Cynthia Ménard

University of Toronto, Toronto, Ontario, Canada

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Publications (191)643.04 Total impact

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    ABSTRACT: Purpose: Validation of MRI-guided tumor boundary delineation for targeted prostate cancer therapy is achieved via correlation with gold-standard histopathology of radical prostatectomy specimens. Challenges to accurate correlation include matching the pathology sectioning plane with the in vivoimaging slice plane and correction for the deformation that occurs between in vivoimaging and histology. A methodology is presented for matching of the histological sectioning angle and position to the in vivoimaging slices.
    No preview · Article · Mar 2016 · Medical Physics
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    ABSTRACT: Purpose: We report clinical observations of a technique using an MRI-only workflow for catheter insertion and treatment planning in patients receiving standard-care high-dose-rate brachytherapy before external beam radiotherapy for prostate cancer. Methods and materials: Forty patients with intermediate or high-risk prostate cancer were enrolled on a prospective clinical trial approved by our institution's research ethics board. Multiparametric MRI with stereotactic navigation was used to guide insertion of brachytherapy catheters, followed by MRI-based treatment planning. Results: Sixty-two implants were performed. Median catheter insertion + imaging time was 100 minutes, and overall anesthesia time was 4.0 hours (range, 2.1-6.9 hours). MRI at the time of brachytherapy restaged 14 patients (35%) who were found to have a higher stage of disease. In 6 patients, this translated in directed insertion of brachytherapy catheters outside the prostate boundary (extracapsular disease [n = 2] or seminal vesicle invasion [n = 4]). Most patients (80%) had gross tumor visible on MRI, which influenced catheter insertion and treatment planning. MRI depicted postimplant anatomic boundaries clearly, with the exception of the apical prostate which was blurred by trauma after catheter insertion. Conventional dose-planning objectives for the rectum (V75 < 1.0 cc) were difficult to achieve, but toxicities were low (acute grade ≥ 2 genitourinary = 20%, late grade ≥ 2 genitourinary = 15%, and late grade ≥ 2 gastrointestinal = 7%). Urethral trauma visualized on MRI led to two transient Grade 3 events. Conclusions: Despite a standard-care approach, MRI acquired throughout the procedure altered catheter insertion and dose-planning strategies. An MRI-only workflow is feasible but must be streamlined for broader acceptance.
    No preview · Article · Jan 2016 · Brachytherapy

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    Full-text · Article · Nov 2015 · Neuro-Oncology

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Diffusion-weighted imaging using echo-planar imaging (EPI) is prone to geometric inaccuracy, which may limit application to image-guided radiation therapy planning, as well as for voxel-based quantitative multi-parametric or multi-modal approaches. This research investigates pelvic applications at 3T of a standard single-shot (ssEPI) and a prototype readout-segmented (rsEPI) technique. Apparent diffusion coefficient (ADC) accuracy and geometric performance of rsEPI and ssEPI were compared using phantoms, and in vivo, involving 8 patients prior to MR-guided brachytherapy for locally advanced cervical cancer, and 19 patients with prostate cancer planned for tumor-targeted radiotherapy. Global and local deviations in geometric performance were tested using Dice Similarity Coefficients (DC) and Hausdorff Distances (HD). In cervix patients, DC increased from 0.76±0.14 to 0.91±0.05 for the high risk clinical target volume, and 0.62±0.26 to 0.85±0.08 for the gross tumor target volume. Tumors in the peripheral zone of the prostate gland were partly projected erroneously outside of the posterior anatomic boundary of the gland by 3.1±1.6mm in 11 of 19 patients using ADC-ssEPI but not with ADC-rsEPI. Both cervix and prostate ssEPI are prone to clinically relevant geometric distortions at 3T. rsEPI provides improved geometric performance without post-processing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Radiotherapy and Oncology
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    ABSTRACT: Evidence suggests hyperglycemia is associated with worse outcomes in glioblastoma (GB). This study aims to confirm the association between glycemia during radiotherapy (RT) and temozolomide (TMZ) treatment and overall survival (OS) in patients with newly diagnosed GB. This retrospective study included GB patients treated with RT and TMZ from 2004 to 2011, randomly divided into independent derivation and validation datasets. Time-weighted mean (TWM) glucose and dexamethasone dose were collected from start of RT to 4 weeks after RT. Univariate (UVA) and multivariable (MVA) analyses investigated the association of TWM glucose and other prognostic factors with overall survival (OS). In total, 393 patients with median follow-up of 14 months were analyzed. In the derivation set (n = 196) the median OS was 15 months and median TWM glucose was 6.3 mmol/L. For patients with a TWM glucose ≤6.3 and >6.3 mmol/L, median OS was 16 and 13 months, respectively (p = 0.03). On UVA, TWM glucose, TWM dexamethasone, age, extent of surgery, and performance status were associated with OS. On MVA, TWM glucose remained an independent predictor of OS (p = 0.03) along with TWM dexamethasone, age, and surgery. The validation set (n = 197), with similar baseline characteristics, confirmed that TWM glucose ≤6.3 mmol/L was independently associated with longer OS (p = 0.005). This study demonstrates and validates that glycemia is an independent predictor for survival in GB patients treated with RT and TMZ.
    Full-text · Article · May 2015 · Journal of Neuro-Oncology
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    ABSTRACT: Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose-positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. These are reviewed with an effort to highlight challenges related to quantification and reproducibility. In addition, several of the emerging applications of these imaging approaches are also highlighted. Finally, the growing community of support for establishing quantitative imaging approaches as we move toward clinical evaluation is summarized and the need for a clinical service in support of the clinical science and delivery of care is proposed.
    No preview · Article · May 2015 · Seminars in radiation oncology
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    ABSTRACT: The purpose of this study was to characterize treatment-related toxicities, health-related quality of life (HRQOL), and biochemical outcomes in patients treated with postoperative image guided intensity modulated radiation therapy (IMRT) for prostate cancer using a consensus guideline for defining the clinical target volume. Between August 2007 and October 2008, patients considered for radiation therapy (RT) after prostatectomy were enrolled. The clinical target volume (prostate bed) was delineated according to published consensus guidelines, and patients were prescribed a dose of 66 Gy in 33 fractions. Radiation treatment planning prioritized rectal dose constraints over target volume coverage. Treatment was delivered by use of IMRT and daily cone beam computed tomographic guidance. Toxicity (graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events) and HRQOL assessments according to the Expanded Prostate Cancer Index Composite (EPIC) questionnaire were collected prospectively at baseline, at week 5 (during RT), at 3 months, and at yearly follow-up visits. Cumulative toxicity and biochemical relapse-free rates were calculated by the Kaplan-Meier method. Paired Student t tests with multiple testing correction were used to assess changes in HRQOL. A total of 68 men were evaluated, with median follow-up of 5.9 years. Fifty-three patients (77.9%) and 15 patients (22.1%) were treated with salvage and adjuvant RT, respectively. Primary planning objectives were met in most cases (97.1%), but planning target volume coverage was compromised in 40% of cases because of large planning target volumes (mean 347.6 cm(3)). There were no grade 3 or 4 acute toxicities. Cumulative 5-year incidence of late gastrointestinal and genitourinary grade 2 toxicities was 12.3% (95% confidence interval [CI], 11.1%-13.5%) and 10.6% (95% CI, 9.5%-11.6%), respectively. No grade 3 or 4 late toxicities were observed. Transient declines in EPIC gastrointestinal domain summary score (mean 87.66 at 3 months vs 92.76 at baseline; P = .006) and genitourinary irritative subscale (week 5 mean score 83.37 vs 89.45 at baseline; P = .007) were observed. Complete recovery occurred between 3 and 12 months after therapy, remaining stable compared with baseline at 5-year follow-up. Sexual HRQOL remained stable at 5 years, with an improving trend in bother subscale. Biochemical relapse-free rate at 5 years was 72.7% (95% CI, 61.9%-83.5%). Guideline-based postprostatectomy image guided IMRT with rigid rectal dose constraints resulted in favorable toxicity profiles; long-term stability in gastrointestinal, genitourinary, and sexual HRQOL; and expected biochemical control rates. Concerns regarding toxicity and HRQOL should not preclude recommendation for RT after prostatectomy. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Apr 2015 · Practical Radiation Oncology

  • No preview · Article · Mar 2015 · Journal of Medical Imaging and Radiation Sciences
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    Caroline Chung · Ur Metser · Cynthia Ménard
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    ABSTRACT: In recent years the management of glioma has evolved significantly, reflecting our better understanding of the underlying mechanisms of tumor development, tumor progression and treatment response. Glioma grade, along with a number of underlying molecular and genetic biomarkers, have been recognized as important prognostic and predictive factors that can help guide the management of patients. This chapter highlights advances in magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), diffusion-tensor imaging (DTI), MR spectroscopy, dynamic contrast-enhanced imaging (DCE-MRI) and perfusion MRI as well as position emission tomography (PET) using various tracers including methyl-11C-L-methionine (11C- MET) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). Use of multiparametric imaging data has improved the diagnostic strength of imaging, introduced the potential to non-invasively interrogate underlying molecular features of low-grade glioma and to guide local therapies such as surgery and radiotherapy.
    Full-text · Article · Feb 2015 · Seminars in Radiation Onchology

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology
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    ABSTRACT: Biomechanical model based deformable image registration has been widely used to account for prostate deformation in various medical imaging procedures. Biomechanical material properties are important components of a biomechanical model. In this study, the effect of incorporating tumor-specific material properties in the prostate biomechanical model was investigated to provide insight into the potential impact of material heterogeneity on the prostate deformation calculations. First, a simple spherical prostate and tumor model was used to analytically describe the deformations and demonstrate the fundamental effect of changes in the tumor volume and stiffness in the modeled deformation. Next, using a clinical prostate model, a parametric approach was used to describe the variations in the heterogeneous prostate model by changing tumor volume, stiffness, and location, to show the differences in the modeled deformation between heterogeneous and homogeneous prostate models. Finally, five clinical prostatectomy examples were used in separately performed homogeneous and heterogeneous biomechanical model based registrations to describe the deformations between 3D reconstructed histopathology images and ex vivo magnetic resonance imaging, and examine the potential clinical impact of modeling biomechanical heterogeneity of the prostate. The analytical formulation showed that increasing the tumor volume and stiffness could significantly increase the impact of the heterogeneous prostate model in the calculated displacement differences compared to the homogeneous model. The parametric approach using a single prostate model indicated up to 4.8 mm of displacement difference at the tumor boundary compared to a homogeneous model. Such differences in the deformation of the prostate could be potentially clinically significant given the voxel size of the ex vivo MR images (0.3 × 0.3 × 0.3 mm). However, no significant changes in the registration accuracy were observed using heterogeneous models for the limited number of clinical prostatectomy patients modeled and evaluated in this study.
    No preview · Article · Dec 2014 · Physics in Medicine and Biology
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    ABSTRACT: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from a 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (Ktrans) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in Ktrans but with large uncertainty (111.6 ± 150.5) %. Parametric voxel-based analysis of 4D DCE CT data resulted in greater accuracy and reliability in measuring changes in perfusion CT-based kinetic metrics, which have the potential to be used as biomarkers in patients with metastatic brain cancer. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: BACKGROUND: Ipilumumab (Ipi), an antibody that enhances T-cell activation, has been shown to improve survival in patients with metastatic melanoma. Ipilumumab may have synergistic effects with radiotherapy but this may result in increased toxicity. This study investigated the incidence of acute radiation effect (ARE) in patients with melanoma brain metastases treated with Ipi and radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODOLOGY: This retrospective study included metastatic melanoma patients treated at our institution from 2008-2013 who received SRS or WBRT for brain metastases within 4 months of Ipi treatment. We evaluated the incidence, timing and factors associated with acute radiation effect (ARE). RESULTS: From 159 patients treated with Ipi, 22 patients also received brain RT within 4 months of treatment. Three patients were excluded for lack of follow-up brain imaging, thus 19 were analysed: 14 males and 5 females, with median age 58 years (range 24-82). Ten were treated with SRS, 7 with WBRT, and 2 with SRS plus WBRT. Median dose for SRS was 21 Gy (range: 15-24 Gy). Five of 13 patients treated with SRS (38%) experienced symptomatic edema requiring steroids within 1 month of starting Ipi, and within 4 months of RT. One patient had a haemorrhage and 1 required surgical resection, which demonstrated viable disease. Therefore 3 patients (23%) treated with SRS developed isolated ARE. These metastases had volumes less than 4.2 cm3 and were treated within 4 months of Ipi to a median dose of 19.5 Gy (range 15-21 Gy). No patients with WBRT alone developed ARE. CONCLUSIONS: Following SRS for brain mets and Ipi, ARE was seen in 23% of patients within 4 months of starting Ipi treatment. This is greater than the commonly reported 10% risk of ARE after SRS alone for brain metastasis. No increased toxicity was seen with WBRT and Ipi.
    Full-text · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: OBJECTIVES: Elevated baseline neutrophil-lymphocyte ratio (NLR) has been associated with worse outcome in various cancers, including glioblastoma (GBM). This retrospective study assesses if change in NLR during focal radiotherapy (RT) with Temozolomide (TMZ) for newly diagnosed GBM predicts outcome. METHODS: Patients treated with concurrent RT and TMZ for newly diagnosed GBM, between January 2004 and September 2010 were included. Age, ECOG performance status (ECOG-PS), dexamethasone dose, extent of surgery, tumor volume, neutrophil and lymphocyte counts (from baseline to 10 weeks) were collected. Statistical analysis included Kaplan Meier analysis and cox proportional hazard models with univariate (UVA) and multivariable (MVA) analyses. RESULTS: A total of 394 patients with median age of 54 (range 18-73) and median follow up 15.2 months (range 1.6-134.6) were analyzed. Median survival was 15.3 months (95% CI 14.3-16.9 months). Median baseline dexamethasone dose was 8mg (0-30mg) and median time-weighted mean dexamethasone dose (TWMdex) was 4.94mg (0.0 -27.4mg). On UVA, older age (HR 1.034, p<0.0001) and ECOG-PS>2 (HR 1.076, p < 0.001) were associated with shorter overall survival (OS). Baseline NLR below the median of 7.5 (HR 0.628, p < 0.0001) and decline in NLR (decNLR) (HR 0.644, p < 0.0001) were associated with better OS. On MVA, decNLR (HR 0.763, p = 0.02; CI 0.603 - 0.964), age (HR 1.032, p < 0.0001; CI 1.018-1.045), TWMdex (HR 1.039, p = 0.002; CI 1.014-1.065) and ECOG-PS (HR 0.593, p = 0.008; CI 0.403-0.873) remained prognostic for OS but not baseline NLR (HR 0.814, p = 0.09; CI 0.641 - 1.032). A low baseline NLR and further decrease in NLR predicted the longest survival (p < 0.0001). No significant linear correlation existed between tumor volume and baseline neutrophils (Rho =0.046, p = 0.42), lymphocytes (Rho = -0.015, p = 0.80) or NLR (Rho = 0.05, p = 0.40). CONCLUSIONS: Reduction in NLR during RT and TMZ for newly diagnosed GBM predicted for longer survival, even after accounting for steroid use.
    Full-text · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: Purpose: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. Materials and methods: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. Results: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). Conclusion: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.
    No preview · Article · Sep 2014 · Radiology

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics

Publication Stats

3k Citations
643.04 Total Impact Points

Institutions

  • 2005-2015
    • University of Toronto
      • • Department of Radiation Oncology
      • • Department of Medical Imaging
      • • Division of Neurosurgery
      • • Institute of Medical Sciences
      Toronto, Ontario, Canada
    • University of Alberta
      Edmonton, Alberta, Canada
  • 2007-2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
    • McMaster University
      Hamilton, Ontario, Canada
  • 2008-2013
    • University Health Network
      Toronto, Ontario, Canada
  • 2003-2006
    • National Cancer Institute (USA)
      • Radiation Oncology Branch
      Maryland, United States
  • 2003-2005
    • National Institutes of Health
      • Branch of Radiation Oncology
      베서스다, Maryland, United States
  • 2004
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
    • Harvard University
      Cambridge, Massachusetts, United States
    • NCI-Frederick
      Фредерик, Maryland, United States