Cynthia Ménard

Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy : the National Cancer Institute Randomized Trial

Between 1979–1987, the National Cancer Institute conducted a randomized, prospective study of mastectomy (MT) versus breast conservation therapy (BCT) in the treatment of patients with early‐stage breast carcinoma. After a median potential follow‐up of 18.4 years, the authors present the updated results.

Design of a novel MRI compatible manipulator for image guided prostate interventions

This paper reports a novel remotely actuated manipulator for access to prostate tissue under magnetic resonance imaging guidance (APT-MRI) device, designed for use in a standard high-field MRI scanner. The device provides three-dimensional MRI guided needle placement with millimeter accuracy under physician control. Procedures enabled by this device include MRI guided needle biopsy, fiducial marker placements, and therapy delivery. Its compact size allows for use in both standard cylindrical and open configuration MRI scanners. Preliminary in vivo canine experiments and first clinical trials are reported.

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner

A technique for transperineal high‐dose‐rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI‐guided transperineal prostate biopsies were obtained followed by placement of 14–15 hollow transperineal catheters for HDR brachytherapy. Mean needle‐placement accuracy was 2.1 mm, 95% of needle‐placement errors were less than 4.0 mm, and the maximum needle‐placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized. Magn Reson Med 52:683–687, 2004. Published 2004 Wiley‐Liss, Inc.

Transrectal Prostate Biopsy and Fiducial Marker Placement in a Standard 1.5T Magnetic Resonance Imaging Scanner

PURPOSEnWe investigated the accuracy and feasibility of a system that provides transrectal needle access to the prostate concurrent with 1.5 Tesla MRI which previously has not been possible.nnnMATERIALS AND METHODSnIn 5 patients with previously diagnosed prostate cancer, MRI guided intraprostatic placement of gold fiducial markers (4 procedures) and/or prostate biopsy (3 procedures) was performed using local anesthesia.nnnRESULTSnMean procedure duration was 76 minutes and all patients tolerated the intervention well. Procedure related adverse events included self-limited hematuria and hematochezia following 3 of 8 procedures (all resolved in less than 1 week). Mean needle placement accuracy was 1.9 mm for the fiducial marker placement studies and 1.8 mm for the biopsy procedures. Mean fiducial marker placement accuracy was 4.8 mm and the mean fiducial marker placement accuracy transverse to the needle direction was 2.6 mm. All patients who underwent the procedure were able to complete their course of radiotherapy without delay or complication.nnnCONCLUSIONSnWhile studies of clinical usefulness are warranted, transrectal 1.5 T MRI guided prostate biopsy and fiducial marker placement is feasible using this system, providing new opportunities for image guided diagnostic and therapeutic prostate interventions.

Patient selection determines the prostate cancer yield of dynamic contrast‐enhanced magnetic resonance imaging‐guided transrectal biopsies in a closed 3‐Tesla scanner

To evaluate the cancer yield of transrectal prostate biopsies in a 3‐T magnetic resonance imaging (MRI) scanner in patients with elevated prostate specific antigen (PSA) levels and recent negative transrectal ultrasonography (TRUS)‐guided prostate biopsies.

Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers

BackgroundWe sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM).Materials and methodsWith the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers.ResultsThe mean and median intra-observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or inter-observer error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm.ConclusionWe have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging.

Microarray analysis in clinical oncology: pre-clinical optimization using needle core biopsies from xenograft tumors

BackgroundDNA microarray profiling performed on clinical tissue specimens can potentially provide significant information regarding human cancer biology. Biopsy cores, the typical source of human tumor tissue, however, generally provide very small amounts of RNA (0.3–15 μg). RNA amplification is a common method used to increase the amount of material available for hybridization experiments. Using human xenograft tissue, we sought to address the following three questions: 1) is amplified RNA representative of the original RNA profile? 2) what is the minimum amount of total RNA required to perform a representative amplification? 3) are the direct and indirect methods of labeling the hybridization probe equivalent?MethodsTotal RNA was extracted from human xenograft tissue and amplified using a linear amplification process. RNA was labeled and hybridized, and the resulting images yielded data that was extracted into two categories using the mAdb system: all genes and outliers. Scatter plots were generated for each slide and Pearson Coefficients of correlation were obtained.ResultsResults show that the amplification of 5 μg of total RNA yields a Pearson Correlation Coefficient of 0.752 (N = 6,987 genes) between the amplified and total RNA samples. We subsequently determined that amplification of 0.5 μg of total RNA generated a similar Pearson Correlation Coefficient as compared to the corresponding original RNA sample. Similarly, sixty-nine percent of total RNA outliers were detected with 5 μg of amplified starting RNA, and 55% of outliers were detected with 0.5 μg of starting RNA. However, amplification of 0.05 μg of starting RNA resulted in a loss of fidelity (Pearson Coefficient 0.669 between amplified and original samples, 44% outlier concordance). In these studies the direct or indirect methods of probe labeling yielded similar results. Finally, we examined whether RNA obtained from needle core biopsies of human tumor xenografts, amplified and indirectly labeled, would generate representative array profiles compared to larger excisional biopsy material. In this analysis correlation coefficients were obtained ranging from 0.750–0.834 between U251 biopsy cores and excised tumors, and 0.812–0.846 between DU145 biopsy cores and excised tumors.ConclusionThese data suggest that needle core biopsies can be used as reliable tissue samples for tumor microarray analysis after linear amplification and either indirect or direct labeling of the starting RNA.

Accuracy analysis in MRI-guided robotic prostate biopsy.

PurposeTo 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.MethodsSeries 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.ResultsA 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.ConclusionThe biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.

Evaluation of copper chelation agents as anti-angiogenic therapy

The design, synthesis and evaluation of N,N,N-tris(2-pyridylmethyl)-cis,cis-1,3,5,-triaminocyclohexane (tachpyr, 1) derivatives as novel anti-angiogenic agents were performed in an in vitro endothelial cell proliferation assay to assess their cytotoxicity and selectivity. The selective nature of the anti-angiogenic agents for human umbilical vein endothelial cells (Huvec) was compared to a normal fibroblast cell line and a human Glioma cell line to evaluate these compounds. N,N,N-tris(2-mercaptoethyl)-cis,cis-1,3,5-triaminocyclohexane trihydrochloride (3b) was superior to tachpyr in terms of selectivity of its inhibitory activity toward the proliferation of Huvec compared to the fibroblast and human Glioma cell lines.

Visualization, Planning, and Monitoring Software for MRI-Guided Prostate Intervention Robot

This paper reports an interactive software interface for visualization, planning, and monitoring of intra-prostatic needle placement procedures performed with a robotic assistant device inside standard cylindrical high-field magnetic resonance imaging (MRI) scanner. We use anatomical visualization and image processing techniques to plan the process and apply active tracking coils to localize the robot in real-time to monitor its motion relative to the anatomy. The interventional system is in Phase-I clinical trials for prostate biopsy and marker seed placement. The system concept, mechanical design, and in-vivo canine studies have been presented earlier [6,10,14]. The software architecture and three-dimensional application software interface discussed in this paper are new additions. This software was tested on pre-recorded patient data.