National Brain Tumor Society

June 2009

In this edition:

NBTS Co-Sponsors Regional Conference with University of Cincinnati Neuroscience Institute Brain Tumor Center on June 20, 2009
NCI Recovery Act Funding for Pediatric Cancers Initiative
Delivery of Temozolomide to the Tumor Bed Via Biodegradable Gel Matricies in a Novel Model of Intracranial Glioma with Resection
The Influence of Pre-Treatment Characteristics and Radiotherapy Parameters on Time Interval to Development of Radiation-Associated Meningioma
Surrogate Markers Predict Angiogenic Potential and Survival in Patients with Glioblastoma Multiforme

1. NBTS Co-Sponsors Regional Conference with University of Cincinnati Neuroscience Institute Brain Tumor Center in Cincinnati, OH on June 20, 2009
On June 20, 2009 don't miss out on our Regional Conference in Cincinnati, OH in partnership with University of Cincinnati Neuroscience Institute Brain Tumor Center. New in 2009 are extended breakout sessions on acoustic and pituitary tumors and 15-minute physician consults are back by popular demand. Spaces are limited so register today!
More information and registration

2. NCI Recovery Act Funding for Pediatric Cancers Initiative
Up to $5 million of the National Cancer Institute's additional funding from the economic stimulus package may be used to expand the TARGET Initiative to identify molecular targets for selected pediatric cancers. NBTS is grateful that brain tumors have been identified as an additional area of NCI's TARGET Initiative. Please share this opportunity with other researchers in the pediatric brain tumor field. NBTS formalized our own commitment to molecular profiling as a key area in the NBTS Pediatric Research Initiative. Our Scientific Advisory Council is currently reviewing pediatric and adult applications for our 2009 research grant cycle.
More information about TARGET

3. Delivery of Temozolomide to the Tumor Bed Via Biodegradable Gel Matricies in a Novel Model of Intracranial Glioma with Resection
Umar Akbar, Terreia Jones, John Winestone, Madison Michael, Atul Shukla, Yichun Sun and Christopher Duntsch

We have completed in vivo safety and efficacy studies of the use of a novel drug delivery system, a gel matrix-temozolomide formulation that is injected intracranially into the post-resection cavity, as a candidate for glioma therapy.

A rat intracranial resection model of C6-GFP intracranial glioma was used for safety and toxicity studies. Biodistribution studies were performed using gel matrix-gallocyanine formulations and were evaluated at various time intervals using real-time analysis of dye distribution. Additionally, the resection model was used to determine the efficacy of gel matrix-temozolomide as compared to blank gel matrix. A subcutaneous human xenograft glioma model was used to further assess the efficacy of gel matrix-temozolomide in reducing the overall tumor load.

Gel matrix-temozolomide exhibited minimal cytotoxicity toward normal brain tissue while displaying high levels of oncolytic activity toward glioma cells. In the intracranial glioma resection and subcutaneous glioma model, administration of gel matrix-temozolomide directly to the tumor bed was well tolerated and effective at reducing the tumor load. A significant reduction of tumor load was observed (P < 0.0001) in the 30% temozolomide group (~95%) as compared to blank control. There was little morbidity and no mortality associated with gel matrix treatment.

Gel matrix-temozolomide appears to be safe and effective when used in vivo to treat intracranial glioma and warrants further development as a potential adjuvant therapy.
Article and more information

Source information:
A Journal of Neuro-Oncology, Publisher Springer Netherlands, ISSN 0167-594X (Print) 1573-7373 (Online) Category Laboratory Investigation - Human/animal tissue DOI 10.1007/s11060-009-9857-9, SpringerLink Date Wednesday, April 01, 2009

4. The Influence of Pre-Treatment Characteristics and Radiotherapy Parameters on Time Interval to Development of Radiation-Associated Meningioma
Arnold C. Paulino M.D., Irfan M. Ahmed M.D., Wei Y. Mai M.D., and Bin S. Teh M.D.

To identify pretreatment characteristics and radiotherapy parameters which may influence time interval to development of radiation-associated meningioma (RAM).

A Medline/PUBMED search of articles dealing with RAM yielded 66 studies between 1981 and 2006. Factors analyzed included patient age and gender, type of initial tumor treated, radiotherapy (RT) dose and volume, and time interval from RT to development of RAM.

A total of 143 patients with a median age at RT of 12 years form the basis of this report. The most common initial tumors or conditions treated with RT were medulloblastoma (n = 27), pituitary adenoma (n = 20), acute lymphoblastic leukemia (n = 20), low-grade astrocytoma (n = 19), and tinea capitis (n = 14). In the 116 patients whose RT fields were known, 55 (47.4%) had a portion of the brain treated, whereas 32 (27.6%) and 29 (25.0%) had craniospinal and whole-brain fields. The median time from RT to develop a RAM or latent time (LT) was 19 years (range, 163 years). Male gender (p = 0.001), initial diagnosis of leukemia (p = 0.001), and use of whole brain or craniospinal field (p ≤ 0.0001) were associated with a shorter LT, whereas patients who received lower doses of RT had a longer LT (p < 0.0001).

The latent time to develop a RAM was related to gender, initial tumor type, radiotherapy volume, and radiotherapy dose.
Article and more information

Source information:
International Journal of Radiation Oncology, Biology, Physics, doi:10.1016/j.ijrobp.2009.01.052

5. Surrogate Markers Predict Angiogenic Potential and Survival in Patients with Glioblastoma Multiforme
Greenfield, Jeffrey P. M.D., Ph.D.; Jin, David K. M.D., Ph.D.; Young, Lauren M. B.S., Christos, Paul J. M.P.H., M.S., Abrey, Lauren M.D., Rafii, Shahin M.D., Gutin, Philip H. M.D.

The neovascularization of malignant brain tumors is a poorly understood phenomenon. Radiographic and histological evidence of increased vascularity correlate with clinical grade of gliomas. However, a quantitative noninvasive assay to assess glioma vascularity and associated clinical aggressiveness has not been developed. Circulating endothelial progenitor cells are unique vascular precursors recruited from the bone marrow through the circulation to form new tumor blood vessels. These cells were measured in patients undergoing surgery for glioblastoma multiforme (GBM). We hypothesized that this might reflect the extent of tumor vascularity, predict prognosis, or be useful as an assay to assess response to antiangiogenesis therapies. In addition, we report on a novel in vitro assay to assess the proangiogenic activity within the plasma samples obtained from glioma patients.

Fifty-six patients with various-grade gliomas had peripheral venous blood collected at the time of surgery and at subsequent visits during the follow-up period. The blood was separated into plasma and cellular fractions. The plasma was utilized in a human umbilical vein endothelial cell-based angiogenic assay. The cellular fraction containing endothelial progenitor cells was isolated, and specific cellular phenotypes were immunologically separated and counted using flow cytometry. Pathological samples were reviewed at the time of initial resection, and each patient's clinical course was monitored until the time of manuscript submission.

Plasma derived from peripheral blood of patients with GBM scored significantly higher on the functional angiogenic scale compared with plasma derived from patients with low-grade gliomas and from controls. In addition, all patients with GBM had measurable numbers of bone marrow-derived endothelial precursor cells coexpressing CD133 and vascular endothelial growth factor receptor 2 in their peripheral circulation at the time of tumor resection. These cells range from less than 0.1% to 1.6% of the entire circulating mononuclear white blood cell population, or approximately 200 000 cells in some patients. A statistically significant relationship was observed between the percentage of endothelial progenitor cells in the peripheral blood at the time of initial GBM resection and survival.

These studies suggest that plasma and circulating CD133+ vascular endothelial growth factor receptor 2+ proangiogenic cells are present in the peripheral blood of patients with glioma and can be used as a surrogate biomarker to measure tumor angiogenicity. These cells can be measured at the time of diagnosis and monitored in the postoperative period. These assays can be used to predict tumor aggressiveness. Also promising is their potential to identify patients with increased angiogenic activity who might respond maximally to antiangiogenesis therapies or to assess tumor response in patients using those therapies as the use of these adjuvant molecular modalities becomes more prevalent in neuro-oncology.
Article and more information

Source information:
Neurosurgery: May 2009 - Volume 64 - Issue 5 - p 819-827, doi: 10.1227/01.NEU.0000343742.06625.DB

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