Cynthia Ménard

The Princess Margaret Hospital, Toronto, Ontario, Canada

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Publications (159)460.69 Total impact

  • [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. · 2.92 Impact Factor
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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.
    International journal of radiation oncology, biology, physics 11/2014; · 4.59 Impact Factor
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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. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 09/2014; · 6.21 Impact Factor
  • Cynthia Ménard, Uulke van der Heide
    Seminars in radiation oncology 07/2014; 24(3):192. · 3.77 Impact Factor
  • Cynthia Ménard, Uulke A van der Heide
    Seminars in radiation oncology 07/2014; 24(3):149-50. · 3.77 Impact Factor
  • Journal of Medical Imaging and Radiation Sciences 06/2014; 45(2):163.
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 05/2014; 41(3):357-62. · 1.60 Impact Factor
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    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. · 4.59 Impact Factor
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    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. · 4.59 Impact Factor
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    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. · 4.59 Impact Factor
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    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; · 3.12 Impact Factor
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    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; · 4.86 Impact Factor
  • Practical radiation oncology. 04/2013; 3(2 Suppl 1):S17-8.
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    ABSTRACT: PURPOSE: To assess retrospectively the clinical accuracy of an magnetic resonance imaging-guided robotic prostate biopsy system that has been used in the US National Cancer Institute for over 6 years. METHODS: Series of 2D transverse volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)- and post (low-resolution)- needle insertions were used to evaluate biopsy accuracy. A three-stage registration algorithm consisting of an initial two-step rigid registration followed by a B-spline deformable alignment was developed to capture prostate motion during biopsy. The target displacement (distance between planned and actual biopsy target), needle placement error (distance from planned biopsy target to needle trajectory), and biopsy error (distance from actual biopsy target to needle trajectory) were calculated as accuracy assessment. RESULTS: A total of 90 biopsies from 24 patients were studied. The registrations were validated by checking prostate contour alignment using image overlay, and the results were accurate to within 2 mm. The mean target displacement, needle placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm, respectively. CONCLUSION: The biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.
    International Journal of Computer Assisted Radiology and Surgery 03/2013; · 1.36 Impact Factor
  • International journal of radiation oncology, biology, physics 02/2013; 85(2):291-2. · 4.59 Impact Factor
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    ABSTRACT: Purpose To characterize nonrespiratory stomach motion in the fasting state and postprandial. Methods and materials Ten healthy volunteers underwent 2-dimensional Fiesta cine magnetic resonance imaging studies in 30-second voluntary breath hold, in axial, coronal, and 2 oblique planes while fasting, and 5, 15, 30, 45, and 60 minutes postmeal. Each stomach contour was delineated and sampled with 200 points. Matching points were found for all contours in the same 30-second acquisition. Using deformable parametric analysis (Matlab, version 7.1), mean magnitude, and standard deviation of displacement of each point were determined for each patient. Maximal, minimal, and median population values in 6 cardinal, and in any direction, were calculated. Results The median of mean displacements for the baseline position of each point was small and rarely exceeded 1.1 mm; greatest value was 1.6 mm superior–inferior. Median displacement (pooled across time) in the right–left, superior–inferior, and anterior–posterior directions was 0.3 (range, − 0.7 to 1.3), 0.8 (− 0.4 to 2.4), and 0.3 (− 1.1 to 1.6) mm, respectively. Fasting and postprandial standard deviation did not differ. Conclusions Nonrespiratory stomach displacement is small and stomach position is stable after a small, standard meal. Radiation therapy may be delivered at any time within the first hour after eating without significant compromise of planned planning target volumes.
    Practical Radiation Oncology. 01/2013;
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    ABSTRACT: Renal cell carcinoma (RCC) and melanoma brain metastases have traditionally been considered radioresistant lesions when treated with conventional radiotherapeutic modalities. Radiosurgery provides high-dose radiation to a defined target volume with steep fall off in dose at lesion margins. Recent evidence suggests that stereotactic radiosurgery (SRS) is effective in improving local control and overall survival for a number of tumor subtypes including RCC and melanoma brain metastases. The purpose of this study was to compare the response rate to SRS between RCC and melanoma patients and to identify predictors of response to SRS for these 2 specific subtypes of brain metastases. We retrospectively reviewed a prospectively maintained database of all brain metastases treated with Gamma Knife SRS at the University Health Network (Toronto, Ontario) between October 2007 and June 2010, studying RCC and melanoma patients. Demographics, treatment history and dosimetry data were collected; and MRIs were reviewed for treatment response. Log rank, Cox proportional hazard ratio and Kaplan-Meier survival analysis using SPSS were performed. A total of 103 brain metastases patients (41 RCC; 62 melanoma) were included in the study. The median age, Karnofsky performance status score and Eastern Cooperative Oncology Group performance score was 52 years (range 27-81), 90 (range 70-100) and 1 (range 0-2), respectively. Thirty-four lesions received adjuvant chemotherapy and 56 received pre-SRS whole brain radiation therapy. The median follow-up, prescription dose, Radiation Therapy Oncology Group conformity index, target volume and number of shots was 6 months (range 1-41 months), 21 Gy (range 15-25 Gy), 1.93 (range 1.04-9.76), 0.4 cm3 (range 0.005-13.36 cm3) and 2 (range 1-22), respectively. Smaller tumor volume (P=0.007) and RCC pathology (P=0.04) were found to be positive predictors of response. Actuarial local control rate for RCC and melanoma combined was 89% at 6 months, 84% at 12 months, 76% at 18 months and 61% at 24 months. Local control at 12 months was 91 and 75% for RCC and melanoma, respectively. SRS is a valuable treatment option for local control of RCC and melanoma brain metastases. Smaller tumor volume and RCC pathology, predictors of response, suggest distinct differences in tumor biology and the extent of radioresponse between RCC and melanoma.
    Oncology Reports 11/2012; · 2.19 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate regional and temporal changes in apparent diffusion coefficient (ADC) and T(2) relaxation during radiation therapy (RT) in patients with low and intermediate risk localized prostate cancer. MATERIALS AND METHODS: Seventeen patients enrolled on a prospective clinical trial where MRI was acquired every 2 weeks throughout eight weeks of image-guided prostate IMRT (78 Gy/39 fractions). ADC and T(2) quantification used entire prostate, central gland, benign peripheral zone, and tumor-dense regions-of-interest, and mean values were evaluated for common response trends. RESULTS: Overall, the RT responses were greater than volunteer measurement repeatability, and week 6 appeared to be an optimum time-point for early detection. RT effects on the entire prostate were best detected using ADC (5-7% by week 2, P < 0.0125), effects on peripheral zone were best detected using T(2) (19% reduction at week 6; P = 0.004) and effects on tumors were best detected using ADC (14% elevation at week 6; P = 0.004). CONCLUSION: ADC and T(2) may be candidate biomarkers of early response to RT warranting further investigation against clinical outcomes. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 10/2012; · 2.57 Impact Factor
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    ABSTRACT: PURPOSE: There is a growing need for noninvasive biomarkers to guide individualized spatiotemporal delivery of radiation therapy (RT) and antiangiogenic (AA) therapy for brain tumors. This study explored early biomarkers of response to RT and the AA agent sunitinib (SU), in a murine intracranial glioma model, using serial magnetic resonance imaging (MRI). METHODS AND MATERIALS: Mice with MRI-visible tumors were stratified by tumor size into 4 therapy arms: control, RT, SU, and SU plus RT (SURT). Single-fraction conformal RT was delivered using MRI and on-line cone beam computed tomography (CT) guidance. Serial MR images (T2-weighted, diffusion, dynamic contrast-enhanced and gadolinium-enhanced T1-weighted scans) were acquired biweekly to evaluate tumor volume, apparent diffusion coefficient (ADC), and tumor perfusion and permeability responses (K(trans), K(ep)). RESULTS: Mice in all treatment arms survived longer than those in control, with a median survival of 35 days for SURT (P<.0001) and 30 days for RT (P=.009) and SU (P=.01) mice vs 26 days for control mice. At Day 3, ADC rise was greater with RT than without (P=.002). Sunitinib treatment reduced tumor perfusion/permeability values with mean K(trans) reduction of 27.6% for SU (P=.04) and 26.3% for SURT (P=.04) mice and mean K(ep) reduction of 38.1% for SU (P=.01) and 27.3% for SURT (P=.02) mice. The magnitude of individual mouse ADC responses at Days 3 and 7 correlated with subsequent tumor growth rate R values of -0.878 (P=.002) and -0.80 (P=.01), respectively. CONCLUSIONS: Early quantitative changes in diffusion and perfusion MRI measures reflect treatment responses soon after starting therapy and thereby raise the potential for these imaging biomarkers to guide adaptive and potentially individualized therapy approaches in the future.
    International journal of radiation oncology, biology, physics 08/2012; · 4.59 Impact Factor
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    ABSTRACT: High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies. Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy. The CRPC-MET patients had increased baseline values (mean 219; 56-513 ng ml(-1); P<0.0001) compared with the localised, non-metastatic group (mean 72; 12-438 ng ml(-1)). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943-0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD. Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.
    British Journal of Cancer 08/2012; 107(5):840-6. · 5.08 Impact Factor

Publication Stats

2k Citations
460.69 Total Impact Points


  • 2007–2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2005–2014
    • University of Toronto
      • Department of Radiation Oncology
      Toronto, Ontario, Canada
  • 2013
    • The University of Western Ontario
      London, Ontario, Canada
  • 2008–2013
    • University Health Network
      • Radiation Medicine Program
      Toronto, Ontario, Canada
  • 2011
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 2010
    • The University of Calgary
      • Faculty of Medicine
      Calgary, Alberta, Canada
  • 2009
    • University of Washington Seattle
      • Department of Radiation Oncology
      Seattle, WA, United States
  • 2006
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia
    • NCI-Frederick
      Maryland, United States
    • National Cancer Institute (USA)
      • Radiation Oncology Branch
      Maryland, United States
  • 2002–2006
    • National Institutes of Health
      • Branch of Radiation Oncology
      Bethesda, MD, United States
  • 2004–2005
    • Johns Hopkins University
      • • Department of Radiology
      • • Department of Biomedical Engineering
      Baltimore, MD, United States