Bio

Bio


Dr. Reena Thomas received her medical degree from Georgetown University School of Medicine in Washington, DC and her PhD from the City of Hope Graduate School in Duarte, California. She completed her training as a resident in Neurology as well as her fellowship training in Neuro-Oncology at Stanford University Hospital. Her research background and interests are focused on immune based cancer therapies and chemokine signaling in glioblastoma brain tumors. She has also been involved in advanced imaging studies of glioblastoma. She is the Director of the Adult Neuro Oncology Fellowship at Stanford.

Clinical Focus


  • Neuro Oncology
  • Fellowship Program Director
  • Neurology
  • Immunotherapy
  • Immuno Oncology
  • Primary Brain Tumors
  • Metastatic Cancer to CNS

Academic Appointments


Administrative Appointments


  • Adult Neuro Oncology Fellowship Program Director, Stanford Hospital (2014 - Present)
  • Director of Diversity and Inclusion, Department of Neurology (2017 - Present)
  • Education Chief of Neuro Oncology, Department of Neurology (2017 - Present)

Honors & Awards


  • Graduating Resident Teaching Award, Stanford Neurology (July 2013)
  • Silicon Valley Top 40 under 40, Silicon Valley Business Journal (December 2014)
  • Principal Investigator of SPARK Grant, Stanford University (2015-2018)
  • Stanford Faculty Development Grant, Hispanic Center of Excellence (2015, 2018)

Boards, Advisory Committees, Professional Organizations


  • Member, American Academy of Neurology (2010 - Present)
  • Member, Society for Neuro Oncology (2011 - Present)
  • Member, Stanford Society of Physician Scholars (2011 - Present)
  • Board Certified, American Board of Psychiatry and Neurology (2014 - Present)
  • Member, American Society of Clinical Oncology (2015 - Present)

Professional Education


  • BA, Cornell University, Biology; Neurobiology and Behavior (2002)
  • PhD, City of Hope Graduate School of Biological Sciences, City of Hope Cancer Center, Molecular Immunology (2006)
  • Medical Education:Georgetown University School of Medicine (2009) DC
  • Internship:Georgetown University School of Medicine Registrar (2010) DC
  • Residency:Stanford University School of Medicine (2013) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2014)
  • Fellowship:Stanford University School of Medicine (2014) CA

Community and International Work


  • Faculty Mentor

    Topic

    Neuroscience Journal Club

    Populations Served

    Bay Area High School Students

    Location

    California

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Board Member

    Topic

    American Youth Soccer Organization

    Location

    California

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Clinical Trials


  • Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma Not Recruiting

    ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA) present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target glioblastoma tumour cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cathy Recht, 650-723-6095.

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  • Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases Not Recruiting

    This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

    Stanford is currently not accepting patients for this trial. For more information, please contact Polly Young, 650-497-7499.

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  • A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE) Not Recruiting

    The purpose of this pivotal, phase 3, randomized, multicenter study is to compare VB-111 plus bevacizumab to bevacizumab in adult patients with recurrent Glioblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • The Toca 5 Trial: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma Not Recruiting

    This is a multicenter, randomized, open-label phase 2/3 study of Toca 511 and Toca FC versus standard of care that comprises Investigator's choice of single agent chemotherapy (lomustine or temozolomide) or bevacizumab administered to subjects undergoing resection for first or second recurrence (including this recurrence) of GBM or AA. Subjects meeting all of the inclusion and none of the exclusion criteria will be randomized prior to surgery in a 1:1 ratio to receive either Toca 511 and Toca FC (Experimental arm, Arm T) or control treatment with one option of standard of care (Arm SOC). Stratification will be done by IDH1 mutation status. A second stratification factor is based on the patient's Karnofsky Performance Score (KPS) (70-80 vs 90-100). Further, to account for potential differences in treatment choices for the control arm in regions, the trial will be stratified by geographical region during the randomization process. Funding Source - FDA OOPD

    Stanford is currently not accepting patients for this trial. For more information, please contact Sophie Bertrand, 650-723-4467.

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  • A Phase 1b/2, Multicenter, Open-label Study of ACP-196 in Subjects With Recurrent Glioblastoma Multiforme (GBM) Not Recruiting

    A Phase 1b/2, multicenter, open-label study designed to evaluate the efficacy and safety of ACP-196 in subjects with recurrent GBM who have progressed after 1 or 2 prior systemic treatment regimens.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cathy Recht, 650-723-6095.

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  • INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) Recruiting

    Phase 1/2 trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab (REGN2810), with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM).

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  • Study of REGN2810 (Anti-PD-1) in Patients With Advanced Malignancies Not Recruiting

    This is a phase 1, open-label, multicenter, ascending-dose escalation study of REGN2810, alone and in combination with other anti-cancer therapies in patients with advanced malignancies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • [18F]DASA-23 and PET Scan in Evaluating Pyruvate Kinase M2 Expression in Patients With Intracranial Tumors or Recurrent Glioblastoma and Healthy Volunteers Recruiting

    This phase I trial studies how well [18F]DASA-23 and positron emission tomography (PET) scan work in evaluating pyruvate kinase M2 (PKM2) expression in patients with intracranial tumors or recurrent glioblastoma and healthy volunteers. PKM2 regulates brain tumor metabolism, a key factor in glioblastoma growth. [18F]DASA-23 is a radioactive substance with the ability to monitor PKM2 activity. A PET scan is a procedure in which a small amount of a radioactive substance, such as [18F]DASA-23, is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the substance is used. Tumor cells usually pick up more of these radioactive substances, allowing them to be found. Giving [18F]DASA-23 with a PET scan may help doctors evaluate PKM2 expression in healthy volunteers and in participants with intracranial tumors or recurrent glioblastoma.

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  • Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery Recruiting

    The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery. Panitumumab-IRDye800 can attach to tumor cells and make them more visible using a special camera during surgery, which may help surgeons better distinguish tumor cells from normal brain tissue and identify small tumors that cannot be seen using current imaging methods.

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  • Hyperpolarized Carbon C 13 Pyruvate Magnetic Resonance Spectroscopic Imaging in Detecting Lactate and Bicarbonate in Participants With Central Nervous System Tumors Recruiting

    This early phase I trial studies how well hyperpolarized carbon C 13 pyruvate magnetic resonance imaging works in detecting lactate and bicarbonate in participants with central nervous system tumors. Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors.

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  • An Investigational Immuno-therapy Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain, Treated With Nivolumab in Combination With Ipilimumab, Followed by Nivolumab by Itself Not Recruiting

    This is a study of Nivolumab combined with Ipilimumab followed by Nivolumab by itself for the treatment of patients with Melanoma that has spread to the brain. Patients with histologically confirmed Malignant Melanoma and asymptomatic brain metastases are eligible for the study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Vani Jain, 650-723-1005.

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  • BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab Recruiting

    This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma or glioblastoma) that has come back and have been previously treated with bevacizumab. BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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Teaching

2018-19 Courses


Graduate and Fellowship Programs


  • Oncology (Fellowship Program)

Publications

All Publications


  • Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. The New England journal of medicine Tawbi, H. A., Forsyth, P. A., Algazi, A., Hamid, O., Hodi, F. S., Moschos, S. J., Khushalani, N. I., Lewis, K., Lao, C. D., Postow, M. A., Atkins, M. B., Ernstoff, M. S., Reardon, D. A., Puzanov, I., Kudchadkar, R. R., Thomas, R. P., Tarhini, A., Pavlick, A. C., Jiang, J., Avila, A., Demelo, S., Margolin, K. 2018; 379 (8): 722–30

    Abstract

    BACKGROUND: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.METHODS: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.RESULTS: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases.CONCLUSIONS: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058 .).

    View details for DOI 10.1056/NEJMoa1805453

    View details for PubMedID 30134131

  • Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study. Radiology Iv, M., Samghabadi, P., Holdsworth, S., Gentles, A., Rezaii, P., Harsh, G., Li, G., Thomas, R., Moseley, M., Daldrup-Link, H. E., Vogel, H., Wintermark, M., Cheshier, S., Yeom, K. W. 2018: 181204

    Abstract

    Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2018181204

    View details for PubMedID 30398435

  • Conditional Probability of Survival as a Proposed Endpoint for Future Single-Arm Clinical Trials in Glioblastoma Patel, C. B., Thomas, R. P., Nagpal, S., Recht, L. D. WILEY. 2017: S206–S207
  • Anti-PD-1-associated inflammatory-demyelinating lesions in patients with brain metastases Samghabadi, P., Makar, S., Thomas, R., Pelpola, J., Reddy, S., Tranvinh, E., Spence, A., Vogel, H., Born, D., Sobel, R. OXFORD UNIV PRESS INC. 2017: 500–501
  • Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

    Abstract

    We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

    View details for DOI 10.1016/j.ijrobp.2017.01.242

    View details for PubMedID 28586949

  • Melanoma central nervous system metastases: current approaches, challenges, and opportunities PIGMENT CELL & MELANOMA RESEARCH Cohen, J. V., Tawbi, H., Margolin, K. A., Amravadi, R., Bosenberg, M., Brastianos, P. K., Chiang, V. L., de Groot, J., Glitza, I. C., Herlyn, M., Holmen, S. L., Jilaveanu, L. B., Lassman, A., Moschos, S., Postow, M. A., Thomas, R., Tsiouris, J. A., Wen, P., White, R. M., Turnham, T., Davies, M. A., Kluger, H. M. 2016; 29 (6): 627-642

    Abstract

    Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area.

    View details for DOI 10.1111/pcmr.12538

    View details for Web of Science ID 000388312900006

    View details for PubMedID 27615400

    View details for PubMedCentralID PMC5398760

  • Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma JOURNAL OF NEURO-ONCOLOGY Nagpal, S., Recht, C. K., Bertrand, S., Thomas, R. P., Ajlan, A., Pena, J., Gershon, M., Coffey, G., Kunz, P. L., Li, G., Recht, L. D. 2015; 123 (2): 277-282

    Abstract

    Patients with recurrence of high-grade glioma (HGG) after bevacizumab (BEV) have an extremely poor prognosis. Etirinotecan pegol (EP) is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Here we report results of a Phase 2, single arm, open-label trial evaluating EP in HGG patients who progressed after BEV. Patients age >18 with histologically proven anaplastic astrocytoma or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy >6 weeks and KPS ≥ 50 were required. The primary endpoint was PFS at 6-weeks. Secondary endpoint was overall survival from first EP infusion. Response was assessed by RANO criteria. Single agent EP was administered IV every 3 weeks at 145 mg/m2. Patients did not receive BEV while on EP. 20 patients (90 % GB) were enrolled with a median age of 50 and median KPS of 70. Three patients with GB (16.7 % of GB) had partial MRI responses. 6-week PFS was 55 %. Median and 6-month PFS were 2.2 months (95 % CI 1.4-3.4 months) and 11.2 % (95 % CI 1.9-28.9 %) respectively. Median overall survival from first EP infusion was 4.5 months (95 % CI 2.4-5.9). Only one patient had grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Three patients had confirmed partial responses according to RANO criteria. These clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in HGG.

    View details for DOI 10.1007/s11060-015-1795-0

    View details for Web of Science ID 000355632800010

    View details for PubMedID 25935109

  • Treatment options for optic pathway gliomas. Current treatment options in neurology Thomas, R. P., Gibbs, I. C., Xu, L. W., Recht, L. 2015; 17 (2): 333-?

    Abstract

    Gliomas that affect the optic pathways are for the most part low-grade neoplasms that often, but not always, have good prognoses. Optimal treatment and management of optic pathway gliomas remains unclear and the decision hinges upon several factors including patient age, tumor location, and visual symptoms. We favor a treatment approach that is dependent on the location of tumor within anterior, chiasmal or posterior/hypothalamic visual pathways. In children who are minimally or not symptomatic, we recommend observation rather than early treatment intervention. Most of these patients will have neurofibromatosis type 1 (NF1) based on the natural history and their pilocytic astrocytoma histology. Serial magnetic resonance imaging studies and formal neuro-ophthalmology testing should enable close observation of these patients, with intervention being reserved for when tumor progression results in significant visual loss or proptosis. Chemotherapy is an accepted first line treatment, and a number of effective medications are available, although no agent has proven clearly superior. If progression is accompanied by the complete loss of vision, surgery can be utilized to help alleviate structural issues (ie, proptosis). Minimally symptomatic chiasmal or hypothalamic tumors that arise in the setting of NF1 can also be observed initially because of their favorable prognosis. Children with NF1 and chiasmal or posterior visual tumors who progress either on imaging or clinical grounds (ie, development of significant visual deficits) should be treated first with chemotherapy rather than radiation therapy to minimize the effects on the developing central nervous system. Individuals without NF1 presenting with a chiasmal or hypothalamic mass are candidates for biopsy to determine the underlying pathology of the lesion. Symptomatic patients with pilocytic astrocytoma should first receive chemotherapy. In contrast, other histologies including malignant optic pathway gliomas should be treated similar to other gliomas that occur in other locations with appropriate doses of radiation and chemotherapy.

    View details for DOI 10.1007/s11940-014-0333-2

    View details for PubMedID 25619537

  • Treatment Options for Optic Pathway Gliomas CURRENT TREATMENT OPTIONS IN NEUROLOGY Thomas, R. P., Gibbs, I. C., Xu, L. W., Recht, L. 2015; 17 (2)

    View details for DOI 10.1007/s11940-014-0333-2

    View details for Web of Science ID 000351159000001

    View details for PubMedID 25619537

  • ARE WE USING TOO MUCH BEVACIZUMAB IN OUR GBM PATIENTS? Ajlan, A., Thomas, P., Thomas, R., Nagpal, S., Recht, L. OXFORD UNIV PRESS INC. 2014
  • COMPLETE RESPONSE TO VEMURAFINIB IN A PATIENT WITH METASTATIC ANAPLASTIC XANTHROASTROCYTOMA Thomas, R., Ajlan, A., Ziskin, J., Soltys, S., Reddy, S., Recht, L., Nagpal, S. OXFORD UNIV PRESS INC. 2014
  • Simultaneous perfusion and permeability measurements using combined spin- and gradient-echo MRI. Journal of cerebral blood flow and metabolism Schmiedeskamp, H., Andre, J. B., Straka, M., Christen, T., Nagpal, S., Recht, L., Thomas, R. P., Zaharchuk, G., Bammer, R. 2013; 33 (5): 732-743

    Abstract

    The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T1-, T2-, and -related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.

    View details for DOI 10.1038/jcbfm.2013.10

    View details for PubMedID 23462570

    View details for PubMedCentralID PMC3652702

  • The incidence and significance of multiple lesions in glioblastoma JOURNAL OF NEURO-ONCOLOGY Thomas, R. P., Xu, L. W., Lober, R. M., Li, G., Nagpal, S. 2013; 112 (1): 91-97

    Abstract

    The location and distribution of glioblastoma (GBM) within the brain parenchyma plays an important role in surgical and radiation planning. Prior studies have reported incidences of multiple lesions at the time of diagnosis ranging from 0.5 to 20 %. Multiple lesions can be further categorized as multifocal (multiple areas involved, but with a clear path of spread from one lesion to another) or multicentric (multiple lesions, no clear path of spread). In this retrospective study, we reviewed our experience with GBM and found the incidence of multiple lesions at time of diagnosis was 35 %, much higher than previously suggested in the literature. Patients with single lesions had an improved overall survival when compared to patients with multiple lesions (18 vs. 10 months). Patients with multicentric lesions fared the worst, with average survival of 3 months. However, the difference between single and multiple lesions (multifocal or multicentric) was no longer significant when taking into consideration age, Karnofsky performance score (KPS) and extent of resection by multivariate analysis. Age, KPS, gross total resection, and MGMT status were independent predictors of outcome. Multiple lesions did not independently confer a worse outcome, but were associated with lower KPS scores and inability to perform gross total resection. These findings suggest that single, multiple and multicentric imaging exams represent a spectrum of presentations of a single disease. The rate of multiple lesions reported here may be the result of improved imaging technology, suggesting that incidence of multiple lesions will continue to increase as imaging technology advances.

    View details for DOI 10.1007/s11060-012-1030-1

    View details for Web of Science ID 000315487900011

    View details for PubMedID 23354652

  • Advances in the management of glioblastoma: the role of temozolomide and MGMT testing. Clinical pharmacology : advances and applications Thomas, R. P., Recht, L., Nagpal, S. 2013; 5: 1-9

    Abstract

    Glioblastoma (GB) is one of the most lethal forms of cancer, with an invasive growth pattern that requires the use of adjuvant therapies, including chemotherapy and radiation, to prolong survival. Temozolomide (TMZ) is an oral chemotherapy with a limited side effect profile that has become the standard of care in GB treatment. While TMZ has made an impact on survival, tumor recurrence and TMZ resistance remain major challenges. Molecular markers, such as O6-methylguanine-DNA methyltransferase methylation status, can be helpful in predicting tumor response to TMZ, and therefore guides clinical decision making. This review will discuss the epidemiology and possible genetic underpinnings of GB, how TMZ became the standard of care for GB patients, the pharmacology of TMZ, the practical aspects of using TMZ in clinic, and how molecular diagnostics - particularly the use of O6-methylguanine-DNA methyltransferase status - affect clinical management.

    View details for DOI 10.2147/CPAA.S26586

    View details for PubMedID 23293540

    View details for PubMedCentralID PMC3534290

  • PRELIMINARY RESULTS UTILIZING VESSEL SIZE IMAGING AS A METRIC OF RESPONSE IN GLIOBLASTOMA MULTIFORME 17th Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) Andre, J. B., Schmiedeskamp, H., Thomas, R. P., Feroze, A., Nagpal, S., Zaharchuk, G., Straka, M., Recht, L., Bammer, R. OXFORD UNIV PRESS INC. 2012: 127–127
  • Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells JOURNAL OF IMMUNOLOGY Brown, C. E., Vishwanath, R. P., Aguilar, B., Starr, R., Najbauer, J., Aboody, K. S., Jensen, M. C. 2007; 179 (5): 3332-3341

    Abstract

    To exert a therapeutic effect, adoptively transferred tumor-specific CTLs must traffic to sites of tumor burden, exit the circulation, and infiltrate the tumor microenvironment. In this study, we examine the ability of adoptively transferred human CTL to traffic to tumors with disparate chemokine secretion profiles independent of tumor Ag recognition. Using a combination of in vivo tumor tropism studies and in vitro biophotonic chemotaxis assays, we observed that cell lines derived from glioma, medulloblastoma, and renal cell carcinoma efficiently chemoattracted ex vivo-expanded primary human T cells. We compared the chemokines secreted by tumor cell lines with high chemotactic activity with those that failed to elicit T cell chemotaxis (Daudi lymphoma, 10HTB neuroblastoma, and A2058 melanoma cells) and found a correlation between tumor-derived production of MCP-1/CCL2 (> or =10 ng/ml) and T cell chemotaxis. Chemokine immunodepletion studies confirmed that tumor-derived MCP-1 elicits effector T cell chemotaxis. Moreover, MCP-1 is sufficient for in vivo T cell tumor tropism as evidenced by the selective accumulation of i.v. administered firefly luciferase-expressing T cells in intracerebral xenografts of tumor transfectants secreting MCP-1. These studies suggest that the capacity of adoptively transferred T cells to home to tumors may be, in part, dictated by the species and amounts of tumor-derived chemokines, in particular MCP-1.

    View details for Web of Science ID 000248991800076

    View details for PubMedID 17709550

  • A quantitative high-throughput chemotaxis assay using bioluminescent reporter cells JOURNAL OF IMMUNOLOGICAL METHODS Vishwanath, R. P., Brown, C. E., Wagner, J. R., Meechoovet, H. B., Naranjo, A., Wright, C. L., Olivares, S., Qian, D., Cooper, L. J., Jensen, M. C. 2005; 302 (1-2): 78-89

    Abstract

    Here we report on a novel biophotonic assay system for the detection and quantitation of chemotaxis, the directed movement of cells in response to chemokine concentration gradients. Our assay employs a firefly luciferase (ffLuc)-generated biophotonic signal to quantify cellular migration in 96-well microplate chemotaxis instruments. When compared to direct cell enumeration, the biophotonic reporter method is superior in accuracy, reproducibility, and sensitivity. As a proof-of-concept, we demonstrate the utility of this assay for quantifying the chemotactic response of ex vivo expanded ffLuc(+) primary human T-cells to recombinant human chemokines MCP-1, RANTES, and IP-10. The 96-well microplate format and in situ biophotonic detection of cells are amenable to high-throughput screening of peptides and small molecule libraries to identify agonists and antagonists of cellular chemotaxis, to analyze biological fluids for chemotactic activity, and to study chemotaxis in a variety of cell types.

    View details for DOI 10.1016/j.jim.2005.04.021

    View details for Web of Science ID 000231490600007

    View details for PubMedID 15987642

  • Biophotonic cytotoxicity assay for high-throughput screening of cytolytic killing JOURNAL OF IMMUNOLOGICAL METHODS Brown, C. E., Wright, C. L., Naranjo, A., Vishwanath, R. P., Chang, W. C., Olivares, S., Wagner, J. R., Bruins, L., Raubitschek, A., Cooper, L. J., Jensen, M. C. 2005; 297 (1-2): 39-52

    Abstract

    We have developed a highly sensitive biophotonic luciferase assay as an alternative to (51)Cr-release for assessment of cell-mediated cytotoxicity. The luciferin/ATP-dependent luminescent signal of target cells stably or transiently transfected with a firefly luciferase reporter gene (fLuc:Zeo) linearly correlates with viable target cell number. Upon incubation of fLuc:Zeo(+) target cells with CD8(+) CTLs, a rapid decrease in bioluminescence was detected that correlated with antigen-specific target cell lysis. The levels of specific lysis measured by (51)Cr-release assays correlated with the attenuation in biophotonic target cell signal, thus validating this approach as a sensitive and accurate method for the measurement of cytolysis. We show that this luminescent-based cytolytic assay (LCA) is amenable for high-throughput screening of effector cell cytolytic activity, allows for the rate of cytolysis to be measured in a single micro-plate, and permits the multiplexing of cytolytic killing with other lymphocyte functional assays such as cytokine release. Importantly, this method accurately measures the cytolytic killing of target cells that are either stably or transiently transfected with a fLuc reporter gene, and thus is ideal for monitoring cytolysis of both primary autologous and immortalized target cell lines. The versatility of the non-radioactive, high-throughput, biophotonic cytolytic assay should make this method an attractive alternative to chromium-release for quantifying effector cell cytolytic activity.

    View details for DOI 10.1016/j.jim.2004.11.021

    View details for Web of Science ID 000228301700004

    View details for PubMedID 15777929

  • Quantification of chemotherapeutic target gene mRNA expression in human breast cancer biopsies: Comparison of real-time reverse transcription-PCR vs. relative quantification reverse transcription-PCR utilizing DNA sequencer analysis of PCR products JOURNAL OF CLINICAL LABORATORY ANALYSIS Juhasz, A., Frankel, P., Cheng, C., Rivera, H., Vishwanath, R., Chiu, A., Margolin, K., Yen, Y., Newman, E. M., Synold, T., Wilczynski, S., Lenz, H. J., Gandara, D., Albain, K. S., Longmate, J., Doroshow, J. H. 2003; 17 (5): 184-194

    Abstract

    The solid tumor mRNA expression of genes related to the mechanism of action of certain antineoplastic agents is often predictive of clinical efficacy. We report here on the development of a rapid and practical real-time RT-PCR method to quantify genetic expression in solid tumors. The genes examined are related to the intracellular pharmacology of gemcitabine and cisplatin, two drugs that are used in the treatment of several types of advanced cancer. We evaluated target gene mRNA levels from breast tumor samples using two quantitative RT-PCR methods: 1) an improved relative RT-PCR method using fluorescence-labeled primers, automated PCR set up, and GeneScan analysis software; and 2) real-time RT-PCR with redesigned primers using an ABI 7900HT instrument, with additional postprocessing of the data to adjust for efficiency differences across the target genes. Using these methods, we quantified mRNA expression levels of deoxycytidine kinase (dCK), deoxycytidylate deaminase (dCDA), the M1 and M2 subunits of ribonucleotide reductase (RRM1, RRM2), and excision cross complementation group 1 (ERCC1) in 35 human "fresh" frozen breast cancer biopsies. While both assay methods were substantially more rapid than traditional RT-PCR, real-time RT-PCR appeared to be superior to the amplification end-point measurement in terms of precision and high throughput, even when a DNA sequencer was used to assess fluorescence-labeled PCR products. This reproducible, highly sensitive real-time RT-PCR method for the detection and quantification of the mRNAs for dCK, dCDA, RRM1, RRM2, and ERCC1 in human breast cancer biopsies appears to be more informative and less time-consuming than either classical radioisotope-dependent RT-PCR or the technique utilizing GeneScan analysis described herein. By allowing the measurement of intratumoral target gene expression, these new methods may prove useful in predicting the clinical utility of gemcitabine- and platinum-containing chemotherapy programs in patients with solid tumors.

    View details for DOI 10.1002/jcla.10091

    View details for Web of Science ID 000186284100008

    View details for PubMedID 12938148