Glenn J Lesser

Wake Forest School of Medicine, Winston-Salem, North Carolina, United States

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Publications (112)489.37 Total impact

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    ABSTRACT: Aim: To investigate the use of clinical head magnetic resonance imaging (MRI) in determining body composition and to evaluate how well it correlates with established measures based on abdominal computed tomography (CT). Materials and methods: Ninety-nine consecutive patients were identified who had undergone both brain MRI and abdominal CT within a 2-week span. Volumes of fat and muscle in the extracranial head were measured utilising several techniques by both abdominal CT and head MRI. Results: MRI-based total fat volumes in the head correlated with CT-based measurements of fat in the abdomen using both single-section (r=0.64, p<0.01) and multisection (r=0.60, p<0.01) techniques. No significant correlation was found between muscle volumes in the abdomen and head. Conclusion: Based on the present results, head MRI-based measures may provide a useful surrogate for CT measurements of abdominal fat, particularly in patients with neurological cancers, as head MRI (and not abdominal CT) is routinely and repeatedly obtained for the purpose of clinical care for these patients.
    No preview · Article · Jan 2016 · Clinical Radiology
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    ABSTRACT: Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy.
    No preview · Article · Dec 2015 · Frontiers in bioscience (Elite edition)

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

  • No preview · Article · Nov 2015 · Neuro-Oncology
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    Full-text · Article · Nov 2015 · Neuro-Oncology

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
  • Glenn J. Lesser
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    ABSTRACT: The absence of any effective combinatorial therapy in patients progressing on bevacizumab and evidence supporting both continuation and discontinuation of bevacizumab in this setting remain important areas for additional clinical trial evaluation in order to better guide our therapeutic decision making in the clinic. © 2015, UBM Medica Healthcare Publications. All rights reserved.
    No preview · Article · Oct 2015 · Oncology (Williston Park, N.Y.)
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    ABSTRACT: We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma (GBM). Between August 2000 and May 2010, 41 patients with GBM and gene expression and methylation data available were treated with radiotherapy with or without concurrent temozolomide. Location of disease progression was categorized as within the high dose (60 Gy) or low dose (46 Gy) volume. Samples were grouped into previously described TCGA genomic groupings: Mesenchymal (m), classical (c), proneural (pn), and neural (n); and were also classified by MGMT-Methylation status and G-Cimp methylation phenotype. Genomic groupings and methylation status were investigated as a possible predictor of disease progression in the high dose region, progression in the low dose region, and time to progression. Based on TCGA category there was no difference in OS (p = 0.26), 60 Gy progression (PN: 71 %, N: 60 %, M: 89 %, C: 83 %, p = 0.19), 46 Gy progression (PN: 57 %, N: 40 %, M: 61 %,C: 50 %, p = 0.8) or time to progression (PN: 9 months, N:15 months, M: 9 months, C: 7 months, p = 0.58). MGMT methylation predicted for improved OS (median 25 vs. 13 months, p = 0.01), improved DFS (median 13 vs. 8 months, p = 0.007) and decreased 60 Gy (p = 0.003) and 46 Gy (p = 0.006) progression. There was a cohort of MGMT methylated patients with late marginal disease progression (4/22 patients, 18 %). TCGA groups demonstrated no difference in survival or progression patterns. MGMT methylation predicted for a statistically significant decrease in in-field and marginal disease progression. There was a cohort of MGMT methylated patients with late marginal progression. Validations of these findings would have implications that could affect radiation field size.
    Full-text · Article · Jul 2015 · Journal of Neuro-Oncology
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    ABSTRACT: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.
    Preview · Article · Jul 2015 · Journal of Cancer Survivorship
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    ABSTRACT: Background: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. Methods: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. Results: From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4-5 toxicities, and the incidence of grade 2-3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes. Conclusion: Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue.
    No preview · Article · May 2015 · Neuro-Oncology
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    ABSTRACT: Gangliogliomas are rare tumors of the central nervous system that are thought to arise from a glioneuronal precursor and consist of both neuronal and glial elements. Grade III, or anaplastic ganglioglioma (AGG), most commonly affects children and young adults, generally arises in a supratentorial location, is highly epileptogenic, and often results in diffuse local and distant failure within the craniospinal axis. Pathologically, these tumors are graded by the degree of malignancy in their glial portion and radiologic diagnosis is difficult due to the wide variation in its degree of solid and cystic components, contrast uptake, and calcification patterns. This report presents three cases of AGG, with initial treatment including subtotal resection followed by conformal radiotherapy. In the case where the AGG developed in the setting of an existent low-grade astrocytoma, the patient received no chemotherapy. Both of the other de novo cases were managed with adjuvant chemoradiotherapy with temozolomide. Recurrence occurred at 6, 16, and 20 months following therapy. Two of the three patients experienced symptomatic decline at recurrence, but experienced Karnofsky performance status (KPS) improvement after salvage therapy, including the reduction of cranial neuropathy and balance. All patients had a significant reduction in presenting symptoms following salvage therapy. Patients died at 23, 20, and 22 months following initial surgical management, respectively. A review of anaplastic and malignant gangliogliomas is presented in the context of these three cases.
    No preview · Article · Apr 2015 · Journal of Neuro-Oncology
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    ABSTRACT: Problems with sexual functioning are common following therapy for breast and gynecologic cancers, although there are few effective treatments. To assess the impact of ArginMax, a nutritional supplement comprised of extracts of L-arginine, ginseng, gingko, and damiana, as well as multivitamins and minerals, on sexual functioning and quality of life in female cancer survivors. This was a 12-week, randomized, placebo-controlled trial of eligible patients who were 6 months or more from active treatment and reporting problems with sexual interest, satisfaction, and functioning after therapy. The participants took 3 capsules of Arginmax or placebo twice daily. Outcome measures were the Female Sexual Function Inventory (FSFI) and the Functional Assessment of Cancer Therapy - General (FACT-G). Assessments were done at baseline, 4, 8, and 12 weeks. 186 patients with a median age of 50 years were accrued between May 10, 2007 and March 24, 2010. 76% of the patients were non-Hispanic white. Most had breast or a gynecologic cancer (78% and 12%, respectively). At 12 weeks, there were no differences between the ArginMax group (n = 96) and placebo (n = 92) group in sexual desire, arousal, lubrication, orgasm,satisfaction or pain. However, FACT-G total scores were significantly better for participants who took ArginMax compared with those who took placebo (least squares [LS] means, 87.5 vs 82.9, respectively; P = .009). The Fact-G subscales that were most affected were Physical (25.37 vs. 23.51, P = .001) and Functional Well-Being (22.46 vs. 20.72, P = .007). Toxicities were similar for both groups. Study results are limited by a lack of data on the participants' psychological and physical symptoms and sexual partner variables. ArginMax had no significant impact on sexual functioning, but patient quality of life was significantly better at 12 weeks in participants who received ArginMax. ©2015 Frontline Medical Communications.
    No preview · Article · Mar 2015
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    ABSTRACT: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. © 2014 American Academy of Neurology.
    No preview · Article · Dec 2014 · Neurology
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    ABSTRACT: BACKGROUND: In a previous investigation, we demonstrated reduced immunogenicity to the standard trivalent inactivated influenza vaccine in patients with primary central nervous system (CNS) malignancy (Neuro-Oncol 2014, PMID 24714522). Other populations with similar reduced responses have shown improved immunogenicity to a high-dose vaccine. OBJECTIVE: A pilot prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® High-Dose influenza vaccine in patients with CNS malignancy. METHODS: Baseline data on diagnosis, chemotherapy, radiation, glucocorticoids, and timing of treatment were collected. All patients underwent vaccination with of the Fluzone® High-Dose influenza vaccine. Serum samples are actively being collected at baseline, day 28, and 3 months following vaccine administration. Hemagglutination inhibition (HAI) titers will be measured to determine seroconversion (4-fold rise) and seroprotection (titer 1:40). RESULTS: A total of 27 patients were enrolled. Mean age at baseline was 52.7 years (+/-12.6); 41% male; 93% white and 7% black. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). At enrollment, 8 patients (30%) were taking glucocorticoids, 4 (15%) were undergoing active radiation, 14 (52%) were on chemotherapy, and 5 (19%) began chemotherapy following vaccine administration. Prior radiation (n = 19, 70%) and chemotherapy (n = 14, 52%) were common. Seven patients (26%) reported post-vaccination symptoms potentially attributable to vaccination; 6 experienced only local soreness or redness at the injection site and 1 suffered headache, nausea, vomiting. All symptoms were transient and resolved completely. At baseline, 8 patients (30%) had absolute CD4 < 300. Serum samples for HAI assay are being collected. Seroconversion and seroprotection rates are forthcoming. CONCLUSION: Studies have shown that populations known to respond poorly to standard yearly influenza vaccination (e.g. the elderly) can mount an effective immunologic response to the high-dose vaccine. This prospective cohort study will provide preliminary data regarding the immunologic response to high-dose vaccination in patients with primary CNS malignancy. Funding: The Fluzone® High Dose vaccine and HAI titer measurements were provided by Sanofi Pasteur. Acknowledgement: This research was supported by the Clinical Research Unit of the Wake Forest Translational Science Institute.
    No preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: BACKGROUND: Identification of reliable biomarkers of tumor vascularity and/or angiogenesis in the peripheral circulation would be useful for screening, diagnosis, prognosis, assessment of treatment efficacy and surveillance in patients with malignant gliomas (MG). Cellular microparticles (MP) are small blood-borne fragments shed from the cell surface after inflammatory activation, injury or apoptosis. MP from vascular endothelial cells in highly angiogenic brain tumors like MG express a specific isoform of aminopeptidase N, CD13, not found on normal endothelium. MP may also contain CD 142 or tissue factor, an initiator of the coagulation cascade, which may reflect thromboembolic risk in patients with MG. METHODS: After obtaining informed consent, serial samples of peripheral blood were obtained from 26 patients with MG prior to the initiation of therapy for newly diagnosed or recurrent disease and at each subsequent clinic visit. Blood was centrifuged and MP were extracted from the platelet-free fraction. MP were labelled with fluorescently tagged antibodies to CD13, CD142 and CD144 (a marker of all endothelial cells) and expression was quantified using established flow cytometric techniques. RESULTS: To date, 14 samples from 7 patients with MG have been analyzed. Using calibration beads, we confirmed that our MP ranged from 0.2 to 1.5 microns in size. Fluorescent antibody expression (% of total MP analyzed in each patient) was as follows: CD13 = 18.2% (range 15 - 25); CD 142 = 9.3% (range 6 - 12); CD 144 = 16.1% (range 7 - 27). CONCLUSIONS: Endothelial markers on MPs are routinely detectable at significant levels in the peripheral blood of patients with MG. When correlated with clinical, laboratory and imaging data, MP have the potential to be useful circulating biomarkers of the vascular compartment in MG.
    No preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: BACKGROUND: This double-blinded randomized phase 2 trial of ICT-107 in newly-diagnosed glioblastoma (GBM) patients rigorously tested efficacy, safety, QoL, and immune response. METHODS: HLA-A1+ and/or -A2+ resected patients with residual tumor <1 cm3 received 6wks of concurrent temozolomide (TMZ) and radiation. 124 patients, randomized 2:1, received ICT-107 (autologous DCs pulsed with 6 synthetic peptide CTL epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or matching control (unpulsed DC). Patients then received induction ICT-107 or control QWx4 followed by maintenance TMZ, 5 days/mo for 12mos. Maintenance vaccinations occurred at 1, 3, and 6mos after induction, and every 6mos thereafter until progression. RESULTS: ICT-107 was generally safe and well tolerated, with no AE imbalance between treated and control. At the 67-event trial completion, median OS had not been reached. Follow-up continues: at 79 events, median OS favored ICT-107 by 1.6mos in the ITT and 1.9mos in the PP (117 patients completing induction) groups, although not statistically significant (p = 0.64 two-sided, HR = 0.89, and p = 0.48, HR = 0.84, respectively). Median PFS was significantly improved in the ICT-107 ITT and PP groups by 2.2mos and 2.4mos (p = 0.01, HR = 0.57, p = 0.006, HR = 0.54, respectively). Treatment extended PFS with sustained QoL assessed by FACT-BR, KPS, and steroid usage. The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher vaccine response (via Elispot) than HLA-A1 patients. PP HLA-A2 patients in both the MGMT methylated and unmethylated pre-specified subgroups saw a clinically meaningful ICT-107 effect, although HLA-A1 patients received no benefit from vaccine. CONCLUSIONS: PFS was significantly improved in ICT-107 treated patients with maintenance of QoL. Patients in the HLA-A2 MGMT subgroups show stronger ICT-107 activity clinically and immunologically, and these groups will be studied in a future phase 3 trial.
    Preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: Bevacizumab is FDA-approved for patients with recurrent GBM. However, the median duration of response is only 4 months. Potential mechanisms of resistance include upregulated FGF signaling and increased PDGF-mediated pericyte coverage. Nintedanib is an oral, small-molecule tyrosine kinase inhibitor of PDGFR α/β, FGFR 1-3, and VEGFR 1-3 that may overcome resistance to anti-VEGF therapy. This was a two-stage phase II trial in adults with first or second recurrence of GBM, stratified by prior bevacizumab therapy (ClinicalTrials.gov number NCT01380782; 1199.94). The primary endpoint was PFS6 in the bevacizumab-naive arm (Arm A) and PFS3 in the post-bevacizumab arm (Arm B). Up to 10 anaplastic glioma (AG) patients were accrued to each arm in exploratory cohorts. Twenty-two patients enrolled in Arm A and 14 in Arm B. Arm A included 12 GBMs (55 %), 13 patients with one prior regimen (59 %), and median age 54 years (range 28-75). Arm B included 10 GBMs (71 %), one patient with one prior regimen (7 %), and median age 52 years (range 32-70). Median KPS overall was 90 (range 60-100). There were no responses. In Arm A (GBM only), PFS6 was 0 %, median PFS 28 days (95 % CI 27-83), and median OS 6.9 months (3.7-8.1). In Arm B (GBM only), PFS3 was 0 %, median PFS 28 days (22-28), and median OS 2.6 months (1.0-6.9). Among AG patients in each arm, PFS6 was 0 %. Treatment was well tolerated. In conclusion, nintedanib is not active against recurrent high-grade glioma, regardless of prior bevacizumab therapy.
    No preview · Article · Oct 2014 · Journal of Neuro-Oncology
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    Full-text · Article · Oct 2014 · The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

Publication Stats

2k Citations
489.37 Total Impact Points

Institutions

  • 1999-2016
    • Wake Forest School of Medicine
      • • Section on Hematology and Oncology
      • • Department of Radiation Oncology
      Winston-Salem, North Carolina, United States
  • 1999-2015
    • Wake Forest University
      • • School of Medicine
      • • Comprehensive Cancer Center
      • • Department of Hematology and Oncology
      • • Department of Radiation Oncology
      • • Department of Internal Medicine
      Winston-Salem, North Carolina, United States
  • 2002
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2001
    • Barrow Neurological Institute
      Phoenix, Arizona, United States
  • 1996
    • U.S. Food and Drug Administration
      • Center for Drug Evaluation and Research
      Washington, Washington, D.C., United States
  • 1994
    • Johns Hopkins University
      • Department of Biomedical Engineering
      Baltimore, Maryland, United States