Cynthia Ménard

The Princess Margaret Hospital, Toronto, Ontario, Canada

Are you Cynthia Ménard?

Claim your profile

Publications (174)573.2 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Journal of Neuro-Oncology 05/2015; DOI:10.1007/s11060-015-1815-0 · 2.79 Impact Factor
  • Seminars in radiation oncology 05/2015; DOI:10.1016/j.semradonc.2015.05.002 · 3.77 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    04/2015; DOI:10.1016/j.prro.2015.02.015
  • Journal of Medical Imaging and Radiation Sciences 03/2015; 46(1):S14. DOI:10.1016/j.jmir.2015.01.087
  • Caroline Chung, Ur Metser, Cynthia Ménard
    [Show abstract] [Hide abstract]
    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.
    Seminars in Radiation Onchology 02/2015; DOI:10.1016/j.semradonc.2015.02.002 · 3.77 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Physics in Medicine and Biology 12/2014; 60(1):195-209. DOI:10.1088/0031-9155/60/1/195 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    International journal of radiation oncology, biology, physics 11/2014; 91(1). DOI:10.1016/j.ijrobp.2014.09.028 · 4.18 Impact Factor
  • [Show abstract] [Hide abstract]
    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. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 09/2014; 274(1):122681. DOI:10.1148/radiol.14122681 · 6.21 Impact Factor
  • Cynthia Ménard, Uulke van der Heide
    Seminars in radiation oncology 07/2014; 24(3):192. DOI:10.1016/j.semradonc.2014.02.010 · 3.77 Impact Factor
  • Cynthia Ménard, Uulke A van der Heide
    Seminars in radiation oncology 07/2014; 24(3):149-50. DOI:10.1016/j.semradonc.2014.02.001 · 3.77 Impact Factor
  • Journal of Medical Imaging and Radiation Sciences 06/2014; 45(2):163. DOI:10.1016/j.jmir.2014.03.012
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 05/2014; 41(3):357-62. DOI:10.1017/S0317167100017303 · 1.60 Impact Factor
  • Brachytherapy 03/2014; 13:S56-S57. DOI:10.1016/j.brachy.2014.02.294 · 1.99 Impact Factor
  • Brachytherapy 03/2014; 13:S38-S39. DOI:10.1016/j.brachy.2014.02.260 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.
    International journal of radiation oncology, biology, physics 01/2014; 88(1):137-142. DOI:10.1016/j.ijrobp.2013.10.003 · 4.18 Impact Factor
  • Radiotherapy and Oncology 01/2014; 111:S169. DOI:10.1016/S0167-8140(15)30529-6 · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose/Objective(s) Geometric accuracy is fundamental for incorporation of functional imaging into radiation therapy, yet these factors are underemphasized in clinically standard diffusion-weighted imaging (DWI) using single-shot echo-planar imaging (EPI). The alternative use of readout-segmented EPI DWI has been shown to reduce distortion by significantly shortening the echo-spacing compared to single-shot EPI. An additional 2D navigator pulse corrects for motion effects between segments. This project investigates readout-segmented-EPI DWI during endorectal coil MRI for treatment planning of patients with prostate cancer enrolled on an ongoing prospective clinical trial of tumor dose escalation. Materials/Methods All studies used a 3 Tesla MRI system combined with a phased-array endo-rectal receiver coil (ERC). DWI was acquired with 1.4 x 1.4 x 3-mm voxels and 4 b-values of 0, 250, 800, and 1000 s/mm2. In vitro: A prostate geometric accuracy phantom was constructed as a set of 3 concentric water-filled cylinders of 1.5, 3, and 6 cm radii consistent with the ERC diameter, anterior border of the peripheral zone, and anterior border of the prostate respectively. Segmented EPI and standard DWI were acquired, meshes for cylinder boundaries were generated, and cylinder boundaries were tracked to quantify distortion (MIPAV). In vivo: In vivo geometric performance improvement was validated in patients with prostate cancer (n = 7), by visualization of distortion relative to T2-weighted (T2w) anatomic images. Results In vitro: Compared to standard DWI, segmented-EPI DWI reduced the mean RMS displacement of inner and middle cylinders 3-fold (to 0.5 mm) and reduced the maximum distortion from 13 to 3 mm. In vivo: In all patients, segmented-EPI DWI provided good image quality with visible tumor. Standard DWI was not performed in the 7th patient. All 6 patients with standard and segmented DWI presented with visible distortion of the posterior prostate boundary abutting the endorectal coil relative to T2w on standard, but not on segmented DWI. In 2 of 4 patients with posterior tumors abutting the prostate boundary, tumors were erroneously displaced outside of the prostate boundary in standard DWI, which was corrected using segmented DWI. Conclusions Readout-segmented DWI improves the geometric performance of clinical endorectal coil prostate DWI at 3T, and should reduce uncertainties in tumor delineation for dose escalation.
    International journal of radiation oncology, biology, physics 10/2013; 87(2):S173-S174. DOI:10.1016/j.ijrobp.2013.06.448 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose/Objective(s) MR imaging provides exquisite visualization of soft tissue anatomy as well as physiological assessment of normal and diseased tissues. Streamlined integration of MR into the RT treatment room without the deleterious effects of electron–B-field interaction requires coordinated operation of the linear accelerator, MR scanner, patient support, and shielding subsystems. The design, construction, and initial performance of a dedicated MR-guided treatment facility providing 1.5T MR imaging, non-coplanar external beam delivery, and HDR brachytherapy capabilities will be described. Materials/Methods A dedicated MR-guidance suite (320 m2) satisfying ACR MR safety specifications has been designed to allow a movable 1.5T MR imager to be employed in three different environments: (i) MR-simulation, (ii) MR-guided HDR brachytherapy (10 Ci, Ir-192), and (iii) MR-guided external beam radiation delivery. MR-simulation includes the provision of a dedicate oncology coil system to enable large field-of-view imaging in the head, neck, and pelvis. The MR-guided HDR suite is shielded to satisfy CNSC radiation shielding requirements, as well as, RF isolation for intra-operative MR imaging during applicator/catheter placement. MR-guided external beam RT is achieved on the same platform through the use of a dedicated non-coplanar treatment machine (Dose Rate: 1400 MU/min), a modified treatment couch, and dedicated shielding systems that move in unison to enable RT delivery within 120s of MR imaging. Dedicated/removable MR imaging surface coils, calibration and data handling sub-systems, and patient support systems have been developed to facilitate the MR-guided external beam treatments. Results The design of the integrated RF and radiation shielding facility with motorized RF-radiation doors has been completed with on-going installation and validation of performance. In-factory testing of the 1.5T MR and modified table have demonstrated compatibility to enable motorized displacement of the patient from accelerator isocenter to MR-imaging position. Mapping of the B field strength proximal to the linear accelerator suggests minimal interference (< 20 G). Repeat imaging studies between magnet displacements (and over time) demonstrate isocenter reproducibility for MR-guidance to be within 0.5 mm (3D MP-RAGE; 1mm isotropic; 4m25s). Image quality tests demonstrate diagnostic SNR performance for the RT-specific, large FOV head and neck and removable pelvis coil systems. Conclusions The development of a novel platform for MR-guided brachytherapy and external beam treatments using state-of-the-art delivery sub-systems is nearing completion. On-going testing during final construction demonstrates the potential for diagnostic MR image quality, efficient integration with current treatment technologies, and geometrically accurate MR-based guidance of RT.
    International journal of radiation oncology, biology, physics 10/2013; 87(2):S13. DOI:10.1016/j.ijrobp.2013.06.039 · 4.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Temozolomide (TMZ) during and after radiotherapy (RT) is recommended for patients with newly diagnosed glioblastoma (GBM). We analyzed the adoption of this new standard of care for GBM in an academic cancer centre in Canada and assessed its impact on survival. GBM patients registered with Cancer Care Ontario between 2004 and 2008 were identified. Those ≥16 years age, newly diagnosed, treated at our institution, had confirmed pathology and complete records were included. Demographics, treatments, toxicity and outcome were captured. For survival analysis patients were stratified by age, ECOG, and treatment modalities including total cycles of TMZ. Descriptive statistics were used for early progressors and long term survivors. Kaplan-Meier curves, log-rank test and Cox proportional hazards model were used for survival analyses. At a median follow-up of 28 months, we compared our outcome to updated EORTC-NCIC CE 3 results. Of 517 patients 433 were included for analysis. Majority were male (63 %), ECOG 0-1 (66 %), and ≤65 years (55 %). 44 % received CRT followed by TMZ, 13 % had CRT only, 30 % had RT only and 13 % had best supportive care. 10 % were early progressors and 9 % survived beyond 2 years. Comparison of our results to NCIC CTG CE.3 study data showed median survival was 15.8 versus 14.6 months, 2 year survival rate for CRT plus TMZ was 35 versus 26 %, and for RT alone 0 versus 10 %, respectively. <50 % of GBM patients complete CRT with TMZ in the real-world setting. Prognosis for most patients with GBM remains dismal particularly if they are not suitable for RT and CRT.
    Journal of Neuro-Oncology 08/2013; 115(2). DOI:10.1007/s11060-013-1230-3 · 2.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dominant cancer foci within the prostate are associated with sites of local recurrence post radiotherapy. In this systematic review we sought to address the question: "what is the clinical evidence to support differential boosting to an imaging defined GTV volume within the prostate when delivered by external beam or brachytherapy". A systematic review was conducted to identify clinical series reporting the use of radiation boosts to imaging defined GTVs. Thirteen papers describing 11 unique patient series and 833 patients in total were identified. Methods and details of GTV definition and treatment varied substantially between series. GTV boosts were on average 8Gy (range 3-35Gy) for external beam, or 150% for brachytherapy (range 130-155%) and GTV volumes were small (<10ml). Reported toxicity rates were low and may reflect the modest boost doses, small volumes and conservative DVH constraints employed in most studies. Variability in patient populations, study methodologies and outcomes reporting precluded conclusions regarding efficacy. Despite a large cohort of patients treated differential boosts to imaging defined intra-prostatic targets, conclusions regarding optimal techniques and/or efficacy of this approach are elusive, and this approach cannot be considered standard of care. There is a need to build consensus and evidence. Ongoing prospective randomized trials are underway and will help to better define the role of differential prostate boosts based on imaging defined GTVs.
    Radiotherapy and Oncology 06/2013; 107(3). DOI:10.1016/j.radonc.2013.04.027 · 4.86 Impact Factor

Publication Stats

2k Citations
573.20 Total Impact Points

Institutions

  • 2007–2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
    • McMaster University
      Hamilton, Ontario, Canada
  • 2005–2014
    • University of Toronto
      • • Department of Radiation Oncology
      • • Department of Medical Imaging
      Toronto, Ontario, Canada
  • 2008–2013
    • University Health Network
      • Radiation Medicine Program
      Toronto, Ontario, Canada
  • 2003–2006
    • National Cancer Institute (USA)
      • Radiation Oncology Branch
      Maryland, United States
  • 2002–2005
    • 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
    • Johns Hopkins University
      • Department of Biomedical Engineering
      Baltimore, Maryland, United States
    • Harvard University
      Cambridge, Massachusetts, United States