Projects (BCDDP). We then discuss experiments with a new high-resolution, computerized IR station and software program acquired by the Ville Marie Breast Center to assess IR imaging's ability to complement clinical examination and mammography in the early detection of breast cancer. Our goal is to show that high-resolution IR imaging provides additional safe, practical, and objective information when produced and interpreted by sufficiently trained breast physicians.
2000-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/53
info:doi/10.1109/51.844378
http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=18309&arnumber=844378&count=16&index=0
Oncology Publications
Scholarship@Western
Breast
Breast Neoplasms
Diagnostic Imaging
Female
History
20th Century
Humans
Infrared Rays
Mammography
History, 20th Century
Bioimaging and Biomedical Optics
Oncology
oai:ir.lib.uwo.ca:oncpub-1054
2009-11-23T00:37:47Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Radiation Treatment for Cervical Esophagus: Patterns of Practice Study in Canada, 1996
Tai, Patricia
Van Dyk, Jake
Yu, Edward
Battista, Jerry
Schmid, Matthew
Stitt, Larry
Tonita, Jon
Coad, Terry
PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat esophageal cancers, using a trans-Canada survey, completed at the end of 1996.
METHODS AND MATERIALS: One of 3 case presentations of different stages of cervical esophageal cancer was randomly assigned and sent to participating radiation oncologists by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline target volumes for the boost phase of radiotherapy. Radiation oncologists from 26 of 27 (96%) of all Canadian centers participated.
RESULTS: High-energy X-rays (>/= 10 MV) were employed by 68% of the respondents in part of the treatment course. The majority (83%) of the radiation oncologists used at least two phases of treatment. Very few, 10 of 59 (17%), responses started with multifield treatment. The most frequently used prescription dose was 60 Gy/30 fractions/6 weeks, given with concurrent chemotherapy. Dose prescriptions were to the isocenter in 39 of 48 (81%) or to a particular isodose line in 9 of 48 (19%) of respondents.
CONCLUSION: There was a variety of radiation treatment techniques in this trans-Canada survey. The majority of the patients had combined cisplatin-based chemoradiation. The isocenter was not used consistently as a dose prescription point.
2000-06-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/54
info:doi/10.1016/S0360-3016(00)00484-3
http://dx.doi.org/10.1016/S0360-3016(00)00484-3
Oncology Publications
Scholarship@Western
Aged
Antineoplastic Combined Chemotherapy Protocols
Canada
Cancer Care Facilities
Combined Modality Therapy
Esophageal Neoplasms
Health Care Surveys
Humans
Male
Physician's Practice Patterns
Radiation Oncology
Radiotherapy Dosage
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1056
2009-11-23T01:02:06Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Does Delay in Breast Irradiation Following Conservative Breast Surgery in Node-Negative Breast Cancer Patients Have an Impact on Risk of Recurrence?
Vujovic, Olga
Perera, Francisco
Dar, A. Rashid
Stitt, Larry
Yu, Edward
Voruganti, Sachi M.
Truong, Pauline T.
PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after definitive breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients.
METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy between January 1, 1985 and December 31, 1992, at the London Regional Cancer Centre. Adjuvant breast irradiation consisted either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0-8 weeks (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16 weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12 weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local recurrence and disease-free survival rates were calculated. The association between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (< or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic vessel invasion, extensive intraductal component, and local recurrence and disease-free survival were investigated using Cox regression techniques.
RESULTS: Median follow-up was 63.5 months. Patients in all 4 time intervals were similar in terms of age and pathologic features. There was no statistically significant difference between the 4 groups in local recurrence or disease-free survival with surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9% (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and 3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52 months). In a stepwise multivariable Cox regression model for disease-free survival, allowing for entry of known risk factors, tumour size (p < 0.001), grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery-radiotherapy interval did not enter the model.
CONCLUSION: This retrospective study suggests that delay in start of breast irradiation beyond 12 and up to 16 weeks does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results are limited by the retrospective nature of this analysis and the lack of information concerning the late local failure rate.
1998-03-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/56
info:doi/10.1016/S0360-3016(97)00922-X
http://dx.doi.org/10.1016/S0360-3016(97)00922-X
Oncology Publications
Scholarship@Western
Adult
Analysis of Variance
Breast Neoplasms
Carcinoma
Ductal
Breast
Carcinoma
Lobular
Combined Modality Therapy
Disease-Free Survival
Female
Humans
Middle Aged
Neoplasm Recurrence
Local
Radiotherapy Dosage
Retrospective Studies
Time Factors
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Neoplasm Recurrence, Local
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1055
2009-11-23T00:47:11Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:medimagingpub
publication:onc
publication:epidempub
Variability of Target Volume Delineation in Cervical Esophageal Cancer
Tai, Patricia
Van Dyk, Jake
Yu, Edward
Battista, Jerry
Stitt, Larry
Coad, Terry
PURPOSE: Three-dimensional (3D) conformal radiation therapy (CRT) assumes and requires the precise delineation of the target volume. To assess the consistency of target volume delineation by radiation oncologists, who treat esophageal cancers, we have performed a transCanada survey.
MATERIALS AND METHODS: One of three case presentations, including CT scan images, of different stages of cervical esophageal cancer was randomly chosen and sent by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline boost target volumes for the primary tumor on CT scans, using ICRU-50 definitions.
RESULTS: Of 58 radiation oncologists who agreed to participate, 48 (83%) responded. The external beam techniques used were mostly anterior-posterior fields, followed by a multifield boost technique. Brachytherapy was employed by 21% of the oncologists, and concurrent chemotherapy by 88%. For a given case, and the three volumes defined by ICRU-50 (i.e., gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) we determined: 1. The total length in the cranio-caudal dimension; 2. the mean diameter in the transverse slice that was located in a CT slice that was common to all participants; 3. the total volume for each ICRU volume; and 4. the (5, 95) percentiles for each parameter. The PTV showed a mean length of 14.4 (9.6, 18.0) cm for Case A, 9.4 (5.0, 15.0) cm for Case B, 11.8 (6.0, 16.0) cm for Case C, a mean diameter of 6.4 (5.0, 9.4) cm for Case A, 4.4 (0.0, 7.3) cm for Case B, 5.2 (3.9, 7.3) cm for Case C, and a mean volume of 320 (167, 840) cm3 for Case A and 176 (60, 362) cm3 for Case C. The results indicate variability factors (95 percentile divided by 5 percentile values) in target diameters of 1.5 to 2.6, and in target lengths of 1.9 to 5.0.
CONCLUSION: There was a substantial inconsistency in defining the planning target volume, both transversely and longitudinally, among radiation oncologists. The potential benefits of 3D treatment planning with high-precision dose delivery could be offset by this inconsistency in target-volume delineation by radiation oncologists. This may be particularly important for multicenter clinical trials, for which quality assurance of this step will be essential to the interpretation of results.
1998-09-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/55
info:doi/10.1016/S0360-3016(98)00216-8
http://dx.doi.org/10.1016/S0360-3016(98)00216-8
Oncology Publications
Scholarship@Western
Aged
Analysis of Variance
Canada
Esophageal Neoplasms
Health Care Surveys
Humans
Male
Medical Oncology
Observer Variation
Radiotherapy Dosage
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Conformal
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Conformal
Epidemiology
Medical Biophysics
Oncology
oai:ir.lib.uwo.ca:oncpub-1057
2009-11-23T01:17:23Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:epidem
publication:onc
publication:epidempub
Superior Vena Cava Obstruction in Small-cell Lung Cancer
Chan, Roscoe H.
Dar, A. Rashid
Yu, Edward
Stitt, Larry W.
Whiston, Francis
Truong, Pauline
Vincent, Mark D.
Kocha, Walter I.
PURPOSE: To identify prognostic or treatment factors influencing the response of superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall survival of SCLC patients with SVCO at presentation; and to assess the role of retreatment in patients with SVCO at recurrent or persistent disease.
METHODS AND MATERIALS: Between January 1983 and November 1993, 76 consecutive patients who had small-cell lung cancer (SCLC) with SVCO were treated in our institution. Analysis was done according to the disease status at diagnosis of SVCO. The first analysis concerned a group of 50 patients who had SVCO at initial presentation. The second analysis concerned a group who had SVCO as a manifestation of persistent or recurrent disease.
RESULTS: In the first analysis, 93% had significant improvement in symptoms of SVCO after chemotherapy and 94% after mediastinal radiation. Response is almost universal despite a wide range of radiation fractionation and total dose used. Seventy percent remained SVCO-free before death. Thirty percent developed recurrence of SVCO symptoms 1-16 months (median 8) after the start of initial treatment. Those who received combined chemotherapy and radiation had a longer time to SVCO recurrence (p = 0.018) compared to those who received chemotherapy alone. This effect is mainly seen in limited-stage patients. The presence of SVCO recurrence tends to have an adverse effect on the overall survival (p = 0.077) irrespective of the time when the recurrences occurred (p = 0.296). The median survival of this whole group of 50 patients in the first analysis was 9.5 months, and the 2-year survival was 10%. Stage was strongly predictive of survival (p < 0.001). Sixteen percent (3 of 19) of the patients with limited-stage diseases were long-term survivors (two patients survived 35 months and one survived 70 months). The early mortality from SVCO was 2%. In the second analysis, 85% had previously been treated with chemotherapy alone. The response rate of SVCO in the analysable patients (n = 39) was 77%. There was no significant difference in the response rate of SVCO to treatment comparing patients treated by chemotherapy first or mediastinal radiation first (p = 0.653), but most patients [82% (32 of 39)] received radiation as the initially treatment of SVCO. Ninety-three percent (38 of 41) received mediastinal radiation as a part of their ultimate retreatment regimen, and 68% (28 of 41) received mediastinal radiation as their sole retreatment regimen. Thirty-two percent (13 of 41) received chemotherapy as a part of their ultimate retreatment regimen, and only 7% received chemotherapy alone as their sole retreatment regimen. Eighty-three percent (25 of 30) of those whose SVCO responded remained free of SVCO before death, with a median survival of 3 months after recurrent or persistent disease documented.
CONCLUSION: Chemotherapy or mediastinal radiation is very effective as an initial treatment in SCLC patients with SVCO at presentation and at recurrent or persistent disease. There is no obvious need to use big radiation fraction sizes for the first few radiation treatment as was previously believed. In patients with recurrent or persistent SCLC with SVCO, especially in those who previously received chemotherapy only, we have more experience in incorporating mediastinal radiation as a major component of the palliative regimen with highly effective and durable palliation achieved.
1997-06-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/57
info:doi/10.1016/S0360-3016(97)00094-1
http://dx.doi.org/10.1016/S0360-3016(97)00094-1
Oncology Publications
Scholarship@Western
Adult
Aged
Aged
80 and over
Carcinoma
Small Cell
Female
Humans
Lung Neoplasms
Male
Middle Aged
Radiotherapy Dosage
Recurrence
Retrospective Studies
Superior Vena Cava Syndrome
Aged, 80 and over
Carcinoma, Small Cell
Epidemiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1058
2009-11-24T08:23:34Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Infrared Imaging of the Breast: Initial Reappraisal Using High-Resolution Digital Technology in 100 Successive Cases of Stage I and II Breast Cancer
Keyserlingk, J. R.
Ahlgren, P. D.
Yu, E.
Belliveau, N.
There is a general consensus that earlier detection of breast cancer should result in improved survival. Current breast imaging relies primarily on mammography. Despite better equipement and regulation, variability in interpretation and tissue density still affect accuracy. A number of adjuvant imaging techniques are currently being used, including doppler ultrasound and gadolinium-enhanced MRI, which can detect cancer-induced neovascularity. In order to assess the potential contribution of currently available high-resolution digital infrared technology capable of recognizing minute regional vascular flow related temperature variation, we retrospecitively reviewed the relative ability of our preoperative clinical exam, mammography, and infrared imaging to detect 100 new cases of ductal carcinoma in situ, stage I and II breast cancer. While the false-negative rate of infrared imaging was 17%, at least one abnormal infrared sign was detected in the remaining 83 cases, including 10 of the 15 patients, a slightly younger cohort, who had nonspecific mammograms. The 85% sensitivity rate of mammography alone thus increased to 95% when combining both imaging modalities. Access to infrared information was also pertinent when confronted with the relatively frequent contributory but equivocal clinical exam (34%) and mammography (19%). The average size of those tumors undetected by mammography or infrared imaging was 1.66 cm and 1.28 cm, respectively, while the false-positive rate of infrared imaging in a concurrent series of 100 successive benign open breast biopsies was 19%. Our initial experience would suggest that, when done concomitantly with clinical exam and mammography, high-resolution digital infrared imaging can provide additional safe, practical, and objective information. Further evaluation, preferably in controlled prospective multicenter trials, would provide valuable data.
1998-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/58
info:doi/10.1046/j.1524-4741.1998.440245.x
http://www3.interscience.wiley.com/journal/119133173/abstract
Oncology Publications
Scholarship@Western
breast
cancer
detection
imaging
infrared
Oncology
oai:ir.lib.uwo.ca:oncpub-1059
2009-12-06T13:38:05Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Vitamin D and Parotid Gland Function in the Rat
Peterfy, C.
Tenenhouse, A.
Yu, E.
1. We previously reported that parotid gland secretion is decreased in rats deprived of vitamin D (Glijer, Peterfy & Tenenhouse, 1985). In the present study we examine whether this effect is a direct result of the absence of vitamin D or due to the secondary systemic effects of vitamin D deficiency. 2. Offspring of rats maintained on a calcium-supplemented (1.2%), vitamin-D-deficient diet were weaned onto the same diet and examined after 8 weeks. Using this method it was possible to maintain serum calcium and parathyroid hormone concentrations within normal limits. Serum 25-hydroxyvitamin D (25(OH)D3) was not detectable, but 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations were normal. 3. Pilocarpine-stimulated flow of parotid saliva was reduced 57% in vitamin-D-deprived animals, but amylase secretion was unchanged. Treatment with vitamin D3 returned flow rates to normal. 4. The concentration of calcium in parotid saliva was normal in vitamin-D-deprived rats, although total parotid calcium output was reduced 57%. 5. Pilocarpine-stimulated salivary flow from submandibular gland, a tissue which does not possess 1,25(OH)2D3 receptors, was normal in vitamin-D-deprived rats. 6. Heart rate and arterial blood pressure changes in response to I.V. pilocarpine administration were identical in normal and vitamin-D-deficient rats. 7. Auriculotemporal nerve-stimulated flow of parotid saliva was also reduced by 50% and administration of vitamin D3 to these rats corrected this abnormality. 8. It is concluded that fluid and electrolyte secretion from parotid gland is directly dependent on vitamin D; abnormal parotid gland function seen in vitamin-D-deficient rats is not due to secondary hypocalcaemia or hyperparathyroidism, nor can it be explained by haemodynamic changes evoked during systemic administration of pilocarpine. We further conclude that the metabolite of vitamin D responsible for this effect is not 1,25(OH)2D3.
1988-04-01T08:00:00Z
article
https://ir.lib.uwo.ca/oncpub/59
http://jp.physoc.org/content/398/1/1.abstract
Oncology Publications
Scholarship@Western
Animals
Calcium
Diet
Female
Hemodynamics
Parotid Gland
Pilocarpine
Rats
Rats
Inbred Strains
Salivation
Vitamin D
Rats, Inbred Strains
Medical Physiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1060
2009-11-25T08:42:45Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
Uptake, Storage and Secretion of 5-hydroxytryptamine and Its Amino Acid Precursor by Dispersed Rat Pancreas Acinar Cells
Stern, Ligia
Tenenhouse, A.
Yu, E. W.-T.
Rat pancreas acinar cells contain 5-hydroxytryptamine (5-HT; 10.86 +/- 2.52 ng/i.u. amylase), all of which can be accounted for by the 5-HT recovered from the zymogen granule fraction of these cells (10.70 +/- 3.06 ng/i.u. amylase). When incubated with [14C]5-HT dispersed acinar cells take up the amine and concentrate it in zymogen granules. These cells will also take up [14C]5-HTP (5-hydroxytryptophan), decarboxylate it and store the [14C]5-HT so produced in zymogen granules. 5-HTP itself is not taken up by the granules. 5-HT is incorporated into zymogen granules early in their formation; no amine is accumulated by mature zymogen granules and the amine within the mature granule is not exchangeable with extragranular amine. When dispersed acinar cells pre-labelled with [14C]5-HT and [3H]leucine are stimulated with caerulein, there is a synchronous increase in amylase activity and secretion of [14C]5-HT and [3H]protein; the ratios of [3H]protein/[14C]5-HT in zymogen granules and in the secretory products are identical. Pancreas acinar cells take up L-DOPA, decarboxylate it and store the dopamine produced in zymogen granules but the dopamine is not retained by the granules (t1/2 approximately equal to 90 min) and dopamine secretion from cells exposed to caerulein could not be demonstrated. It is concluded that 5-HT is a normal component of rat pancreas acinar cell zymogen granule. The granular amine has a turnover rate similar to that of granular protein and is released when the cells are stimulated to secrete protein. All the 5-HT released from the cell originates in zymogen granules.
1983-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/60
http://jp.physoc.org/content/340/1/555.abstract
Oncology Publications
Scholarship@Western
5-Hydroxytryptophan
Amylases
Animals
Caerulein
Cytoplasmic Granules
Dopamine
Enzyme Precursors
Pancreas
Proteins
Rats
Rats
Inbred Strains
Serotonin
Subcellular Fractions
Time Factors
Rats, Inbred Strains
Medical Physiology
Oncology
oai:ir.lib.uwo.ca:oncpub-1061
2009-12-21T00:38:45Z
publication:physics
publication:biophysicspub
publication:oncpub
publication:pmid
publication:medimaging
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:medimagingpub
publication:onc
publication:epidempub
Variability of Target Volume Delineation in Cervical Esophageal Cancer
Tai, Patricia
Van Dyk, Jake
Yu, Edward
Battista, Jerry
Stitt, Larry
Coad, Terry
1999-01-01T08:00:00Z
book_contribution
https://ir.lib.uwo.ca/oncpub/61
Oncology Publications
Scholarship@Western
Aged
Analysis of Variance
Canada
Esophageal Neoplasms
Health Care Surveys
Humans
Male
Medical Oncology
Observer Variation
Radiotherapy Dosage
Radiotherapy Planning
Computer-Assisted
Radiotherapy
Conformal
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Conformal
Oncology
oai:ir.lib.uwo.ca:oncpub-1062
2009-12-21T00:49:04Z
publication:biophysicspub
publication:oncpub
publication:faculties
publication:biophysics
publication:onc
Esophageal Cancer
Yu, Edward
2007-01-01T08:00:00Z
book_contribution
application/pdf
https://ir.lib.uwo.ca/oncpub/62
https://ir.lib.uwo.ca/context/oncpub/article/1062/viewcontent/Esophageal.pdf
Oncology Publications
Scholarship@Western
esophageal cancer
Oncology
oai:ir.lib.uwo.ca:oncpub-1063
2009-11-28T06:53:58Z
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:faculties
publication:electricalpub
publication:biophysics
publication:epidem
publication:electrical
publication:robarts
publication:surgery
publication:institutes
publication:onc
publication:epidempub
MIRA V: An Integrated System for Minimally Invasive Robot-assisted Lung Brachytherapy
Trejos, A. L.
Lin, A. W.
Mohan, S.
Bassan, H.
Edirisinghe, C.
Patel, R. V.
Lewis, C.
Yu, E.
Fenster, A.
Malthaner, R. A.
An integrated system for minimally invasive robot-assisted image-guided lung brachytherapy has been developed. The system incorporates an experimental setup for accurate radioactive seed placement with commercially available dosimetry planning software. The end result is a complete system that allows planning and executing a brachytherapy procedure with increased accuracy. The results of the in vitro seed placement evaluation show that seed misplacement has a significant effect on the volume receiving more than 200% of the dose (V200), and the minimum dosage received by 90% of the volume (D90).
2008-05-01T07:00:00Z
conference
https://ir.lib.uwo.ca/oncpub/63
info:doi/10.1109/ROBOT.2008.4543663
http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=4543169&arnumber=4543663&count=669&index=492
Oncology Publications
Scholarship@Western
lung brachytherapy
lung cancer
robotics
Electrical and Computer Engineering
Oncology
Surgery
oai:ir.lib.uwo.ca:oncpub-1064
2009-12-05T02:01:21Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
The Management of Thymoma: A Systematic Review and Practice Guideline
Falkson, Conrad B.
Bezjak, Andrea
Darling, Gail
Gregg, Richard
Malthaner, Richard
Maziak, Donna E.
Yu, Edward
Smith, Christopher A.
McNair, Sheila
Ung, Yee C.
Evans, William K.
Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care
INTRODUCTION: Thymoma is a rare tumor for which there is little randomized evidence to guide treatment. Because of the lack of high-quality evidence, a formal consensus-based approach was used to develop recommendations on treatment.
METHODS: A systematic refview of the literature was performed. Recommendations were formed from available evidence and developed through a two-round modified Delphi consensus approach.
RESULTS: The treatment recommendations are summarized as follows: Stage I--complete resection of the entire thymus without neoadjuvant or adjuvant therapy. Stage II--complete resection of the entire thymus with consideration of adjuvant radiation for high-risk tumors. Stage IIIA--surgery either initially or after neoadjuvant therapy, or surgery followed by adjuvant therapy. Stage IIIB--treatment may include a combination of chemotherapy, radiation, and/or surgery, or if technically possible, surgery in combination with chemoradiotherapy (concurrent cisplatin based). For bulky tumors, consideration should be given to sequential chemotherapy followed by radiation. Stage IVA--as per stage III, with surgery only if metastases can be resected. Stage IVB--treatment on an individual case basis (no generic recommendations). Recurrent disease--consider surgery, radiation, and/or chemoradiation. Chemoradiation should be considered in all medically inoperable and technically inoperable patients.
CONCLUSION: Consensus was achieved on these recommendations, which serve to provide practical guidance to the physician treating this rare disease.
2009-07-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/64
info:doi/10.1097/JTO.0b013e3181a4b8e0
http://journals.lww.com/jto/Abstract/2009/07000/The_Management_of_Thymoma__A_Systematic_Review_and.22.aspx
Oncology Publications
Scholarship@Western
Combined Modality Therapy
Delphi Technique
Humans
Neoplasm Metastasis
Neoplasm Staging
Thymoma
Thymus Neoplasms
Oncology
oai:ir.lib.uwo.ca:vascularpub-1016
2009-12-08T07:34:25Z
publication:vascularpub
publication:biophysicspub
publication:physpharmpub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:physpharm
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:institutes
NAD+, Sirtuins, and Cardiovascular Disease
Borradaile, Nica M.
Pickering, J. Geoffrey
Cardiovascular disease (CVD) is the most prevalent disease worldwide and there is intense interest in pharmaceutical approaches to reduce the burden of this chronic, aging-related condition. The sirtuin (SIRT) family of NAD(+)-dependent protein deacetylases and ADP-ribosyltransferases have emerged as exciting targets for CVD management that can impact the cardiovascular system both directly and indirectly, the latter by modulating whole body metabolism. SIRT1-4 regulate the activities of a variety of transcription factors, coregulators, and enzymes that improve metabolic control in adipose tissue, liver, skeletal muscle, and pancreas, particularly during obesity and aging. SIRT1 and 7 can control myocardial development and resist stress- and aging-associated myocardial dysfunction through the deacetylation of p53 and forkhead box O1 (FoxO1). By modulating the activity of endothelial nitric oxide synthase (eNOS), FoxO1, and p53, and the expression of angiotensin II type 1 receptor (AT1R), SIRT1 also promotes vasodilatory and regenerative functions in endothelial and smooth muscle cells of the vascular wall. Given the array of potentially beneficial effects of SIRT activation on cardiovascular health, interest in developing specific SIRT agonists is well-substantiated. Because SIRT activity depends on cellular NAD+ availability, enzymes involved in NAD+ biosynthesis, including nicotinamide phosphoribosyltransferase (Nampt), may also be valuable pharmaceutical targets for managing CVD. Herein we review the actions of the SIRT proteins on the cardiovascular system and consider the potential of modulating SIRT activity and NAD+ availability to control CVD.
2009-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/vascularpub/16
http://www.bentham.org/cpd/contabs/cpd15-1.htm#11
Robarts Vascular Research Publications
Scholarship@Western
Cardiovascular Diseases
Gene Expression Regulation
Enzymologic
Humans
Myocardium
NAD
Sirtuins
Gene Expression Regulation, Enzymologic
Cardiology
oai:ir.lib.uwo.ca:vascularpub-1025
2009-12-21T02:22:44Z
publication:vascularpub
publication:mnipub
publication:biophysicspub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:biophysics
publication:biochempub
publication:mni
publication:robarts
publication:biochem
publication:institutes
Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells
Frontini, Matthew J.
O'Neil, Caroline
Sawyez, Cynthia
Chan, Bosco M. C.
Huff, Murray W.
Pickering, J. Geoffrey
A vital role of vascular smooth muscle cells (SMCs) is to stabilize the artery wall by elaborating fibrils of type I collagen. This is especially important in atherosclerotic lesions. However, SMCs in these lesions can be laden with lipids and the impact of this modification on collagen fibril formation is unknown. To address this, we converted human vascular SMCs to a foam cell state by incubating them with either LDL or VLDL. Biochemical markers of a SMC phenotype were preserved. However, microscopic tracking revealed a profound perturbation in the ability of the cells to assemble collagen fibrils, reducing assembly by up to 79%. This dysfunction was mirrored by an inability of smooth muscle foam cells to assemble fibronectin. Lipid-loaded SMCs did not display a generalized defect in the actin cytoskeleton and the formation of vinculin-containing focal adhesion complexes was preserved. However, lipid-loaded SMCs were unable to assemble fibrillar adhesion complexes and clustering of tensin and alpha5beta1 integrin was disordered. Moreover, phosphorylation of tensin, required for fibrillar adhesion complex formation, was suppressed by up to 57%, with a concomitant decrease in activation of Src and FAK and restriction of activated Src to the cell edges. Forced activation of Src-FAK signaling in lipid-engorged SMCs rescued both fibrillar adhesion formation and fibrillogenesis. We conclude that lipid accumulation by SMCs disables the machinery for collagen and fibronectin assembly. This previously unknown relationship between atherogenic lipids and integrin-based signaling could underlie plaque vulnerability.
2009-04-10T07:00:00Z
article
https://ir.lib.uwo.ca/vascularpub/26
info:doi/10.1161/CIRCRESAHA.108.187302
http://circres.ahajournals.org/cgi/content/abstract/104/7/832
Robarts Vascular Research Publications
Scholarship@Western
Atherosclerosis
Cell Line
Collagen Type I
Fibronectins
Foam Cells
Focal Adhesion Kinase 1
Focal Adhesions
Humans
Lipoproteins
LDL
Lipoproteins
VLDL
Microfilament Proteins
Muscle
Smooth
Vascular
Myocytes
Smooth Muscle
Particle Size
Phenotype
Phosphorylation
Receptors
Vitronectin
Signal Transduction
Time Factors
Transduction
Genetic
Vinculin
src-Family Kinases
Lipoproteins, LDL
Lipoproteins, VLDL
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Receptors, Vitronectin
Transduction, Genetic
Medical Biochemistry
Medical Biophysics
Medical Immunology
oai:ir.lib.uwo.ca:physpharmpub-1027
2009-12-23T21:07:48Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:biochem
publication:surgery
An Alternative Kinase Activity Assay for Primary Cultures Derived from Clinical Isolates
McLean, Kristopher
Wu, Yan
Gan, Bing Siang
O'Gorman, David B.
PURPOSE: The measurement of protein kinase activity is central to understanding the signaling pathways that regulate cellular proliferation and apoptosis in virtually all disease processes. These measurements typically involve either indirect, time consuming assessment methods that require large amounts of sample, such as western immunoblotting, or the use of high maintenance, specialized equipment not typically available to a small clinical research facility. The purpose of this project was to determine if a benchtop Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) unit could be used to detect and directly assess kinase activity of the serine/threonine kinase Akt.
METHOD: Biotinylated substrate peptides, predicted to be recognized and phosphorylated by Akt to varying extents, were incubated in crude lysates of primary cells derived directly from clinical isolates. Streptavidin-coated chips were then used to isolate the substrate peptides from the lysates after incubation. Finally SELDI-TOF-MS was used to detect the peptide substrates and identify any changes in mass resulting from phosphorylation.
RESULTS: The biotinylated peptide substrates were readily detected and a simple, rapid procedure that allows direct measurement of Akt activity in less than 1 microg of cell lysate in a 2microL volume was developed. Further, a linear correlation between native to phospho-peptide ratios and SELDI-TOF-MS output demonstrated that this approach is semi-quantitative.
CONCLUSION: This assay avoids many of the pitfalls associated with the currently available kinase protocols as well as labour-intensive mass-spectrometry analysis by specialist laboratories. We propose that this approach may be a viable alternative for clinical research laboratories aiming to measure the activity of kinases in clinical isolates.
2009-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/physpharmpub/25
http://cimonline.ca/index.php/cim/article/view/6025
Physiology and Pharmacology Publications
Scholarship@Western
Biological Assay
Biotinylation
Cells
Cultured
Humans
Peptides
Phosphorylation
Proto-Oncogene Proteins c-akt
Reproducibility of Results
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Cells, Cultured
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
oai:ir.lib.uwo.ca:vascularpub-1026
2009-12-23T21:15:27Z
publication:vascularpub
publication:biophysicspub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:institutes
Nicotinamide Phosphoribosyltransferase Imparts Human Endothelial Cells with Extended Replicative Lifespan and Enhanced Angiogenic Capacity in a High Glucose Environment
Borradaile, Nica M.
Pickering, J. Geoffrey
Endothelial dysfunction is a characteristic of aging-related vascular disease and is worsened during diabetes. High glucose can impair endothelial cell (EC) function through cellular accumulation of reactive oxygen species, an insult that can also limit replicative lifespan. Nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF and visfatin, is rate-limiting for NAD+ salvage from nicotinamide and confers resistance to oxidative stress via SIRT1. We therefore sought to determine if Nampt expression could resist the detrimental effects of high glucose and confer a survival advantage to human vascular EC in this pathologic environment. Human aortic EC were infected with retrovirus encoding eGFP or eGFP-Nampt, and FACS-selected to yield populations with similar, modest transgene expression. Using a chronic glucose exposure model we tracked EC populations to senescence, assessed cellular metabolism, and determined in vitro angiogenic function. Overexpression of Nampt increased proliferation and extended replicative lifespan, and did so preferentially during glucose overload. Nampt expression delayed markers of senescence and limited reactive oxygen species accumulation in high glucose through a modest increase in aerobic glycolysis. Furthermore, tube networks formed by Nampt-overexpressing EC were more extensive and glucose-resistant, in accordance with SIRT1-mediated repression of the anti-angiogenic transcription factor, FoxO1. We conclude that Nampt enables proliferating human EC to resist the oxidative stress of aging and of high glucose, and to productively use excess glucose to support replicative longevity and angiogenic activity. Enhancing endothelial Nampt activity may thus be beneficial in scenarios requiring EC-based vascular repair and regeneration during aging and hyperglycemia, such as atherosclerosis and diabetes-related vascular disease.
2009-04-01T07:00:00Z
article
https://ir.lib.uwo.ca/vascularpub/27
info:doi/10.1111/j.1474-9726.2009.00453.x
http://www3.interscience.wiley.com/journal/122261398/abstract
Robarts Vascular Research Publications
Scholarship@Western
Atherosclerosis
Biological Markers
Blood Vessels
Cell Aging
Cell Proliferation
Cells
Cultured
Cytokines
Diabetes Complications
Endothelial Cells
Forkhead Transcription Factors
Gene Expression Regulation
Enzymologic
Genetic Vectors
Glucose
Humans
Neovascularization
Physiologic
Nicotinamide Phosphoribosyltransferase
Sirtuin 1
Sirtuins
Transfection
Cells, Cultured
Gene Expression Regulation, Enzymologic
Neovascularization, Physiologic
Medical Biochemistry
Medical Biophysics
oai:ir.lib.uwo.ca:robartspub-1002
2009-12-27T23:57:02Z
publication:animalpub
publication:animal
publication:robartspub
publication:biophysicspub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:surgery
publication:institutes
publication:campusunits
In vivo Micro-CT Analysis of Bone Remodeling in a Rat Calvarial Defect Model
Umoh, Joseph U.
Sampaio, Arthur V.
Welch, Ian
Pitelka, Vasek
Goldberg, Harvey A.
Underhill, T. Michael
Holdsworth, David W.
The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 microm. At 6 weeks, the BMC in control animals (4.37 +/- 0.66 mg) was significantly lower (p < 0.05) than that in treated rats (11.29 +/- 1.01 mg). Linear regression between the BMC and bone fractional area, from 20 rats, showed a strong correlation (r(2) = 0.70, p < 0.0001), indicating that the BMC can be used, in place of previous destructive analysis techniques, to characterize bone growth. The high precision (2.5%) of the micro-CT methodology indicates its utility in detecting small BMC changes in animals.
2009-04-07T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/3
info:doi/10.1088/0031-9155/54/7/020
http://www.iop.org/EJ/abstract/0031-9155/54/7/020
Robarts Imaging Publications
Scholarship@Western
Animals
Bone Density
Bone Remodeling
Disease Models
Animal
Drug Evaluation
Preclinical
Longitudinal Studies
Male
Rats
Rats
Wistar
Sensitivity and Specificity
Skull
Time Factors
Tomography
X-Ray Computed
Disease Models, Animal
Drug Evaluation, Preclinical
Rats, Wistar
Tomography, X-Ray Computed
Bioimaging and Biomedical Optics
Medical Biochemistry
Medical Biophysics
Surgery
oai:ir.lib.uwo.ca:robartspub-1003
2009-12-28T22:00:36Z
publication:anatomy
publication:robartspub
publication:rwkex_researcharticles
publication:biophysicspub
publication:pmid
publication:medimaging
publication:faculties
publication:anatomypub
publication:rwkex
publication:biophysics
publication:biochempub
publication:medimagingpub
publication:robarts
publication:biochem
publication:institutes
Comparison of Gadofluorine-M and Gd-DTPA for Noninvasive Staging of Atherosclerotic Plaque Stability Using MRI
Ronald, John A.
Chen, Yuanxin
Belisle, Andre J.-L.
Hamilton, Amanda M.
Rogers, Kem A.
Hegele, Robert A.
Misselwitz, Bernd
Rutt, Brian K.
BACKGROUND: Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA.
METHODS AND RESULTS: Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T(1)-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.
CONCLUSIONS: GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.
2009-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/4
info:doi/10.1161/CIRCIMAGING.108.826826
http://circimaging.ahajournals.org/cgi/content/abstract/2/3/226
Robarts Imaging Publications
Scholarship@Western
Animals
Aortic Diseases
Aortic Rupture
Atherosclerosis
Contrast Media
Disease Models
Animal
Feasibility Studies
Gadolinium DTPA
Injections
Magnetic Resonance Angiography
Male
Organometallic Compounds
Predictive Value of Tests
Rabbits
Disease Models, Animal
Bioimaging and Biomedical Optics
Medical Anatomy
Medical Biophysics
oai:ir.lib.uwo.ca:surgerypub-1022
2010-01-01T02:38:39Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:biochem
publication:surgery
Periostin Differentially Induces Proliferation, Contraction and Apoptosis of Primary Dupuytren's Disease and Adjacent Palmar Fascia Cells
Vi, Linda
Feng, Lucy
Zhu, Rebecca D.
Wu, Yan
Satish, Latha
Gan, Bing Siang
O'Gorman, David B.
Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.
2009-12-10T08:00:00Z
article
https://ir.lib.uwo.ca/surgerypub/21
info:doi/10.1016/j.yexcr.2009.07.015
http://dx.doi.org/10.1016/j.yexcr.2009.07.015
Surgery Publications
Scholarship@Western
Dupuytren's disease
palmar fascia cell
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
oai:ir.lib.uwo.ca:vascularpub-1031
2010-01-01T02:47:24Z
publication:vascularpub
publication:biophysicspub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:institutes
Nuclear Degradation of Wilms Tumor 1-associating Protein and Survivin Splice Variant Switching Underlie IGF-1-mediated Survival
Small, Theodore W.
Pickering, J. Geoffrey
WTAP (Wilms tumor 1-associating protein) is a recently identified nuclear protein that is essential for mouse embryo development. The Drosophila homolog of WTAP, Fl(2)d, regulates pre-mRNA splicing; however, the role of WTAP in mammalian cells is uncertain. To elucidate a context for WTAP action, we screened growth and survival factors for their effects on WTAP expression in vascular smooth muscle cells (SMCs), a cell type previously found to express WTAP dynamically. This revealed that insulin-like growth factor-1 (IGF-1) uniquely reduced WTAP abundance. This decline in WTAP proved to be necessary for IGF-1 to confer its antiapoptotic properties, which were blocked by transducing the WTAP gene into SMCs. WTAP down-regulation by IGF-1 was mediated by an IGF-1 receptor-phosphatidylinositol 3-kinase-Akt signaling axis that directed WTAP degradation via a nuclear 26 S proteasome. Moreover, by promoting the degradation of WTAP, IGF-1 shifted the pre-mRNA splicing program for the survival factor, survivin, to reduce expression of survivin-2B, which is proapoptotic, and increase expression of survivin, which is antiapoptotic. Knockdown of survivin-2B rescued the ability of IGF-1 to promote survival when WTAP was overexpressed. These data uncover a novel regulatory cascade for human SMC survival based on adjusting the nuclear abundance of WTAP to define the splice variant balance among survivin isoforms.
2009-09-11T07:00:00Z
article
https://ir.lib.uwo.ca/vascularpub/32
info:doi/10.1074/jbc.M109.034629
http://www.jbc.org/content/284/37/24684.abstract
Robarts Vascular Research Publications
Scholarship@Western
1-Phosphatidylinositol 3-Kinase
Alternative Splicing
Apoptosis
Cell Nucleus
Cell Survival
Enzyme Inhibitors
Humans
Insulin-Like Growth Factor I
Microtubule-Associated Proteins
Models
Biological
Myocytes
Smooth Muscle
Nuclear Proteins
Proteasome Endopeptidase Complex
Protein Isoforms
RNA
Messenger
Models, Biological
Myocytes, Smooth Muscle
RNA, Messenger
Cardiology
Medical Biochemistry
Medical Biophysics
oai:ir.lib.uwo.ca:robartspub-1004
2010-01-03T04:55:30Z
publication:vascularpub
publication:anatomy
publication:robartspub
publication:rwkex_researcharticles
publication:biophysicspub
publication:pmid
publication:medimaging
publication:faculties
publication:anatomypub
publication:rwkex
publication:biophysics
publication:biochempub
publication:medimagingpub
publication:robarts
publication:biochem
publication:institutes
Enzyme-Sensitive Magnetic Resonance Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques
Ronald, John A.
Chen, John W.
Chen, Yuanxin
Hamilton, Amanda M.
Rodriguez, Elisenda
Reynolds, Fred
Hegele, Robert A.
Rogers, Kem A.
Querol, Manel
Bogdanov, Alexei
Weissleder, Ralph
Rutt, Brian K.
BACKGROUND: Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase is a central inflammatory enzyme secreted by activated macrophages and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance agent can visualize myeloperoxidase activity in atherosclerotic plaques in a rabbit model.
METHODS AND RESULTS: We performed magnetic resonance imaging of the thoracic aorta of New Zealand White rabbits fed a cholesterol (n=14) or normal (n=4) diet up to 2 hours after injection of the myeloperoxidase sensor bis-5HT-DTPA(Gd) [MPO(Gd)], the conventional agent DTPA(Gd), or an MPO(Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hours after injection) showed focal areas of increased contrast (>2-fold) in diseased wall but not in normal wall (P=0.84) compared with both DTPA(Gd) (n=11; P<0.001) and bis-tyr-DTPA(Gd) (n=3; P<0.05). Biochemical assays confirmed that diseased wall possessed 3-fold elevated myeloperoxidase activity compared with normal wall (P<0.01). Areas detected by MPO(Gd) imaging colocalized and correlated with myeloperoxidase-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, P<0.0001). Although macrophages were the main source of myeloperoxidase, not all macrophages secreted myeloperoxidase, which suggests that distinct subpopulations contribute differently to atherogenesis and supports our functional approach.
CONCLUSIONS: The present study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme to noninvasively provide both anatomic and functional information in vivo.
2009-08-18T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/5
info:doi/10.1161/CIRCULATIONAHA.108.813998
http://circ.ahajournals.org/cgi/content/abstract/120/7/592
Robarts Imaging Publications
Scholarship@Western
Animals
Aorta
Thoracic
Atherosclerosis
Disease Models
Animal
Gadolinium DTPA
Hypercholesterolemia
Inflammation
Macrophages
Magnetic Resonance Imaging
Male
Peroxidase
Rabbits
Regression Analysis
Aorta, Thoracic
Disease Models, Animal
Bioimaging and Biomedical Optics
Medical Anatomy
Medical Biochemistry
Medical Cell Biology
oai:ir.lib.uwo.ca:oncpub-1067
2010-01-03T03:59:33Z
publication:anatomy
publication:patholpub
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:anatomypub
publication:pathol
publication:biophysics
publication:biochempub
publication:biochem
publication:onc
Lymphatic Metastasis of Breast Cancer Cells Is Associated with Differential Gene Expression Profiles that Predict Cancer Stem Cell-like Properties and the Ability to Survive, Establish and Grow in a Foreign Environment
Pandit, Terlika S.
Kennette, Wendy
Mackenzie, Lisa
Zhang, Guihua
Al-Katib, Waleed
Andrews, Joseph
Vantyghem, Sharon A.
Ormond, D. George
Allan, Alison L.
Rodenhiser, David I.
Chambers, Ann F.
Tuck, Alan B.
Although lymphatic dissemination is a major route for breast cancer metastasis, there has been little work to determine what factors control the ability of tumor cells to survive, establish and show progressive growth in a lymph node environment. This information is of particular relevance now, in the era of sentinel lymph node biopsy, where smaller intranodal tumor deposits are being detected earlier in the course of disease, the clinical relevance of which is uncertain. In this study, we compared differentially expressed genes in cell lines of high (468LN) vs. low (468GFP) lymphatic metastatic ability, and related these to clinical literature on genes associated with lymphatic metastatic ability and prognosis, to identify genes of potential clinical relevance. This approach revealed differential expression of a set of genes associated with 'cancer stem cell-like' properties, as well as networks of genes potentially associated with survival and autonomous growth. We explored these differences functionally and found that 468LN cells have a higher proportion of cells with a cancer stem cell-like (CD44+/CD24-) phenotype, have a higher clonogenic potential and a greater ability to survive, establish and grow in a foreign (lymph node and 3D Matrigel) microenvironment, relative to 468GFP cells. Differentially expressed genes which reflect these functions provide candidates for investigation as potential targets for therapy directed against early lymphatic metastasis.
2009-08-01T07:00:00Z
article
https://ir.lib.uwo.ca/oncpub/67
http://www.spandidos-publications.com/ijo/35/2/297
Oncology Publications
Scholarship@Western
Animals
Antigens
CD24
Antigens
CD44
Breast Neoplasms
Cell Proliferation
Cell Survival
Female
Flow Cytometry
Gene Expression Profiling
Humans
Lymphatic Metastasis
Mice
Neoplastic Stem Cells
Antigens, CD24
Antigens, CD44
Medical Anatomy
Medical Biochemistry
Medical Biophysics
Medical Pathology
Oncology
oai:ir.lib.uwo.ca:vascularpub-1032
2010-01-03T02:33:33Z
publication:vascularpub
publication:mnipub
publication:biophysicspub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:biophysics
publication:biochempub
publication:mni
publication:robarts
publication:biochem
publication:institutes
SIRT1 Markedly Extends Replicative Lifespan if the NAD+ Salvage Pathway Is Enhanced
Ho, Cynthia
van der Veer, Eric
Akawi, Oula
Pickering, J. Geoffrey
Sir2 mediates lifespan extension in lower eukaryotes but whether its mammalian homolog, sirtuin 1, silent mating type information regulation 2 homolog (SIRT1), is a longevity protein is controversial. We stably introduced the SIRT1 gene into human vascular smooth muscle cells (SMCs) and observed minimal extension of replicative lifespan. However, SIRT1 activity was found to be exquisitely dependent on nicotinamide phosphoribosyltransferase (Nampt) activity. Moreover, overexpression of Nampt converted SIRT1-overexpressing SMCs to senescence-resistant cells together with heightened SIRT1 activity, suppressed p21, and strikingly lengthened replicative lifespan. Thus, SIRT1 can markedly postpone SMC senescence, but this requires overcoming an otherwise vulnerable nicotinamide adenine dinucleotide salvage reaction in aging SMCs.
2009-09-17T07:00:00Z
article
https://ir.lib.uwo.ca/vascularpub/33
info:doi/10.1016/j.febslet.2009.08.031
http://dx.doi.org/10.1016/j.febslet.2009.08.031
Robarts Vascular Research Publications
Scholarship@Western
Cell Aging
Cells
Cultured
Cytokines
Humans
Muscle
Smooth
Vascular
Myocytes
Smooth Muscle
NAD
Nicotinamide Phosphoribosyltransferase
Sirtuin 1
Sirtuins
Transfection
rho GTP-Binding Proteins
Cells, Cultured
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Cardiology
Medical Biochemistry
Medical Biophysics
Medical Microbiology
oai:ir.lib.uwo.ca:robartspub-1005
2010-01-04T00:23:35Z
publication:robartspub
publication:biophysicspub
publication:pmid
publication:faculties
publication:biophysics
publication:biochempub
publication:chempub
publication:robarts
publication:biochem
publication:institutes
publication:chem
Optimized MRI Contrast for On-resonance Proton Exchange Processes of PARACEST Agents in Biological Systems
Li, Alex X.
Suchy, Mojmir
Jones, Craig K.
Hudson, Robert H. E.
Menon, Ravi S.
Bartha, Robert
Image contrast associated with paramagnetic chemical exchange saturation transfer agents can be generated by off-resonance irradiation of agent-bound water or amide protons or on-resonance irradiation of bulk water. Previously, a four-pool model was developed to describe an in vivo system. The model incorporated the magnetization transfer effect from macromolecules when using off-resonance irradiation. In the current study, this four-pool model is modified to describe the in vivo system when using on-resonance irradiation. The influences of pulse power, pulse duration, the chemical shift of bound water, the proton exchange rate between bulk water and bound water, and agent concentration on the on-resonance paramagnetic agent chemical exchange effects were simulated using a WALTZ-16 pulse train in the absence and presence of the macromolecule pool. The results demonstrated that while contrast increases with pulse duration in aqueous solution, there is an optimal pulse duration that maximizes on-resonance paramagnetic agent chemical exchange effects contrast in vivo. This predication was verified by experimental spectroscopic and imaging results from aqueous solution, bovine serum albumin phantoms, and a tissue phantom containing thulium-DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetamide)-glycine-lysine. This model can be used to optimize sequence parameters to maximize in vivo on-resonance paramagnetic agent chemical exchange effects contrast.
2009-11-01T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/6
info:doi/10.1002/mrm.22134
http://www3.interscience.wiley.com/journal/122608400/abstract
Robarts Imaging Publications
Scholarship@Western
PARACEST contrast agent
chemical exchange
CEST
magnetization transfer
OPARACHEE
macromolecules
Bioimaging and Biomedical Optics
Medical Biochemistry
Medical Biophysics
oai:ir.lib.uwo.ca:paedpub-1013
2010-01-03T22:40:30Z
publication:biophysicspub
publication:paed
publication:pmid
publication:medimaging
publication:faculties
publication:biophysics
publication:biochempub
publication:medimagingpub
publication:biochem
publication:paedpub
Females Follow a More “Compact” Early Human Brain Development Model Than Males. A Case-Control Study of Preterm Neonates
Vasileiadis, George T T.
Thompson, R. Terry
Han, Victor K. M.
Gelman, Neil
The pattern of sexual differentiation of the human brain is not well understood, particularly at the early stages of development when intense growth and multiple maturational phenomena overlap and interrelate. A case-control study of 20 preterm males and females matched for age was conducted. Three-dimensional images were acquired with 3 T MRI. The cerebral volume and the cortical folding area (FA), defined as the surface area of the interface between cortical gray and white matter, were compared between males and females. Females had smaller cerebra than males even after removing the influence of overall size differences between the subjects. The cortical FA increased in relation to volume by a power of 4/3 in both groups. Females had larger cortical FA compared with males with similar cerebral volumes. The study provides in vivo evidence of sexually dimorphic early human brain development. The relatively more "compact" female model may well relate to sex differences in neural circuitry and cognitive domains.
2009-11-01T07:00:00Z
article
https://ir.lib.uwo.ca/paedpub/13
info:doi/10.1203/PDR.0b013e3181ba1ae7
http://journals.lww.com/pedresearch/Abstract/2009/11000/Females_Follow_a_More__Compact__Early_Human_Brain.12.aspx
Paediatrics Publications
Scholarship@Western
sexual differentiation
human brain
cerebral tissue volume
Bioimaging and Biomedical Optics
Medical Biochemistry
Medical Biophysics
Pediatrics
oai:ir.lib.uwo.ca:physpharmpub-1030
2010-01-10T02:43:38Z
publication:vascularpub
publication:biophysicspub
publication:physpharmpub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:physpharm
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:institutes
Polyploidy Impairs Human Aortic Endothelial Cell Function and Is Prevented by Nicotinamide Phosphoribosyltransferase
Borradaile, Nica M.
Pickering, J. Geoffrey
Polyploid endothelial cells are found in aged and atherosclerotic arteries. However, whether increased chromosome content has an impact on endothelial cell function is unknown. We show here that human aortic endothelial cells become tetraploid as they approach replicative senescence. Furthermore, accumulation of tetraploid endothelial cells was accelerated during growth in high glucose. Interestingly, induction of polyploidy was completely prevented by modest overexpression of the NAD+ regenerating enzyme, nicotinamide phosphoribosyltransferase (Nampt). To determine the impact of polyploidy on endothelial cell function, independent of replicative senescence, we induced tetraploidy using the spindle poison, nocodazole. Global gene expression analyses of tetraploid endothelial cells revealed a dysfunctional phenotype characterized by a cell cycle arrest profile (decreased CCNE2/A2, RBL1, BUB1B; increased CDKN1A) and increased expression of genes involved in inflammation (IL32, TNFRSF21/10C, PTGS1) and extracellular matrix remodeling (COL5A1, FN1, MMP10/14). The protection from polyploidy conferred by Nampt was not associated with enhanced poly(ADP-ribose) polymerase-1 or sirtuin (SIRT) 2 activity, but with increased SIRT1 activity, which reduced cellular reactive oxygen species and the associated oxidative stress stimulus for the induction of polyploidy. We conclude that human aortic endothelial cells are prone to chromosome duplication that, in and of itself, can induce characteristics of endothelial dysfunction. Moreover, the emergence of polyploid endothelial cells during replicative aging and glucose overload can be prevented by optimizing the Nampt-SIRT1 axis.
2010-01-01T08:00:00Z
article
https://ir.lib.uwo.ca/physpharmpub/31
info:doi/10.1152/ajpcell.00357.2009
http://ajpcell.physiology.org/cgi/content/abstract/298/1/C66
Physiology and Pharmacology Publications
Scholarship@Western
Polyploid endothelial cell
artery
Medical Biochemistry
Medical Biophysics
Medical Physiology
oai:ir.lib.uwo.ca:oncpub-1070
2010-04-20T22:24:52Z
publication:biophysicspub
publication:oncpub
publication:pmid
publication:faculties
publication:biophysics
publication:onc
A Review of Autoimmune Diseases Associated with Cancer
Tai, Patricia
Yu, Edward
Joseph, Kurian
Miale, Thomas
The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.
2010-01-01T08:00:00Z
article
application/pdf
https://ir.lib.uwo.ca/oncpub/70
info:doi/10.2741/73
https://ir.lib.uwo.ca/context/oncpub/article/1070/viewcontent/Autoimmune__malig_Tai_2008.pdf
Oncology Publications
Scholarship@Western
autoantibody
autoimmunity
AIDS
cytokine
cancer
Bioimaging and Biomedical Optics
Oncology
Radiology
oai:ir.lib.uwo.ca:robartspub-1006
2010-05-09T07:52:57Z
publication:robartspub
publication:biophysicspub
publication:pmid
publication:faculties
publication:biophysics
publication:biochempub
publication:chempub
publication:robarts
publication:biochem
publication:institutes
publication:chem
In Vivo Detection of PARACEST Agents with Relaxation Correction
Jones, Craig K.
Li, Alex X.
Suchý, Mojmír
Hudson, Robert H. E.
Menon, Ravi S.
Bartha, Robert
Several pulse sequences have been used to detect paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents in animals to quantify the uptake over time following a bolus injection. The observed signal change is a combination of relaxation effects and PARACEST contrast. The purpose of the current study was to isolate the PARACEST effect from the changes in bulk water relaxation induced by the PARACEST agent in vivo for the fast low-angle shot pulse sequence. A fast low-angle shot-based pulse sequence was used to acquire continuous images on a 9.4-T MRI of phantoms and the kidneys of mice following PARACEST agent (Tm(3+)-DOTAM-Gly-Lys) injection. A WALTZ-16 pulse was applied before every second image to generate on-resonance paramagnetic chemical exchange effects. Signal intensity changes of up to 50% were observed in the mouse kidney in the control images (without a WALTZ-16 preparation pulse) due to altered bulk water relaxation induced by the PARACEST agent. Despite these changes, a clear on-resonance paramagnetic chemical exchange effect of 4-7% was also observed. A four-pool exchange model was used to describe image signal intensity. This study demonstrates that in vivo on-resonance paramagnetic chemical exchange effect contrast can be isolated from tissue relaxation time constant changes induced by a PARACEST agent that dominate the signal change.
2010-05-01T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/7
info:doi/10.1002/mrm.22340
http://dx.doi.org/10.1002/mrm.22340
Robarts Imaging Publications
Scholarship@Western
PARACEST
in-vivo
kidney
OPARACHEE
contrast agent
MRI
chemical exchange
relaxation
mouse
Bioimaging and Biomedical Optics
Chemistry
Medical Biochemistry
Medical Biophysics
oai:ir.lib.uwo.ca:chempub-1020
2010-06-21T01:08:21Z
publication:robartspub
publication:biophysicspub
publication:physpharmpub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:mbrainpub
publication:chempub
publication:robarts
publication:biochem
publication:institutes
publication:chem
A Paramagnetic Chemical Exchange-based MRI Probe Metabolized by Cathepsin D: Design, Synthesis and Cellular Uptake Studies
Suchý, Mojmír
Ta, Robert
Li, Alex X.
Wojciechowski, Filip
Pasternak, Stephen H.
Bartha, Robert
Hudson, Robert H. E.
Overexpression of the aspartyl protease cathepsin D is associated with certain cancers and Alzheimer's disease; thus, it is a potentially useful imaging biomarker for disease. A dual fluorescence/MRI probe for the potential detection of localized cathepsin D activity has been synthesized. The probe design includes both MRI and optical reporter groups connected to a cell penetrating peptide by a cathepsin D cleavable sequence. This design results in the selective intracellular deposition (determined fluorimetrically) of the MRI and optical reporter groups in the presence of overexpressed cathepsin D. The probe also provided clearly detectable in vitro MRI contrast by the mechanism of paramagnetic chemical exchange effects (OPARACHEE).
2010-06-07T07:00:00Z
article
https://ir.lib.uwo.ca/chempub/21
info:doi/10.1039/b926639a
http://dx.doi.org/10.1039/b926639a
Chemistry Publications
Scholarship@Western
Cathepsin D
MRI
Biochemistry, Biophysics, and Structural Biology
Chemistry
Medical Biophysics
Medical Pharmacology
Medical Physiology
oai:ir.lib.uwo.ca:robartspub-1008
2010-11-22T01:10:38Z
publication:kin
publication:robartspub
publication:rwkex_researcharticles
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:medimaging
publication:faculties
publication:rwkex
publication:kinpub
publication:biophysics
publication:biochempub
publication:medimagingpub
publication:robarts
publication:biochem
publication:surgery
publication:institutes
publication:onc
Rapid in Vivo Whole Body Composition of Rats Using Cone Beam µCT
Granton, Patrick V.
Norley, Chris J. D.
Umoh, Joseph
Turley, Eva A.
Frier, Bruce C.
Noble, Earl G.
Holdsworth, David W.
Precise, noninvasive analysis and quantification of in vivo body composition is essential for research involving longitudinal, small-animal disease models. We investigated the feasibility and precision of a rapid, flat-panel μCT scanner to report whole body adipose tissue volume (ATV), lean tissue volume (LTV), skeletal tissue volume (STV), and bone mineral content (BMC) in 25 postmortem female and 52 live male Sprague-Dawley rats. μCT images, acquired in three 90-mm segments and reconstructed with 308 μm of isotropic voxel spacing, formed contiguous image volumes of each entire rat specimen. Three signal-intensity thresholds (determined to be -186, 5, and 155 HU) were used to classify each voxel as adipose, lean, or skeletal tissue, respectively. Tissue masses from the volume fractions of ATV, LTV, and STV were calculated from assumed tissue densities of 0.95, 1.05, and 1.92 g/cm(-3), respectively. A CT-derived total mass was calculated for each rat and compared with the gravimetrically measured mass, which differed on average for the postmortem female and the live male group by 2.5 and 1.1%, respectively. To evaluate the accuracy of the CT-derived body composition technique, following the live male study excised muscle tissue in the lower right leg of all rats in group B were compared with the image-derived LT measurement of the same regional compartment and found to differ on average by 2.2%. Through repeated CT measurements of postmortem specimens, the whole body ATV, LTV, STV, and BMC measurement analysis gave a precision value of ±0.6, 1.9, 1.7, and 0.5% of the average value, respectively.
2010-10-01T07:00:00Z
article
https://ir.lib.uwo.ca/robartspub/9
info:doi/10.1152/japplphysiol.00016.2010
http://dx.doi.org/10.1152/japplphysiol.00016.2010
Robarts Imaging Publications
Scholarship@Western
Microcomputed tomography
Body composition
Bone mineral content
Rodents
Bioimaging and Biomedical Optics
Medical Biochemistry
Medical Biophysics
Oncology
Surgery
847958/oai_dc/100//